Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined.
We completed a comprehensive literature ...search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed.
One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0–12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9–34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4–31.1. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01–16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ2 = 2.12, P = 0.5473).
The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.
Experimental realization of a universal set of quantum logic gates is the central requirement for the implementation of a quantum computer. In an 'all-geometric' approach to quantum computation, the ...quantum gates are implemented using Berry phases and their non-Abelian extensions, holonomies, from geometric transformation of quantum states in the Hilbert space. Apart from its fundamental interest and rich mathematical structure, the geometric approach has some built-in noise-resilience features. On the experimental side, geometric phases and holonomies have been observed in thermal ensembles of liquid molecules using nuclear magnetic resonance; however, such systems are known to be non-scalable for the purposes of quantum computing. There are proposals to implement geometric quantum computation in scalable experimental platforms such as trapped ions, superconducting quantum bits and quantum dots, and a recent experiment has realized geometric single-bit gates in a superconducting system. Here we report the experimental realization of a universal set of geometric quantum gates using the solid-state spins of diamond nitrogen-vacancy centres. These diamond defects provide a scalable experimental platform with the potential for room-temperature quantum computing, which has attracted strong interest in recent years. Our experiment shows that all-geometric and potentially robust quantum computation can be realized with solid-state spin quantum bits, making use of recent advances in the coherent control of this system.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heat stable antifungal factor (HSAF) is considered to be a potential biological pesticide due to its broad antifungal activity and novel mode of action. However, few studies have reported on HSAF ...production during fermentation. Thus, this work was executed to optimize the medium composition to maximize HSAF production by Lysobacter enzymogenes OH11, with soybean flour, glucose and CaCl2 identified as suitable nutrients with concentrations of 8·00, 7·89 and 0·72 g l−1 respectively. Simultaneously, the quantitative analysis of HSAF production was established by eliminating the emulsification problem, and the highest HSAF production was determined to be 356·34 ± 13·86 mg l−1 using the optimized medium, 12‐fold higher than when using the 10% TSB medium (29·34 ± 2·57 mg l−1). Furthermore, the cost of this medium was assessed and nearly 31‐fold lower than that of 10% TSB. This study suggests that the optimized medium is not only effective but also economical for HSAF production.
Significance and Impact of the Study
Significance and Impact of the Study: Heat stable antifungal factor (HSAF) exhibits a potent and broad antifungal activity with a novel mode of action. Increased production and reduced cost of raw materials are particularly important for the future production of HSAF, however, no report was involved in these studies. This study aimed to improve the production of HSAF with cheap raw materials through the medium optimization, which would lay the foundation for the application of HSAF in biological control.
Significance and Impact of the Study: Heat stable antifungal factor (HSAF) exhibits a potent and broad antifungal activity with a novel mode of action. Increased production and reduced cost of raw materials are particularly important for the future production of HSAF, however, no report was involved in these studies. This study aimed to improve the production of HSAF with cheap raw materials through the medium optimization, which would lay the foundation for the application of HSAF in biological control.
Summary
Background
Deregulation of mammalian target of rapamycin (mTOR) signalling is common in human hepatocellular carcinoma (HCC).
Aim
To determine the maximum tolerated dose (MTD) of the oral ...mTOR inhibitor everolimus in advanced HCC patients.
Methods
Patients with locally advanced or metastatic HCC (Child‐Pugh class A or B) were enrolled in an open‐label phase 1 study and randomly assigned to daily (2.5–10 mg) or weekly (20–70 mg) everolimus in a standard 3 + 3 dose‐escalation design. MTD was based on the rate of dose‐limiting toxicities (DLTs). Secondary endpoints included safety, pharmacokinetics and tumour response. In a post hoc analysis, serum hepatitis B virus (HBV) DNA levels were quantified.
Results
Thirty‐nine patients were enrolled. DLTs occurred in five of 21 patients in the daily and two of 19 patients in the weekly cohort. Daily and weekly MTDs were 7.5 mg and 70 mg respectively. Grade 3/4 adverse events with a ≥10% incidence were thrombocytopenia, hypophosphataemia and alanine transaminase (ALT) elevation. In four hepatitis B surface antigen (HBsAg)‐seropositive patients, grade 3/4 ALT elevations were accompanied by significant (>1 log) increases in serum HBV levels. The incidence of hepatitis flare (defined as ALT increase >100 IU/mL from baseline) in HBsAg‐seropositive patients with and without detectable serum HBV DNA before treatment was 46.2% and 7.1% respectively (P < 0.01, Fisher exact test). Disease control rates in the daily and weekly cohorts were 71.4% and 44.4% respectively.
