bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policy‐induced selection bias in pharmacoepidemiology: The example of coverage for Alzheimer's medications in British Columbia
Authors: Fisher Anat , Carney Greg , Bassett Ken , Maclure K. Malcolm , Dormuth Colin R. 
Published: July 2019

AbstractPurposesTo assess the impact of a government‐sponsored reimbursement policy for cholinesterase inhibitors (ChEIs) on trends in physician visits with a diagnosis of Alzheimer's disease (AD).MethodsLongitudinal population‐based study using interrupted time series methods. British Columbia outpatient claims data for individuals aged 65 and older were used to compute monthly AD visit rates and examine the impact of the ChEI reimbursement policy on the coding of AD. We examined trends in the number of patients with AD visits, the number of AD visits per patient, and visits with “competing” diagnoses (mental, neurological, and cerebrovascular disorders and accidental falls). Finally, we described demographic and clinical features of diagnosed patients.ResultsWe analyzed 1.9 million AD visits. Faster growth in recorded AD visits was observed after the policy was implemented, from monthly growth of 7.5 visits per 100 000 person‐months before the policy (95% confidence interval [CI], 6.1‐8.9) to monthly growth of 16.5 per 100 000 person‐months after the policy (95% CI, 14.8‐18.3). After the implementation of the policy, we observed increased growth in the number of patients with recorded AD visits and the number of AD visits per patient, as well as a shift in diagnoses away from mental diseases and accidental falls to AD (diagnosis substitution).ConclusionsBritish Columbia's reimbursement policy for ChEIs was associated with a significant acceleration in Alzheimer's visits. Evaluations of health services utilization and clinical outcomes following drug policy changes need to consider policy‐induced influences on the reliability of the data used in the analysis.
Study on the Initiation Mechanism of Non‐Premixed Shock Induced Combustion in Supersonic Propellant Gas Jet
Authors: Qin Qiongyao , Zhang Xiaobing 
Published: July 2019

AbstractThe reflection of a supersonic propellant gas jet always happens during the firing of the weapon system of aircraft. The reflection induces complex non‐premixed shock induced combustion. It is of great importance to investigate the initiation mechanism of the combustion in the supersonic jet of propellant gas. The mechanism is vital for the design of any suppression method of the secondary combustion. To investigate the combustion in the reflected supersonic jet, a solid propellant combustion model and a numerical model based on compressible multispecies Navier‐Stokes equations are established. A detailed reaction mechanism consisting of 9 species and 12 reactions is utilized for the combustion of the propellant gas. Based on the models, the supersonic precursor flow field and the supersonic propellant gas jet flow are obtained and discussed. A secondary jet is observed which has not been reported before. A sandwich structure is proposed to reveal the initiation of the combustion. The oxygen supply in the secondary jet is found to be dominated by a vortex. An inert gas atmosphere can be adopted to suppress the mass transfer at the contact surface. Special devices could be designed to suppress the formation of the vortex in the secondary propellant jet.
MicroRNA‐139 is a predictor of prostate cancer recurrence and inhibits growth and migration of prostate cancer cells through cell cycle arrest and targeting IGF1R and AXL
Authors: Nam Robert K. , Benatar Tania , Wallis Christopher J. D. , Kobylecky Elizabeth , Amemiya Yutaka , Sherman Christopher , Seth Arun 
Published: July 2019

