Tandem mass spectrometryfor the determination of the sitesof DNA interstrand cross-link

Formation of DNA interstrand cross-link is implicated in the mechanism of anticancer activity of some drugs. Here we examined the fragmentation of deprotonated ions of double-stranded oligodeoxynucleotides (ODNs) that are covalently held together with either a mitomycin C or a 4,5′,8-trimethylpsoralen. Our results showed that, upon collisional activation, the covalently-bound duplex ODNs cleaved to give a series of wn and [an − base] ions; the sites of interstrand cross-linking could be determined from the mass shifts of some product ions. In addition, compared with the product-ion spectra acquired on an ion trap, those obtained from sustained off-resonance irradiation-collisionally activated dissociation (SORI-CAD) on a Fourier transform mass spectrometer offered high mass-resolving power, which facilitated unambiguous assignment of product ions and made it an effective method for locating the cross-linking sites

Acute Effects of Particulate Air Pollution on Ischemic Stroke and Hemorrhagic Stroke Mortality

Background and Purpose: A large body of literature reported the association of particulate matter (PM) with stroke in high-income countries. Few studies have examined the association between PM and stroke in middle- and low-income countries and considered the types of stroke. In this study, we examined the short-term effects of particulate matter <2.5 μm in diameter (PM2.5) and particulate matter <10 μm in diameter (PM10) on ischemic stroke mortality and hemorrhagic stroke mortality in Beijing, China.Methods: We used an ecological study design and quasi-Poisson generalized additive models to evaluate the association of PM2.5 and PM10 and cerebrovascular diseases mortality, as well as ischemic- and hemorrhagic stroke mortality. In the model, we controlled long-term and season trends, temperature, and relative humidity, the day of the week and air pollution. For cerebrovascular diseases mortality, we examined the effects stratified by sex and age with different lag days.Results: A total of 48,122 deaths for cerebrovascular disease (32,799 deaths for ischemic stroke and 13,051 deaths for hemorrhagic stroke) were included in the study. PM2.5 was associated with stroke mortality. The 10 μg/m3 increase of PM2.5 was associated with the increase of mortality, 0.27% (95% CI, 0.12–0.43%) for cerebrovascular diseases, 0.23% (95% CI, 0.04–0.42%) for ischemic stroke and 0.37% (95% CI, 0.07–0.67%) for hemorrhagic stroke -. The associations between PM10 and mortality were also detected for cerebrovascular diseases and ischemic stroke, but not in hemorrhagic stroke. The stratified analysis suggested age and gender did not modify the effects of PM on mortality significantly.Conclusions: Our study suggested that short-term exposure to ambient PM was associated with the risk of stroke mortality

Construction of Urban Design Support System using Cloud Computing Type Virtual Reality and Case Study

This paper contributes a design support system based on cloud-computing type virtual reality (cloud-based VR) for urban planning and urban design. A platform for Cloud-based VR technology, i.e. a VR-Cloud server, is used to open a VR dataset to public collaboration over the Internet. The digital attributes representing the design scheme of design concepts includes the land use zone, building regulations, urban design style, and other design details of architectural design, landscape, and traffic/architectural environment/sunshine/wheather/noise/inundation/tsunami/earthquake/evacuati on simulation. Then practice using this cloud-based VR urban design support system is categorized into three applicable case ‘types’, synchronized, distributed synchronized and distributed non-synchronized. The effect of the use of this system in urban design and in urban planning processes is evaluated

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

BackgroundCorona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients.MethodsThe four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockToolsResultsFirstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2.ConclusionIn the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2

Physical activity modifies the association of the composite dietary antioxidant index with all-cause mortality in the US osteoarthritis population

