Previous studies have identified several common genetic variants in VDR, GC and CYP2R1 to be associated with circulating levels of 25-hydroxyvitamin D 25(OH)D and vitamin D deficiency in Western ...populations. We aimed to investigate the associations of these variants with serum levels of 25(OH)D and vitamin D status in 1,199 Chinese. Nine common variants of VDR, GC and CYP2R1 were genotyped using multiple SNaPshot assay, and serum 25(OH)D was detected by radioimmunoassay. The prevalence of vitamin D deficiency (<50 nmol/L) was 38.8%, which is higher in women (46.2%) than in men (34.3%, P<0.0001). The risk alleles of three common variants of GC (rs7041, rs4588, and rs2282679) were significantly associated with a lower serum levels of 25(OH)D (-1.789 ≤β ≤-3.549, P ≤0.006), while common variants in VDR and CYP2R1 were not associated with serum levels of 25(OH)D after adjusted for covariates (P ≥0.30). None of the nine common variants were associated with the presence of vitamin D deficiency in multivariable adjusted logistic regression analyses (P ≥0.17). Haplotype-based analyses of GC-rs7041 and rs4588 showed that the haplotype Gc2-2 (rs7041 AA and rs4588 TT) had the lowest levels of 25(OH)D compared with other haplotypes that contained at least one copy of Gc1 allele (Ptrend <0.0001). Our results suggest that the common variants of GC are genetic determinants of serum 25(OH)D in Chinese.
Sentence similarity modeling lies at the core of many natural language processing applications, and thus has received much attention. Owing to the success of word embeddings, recently, popular neural ...network methods achieved sentence embedding. Most of them focused on learning semantic information and modeling it as a continuous vector, yet the syntactic information of sentences has not been fully exploited. On the other hand, prior works have shown the benefits of structured trees that include syntactic information, while few methods in this branch utilized the advantages of word embeddings and another powerful technique-attention weight mechanism. This paper suggests to absorb their advantages by merging these techniques in a unified structure, dubbed as attention constituency vector tree (ACVT). Meanwhile, this paper develops a new tree kernel, known as ACVT kernel, which is tailored for sentence similarity measure based on the proposed structure. The experimental results, based on 19 widely used semantic textual similarity datasets, demonstrate that our model is effective and competitive, when compared against state-of-the-art models. Additionally, the experimental results validate that many attention weight mechanisms and word embedding techniques can be seamlessly integrated into our model, demonstrating the robustness and universality of our model.
The first photocatalytic trichloromethyl radical-triggered annulative reactions of amide-linked 1,7-diynes with polyhalomethanes were established for the flexible assembly of functionalized ...quinolin-2(1H)-ones with generally acceptable yields. With the installation of the aryl group (R
) into the alkynyl moiety,
-center radical-initiated Kharasch-type addition/nucleophilic substitution/elimination cascade to produce quinolin-2(1H)-ones-incorporating
-dihaloalkene, whereas three examples of polyhalogenated quinolin-2(1H)-ones were afforded when amide-linked 1,7-diynes bearing two terminal alkyne units were subjected to BrCX
by exploiting dry acetonitrile as a solvent.
Anhui Province has been one of typical epidemic areas of schistosomiasis in East China as a wide range of large lake and marshland regions provide an ideal environment for growth and reproduction of ...the intermediate snail host. With the completion of the Yangtze River-Huaihe River Water Transfer Project (YHWTP), launched by the end of 2016, the epidemic areas are expected to expand and controlling schistosomiasis remains a challenge. Based on annual surveillance data at the county level in Anhui for the period 2006–2015, spatial and temporal cluster analyses were conducted to assess the pattern of risk through spatial (Local Moran's I and flexible scan statistic) and space-time scan statistic (Kulldorff). It was found that schistosomiasis sero-prevalence was dramatically reduced and maintained at a low level. Cluster results showed that spatial extent of schistosomiasis contracted, but snail distribution remained geographically stable across the study area. Clusters, both for schistosomiasis and snail presence, were common along the Yangtze River. Considering the effect of the ongoing YHWTP on the potential spread of schistosomiasis, Zongyang County and Anqing, which will be transected by the new water-transfer route, should be given a priority for strengthened surveillance and control. Attention should also be paid to Guichi since it is close to one of the planned inlets of the YHWTP.
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•Spatial and spatio-temporal pattern of schistosomiasis and snail were assessed in Anhui Province, China.•Three cluster detection methods were used in the study.•The spatial extent of schistosomiasis was reduced while snail distribution remained geographically constant.•Zongyang and Anqing should be given a priority for specific surveillance and control, as well as Guichi.