AbstractBackground: We previously identified a panel of five microRNAs (miRNAs) associated with biochemical recurrence and metastasis following prostatectomy from prostate cancer patients using next‐generation sequencing‐based whole miRNome sequencing and quantitative polymerase chain reaction‐based validation analysis. In this study, we examined the mechanism of action of miR‐139‐5p, one of the downregulated miRNAs identified in the panel.Methods: Using a cohort of 585 patients treated with radical prostatectomy, we examined the prognostic significance of miR‐139 (dichotomized around the median) using the Kaplan‐Meier method and Cox proportional hazard models. We validated these results using The Cancer Genome Atlas (TCGA) data. We created cell lines that overexpressed miR‐139 to confirm its targets as well as examine pathways through which miR‐139 may function using cell‐based assays.Results: Low miR‐139 expression was significantly associated with a variety of prognostic factors in prostate cancer, including Gleason score, pathologic stage, margin positivity, and lymph node status. MiR‐139 expression was associated with prognosis: the cumulative incidence of biochemical recurrence and metastasis were significantly lower among patients with high miR‐139 expression (P = .0004 and .038, respectively). Validation in the TCGA data set showed a significant association between dichotomized miR‐139 expression and biochemical recurrence (odds ratio, 0.52; 95% confidence interval, 0.33‐0.82). Overexpression of miR‐139 in prostate cancer cells led to a significant reduction in cell proliferation and migration compared with control cells, with cells arrested in G2 of cell cycle. IGF1R and AXL were identified as potential targets of miR‐139 based on multiple miRNA‐binding sites in 3′‐untranslated regions of both the genes and their association with prostate cancer growth pathways. Luciferase assays verified AXL and IGF1R as direct targets of miR‐139. Furthermore, immunoblotting of prostate cancer cells demonstrated IGF1R and AXL protein expression were inhibited by miR‐139 treatment, which was reversed by the addition of miR‐139 antagomir. Examination of the molecular mechanism of growth inhibition by miR‐139 revealed the downregulation of activated AKT and cyclin D1, with upregulation of the CDK inhibitor p21.Conclusions: miR‐139 is associated with improved prognosis in patients with localized prostate cancer, which may be mediated through downregulation of IGF1R and/or AXL and associated signaling pathway components.
The pathological upgrading after radical prostatectomy in low‐risk prostate cancer patients who are eligible for active surveillance: How safe is it to depend on bioptic pathology?
Authors: Verep Samed , Erdem Selcuk , Ozluk Yasemin , Kilicaslan Isin , Sanli Oner , Ozcan Faruk 
Published: July 2019

AbstractBackgroundActive surveillance (AS) is one of the treatment alternatives in low‐risk prostate cancer (PCa). The pathological upgrading after radical prostatectomy (RP) were investigated in patients who were eligible for AS in the present study.MethodsBetween August 2006 and July 2017, 627 patients underwent RP in our institution. One hundred and thirty‐six patients who were eligible for AS at the time of RP were included in this study. The previously defined AS criteria Gleason 3 + 3=6 adenocarcinoma at maximum two biopsy cores, prostate‐specific antigen (PSA) < 10 ng/mL and clinical T stage ≤ 2a were used in the study. The demographics, clinical, and histopathological outcomes were retrospectively compared between two groups, which were divided in accordance with the upgrading status at final pathology as Group 1 (n = 67, upgrading) and Group 2 (n = 69, nonupgrading).ResultsGleason upgrading (GU) was found in 67 (49.3%) patients, and 17 patients (12.5%) were upstaged to pT3a. The upgrading to Gleason 3 + 4 was reported in 38.7% of patients, however, 7.4%, and 3.7% of the patients were upgraded to Gleason 4 + 3, and Gleason 4 + 4, respectively. The 10.3% of the patients had extraprostatic involvement, and the rate (19.4% vs 1.4%, P = .002) was significantly higher in Group 1. PSA density (P = .001), tumor size (P < .001), tumor percentage (P < .001), apical involvement (P = .013), and perineural invasion (P < .001) in RP specimen were higher in Group 1. Multivariate analysis showed that perineural invasion (OR = 4.26; 95%CI: 1.76‐10.33; P = .001) and pathologic T stage (OR = 5.45; 95%CI: 1.08‐27.4; P = .04) were independently associated with GU.ConclusionsSince 12.5% of the patients upstaged to pT3a disease, and there is a possible risk of Gleason 4 pattern, upgrading of the tumor should carefully be kept in mind before offering AS to low‐risk patients with PCa.
Production of pyrrolizidine alkaloids and shikonins in Echium plantagineum L. in response to various plant stressors
Authors: Skoneczny Dominik , Zhu Xiaocheng , Weston Paul A , Gurr Geoff M , Callaway Ragan M , Weston Leslie A 
Published: July 2019

ABSTRACTBackgroundEchium plantagineum, a native of Europe and Africa, is a noxious invasive weed in Australia forming monocultural stands in pastures and rangelands. It produces a complex mixture of bioactive secondary metabolites, including toxic pyrrolizidine alkaloids (PAs), that protect the plant from insect and livestock herbivory and naphthoquinones (NQs), which suppress competition from weeds, insects and pathogens, and also influence invasion success. However, the extent to which allelochemical production is impacted by environmental factors, thereby influencing plant defense against pests, remains unclear.ResultsFollowing plant stress induced by drought, herbivory and high temperature, extracts of E. plantagineum shoots and roots were subjected to metabolic profiling by UPLC‐MS‐DAD‐ QToF mass spectrometry. Abundance of NQs, especially deoxyshikonin, shikonin and dimethylacrylshikonin, rapidly increased in roots exposed to elevated temperatures. Water withholding initially increased NQ abundance, but prolonged drought resulted in reduced total PAs and NQs. Intraspecific competition elevated the production of NQs, whereas simulated herbivory had no initial effect on NQs. Following herbivory, the abundance of the PA 3′‐O‐acetylechimidine‐N‐oxide in seedling shoots was increased.ConclusionsDifferential accumulation of defense metabolites by E. plantagineum following exposure to various stressors suggested stress‐dependent biosynthetic regulation, particularly with respect to NQ production, which was rapidly induced following drought, intraspecific competition and high temperature treatment, thereby positively impacting resistance or defense against herbivores, weeds and pathogens. We propose that trade‐offs between above‐ and below‐ground metabolism in E. plantagineum may facilitate allelochemical production in response to stress, rendering plants with an enhanced ability to defend against other neighboring plants, insects and microbes, with allelochemical production further facilitated by catabolic recycling following lengthier exposure to stress. © 2019 Society of Chemical Industry
Empirical evaluation of the implementation of the EMA guideline on missing data in confirmatory clinical trials: Specification of mixed models for longitudinal data in study protocols
Authors: Häckl Sebastian , Koch Armin , Lasch Florian 
Published: July 2019

