Nasopharyngeal carcinoma Chen, Yu-Pei; Chan, Anthony T C; Le, Quynh-Thu ...
The Lancet (British edition),
07/2019, Volume:
394, Issue:
10192
Journal Article
Peer reviewed
Nasopharyngeal carcinoma is characterised by distinct geographical distribution and is particularly prevalent in east and southeast Asia. Epidemiological trends in the past decade have shown that its ...incidence has declined gradually but progressively, and mortality has been reduced substantially. These findings probably reflect lifestyle and environmental changes, enhanced understanding of the pathogenesis and risk factors, population screening, advancements in imaging techniques, and individualised comprehensive chemoradiotherapy strategies. In particular, plasma Epstein-Barr virus (EBV) DNA has been used for population screening, prognostication, predicting treatment response for therapeutic adaptation, and disease surveillance. Moreover, the widespread application of intensity-modulated radiotherapy and optimisation of chemotherapy strategies (induction, concurrent, adjuvant) have contributed to improved survival with reduced toxicities. Among the existing developments in novel therapeutics, immune checkpoint therapies have achieved breakthroughs for treating recurrent or metastatic disease and represent a promising future direction in nasopharyngeal carcinoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Deer genera around the globe are threatened by anthropogenic interference. The translocation of alien species and their subsequent genetic introgression into indigenous deer populations is ...particularly harmful to the species of greatest conservation concern. Products derived from deer, including venison and antler velvet, are also at risk of fraudulent labeling. The current molecular markers used to genetically identify deer species were developed from genome sequences and have limited applicability for cross-species amplification. The absence of efficacious diagnostic techniques for identifying deer species has hampered conservation and wildlife crime investigation efforts. Expressed sequence tag-simple sequence repeat (EST-SSR) markers are reliable tools for individual and species identification, especially in terms of cross-species genotyping. We conducted transcriptome sequencing of sambar (Rusa unicolor) antler velvet and acquired 11,190 EST-SSRs from 65,074 newly assembled unigenes. We identified a total of 55 unambiguous amplicons in sambar (n = 45), which were selected as markers to evaluate cross-species genotyping in sika deer (Cervus nippon, n = 30) and red deer (Cervus elaphus, n = 46), resulting in cross-species amplification rates of 94.5% and 89.1%, respectively. Based on polymorphic information content (>0.25) and genotyping fidelity, we selected 16 of these EST-SSRs for species identification. This marker set revealed significant genetic differentiation based on the fixation index and genetic distance values. Principal coordinate analysis and STRUCTURE analysis revealed distinct clusters of species and clearly identified red-sika hybrids. These markers showed applicability across different genera and proved suitable for identification and phylogenetic analyses across deer species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abnormal tumour vasculature has a significant impact on tumour progression and response to therapy. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis and, thus, can be ...delivered to normalize tumour vasculature. However, a NO-delivery system with a prolonged half-life and a sustained release mechanism is currently lacking. Here we report the development of NanoNO, a nanoscale carrier that enables sustained NO release to efficiently deliver NO into hepatocellular carcinoma. Low-dose NanoNO normalizes tumour vessels and improves the delivery and effectiveness of chemotherapeutics and tumour necrosis factor-related, apoptosis-inducing, ligand-based therapy in both primary tumours and metastases. Furthermore, low-dose NanoNO reprogrammes the immunosuppressive tumour microenvironment toward an immunostimulatory phenotype, thereby improving the efficacy of cancer vaccine immunotherapy. Our findings demonstrate the ability of nanoscale NO delivery to efficiently reprogramme tumour vasculature and immune microenvironments to overcome resistance to cancer therapy, resulting in a therapeutic benefit.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
Systematic review and network meta-analysis.
...Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
PROSPERO CRD42017082553.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Catalysts play an important role in the energy conversion reaction process. With the continuous development of the energy sector, researchers are constantly exploring and developing new ...high-performance, inexpensive catalysts to meet the demand. Transition metal phosphides (TMPs) as ever-evolving catalytic materials have received more and more attention. Many studies have suggested that transition metal phosphides could be ideal catalysts due to their low cost, abundance, and high efficiency. In many areas, TMPs can be applied as stable and efficient catalytic materials. Therefore, many kinds of TMPs are designed and synthesized by different methods. This article has summarized the recent research progress of TMPs, including their preparation methods and morphologies. Moreover, the application and catalytic performance of TMPs in different catalytic fields are further elaborated, and views on the opportunities and challenges faced by phosphide catalysts are presented.
Catalysts play an important role in the energy conversion reaction process.
