Sun Yat-sen University

About: Sun Yat-sen University is a education organization based out in Guangzhou, Guangdong, China. It is known for research contribution in the topics: Population & Cancer. The organization has 115149 authors who have published 113763 publications receiving 2286465 citations. The organization is also known as: Zhongshan University & SYSU.

Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.

Abstract: Summary Background Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. Methods Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. Findings 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6·5 months (95% CI 5·56–7·56) in patients treated with sorafenib, compared with 4·2 months (3·75–5·46) in those who received placebo (hazard ratio [HR] 0·68 [95% CI 0·50–0·93]; p=0·014). Median TTP was 2·8 months (2·63–3·58) in the sorafenib group compared with 1·4 months (1·35–1·55) in the placebo group (HR 0·57 [0·42–0·79]; p=0·0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10·7%]), diarrhoea (nine patients [6·0%]), and fatigue (five patients [3·4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11·4%]) and diarrhoea (11 patients [7·4%]); these adverse events rarely led to discontinuation. Interpretation Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma. Funding Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc.

Planck 2018 results. VI. Cosmological parameters

Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the cosmic microwave background (CMB) anisotropies, combining information from the temperature and polarization maps and the lensing reconstruction Compared to the 2015 results, improved measurements of large-scale polarization allow the reionization optical depth to be measured with higher precision, leading to significant gains in the precision of other correlated parameters Improved modelling of the small-scale polarization leads to more robust constraints on manyparameters,withresidualmodellinguncertaintiesestimatedtoaffectthemonlyatthe05σlevelWefindgoodconsistencywiththestandard spatially-flat6-parameter ΛCDMcosmologyhavingapower-lawspectrumofadiabaticscalarperturbations(denoted“base ΛCDM”inthispaper), from polarization, temperature, and lensing, separately and in combination A combined analysis gives dark matter density Ωch2 = 0120±0001, baryon density Ωbh2 = 00224±00001, scalar spectral index ns = 0965±0004, and optical depth τ = 0054±0007 (in this abstract we quote 68% confidence regions on measured parameters and 95% on upper limits) The angular acoustic scale is measured to 003% precision, with 100θ∗ = 10411±00003Theseresultsareonlyweaklydependentonthecosmologicalmodelandremainstable,withsomewhatincreasederrors, in many commonly considered extensions Assuming the base-ΛCDM cosmology, the inferred (model-dependent) late-Universe parameters are: HubbleconstantH0 = (674±05)kms−1Mpc−1;matterdensityparameterΩm = 0315±0007;andmatterfluctuationamplitudeσ8 = 0811±0006 We find no compelling evidence for extensions to the base-ΛCDM model Combining with baryon acoustic oscillation (BAO) measurements (and consideringsingle-parameterextensions)weconstraintheeffectiveextrarelativisticdegreesoffreedomtobe Neff = 299±017,inagreementwith the Standard Model prediction Neff = 3046, and find that the neutrino mass is tightly constrained toPmν < 012 eV The CMB spectra continue to prefer higher lensing amplitudesthan predicted in base ΛCDM at over 2σ, which pulls some parameters that affect thelensing amplitude away from the ΛCDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAOdataThejointconstraintwithBAOmeasurementsonspatialcurvatureisconsistentwithaflatuniverse, ΩK = 0001±0002Alsocombining with Type Ia supernovae (SNe), the dark-energy equation of state parameter is measured to be w0 = −103±003, consistent with a cosmological constant We find no evidence for deviations from a purely power-law primordial spectrum, and combining with data from BAO, BICEP2, and Keck Array data, we place a limit on the tensor-to-scalar ratio r0002 < 006 Standard big-bang nucleosynthesis predictions for the helium and deuterium abundances for the base-ΛCDM cosmology are in excellent agreement with observations The Planck base-ΛCDM results are in good agreement with BAO, SNe, and some galaxy lensing observations, but in slight tension with the Dark Energy Survey’s combined-probe results including galaxy clustering (which prefers lower fluctuation amplitudes or matter density parameters), and in significant, 36σ, tension with local measurements of the Hubble constant (which prefer a higher value) Simple model extensions that can partially resolve these tensions are not favoured by the Planck data

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.

Abstract: SARS-CoV-2 Viral Load in Upper Respiratory Specimens The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19....