Adding three cycles of induction chemotherapy with gemcitabine and cisplatin to concurrent chemoradiotherapy improved 3-year recurrence-free survival (85.3%, vs. 76.5% with concurrent ...chemoradiotherapy alone) and overall survival (94.6% vs. 90.3%). Patients receiving induction chemotherapy were more likely to have grade 3 or 4 myelosuppression, nausea, and vomiting.
Mouse models are widely used for studying gastrointestinal (GI) tract-related diseases. It is necessary and important to develop a new set of primers to monitor the mouse gut microbiota. In this ...study, 16S rRNA gene-targeted group-specific primers for Firmicutes, Actinobacteria, Bacteroidetes, Deferribacteres, "Candidatus Saccharibacteria," Verrucomicrobia, Tenericutes, and Proteobacteria were designed and validated for quantification of the predominant bacterial species in mouse feces by real-time PCR. After confirmation of their accuracy and specificity by high-throughput sequencing technologies, these primers were applied to quantify the changes in the fecal samples from a trinitrobenzene sulfonic acid-induced colitis mouse model. Our results showed that this approach efficiently predicted the occurrence of colitis, such as spontaneous chronic inflammatory bowel disease in transgenic mice. The set of primers developed in this study provides a simple and affordable method to monitor changes in the intestinal microbiota at the phylum level.
Abstract
Long-duration GRB 200829A was detected by Fermi-GBM and Swift-BAT/XRT, and then rapidly observed by other ground-based telescopes. It has a weak
γ
-ray emission in the very early phase and ...is followed by a bright spiky
γ
-ray emission pulse. The radiation spectrum of the very early emission is best fitted by a power-law function with index ∼−1.7. However, the bright spiky
γ
-ray pulse, especially the time around the peak, exhibits a distinct two-component radiation spectrum, i.e., Band function combined with a blackbody radiation spectrum. We infer the photospheric properties and reveal a medium magnetization at a photospheric position by adopting the initial size of the outflow as
r
0
= 10
9
cm. It implies that the Band component in this pulse may be formed during the dissipation of the magnetic field. The power-law radiation spectra found in the very early prompt emission may imply the external-shock origination of this phase. Then, we perform the Markov Chain Monte Carlo method fitting on the light curves of this burst, where the jet corresponding to the
γ
-ray pulse at around 20 s is used to refresh the external shock. It is shown that the light curves of the very early phase and X-ray afterglow after 40 s, involving the X-ray bump at around 100 s, can be well modeled in the external-shock scenario. For the obtained initial outflow, we estimate the minimum magnetization factor of the jet based on the fact that the photospheric emission of this jet is missed in the very early phase.
Abstract
It is well known that most gamma-ray bursts (GRBs) are dominated by positive spectral lags, while a small fraction of GRBs show negative lags. However, Wei et al. first identified a ...well-defined transition from positive lags to negative lags in GRB 160625B, and then got robust limits on a possible violation of Lorentz invariance (LIV) based on the observation. Recently, such a transition has been found in three different emission episodes in GRB 190530A by Gunapati et al., which provides us a great opportunity to investigate whether the transition results from LIV-induced observed spectral lags. Our analysis shows that the LIV model cannot be compatible with the current observations, whereas, only the spectral evolution induced spectral lags could responsible for the transition. So, spectral evolution can also explain the positive to negative lag in GRB 190530A.
Late-onset Alzheimer's disease (LOAD) risk is strongly influenced by genetic factors such as the presence of the apolipoprotein E ε4 allele (referred to here as APOE4), as well as non-genetic ...determinants including ageing. To pursue mechanisms by which these affect human brain physiology and modify LOAD risk, we initially analysed whole-transcriptome cerebral cortex gene expression data in unaffected APOE4 carriers and LOAD patients. APOE4 carrier status was associated with a consistent transcriptomic shift that broadly resembled the LOAD profile. Differential co-expression correlation network analysis of the APOE4 and LOAD transcriptomic changes identified a set of candidate core regulatory mediators. Several of these--including APBA2, FYN, RNF219 and SV2A--encode known or novel modulators of LOAD associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. Furthermore, a genetic variant within RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. These data implicate an APOE4 associated molecular pathway that promotes LOAD.
Display omitted
•A novel FUNP analysis on QFPD function.•QFPD act on COVID-19 via anti-viral, anti-inflammatory and metabolic programming.•9 QFPD ingredients presented good molecular docking score ...for 2019-nCov.•SGMH, MXSG and Others are the top 3 efficient formula for COVID-19.
Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.