SummaryIn confirmatory clinical trials, the prespecification of the primary analysis model is a universally accepted scientific principle to allow strict control of the type I error. Consequently, both the ICH E9 guideline and the European Medicines Agency (EMA) guideline on missing data in confirmatory clinical trials require that the primary analysis model is defined unambiguously. This requirement applies to mixed models for longitudinal data handling missing data implicitly. To evaluate the compliance with the EMA guideline, we evaluated the model specifications in those clinical study protocols from development phases II and III submitted between 2015 and 2018 to the Ethics Committee at Hannover Medical School under the German Medicinal Products Act, which planned to use a mixed model for longitudinal data in the confirmatory testing strategy. Overall, 39 trials from different types of sponsors and a wide range of therapeutic areas were evaluated. While nearly all protocols specify the fixed and random effects of the analysis model (95%), only 77% give the structure of the covariance matrix used for modeling the repeated measurements. Moreover, the testing method (36%), the estimation method (28%), the computation method (3%), and the fallback strategy (18%) are given by less than half the study protocols. Subgroup analyses indicate that these findings are universal and not specific to clinical trial phases or size of company. Altogether, our results show that guideline compliance is to various degrees poor and consequently, strict type I error rate control at the intended level is not guaranteed.
Geographic authentication of the traditional Chinese medicine Atractylodes macrocephala Koidz. (Baizhu) using stable isotope and multielement analyses
Authors: Hu Ling , Chen Xianfeng , Yang Jian , Guo Lanping 
Published: July 2019

RationaleAtractylodes macrocephala Koidz (Baizhu) is a valuable traditional Chinese medicine, and medicines of that type originating from Zhejiang province are the most famous and much more expensive than those from other regions. Driven by the great difference in prices, fraudulent labeling often occurs. In order to protect the interests of consumers, producers and honest traders, reliable techniques for the geographic authentication of Baizhu are needed urgently.MethodsThe stable isotope ratios of five light elements (C, N, H, O and S) in Baizhu samples originating from four provinces of China were determined with an elemental analyzer coupled to isotope ratio mass spectrometry, and the concentrations of 45 elements in these samples were measured using inductively coupled plasma mass spectrometry. Chemometric approaches including principal component analysis (PCA) and orthodox partial least squares discriminant analysis (OPLS‐DA) were applied to the obtained data.ResultsThe PCA results showed that the techniques enabled clear classification of the Baizhu samples into three clusters: A (Zhejiang province), B (Shaanxi province) and C (Hebei and Ahui provinces). Furthermore, OPLS‐DA using 27 key variables provided 100% correct discrimination between samples originating from Zhejiang province and those from the other three provinces.ConclusionsStable isotope ratio and multielement analyses in combination with chemometric approaches showed great potential for the geographic authentication of Baizhu, providing a promising method for the control of fraudulent labeling that frequently occurs with traditional herbal medicines in China.
Neurosurgery medical robot Remebot for the treatment of 17 patients with hypertensive intracerebral hemorrhage
Authors: Wang Tao , Zhao Quan‐Jun , Gu Jian‐Wen , Shi Tie‐Jun , Yuan Xujun , Wang Jia , Cui Shao‐Jie 
Published: July 2019

