Topological semimetals are characterized by symmetry-protected band crossings, which can be preserved in different dimensions in momentum space, forming zero-dimensional nodal points, one-dimensional ...nodal lines, or even two-dimensional nodal surfaces. Materials harboring nodal points and nodal lines have been experimentally verified, whereas experimental evidence of nodal surfaces is still lacking. Here, using angle-resolved photoemission spectroscopy (ARPES), we reveal the coexistence of Dirac nodal surfaces and nodal lines in the bulk electronic structures of ZrSiS. As compared with previous ARPES studies on ZrSiS, we obtained pure bulk states, which enable us to extract unambiguously intrinsic information of the bulk nodal surfaces and nodal lines. Our results show that the nodal lines are the only feature near the Fermi level and constitute the whole Fermi surfaces. We not only prove that the low-energy quasiparticles in ZrSiS are contributed entirely by Dirac fermions but also experimentally realize the nodal surface in topological semimetals.
Cell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly ...fragmented and possess information related to their tissues of origin. Pathologies causing death of cells from particular tissues result in perturbations in the relative distribution of DNA from the affected tissues. Such tissue-of-origin analysis is particularly useful in the development of liquid biopsies for cancer. It is therefore of value to accurately determine the relative contributions of the tissues to the plasma DNA pool in a simultaneous manner. In this work, we report that in open chromatin regions, cfDNA molecules show characteristic fragmentation patterns reflected by sequencing coverage imbalance and differentially phased fragment end signals. The latter refers to differences in the read densities of sequences corresponding to the orientation of the upstream and downstream ends of cfDNA molecules in relation to the reference genome. Such cfDNA fragmentation patterns preferentially occur in tissue-specific open chromatin regions where the corresponding tissues contributed DNA into the plasma. Quantitative analyses of such signals allow measurement of the relative contributions of various tissues toward the plasma DNA pool. These findings were validated by plasma DNA sequencing data obtained from pregnant women, organ transplantation recipients, and cancer patients. Orientation-aware plasma DNA fragmentation analysis therefore has potential diagnostic applications in noninvasive prenatal testing, organ transplantation monitoring, and cancer liquid biopsy.
The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer ...endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation.
Although fish consumption may have an influence on specific mortality of major chronic diseases, the relationship between fish consumption and all-cause mortality remains inconsistent.
We performed a ...systematic search of publications using PubMed and Web of science up to 31 December 2014. Summary relative risk (RR) for the highest versus lowest category of fish consumption on risk of all-cause mortality was calculated by using a random effects model. Potential nonlinear relation was tested by modeling fish intake using restricted cubic splines with three knots at fixed percentiles of the distribution.
Twelve prospective cohort studies with 672,389 participants and 57,641 deaths were included in this meta-analysis. Compared with the lowest category, the highest category of fish intake was associated with about a 6% significantly lower risk of all-cause mortality (RR=0.94, 95% confidence interval (CI): 0.90, 0.98; I(2)=39.1%, P=0.06). The dose-response analysis indicated a nonlinear relationship between fish consumption and all-cause mortality. Compared with never consumers, consumption of 60 g of fish per day was associated with a 12% reduction (RR=0.88, 95% CI: 0.83, 0.93) in risk of total death.
These results imply that fish consumption was associated with a reduced risk of all-cause mortality.
Topological materials with exotic quantum properties are promising candidates for quantum spin electronics. Different classes of topological materials, including Weyl semimetal, topological ...superconductor, topological insulator and Axion insulator, etc., can be connected to each other via quantum phase transition. For example, it is believed that a trivial band insulator can be twisted into topological phase by increasing spin-orbital coupling or changing the parameters of crystal lattice. With the results of LDA calculation and measurement by angle-resolved photoemission spectroscopy (ARPES), we demonstrate in this work that the electronic structure of SrSn2As2 single crystal has the texture of band inversion near the critical point. The results indicate the possibility of realizing topological quantum phase transition in SrSn2As2 single crystal and obtaining different exotic quantum states.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
Objective
To assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer ...(EEC).
Design
A randomised, single‐centre, open‐label, controlled trial conducted between October 2013 and December 2017.
Setting
Shanghai OBGYN Hospital of Fudan University, China.
Population
A total of 150 patients (18–45 years old) with primary AEH or well‐differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).
Methods
Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).
Main outcomes and measures
The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w‐CR rate); the secondary efficacy parameters were 30w‐CR rate and adverse events.
Results
The 16w‐CR rate was higher in the metformin plus MA group than in the MA‐only group (34.3 versus 20.7%, odds ratio OR 2.0, 95% confidence interval CI 0.89–4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06–6.21, P = 0.04). This effect of metformin was also significant in non‐obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22–8.84, P = 0.02) and insulin‐sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03–8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.
Conclusion
As a fertility‐sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve a higher early CR rate compared with MA alone.
Tweetable
For AEH patients, metformin plus MA might be a better fertility‐sparing treatment to achieve higher early CR rate compared with MA alone.
Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine ...degrading enzyme—arginine deiminase—conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy.
Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4–5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives.
A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion.
ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway.
www.clinicaltrials.gov (NCT 01287585).
Asymptomatic patients, together with those with mild symptoms of coronavirus disease 2019 (COVID-19), may play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...transmission. However, the dynamics of virus shedding during the various phases of the clinical course of COVID-19 remains unclear at this stage.
A total of 18 patients found to be positive for SARS-CoV-2 infection by real-time reverse transcription PCR (RT-PCR) assay and admitted to Chongqing University Central Hospital between 29 January and 5 February 2020 were enrolled into this study. Medical data, pulmonary computed tomographic (CT) scan images and RT-PCR results were periodically collected during the patients' hospital stay. All participants were actively followed up for 2 weeks after discharge.
A total of nine (50%) asymptomatic patients and nine (50%) patients with mild symptoms of COVID-19 were identified at admission. Six patients (66.7%) who were asymptomatic at admission developed subjective symptoms during hospitalization and were recategorized as being presymptomatic. The median duration of virus shedding was 11.5, 28 and 31 days for presymptomatic, asymptomatic and mildly symptomatic patients, separately. Seven patients (38.9%) continued to shed virus after hospital discharge. During the convalescent phase, detectable antibodies to SARS-CoV-2 and RNA were simultaneously observed in five patients (27.8%).
Long-term virus shedding was documented in patients with mild symptoms and in asymptomatic patients. Specific antibody production to SARS-CoV-2 may not guarantee virus clearance after discharge. These observations should be considered when making decisions regarding clinical and public health, and when considering strategies for the prevention and control of SARS-CoV-2 infection.
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