Summary
By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures ...according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo.
Introduction
No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups.
Methods
We searched different databases to select relevant studies. We performed Bayesian random effects network meta-analysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture.
Results
We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28–0.57), romosozumab (HR 0.49, 95% CI 0.29–0.75), risedronate (HR 0.62, 95% CI 0.50–0.79), zoledronate (HR 0.67, 95% CI 0.47–0.96), and alendronate (HR 0.69, 95% CI 0.47–0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33–0.92), romosozumab (HR 0.67, 95% CI 0.47–0.95), and denosumab (HR 0.68, 95% CI 0.50–0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4–2.6) and abaloparatide (RR 1.6, 95% CI 1.2–2.3).
Conclusion
Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo.
Summary
In this study, we analyzed 93 whole genomes from Chinese spot‐billed ducks (CSB), meat‐type ducks (MET), and egg and dual purpose‐type ducks (EDT) to characterize the genetic material flowing ...between the CSB and modern ducks. Using a frequency of shared identical‐by‐descent method, approximately 10.9 Mb introgression segments containing 140 genes were identified showing the signatures of introgression between CSB and EDT. Meanwhile, nearly 10.6 M introgression regions containing 149 genes were identified between CSB and MET. Based on the haplotypes tree of each segment, we found that the introgression between CSB and domesticated ducks was asymmetric with a high level of gene flow from domestic to CSB and a low level of migration in the opposite direction. Moreover, we identified several genes that were introgressions from CSB and showed the signature of positive selection, which may contribute to the breeding of modern ducks. Our results provide new insight into the evolution and breeding history of domestic ducks and may be useful for the future management of wild and domestic duck populations.
Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those ...time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 10
records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications.
A simple, efficient scheme was developed to obtain near-gigaelectronvolt electron beams with energy spreads of few per-mille level in a single-stage laser wakefield accelerator. Longitudinal plasma ...density was tailored to control relativistic laser-beam evolution, resulting in injection, dechirping, and a quasi-phase-stable acceleration. With this scheme, electron beams with peak energies of 780–840 MeV, rms energy spreads of 2.4‰–4.1‰, charges of 8.5–23.6 pC, and rms divergences of 0.1–0.4 mrad were experimentally obtained. Quasi-three-dimensional particle-in-cell simulations agreed well with the experimental results. The dechirping strength was estimated to reach up to 11 TeV/mm/m, which is higher than previously obtained results. Such high-quality electron beams will boost the development of compact intense coherent radiation sources and x-ray free-electron lasers.
We performed the broadband (1-100 keV) spectral analysis of the first Galactic Be ultraluminous X-ray pulsar (BeULX) Swift J0243.6+6124 observed by Insight-HXMT during the 2017−2018 outburst. The ...results show spectral transitions at two typical luminosities, roughly consistently with those reported previously via pure timing analysis. We find that the spectrum evolves and becomes softer and has higher cutoff energies until the luminosity reaches L1 (∼1.5 × 1038 erg s−1). Afterwards the spectrum becomes harder with lower cutoff energies until the luminosity increases to L2 (∼4.4 × 1038 erg s−1), around which the second spectral transition occurs. Beyond L2, the spectrum softens again and has larger cutoff energies. Similar behaviors were observed previously in other high-mass X-ray binary systems (HMXBs), especially for the second transition at higher luminosities, which is believed to have a correlation with the magnetic field of the harbored neutron star. Accordingly, we speculate that Swift J0243.6+6124 owns a neutron star with magnetic field strength >1013 G. The spectral transition at around L1 of Swift J0243.6+6124 is first observed thoroughly for any HMXB outburst characterized by strong evolution of the thermal component: the temperature of the blackbody drops sharply accompanied by a sudden increase of the blackbody radius. These spectral transitions can in principle be understood in a general scenario of balancing the emission patterns between the pencil and the fan beams at the magnetic pole, for which the extreme brightness of Swift J0243.6+6124 may provide an almost unique lab to probe the details.
We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic ...role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB.
The stacking fault energy (SFE) values of several typical face-centered-cubic (fcc) high-entropy alloys (HEAs) were experimentally measured by weak-beam dark-field transmission electron microscopy. ...It was found that the SFE of the Fe-Co-Ni-Cr-Mn HEA system strongly depends on the SFE of the individual constituents. Specifically, the SFE of this HEA system is closely associated with the Ni concentration in the alloys. Additionally, the lower SFE tends to promote formation of more deformation twins with a smaller thickness under loading, leading to better mechanical properties, especially at low temperatures.
•SFE of six Fe-Co-Ni-Cr-Mn HEAs was measured experimentally.•Constituents play an important role in the SFE, particularly the Ni content.•Lower SFE promotes formation of thinner twins during loading and better properties.
The effects of pH, ionic strength, and temperature on sorption of Eu(III) on attapulgite were investigated in the presence and absence of fulvic acid (FA) and humic acid (HA). The results indicated ...that the sorption of Eu(III) on attapulgite was strongly dependent on pH and ionic strength, and independent of temperature. In the presence of FA/HA, Eu(III) sorption was enhanced at pH < 4, decreased at pH range of 4−6, and then increased again at pH > 7. The X-ray photoelectron spectroscopy (XPS) analysis suggested that the sorption of Eu(III) might be expressed as ≡X3Eu0, ≡SwOHEu3+, and ≡SOEu−OOC−/HA in the ternary Eu/HA/attapulgite system. The extended X-ray absorption fine structure (EXAFS) analysis of Eu−HA complexes indicated that the distances of d(Eu−O) decreased from 2.415 to 2.360 Å with increasing pH from 1.76 to 9.50, whereas the coordination number (N) decreased from ∼9.94 to ∼8.56. Different complexation species were also found for the different addition sequences of HA and Eu(III) to attapulgite suspension. The results are important to understand the influence of humic substances on Eu(III) behavior in the natural environment.