A novel fluidic thrust-vectoring (FTV) control method based on dual synthetic jets actuator (DSJA) is proposed and evaluated. Numerical simulations are governed by the compressible Unsteady ...Reynolds-Averaged Navier–Stokes (URANS) equations. According to the results, DSJA is capable of deflecting a primary jet with a velocity of 100 m/s and a height of 50 mm by approximately 18 degrees with a momentum coefficient of 1.96%. It produces comparatively linear control characteristics in almost all deflection angles evaluated (0~23 degrees). The low pressure generated by DSJA, the ejecting enhanced by DSJA, and the co-flow effect produced by the accelerated secondary jet all play roles in the deflection of the primary jet. Since the primary jet is strong enough, the potential of DSJA to provide thrust vector control is revealed.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for ...chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented β-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-β1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3β Ser9 (p-GSK-3β S9), thereby reactivating GSK-3β. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3β/β-catenin axis downstream of TGF-β1. Thus, BT could be a potential option to be further explored in IPF treatment.
Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on ...acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia.
Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.
In this paper we study the reachable region queries for objects moving in obstacle space. Loosely speaking, given any one of moving objects and many other information, we are asked to return the ...whole region in which each location has the non-zero probability to be reachable for the moving object. To solve this problem, this paper presents an efficient algorithm that runs in O(nlog n) time and consumes O(nlog n) space, where n is the number of vertices of obstacles. Moreover, this paper establishes the lower bound for the proposed problem, showing that our solution essentially is optimal in terms of random access memory (RAM) model. Empirical study based on both real and synthetic datasets demonstrates the effectiveness and efficiency of our solution.
Colorectal cancer (CRC) ranked second in terms of cancer mortality worldwide. It is associated with a substantial global disease burden. We aimed to examine whether the theory of planned behaviour ...(TPB) could predict the uptake of faecal immunochemical test to inform novel strategies for enhancing CRC screening participation in population-based programmes.
Cross-sectional study.
A Hong Kong-based and territory-wide telephone survey was conducted during the study period from October 2017 to November 2018.
4800 asymptomatic individuals aged 61-70 years who can communicate in Cantonese were recruited during the survey period. Those who had a history of CRC, chronic bowel inflammation, two or more first-degree relatives with CRC, and received colonoscopy in the past 10 years or faecal occult blood test in the past 5 years were excluded.
The association between CRC screening uptake and the factors pertinent to TPB was analysed by univariable and multivariable regression models and the mediating effect of intention. We adjusted for age, gender, educational level, marital and working status, as well as household income.
Multivariable regression analysis showed that high perceived behavioural control (adjusted OR (AOR)=12.35, 95% CI 8.21 to 18.60, p<0.001), high intention for CRC screening (AOR=7.86, 95% CI 6.60 to 9.36, p<0.001) and positive attitude towards CRC screening (accuracy and effectiveness: AOR=1.19, 95% CI 1.03 to 1.38, p<0.05; embarrassment and apprehension: AOR=4.27, 95% CI 3.13 to 5.82, p<0.001) were significantly associated with CRC screening uptake. Mediation analysis found that the effect of social norms on screening behaviour was primarily mediated by intention (83.2%), and this indirect, mediated effect accounted for 21.7% to 24.1% of total effects of other constructs in TPB on screening behaviour.
The variables pertinent to TPB could successfully predict CRC screening uptake. Promotion of CRC screening based on interventions that increase perceived behavioural control and behavioural intention could potentially enhance screening uptake. Further studies are needed to establish the cause and effect relationship among these variables and screening uptake, as well as to evaluate the cost-effectiveness of such interventions.
As one of most important aspects of condition-based maintenance (CBM), failure prognosis has attracted an increasing attention with the growing demand for higher operational efficiency and safety in ...industrial systems. Currently there are no effective methods which can predict a hidden failure of a system real-time when there exist influences from the changes of environmental factors and there is no such an accurate mathematical model for the system prognosis due to its intrinsic complexity and operating in potentially uncertain environment. Therefore, this paper focuses on developing a new hidden Markov model (HMM) based method which can deal with the problem. Although an accurate model between environmental factors and a failure process is difficult to obtain, some expert knowledge can be collected and represented by a belief rule base (BRB) which is an expert system in fact. As such, combining the HMM with the BRB, a new prognosis model is proposed to predict the hidden failure real-time even when there are influences from the changes of environmental factors. In the proposed model, the HMM is used to capture the relationships between the hidden failure and monitored observations of a system. The BRB is used to model the relationships between the environmental factors and the transition probabilities among the hidden states of the system including the hidden failure, which is the main contribution of this paper. Moreover, a recursive algorithm for online updating the prognosis model is developed. An experimental case study is examined to demonstrate the implementation and potential applications of the proposed real-time failure prognosis method.
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