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

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Secure search for encrypted personal health records from big data NoSQL databases in cloud

© 2019, Springer-Verlag GmbH Austria, part of Springer Nature. As the healthcare industry adopts the use of cloud to store personal health record (PHR), there is a need to ensure that we maintain the ability to perform efficient search on encrypted data (stored in the cloud). In this paper, we propose a secure searchable encryption scheme, which is designed to search on encrypted personal health records from a NoSQL database in semi-trusted cloud servers. The proposed scheme supports almost all query operations available in plaintext database environments, especially multi-dimensional, multi-keyword searches with range query. Specifically, in the proposed scheme, an Adelson-Velsky Landis (AVL) tree is utilized to construct the index, and an order-revealing encryption (ORE) algorithm is used to encrypt the AVL tree and realize range query. As document-based databases are probably the most popular NoSQL database, due to their flexibility, high efficiency, and ease of use, MongoDB, a document-based NoSQL database, is chosen to store the encrypted PHR data in our scheme. Experimental results show that the scheme can achieve secure and practical searchable encryption for PHRs. A comparison of the range query demonstrates that the time overhead of our ORE-based scheme is 25.5% shorter than that of the mOPE-based Arx (an encrypted database system) scheme

Building knowledge base of urban emergency events based on crowdsourcing of social media

Copyright © 2016 John Wiley & Sons, Ltd. An emergency event is an unexceptional event that exceeds the capacity of normal resources and organization to cope and a situation that poses an immediate risk to health, life, property, or environment. Crowdsourcing connects unobtrusive and ubiquitous sensing technologies, advanced data management and analytics models, and novel visualization methods, to create solutions that improve urban environment, human life quality, and city operation systems. The crowdsourcing on social media can be used to detect and analyze urban emergency events. In this paper, in order to detect and describe the real-time urban emergency event, the knowledge base model is proposed. The crowdsourcing-based knowledge base model is firstly introduced, which uses the information from social media. Secondly, the basic definition of the proposed knowledge base model including keywords, patterns, positive sentences, and knowledge graph is given. Thirdly, the temporal information is added to the proposed knowledge base model. The case study on real data sets shows that the proposed algorithm has good performance and high effectiveness in the analysis and detection of emergency events. Copyright © 2016 John Wiley & Sons, Ltd