CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
The field of quantum computing has grown from concept to demonstration devices over the past 20 years. Universal quantum computing offers efficiency in approaching problems of scientific and ...commercial interest, such as factoring large numbers, searching databases, simulating intractable models from quantum physics, and optimizing complex cost functions. Here, we present an 11-qubit fully-connected, programmable quantum computer in a trapped ion system composed of 13
Yb
ions. We demonstrate average single-qubit gate fidelities of 99.5Formula: see text, average two-qubit-gate fidelities of 97.5Formula: see text, and SPAM errors of 0.7Formula: see text. To illustrate the capabilities of this universal platform and provide a basis for comparison with similarly-sized devices, we compile the Bernstein-Vazirani and Hidden Shift algorithms into our native gates and execute them on the hardware with average success rates of 78Formula: see text and 35Formula: see text, respectively. These algorithms serve as excellent benchmarks for any type of quantum hardware, and show that our system outperforms all other currently available hardware.
The continuous increase in synthetic plastic production and poor management in plastic waste have led to a tremendous increase in the dumping into our aqueous environment. Consequently, microplastics ...commonly defined as sizes less than 5 mm are produced and stay in both seawater and freshwater environment. The presence of microplastics as a new type of emerging contaminant has become a great issue of concerns from public and government authorities. The sources of microplastics to freshwater systems are many with the largest portion from wastewater treatment plants. The abundance of microplastics varies with the location, from above 1 million pieces per cubic meter to less than 1 piece in 100 cubic meters.
Microplastics can cause several harmful physical effects on humans and living organisms through such mechanisms as entanglement and ingestion. The microplastics can act as carriers of various toxins such as additives from industrial production processes and persistent contaminants by the sorption in waters. Those toxins may cause great health problems to humans. A few studies on the fishes demonstrated that the microplastics and the associated toxins are bio-accumulated and cause such problems as intestinal damage and change in metabolic profiles.
In studies of microplastics, fresh water is first sampled by the nets with typical mesh size of 330 μm for collection of microplastics. After the volume reducing process, the samples will then go through the purification process including density separation by such inorganic salts as sodium chloride and digestion process by oxidizing agents or enzymes. The sequence of these two processes (namely purification and digestion) is dependent on the sample type. The purified samples can be studied by several analytical methods. The commonly used methods for the qualification studies are FTIR spectroscopy, Raman spectroscopy, pyrolysis-GC/MS, and liquid chromatography. A tagging method can be used in the quantification study. Our literature study finds that there is still no universal accepted quantification and qualification tools of microplastics in fresh waters. More work is anticipated so as to obtain accurate information on microplastics in freshwater, which can then be used for the better assessment of the environmental risk.
•Microplastics exhibit high abundance in freshwater systems.•The knowledge about health impacts of freshwater microplastics is limited.•A summary of current microplastics research methodology is included.•Combination of appropriate analytical approaches should be adopted to assess microplastics in freshwaters.
Current staging methods are inadequate for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene signature that is closely associated with survival of ...patients with NSCLC.
We used computer-generated random numbers to assign 185 frozen specimens for microarray analysis, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, or both. We studied gene expression in frozen specimens of lung-cancer tissue from 125 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. We used risk scores and decision-tree analysis to develop a gene-expression model for the prediction of the outcome of treatment of NSCLC. For validation, we used randomly assigned specimens from 60 other patients.
Sixteen genes that correlated with survival among patients with NSCLC were identified by analyzing microarray data and risk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision-tree analysis. The five-gene signature was an independent predictor of relapse-free and overall survival. We validated the model with data from an independent cohort of 60 patients with NSCLC and with a set of published microarray data from 86 patients with NSCLC.
Our five-gene signature is closely associated with relapse-free and overall survival among patients with NSCLC.
