There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real‐time PCR analysis, we evaluated the expression profiles from a large panel of genes in TB patients and healthy individuals in an Indian cohort. Classification models were built and validated for their capacity to discriminate samples from TB patients and controls within this cohort and on external independent gene expression datasets. A combination of only four genes distinguished TB patients from healthy individuals in both cross‐validations and on separate validation datasets with very high accuracy. An external validation on two distinct cohorts using a real‐time PCR setting confirmed the predictive power of this 4‐gene tool reaching sensitivity scores of 88% with a specificity of around 75%. Moreover, this gene signature demonstrated good classification power in HIV + populations and also between TB and several other pulmonary diseases. Here we present proof of concept that our 4‐gene signature and the top classifier genes from our models provide excellent candidates for the development of molecular point‐of‐care TB diagnosis in endemic areas.

No abstract

Background Candida auris is a new pathogen called “superbug fungus” which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris. Methods We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0. Results It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%). Conclusions Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management.

Abstract-Named Data Networking (NDN) is a recently proposed general-purpose network architecture that leverages the strengths of Internet architecture while aiming to address its weaknesses. NDN names packets rather than end-hosts, and most of NDN's characteristics are a consequence of this fact. In this paper, we focus on the packet forwarding model of NDN. Each packet has a unique name which is used to make forwarding decisions in the network. NDN forwarding differs substantially from that in IP; namely, NDN forwards based on variable-length names and has a read-write data plane. Designing and evaluating a scalable NDN forwarding node architecture is a major effort within the overall NDN research agenda. In this paper, we present the concepts, issues and principles of scalable NDN forwarding plane design. The essential function of NDN forwarding plane is fast name lookup. By studying the performance of the NDN reference implementation, known as CCNx, and simplifying its forwarding structure, we identify three key issues in the design of a scalable NDN forwarding plane: 1) exact string matching with fast updates, 2) longest prefix matching for variable-length and unbounded names and 3) large-scale flow maintenance. We also present five forwarding plane design principles for achieving 1 Gbps throughput in software implementation and 10 Gbps with hardware acceleration.

The role of microRNA in the aberrant autophagy that occurs in pancreatic cancer remains controversial. Because hypoxia is known to induce autophagy, we screened for differentially expressed microRNAs using a miRNA microarray with pancreatic cancer cells cultured under normoxic and hypoxic conditions. We found that miR-138-5p was among the most downregulated miRNA in hypoxia-stimulated cells, and that overexpression of miR-138-5p substantially reduced expression of autophagy markers. In addition, western blot and immunofluorescence analyses and electron microscopy revealed that miR-138-5p inhibited autophagy in pancreatic cancer cells and blocked serum starvation-induced autophagic flux independently of the typical autophagic signaling pathway. miR-138-5p had no effect on ATG3, ATG5, or ATG7, three primary autophagy-associated genes. Instead, miR-138-5p specifically targeted the SIRT1 3′ untranslated region and suppressed autophagy by reducing the level of SIRT1, which acetylates FoxO1 and regulates autophagy via FoxO1/Rab7. SIRT1 or Rab7 knockdown blocked the SIRT1/FoxO1/Rab7 axis and suppressed autophagic inhibition by miR-138-5p. Finally, we found that miR-138-5p inhibited autophagy and tumor growth in vivo. These results indicate that miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1.