Highlights Established blood tests can be used in primary care to stratify patients with fatty liver disease. A 2-step pathway (FIB-4 followed by ELF TM if required) reduced unnecessary referrals by 80%. This pathway also improved the detection of cases of advanced fibrosis 5-fold and cirrhosis 3-fold. This pathway can be used in primary care to identify patients who might benefit from referral to liver specialists. This should reduce unnecessary referrals while at the same time improving the detection of cirrhosis.

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Due to the proliferation of ICT during the last few decades, there is an exponential increase in the usage of various smart applications such as smart farming, smart healthcare, supply-chain & logistics, business, tourism and hospitality, energy management etc. However, for all the aforementioned applications, security and privacy are major concerns keeping in view of the usage of the open channel, i.e., Internet for data transfer. Although many security solutions and standards have been proposed over the years to enhance the security levels of aforementioned smart applications, but the existing solutions are either based upon the centralized architecture (having single point of failure) or having high computation and communication costs. Moreover, most of the existing security solutions have focussed only on few aspects and fail to address scalability, robustness, data storage, network latency, auditability, immutability, and traceability. To handle the aforementioned issues, blockchain technology can be one of the solutions. Motivated from these facts, in this paper, we present a systematic review of various blockchain-based solutions and their applicability in various Industry 4.0-based applications. Our contributions in this paper are in four fold. Firstly, we explored the current state-of-the-art solutions in the blockchain technology for the smart applications. Then, we illustrated the reference architecture used for the blockchain applicability in various Industry 4.0 applications. Then, merits and demerits of the traditional security solutions are also discussed in comparison to their countermeasures. Finally, we provided a comparison of existing blockchain-based security solutions using various parameters to provide deep insights to the readers about its applicability in various applications.

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Optimal immune activation of naïve CD8 T cells requires signal 1 mediated by the T cell receptor, signal 2 mediated by co-stimulation and signal 3 provided by pro-inflammatory cytokines. However, the potential for signal 3 cytokines to rescue anti-viral responses in functionally exhausted T cells has not been defined. We investigated the effect of using third signal cytokines IL-12 or IFN-α to rescue the exhausted CD8 T cell response characteristic of patients persistently infected with hepatitis B virus (HBV). We found that IL-12, but not IFN-α, potently augmented the capacity of HBV-specific CD8 T cells to produce effector cytokines upon stimulation by cognate antigen. Functional recovery mediated by IL-12 was accompanied by down-modulation of the hallmark inhibitory receptor PD-1 and an increase in the transcription factor T-bet. PD-1 down-regulation was observed in HBV but not CMV-specific T cells, in line with our finding that the highly functional CMV response was not further enhanced by IL-12.IL-12 enhanced a number of characteristics of HBV-specific T cells important for viral control: cytotoxicity, polyfunctionality and multispecificity. Furthermore, IL-12 significantly decreased the pro-apoptotic molecule Bim, which is capable of mediating premature attrition of HBV-specific CD8 T cells. Combining IL-12 with blockade of the PD-1 pathway further increased CD8 functionality in the majority of patients. These data provide new insights into the distinct signalling requirements of exhausted T cells and the potential to recover responses optimised to control persistent viral infections.

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Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy‐proven NAFLD were included in this study. Eighty‐four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77‐0.82 in patients with F0‐2 fibrosis and 0.82‐0.84 in patients with F0‐3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85‐0.87. Conclusion: PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH. (HEPATOLOGY 2013)