BackgroundIt remains unclear how antioxidant intake affects all-cause mortality in osteoarthritis (OA) patients. In this prospective cohort study, we aim to explore the association of the Composite Dietary Antioxidant Index (CDAI) with all-cause mortality and investigate the interaction of physical activity (PA) and CDAI on all-cause mortality in OA populations.MethodsA total of 3,197 adults with OA in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were included in this study. Death outcomes were obtained from National Death Index (NDI) records. Multivariable Cox regression analyses with cubic spines were applied to estimate the association of CDAI with all-cause mortality. The interaction between CDAI and PA on all-cause mortality was further assessed in stratified analysis and interaction tests.ResultsThe hazard ratios for all-cause mortality were 0.95 (0.77–1.17) for Q2, 0.75 (0.59–0.97) for Q3, and 0.71 (0.55–0.92) for Q4 (P for trend <0.001), compared with the lowest quartile of CDAI. A negative linear association was found between CDAI and all-cause mortality. In the stratified analyses, CDAI was negatively associated with all-cause mortality in the insufficient PA group. While in the low and sufficient PA group, there were nonlinear relationships of CDAI with all-cause mortality.ConclusionA negative linear relationship was observed between CDAI and all-cause mortality in OA patients, and this association was significantly modified by PA. Higher intake of dietary antioxidants might be the interventional objective to reduce the risk of all-cause mortality in the US OA population

Substantial Progress Yet Significant Opportunity for Improvement in Stroke Care in China

BACKGROUND AND PURPOSE: Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended ischemic stroke performance metrics in the past decade has been previously shown to be suboptimal. Since then, several nationwide stroke quality management initiatives have been conducted in China. We sought to determine whether adherence had improved since then. METHODS: Data were obtained from the 2 phases of China National Stroke Registries, which included 131 hospitals (12 173 patients with acute ischemic stroke) in China National Stroke Registries phase 1 from 2007 to 2008 versus 219 hospitals (19 604 patients) in China National Stroke Registries phase 2 from 2012 to 2013. Multiple regression models were developed to evaluate the difference in adherence to performance measure between the 2 study periods. RESULTS: The overall quality of care has improved over time, as reflected by the higher composite score of 0.76 in 2012 to 2013 versus 0.63 in 2007 to 2008. Nine of 13 individual performance metrics improved. However, there were no significant improvements in the rates of intravenous thrombolytic therapy and anticoagulation for atrial fibrillation. After multivariate analysis, there remained a significant 1.17-fold (95% confidence interval, 1.14-1.21) increase in the odds of delivering evidence-based performance metrics in the more recent time periods versus older data. The performance metrics with the most significantly increased odds included stroke education, dysphagia screening, smoking cessation, and antithrombotics at discharge. CONCLUSIONS: Adherence to stroke performance metrics has increased over time, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China

A Neuroimaging Marker Based on Diffusion Tensor Imaging and Cognitive Impairment Due to Cerebral White Matter Lesions

Background: The peak width of skeletonized mean diffusivity (PSMD) is a new, fully automated, robust imaging marker for cerebral small vessel disease (SVD), strongly associated with processing speed. However, it has never been applied to cerebral white matter lesions (WMLs). Our study aimed to investigate the correlation between PSMD and cognition, particularly in the executive function of patients with WMLs.Methods: A total of 111 WML patients and 50 healthy controls (HCs) were enrolled, and their demographic information and cardiovascular disease risk factors were recorded. Subjects were divided into three groups: WMLs with normal cognition (WMLs-NC), WMLs with vascular cognitive impairment (WMLs-VCI), and HCs. They underwent conventional head magnetic resonance imaging and diffusion tensor imaging (DTI), followed by neuropsychological and psychological examinations, including the Montreal Cognitive Assessment (MoCA), and the executive function tests. We compared executive function and PSMD among the three groups and analyzed the correlation between PSMD and cognitive function in all subjects.Results: There were no significant differences in demographic characteristics (age, sex, education level, and cardiovascular disease risk factors) among the three groups (P > 0.05), but there were significant differences in global cognition (P < 0.0001), executive function (P < 0.0001), and PSMD (P < 0.0001). The average PSMD value (×10−4 mm2/s) was 2.40 ± 0.23, 2.68 ± 0.30, and 4.51 ± 0.39 in the HC, WMLs-NC, and WMLs-VCI groups, respectively. There was no correlation between PSMD and cognition in the HC group, but PSMD was significantly correlated with MoCA scores (r = −0.3785, P < 0.0001) and executive function (r = −0.4744, P < 0.0001) in the WMLs-NC group and in the WMLs-VCI group (r = −0.4448, P < 0.0001 and r = −0.6279, P < 0.0001, respectively).Conclusions: WML patients have higher PSMD and worse cognitive performance than HCs, and PSMD is strongly associated with global cognition and executive functions in WML patients. This result provides new insights into the pathophysiology of cognitive impairment in WML patients. PSMD could be a surrogate marker for disease progression and could thus be used in therapeutic trials involving WML patients