Online product ratings offer information on product quality. Scholars have recently proposed the potential of designing multidimensional rating systems to better convey information on multiple ...dimensions of products. This study investigates whether and how multidimensional rating systems affect consumer satisfaction (measured by product ratings), based on both observational data and two randomized experiments. Our identification strategy of the observational study hinges on a natural experiment on TripAdvisor when the website started to allow consumers to rate multiple dimensions of the restaurants, as opposed to only providing an overall rating, in January 2009. We further obtain rating data on the same set of restaurants from Yelp, which controls for the unobserved restaurant quality over time and allows us to identify the causal effect using a difference-in-differences approach. Results from the econometric analyses show that ratings in a single-dimensional rating system have a downward trend and a higher dispersion, whereas ratings in a multidimensional rating system are significantly higher and convergent. Findings from two randomized experiments suggest that the multidimensional rating system helps consumers find products that better fit their preferences and increases the confidence of their choices. We also show that the observed results cannot be explained by the priming effect due to rating system interface or a list of other alternative explanations. The combined evidence from the natural experiment and randomized experiments support the view that the multidimensional rating system enhances rating informativeness and provide implications for designing online rating systems that help consumers match their preferences with product attributes.
Data and the online appendix are available at
https://doi.org/10.1287/mnsc.2017.2852
.
This paper was accepted by Anandhi Bharadwaj, information systems.
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CEKLJ, IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
Organic–inorganic hybrid perovskites have realized a high power conversion efficiency (PCE) in both n–i–p and p–i–n device configurations. However, since the p–i–n structure exempts the sophisticated ...processing of charge‐transporting layers, it seems to possess better potential for practical applications than the n–i–p one. Currently, the inorganic NiOx is the most prevailing hole‐transporting layer (HTL) used in p–i–n perovskite solar cells. Nevertheless, defects might exist on its surface to influence the charge transfer/extraction across the interface with perovskite and to affect the quality of the perovskite film grown on it. Herein, two novel 7helicenes with stable open‐shell singlet biradical ground states at room temperature are demonstrated as an effective surface modifier of the NiOx HTL. Their nonpolar feature effectively promotes the crystallinity of the perovskite film grown on them; meanwhile, their unique partial biradical character seems to provide a certain degree of defect passivation function at the perovskite interface to facilitate interfacial charge transfer/extraction. As a result, both 1ab‐ and 1bb‐modifed devices yield a PCE of >18%, exceeding the value (15.6%) of the control device using a sole NiOx HTL, and the maximum PCE can reach 19%. Detailed characterizations are carefully conducted to understand the underlying reasons behind such enhancement.
The 7helicenes with stable partial open‐shell biradical ground states are demonstrated as effective surface modifiers of the inorganic NiOx hole‐transporting layer in p–i–n perovskite solar cells. Their nonpolar feature improves the crystallinity of the perovskite films grown on them. Meanwhile, their biradical character provides a certain defect passivation function to facilitate charge transfer/extraction across the perovskite interface.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Contests have long existed to source ideas and solutions. The emergence of crowdsourcing contest platforms greatly reduces the costs and broadens the reach of running contests by facilitating access ...to a large pool of labor, making contests a cost‐efficient approach to procure ideas/solutions even for employers of limited resources. As a result, the use of contests surges and there is a flux of small‐to‐medium size contests to these platforms. This study focuses on these new waves of small‐to‐medium‐size contests on crowdsourcing contest platforms and extends the literature in several ways: First, prior literature focuses extensively on contest prize, we also consider the effect of contest duration, which plays salient role on contest platforms. Our findings provide evidence that contest duration affects both the number and the quality of contestants attracted to a contest. Second, prior literature assumes contests exist independently and that the quality distribution of contestants is exogenous; accordingly, the number of contestants can be regarded as a proxy of contest performance. We show that contest design parameters have direct effects on the quality distribution of contestants. Specifically, increasing contest duration, while attracting more contestants, results in a downward shift on the quality distribution of the contestants attracted to the contest. Third, recognizing that each contest does not exist independently on crowdsourcing contest platforms, we also incorporate the number of competing contests in our model. Our results provide practical recommendations on how to set up successful contests and attract high‐quality contestants to a contest on a crowdsourcing contest platform.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of immune checkpoint blockade (ICB)-based immunotherapy has dramatically changed methods of cancer treatment. This approach triggers a durable treatment response and prolongs ...patients' survival; however, not all patients can benefit. Accumulating evidence demonstrated that the efficacy of ICB is dependent on a robust antitumor immune response that is usually damaged in most tumors. Conventional chemotherapy and targeted therapy promote the antitumor immune response by increasing the immunogenicity of tumor cells, improving CD8+ T cell infiltration, or inhibiting immunosuppressive cells in the tumor microenvironment. Such immunomodulation provides a convincing rationale for the combination therapy of chemotherapeutics and ICBs, and both preclinical and clinical investigations have shown encouraging results. However, the optimal drug combinations, doses, timing, and sequence of administration, all of which affect the immunomodulatory effect of chemotherapeutics, as well as the benefit of combination therapy, are not yet determined. Future studies should focus on these issues and help to develop the optimal combination regimen for each cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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