Conclusions
The recommended everolimus dosing schedule for future hepatocellular carcinoma studies is 7.5 mg daily. Prophylactic anti‐viral therapy should be mandatory for HBsAg‐seropositive patients (ClinicalTrials.gov NCT00390195).
Topological Dirac and Weyl semimetals not only host quasiparticles analogous to the elementary fermionic particles in high-energy physics, but also have a non-trivial band topology manifested by ...gapless surface states, which induce exotic surface Fermi arcs1,2. Recent advances suggest new types of topological semimetal, in which spatial symmetries protect gapless electronic excitations without high-energy analogues3–11. Here, using angle-resolved photoemission spectroscopy, we observe triply degenerate nodal points near the Fermi level of tungsten carbide with space group \P\bar{6}m2\ (no. 187), in which the low-energy quasiparticles are described as three-component fermions distinct from Dirac and Weyl fermions. We further observe topological surface states, whose constant-energy contours constitute pairs of ‘Fermi arcs’ connecting to the surface projections of the triply degenerate nodal points, proving the non-trivial topology of the newly identified semimetal state.
Abstract
A spectral-energy distribution (SED) model for Type Ia supernovae (SNe Ia) is a critical tool for measuring precise and accurate distances across a large redshift range and constraining ...cosmological parameters. We present an improved model framework, SALT3, which has several advantages over current models—including the leading SALT2 model (SALT2.4). While SALT3 has a similar philosophy, it differs from SALT2 by having improved estimation of uncertainties, better separation of color and light-curve stretch, and a publicly available training code. We present the application of our training method on a cross-calibrated compilation of 1083 SNe with 1207 spectra. Our compilation is 2.5× larger than the SALT2 training sample and has greatly reduced calibration uncertainties. The resulting trained SALT3.K21 model has an extended wavelength range 2000–11,000 Å (1800 Å redder) and reduced uncertainties compared to SALT2, enabling accurate use of low-
z I
and
iz
photometric bands. Including these previously discarded bands, SALT3.K21 reduces the Hubble scatter of the low-
z
Foundation and CfA3 samples by 15% and 10%, respectively. To check for potential systematic uncertainties, we compare distances of low (0.01 <
z
< 0.2) and high (0.4 <
z
< 0.6) redshift SNe in the training compilation, finding an insignificant 3 ± 14 mmag shift between SALT2.4 and SALT3.K21. While the SALT3.K21 model was trained on optical data, our method can be used to build a model for rest-frame NIR samples from the Roman Space Telescope. Our open-source training code, public training data, model, and documentation are available at
https://saltshaker.readthedocs.io/en/latest/
, and the model is integrated into the
sncosmo
and
SNANA
software packages.
Summary
The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were ...collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never‐smokers (adjusted hazard ratio 0.69; 95% CI 0.62–0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack‐years of smoking among current smokers (Ptrend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
Abstract
Various methods of evaluating a humectant’s moisture retention have unique mechanisms. Hence, for designing advanced or efficient ingredients of cosmetic products, a clear understanding of ...differences among methods is required. The aim of this study was to analyze the moisture-retention capacity of glycerin, a common ingredient in cosmetic products. Specifically, this study applied gravimetric analysis, transepidermal water loss (TEWL) analysis, and differential scanning calorimetry (DSC) to examine the evaporation of glycerin solutions of different concentrations. The results revealed that the moisture-retention capacity of glycerin increased with the glycerin concentration from 0 to 60 wt%, and glycerin at concentration of 60–70 wt% did not exhibit weight change during the evaporation process. When the glycerin concentration exceeded 70 wt%, moisture sorption occurred in the glycerin solution. Furthermore, the results revealed a deviation between the evaporation rates measured using gravimetric analysis and those measured using TEWL analysis. However, normalizing the results of these analyses yielded the relative evaporation rates to water, which were consistent between these two analyses. DSC thermograms further confirmed the consistent results and identified two hydrated water microstructures (nonfreezable water and free water) in the glycerin solutions, which explained why the measured evaporation rate decreased with the glycerin concentration. These findings can be applied to prove the moisture-retention capacity of a humectant in cosmetic products by different measuring methods.
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