Safety and Efficacy of Low-Dose Tirofiban Combined With Intravenous Thrombolysis and Mechanical Thrombectomy in Acute Ischemic Stroke: A Matched-Control Analysis From a Nationwide Registry

Purpose: Tirofiban administration to acute ischemic stroke patients undergoing mechanical thrombectomy with preceding intravenous thrombolysis remains controversial. The aim of the current study was to evaluate the safety and efficacy of low-dose tirofiban during mechanical thrombectomy in patients with preceding intravenous thrombolysis.Methods: Patients with acute ischemic stroke undergoing mechanical thrombectomy and preceding intravenous thrombolysis were derived from “ANGEL-ACT,” a multicenter, prospective registry study. The patients were dichotomized into tirofiban and non-tirofiban groups based on whether tirofiban was administered. Propensity score matching was used to minimize case bias. The primary safety endpoint was symptomatic intracerebral hemorrhage (sICH), defined as an intracerebral hemorrhage (ICH) associated with clinical deterioration as determined by the Heidelberg Bleeding Classification. All ICHs and hemorrhage types were recorded. Clinical outcomes included successful recanalization, dramatic clinical improvement, functional independence, and mortality at the 3-month follow-up timepoint. Successful recanalization was defined as a modified Thrombolysis in Cerebral Ischemia score of 2b or 3. Dramatic clinical improvement at 24 h was defined as a reduction in NIH stroke score of ≥10 points compared with admission, or a score ≤1. Functional independence was defined as a Modified Rankin Scale (mRS) score of 0–2 at 3-months.Results: The study included 201 patients, 81 in the tirofiban group and 120 in the non-tirofiban group, and each group included 68 patients after propensity score matching. Of the 201 patients, 52 (25.9%) suffered ICH, 15 (7.5%) suffered sICH, and 18 (9.0%) died within 3-months. The median mRS was 3 (0–4), 99 (49.3%) achieved functional independence. There were no statistically significant differences in safety outcomes, efficacy outcomes on successful recanalization, dramatic clinical improvement, or 3-month mRS between the tirofiban and non-tirofiban groups (all p > 0.05). Similar results were obtained after propensity score matching.Conclusion: In acute ischemic stroke patients who underwent mechanical thrombectomy and preceding intravenous thrombolysis, low-dose tirofiban was not associated with increased risk of sICH or ICH. Further randomized clinical trials are needed to confirm the effects of tirofiban in patients undergoing bridging therapy

CT characteristics of non-small cell lung cancer with epidermal growth factor receptor mutation: a systematic review and meta-analysis

BACKGROUND: To systematically investigate the relationship between CT morphological features and the presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). METHODS: All studies about the CT morphological features of NSCLC with EGFR mutations published between January 1, 2000 and March 15, 2015 were searched in the PubMed and EMBASE databases. Qualified studies were selected according to inclusion criteria. The frequency of EGFR mutations and CT features of ground-glass opacity (GGO) content, tumor size, cavitation, air-bronchogram, lobulation, and spiculation were extracted. The relationship between EGFR mutations and each of these CT features was tested based upon the weighted mean difference or inverse variance in the form of an odds ratio at a 95% confidence interval using Forest Plots. The publication bias was examined using Egger’s test. RESULTS: A total of 13 studies, consisting of 2146 NSCLC patients, were included, and 51.12% (1097/2146) of patients had EGFR mutations. The EGFR mutations were present in NSCLC with part-solid GGO in contrast to nonsolid GGO (OR = 0.49, 95% CI = 0.25–0.96, P = 0.04). Other CT features such as tumor size, cavitation, air-bronchogram, lobulation and spiculation did not demonstrate statistically significant correlation with EGFR mutations individually (P = 0.91; 0.67; 0.12; 0.45; and 0.36, respectively). No publication bias among the selected studies was noted in this meta-analysis (Egger’s tests, P > 0.05 for all). CONCLUSION: This meta-analysis demonstrated that NSCLC with CT morphological features of part-solid GGO tended to be EGFR mutated, which might provide an important clue for the correct selection of patients treated with molecular targeted therapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12880-016-0175-3) contains supplementary material, which is available to authorized users