Abstract
Knowledge about the Lorentz factor and its evolution of relativistic jets in gamma-ray bursts (GRBs) is crucial to understand their physics. An exact value of the bulk Lorentz factor can be ...estimated based on a high-energy spectral cutoff, which may appear in the GRBs’ prompt emission owing to the absorption of photon–photon pair production. In this work, we focus on an investigation of the bulk Lorentz factor evolution of jets in an individual burst. Based on Fermi observations, we search for bursts with multiple GRB pulses characterized by a high-energy spectral cutoff, and nine GRBs are obtained. Together with the estimation of the pulse duration and radiation spectrum, the Lorentz factor of jets corresponding to different pulses in an individual GRB is estimated. It is shown that the Lorentz factor of jets in an individual GRB fluctuates within a certain range and without a general trend in these nine GRBs. In addition, the Lorentz factors of the jets in GRBs 130821A, 160509A, and 160625B seem to increase with time. We also study the relations among
L
iso
,
E
p,z
, and Γ for the pulses in our sample, which are found to be consistent with those found in previous works.
The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard ...whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.
This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18–65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0–N1 disease (according to International Union Against Cancer–American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66–70 Gy (for the involved cervical lymph nodes), 60–62 Gy (for the high-risk target volume), and 54–56 Gy (for the low-risk target volume) were administered in 30–33 fractions, five fractions per week. Patients with stage II–IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.
Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46–59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% 95% CI 95·7–99·7 in the UNI group vs 96·3% 93·8–98·8 in the WNI group; difference −1·4% 95% CI −4·6 to 1·8; pnon-inferiority<0·0001). Although acute radiation-related toxic effects were similar between the groups, the incidence of late toxicity was lower in the UNI group than in the WNI group, including any-grade hypothyroidism (66 30% of 222 patients vs 87 39% of 221), skin toxicity (32 14% vs 55 25%), dysphagia (38 17% vs 71 32%), and neck tissue damage (50 23% vs 88 40%). No patients died during treatment. After treatment, one patient in the WNI group died from a non-cancer-related cause (dermatomyositis).
Elective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma.
Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.
For the Chinese translation of the abstract see Supplementary Materials section.
Cholesteryl ester transfer protein (CETP) mediates a step in reverse cholesterol transport, which channels cholesterol from peripheral tissues back to the liver. Mice and rats are CETP-deficient ...species, which assumedly contribute to rodent atherosclerosis resistance. Both pro- and anti-atherogenic effects have been shown in studies of CETP-transgenic rodent models thus far. As the results of pharmacological studies of CETP modification are largely controversial in humans, further knowledge about the impact of CETP on atherogenic phenotypes is required to evaluate its clinical utility for the prevention of cardiovascular and other organ damage associated with metabolic syndrome. Therefore, we newly generated a human CETP-transgenic (TghCETP) strain on the genetic background of spontaneously hypertensive rats (SHRs), which are characterized by the spontaneous occurrence of hypertension and insulin resistance. This allowed us to assess the in vivo role of CETP on cardiometabolic phenotypes in combination with hypertension. In TghCETP SHRs fed normal rat chow, systolic blood pressure was markedly elevated by 20-37 mmHg throughout the study period, and the development of fatty liver was accelerated with appreciable changes in the plasma lipid profile (HDL cholesterol reduction and triglyceride elevation). These phenotypic changes are in accordance with the assumption of proatherogenic effects inducible by the overexpression of CETP. However, with plasma LDL cholesterol levels concomitantly reduced, no apparent progression of atherosclerosis was detected in either the aorta or coronary arteries of TghCETP SHRs fed a high-fat, high-cholesterol diet. Our data provide new insight into the multifaceted regulation of cardiometabolic phenotypes via the modification of CETP.
This paper proposes a differential filtering method for the identification of modal parameters of bridges from unmanned aerial vehicle (UAV) measurement. The determination of the modal parameters of ...bridges is a key issue in bridge damage detection. Accelerometers and fixed cameras have disadvantages of deployment difficulty. Hence, the actual displacement of a bridge may be obtained by using the digital image correlation (DIC) technology from the images collected by a UAV. As drone movement introduces false displacement into the collected images, the homography transformation is commonly used to achieve geometric correction of the images and obtain the true displacement of the bridge. The homography transformation is not always applicable as it is based on at least four static reference points on the plane of target points. The proposed differential filtering method does not request any reference points and will greatly accelerate the identification of the modal parameters. The displacement of the points of interest is tracked by the DIC technology, and the obtained time history curves are processed by differential filtering. The filtered signals are input into the modal analysis system, and the basic modal parameters of the bridge model are obtained by the operational modal analysis (OMA) method. In this paper, the power spectral density (PSD) is used to identify the natural frequencies; the mode shapes are determined by the ratio of the PSD transmissibility (PSDT). The identification results of three types of signals are compared: UAV measurement with differential filtering, UAV measurement with homography transformation, and accelerometer-based measurement. It is found that the natural frequencies recognized by these three methods are almost the same. This paper demonstrates the feasibility of UAV-differential filtering method in obtaining the bridge modal parameters; the problems and challenges in UAV measurement are also discussed.
PDF