Background. The study aimed to evaluate the risk of hepatitis C virus (HCV) infection on hepatic and extrahepatic deaths. Methods. A cohort of 23 820 adults aged 30—65 years old were enrolled during ...1991—1992. The seromarkers hepatitis B surface antigen (HBsAg), anti-HCV, and serum HCV RNA levels at study entry were tested. The vital status was ascertained through computerized linkage with national death certification profiles from 1991 to 2008. Results. There were 19 636 HBsAg-seronegatives, including 18 541 anti-HCV seronegatives and 1095 anti-HCV seropositives. Among anti-HCV seropositives, 69.4% had detectable serum HCV RNA levels. There were 2394 deaths that occurred during an average follow-up period of 16.2 years. Compared with anti-HCV seronegatives, anti-HCV seropositives had higher mortality from both hepatic and extrahepatic diseases, showing multivariate-adjusted hazard ratio (95% confidence interval) of 1.89 (1.66—2.15) for all causes of death; 12.48 (9.34—16.66) for hepatic diseases; 1.35 (1.15—1.57) for extrahepatic diseases; 1.50 (1.10—2.03) for circulatory diseases; 2.77 (1.49—5.15) for nephritis, nephrotic syndrome, and nephrosis; 4.08 (1.38—12.08) for esophageal cancer; 4.19 (1.18—14.94) for prostate cancer; and 8.22 (1.36—49.66) for thyroid cancer. Anti-HCV seropositives with detectable HCV RNA levels had significantly higher mortality from hepatic and extrahepatic diseases than anti-HCV seropositives with undetectable HCV RNA. Conclusions. Monitoring HCV RNA in anti-HCV seropositives is essential for the prediction of mortality associated with hepatitis C.
Besides its role as the blueprint of life, DNA can also alert the cell to the presence of microbial pathogens as well as damaged or malignant cells. A major sensor of DNA that triggers the innate ...immune response is cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP activates stimulator of interferon genes (STING), which activates a signaling cascade leading to the production of type I interferons and other immune mediators. Recent research has demonstrated an expanding role of the cGAS-cGAMP-STING pathway in many physiological and pathological processes, including host defense against microbial infections, anti-tumor immunity, cellular senescence, autophagy, and autoimmune and inflammatory diseases. Biochemical and structural studies have elucidated the mechanism of signal transduction in the cGAS pathway at the atomic resolution. This review focuses on the structural and mechanistic insights into the roles of cGAS and STING in immunity and diseases revealed by these recent studies.
The cGAS-STING pathway mediates innate immune responses to pathogenic DNA from microbes or damaged cells. In this review, Zhang et al. focus on recent biochemical and structural studies of key proteins in the cGAS-STING pathway that provide mechanistic insights into immunity and diseases.
The unprecedented ability of computations to probe atomic-level details of catalytic systems holds immense promise for the fundamentals-based bottom-up design of novel heterogeneous catalysts, which ...are at the heart of the chemical and energy sectors of industry. Here, we critically analyze recent advances in computational heterogeneous catalysis. First, we will survey the progress in electronic structure methods and atomistic catalyst models employed, which have enabled the catalysis community to build increasingly intricate, realistic, and accurate models of the active sites of supported transition-metal catalysts. We then review developments in microkinetic modeling, specifically mean-field microkinetic models and kinetic Monte Carlo simulations, which bridge the gap between nanoscale computational insights and macroscale experimental kinetics data with increasing fidelity. We finally review the advancements in theoretical methods for accelerating catalyst design and discovery. Throughout the review, we provide ample examples of applications, discuss remaining challenges, and provide our outlook for the near future.
The recognition of microbial nucleic acids is a major mechanism by which the immune system detects pathogens. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate ...immune responses through production of the second messenger cGAMP, which activates the adaptor STING. The cGAS-STING pathway not only mediates protective immune defense against infection by a large variety of DNA-containing pathogens but also detects tumor-derived DNA and generates intrinsic antitumor immunity. However, aberrant activation of the cGAS pathway by self DNA can also lead to autoimmune and inflammatory disease. Thus, the cGAS pathway must be properly regulated. Here we review the recent advances in understanding of the cGAS-STING pathway, focusing on the regulatory mechanisms and roles of this pathway in heath and disease.
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