AbstractObjectiveTo verify the minimally invasive surgical approach and therapeutic effects of using the medical neurosurgery robot Remebot to treat hypertensive intracerebral hemorrhage (HICH).MethodsClinical data for 17 HICH patients were analyzed retrospectively. Hematoma evacuation and tube drainage using Remebot frameless stereotaxic techniques were performed for all patients, and urokinase was injected into the hematomas after the operations.ResultsRobot‐assisted stereotactic techniques can accurately guide hematoma punctures, and no deaths occurred among these patients. The average positioning error was 1.28 ± 0.49 mm. The average drainage duration was 3.4 days. The 3‐month postoperative follow‐up revealed improved neurological functions and quality of life for all patients.ConclusionsThe medical neurosurgery robot Remebot is minimally invasive, has high positional accuracy, and facilitates surgical planning according to the shape of the hematoma. Therefore, robot‐assisted surgery using Remebot represents a safe and effective treatment method for hematoma evacuation and tube drainage in HICH patients.
H∞ boundary control for a class of nonlinear stochastic parabolic distributed parameter systems
Authors: Zhang Xiu‐Mei , Wu Huai‐Ning 
Published: July 2019

SummaryThis paper addresses the problem of H∞ boundary control for a class of nonlinear stochastic distributed parameter systems expressed by parabolic stochastic partial differential equations (SPDEs) of Itô type. A simple but effective H∞ boundary static output feedback (SOF) control scheme with collocated boundary measurement is introduced to ensure the local exponential stability in the mean square sense with an H∞ performance. By using the semigroup theory, the disturbance‐free closed‐loop well‐posedness analysis is first given. Then, based on the SPDE model, a general linear matrix inequality based H∞ boundary SOF control design is provided via Lyapunov technique and infinite‐dimensional infinitesimal operator, such that the disturbance‐free closed‐loop system is locally exponentially stable in the mean square sense and the H∞ performance of disturbance attenuation can also be achieved in the presence of disturbances. Finally, simulation results on a stochastic Fisher‐Kolmogorov‐Petrovsky‐Piscounov equation illustrate the effectiveness of the proposed method.
Control of Catalytic Activity of Nano‐Au through Tailoring the Fermi Level of Support
Authors: Liu Yinglei , Chen Hao , Xu Changjin , Sun Yuming , Li Song , Jiang Min , Qin Gaowu 
Published: July 2019

AbstractThe catalytic properties of nanometals are strongly dependent on their electronic states which, are influenced by the interaction with the supports. However, a precise manipulation of the electronic interaction is lacking, and the nature of the interaction is still ambiguous. Herein, using Au/ZnFexCo2−xO4 (x = 0–2) as a model system with continuously tuned Fermi levels of supports, the electronic structure of the Au catalyst can be precisely controlled by changing the Fermi level of the support, which arises from the charge redistribution between the two phases. A higher Fermi level of ZnFe2O4 support makes nano‐Au negatively charged and thus facilitates the oxidation of CO, and in contrast, a lower Fermi level of ZnCo2O4 support makes nano‐Au positively charged and is preferential to the oxidation of benzyl alcohol. This work represents a solid step towards exploration of advanced catalysts with deliberate design of electronic structure and catalytic properties.
Guiding the Morphology of Amyloid Assemblies by Electrostatic Capping: from Polymorphic Twisted Fibrils to Uniform Nanorods
Authors: Zottig Ximena , Al‐Halifa Soultan , Babych Margaryta , Quittot Noé , Archambault Denis , Bourgault Steve 
Published: July 2019

AbstractPeptides that self‐assemble into cross‐β‐sheet amyloid structures constitute promising building blocks to construct highly ordered proteinaceous materials and nanoparticles. Nevertheless, the intrinsic polymorphism of amyloids and the difficulty of controlling self‐assembly currently limit their usage. In this study, the effect of electrostatic interactions on the supramolecular organization of peptide assemblies is investigated to gain insights into the structural basis of the morphological diversities of amyloids. Different charged capping units are introduced at the N‐terminus of a potent β‐sheet‐forming sequence derived from the 20–29 segment of islet amyloid polypeptide, known to self‐assemble into polymorphic fibrils. By tuning the charge and the electrostatic strength, different mesoscopic morphologies are obtained, including nanorods, rope‐like fibrils, and twisted ribbons. Particularly, the addition of positive capping units leads to the formation of uniform rod‐like assemblies, with lengths that can be modulated by the charge number. It is proposed that electrostatic repulsions between N‐terminal positive charges hinder β‐sheet tape twisting, leading to a unique control over the size of these cytocompatible nanorods by protofilament growth frustration. This study reveals the high susceptibility of amyloid formation to subtle chemical modifications and opens to promising strategies to control the final architecture of proteinaceous assemblies from the peptide sequence.
Is My Phone Listening in? On the Feasibility and Detectability of Mobile Eavesdropping
Authors: Kröger Jacob Leon , Raschke Philip 
Published: July 2019

Abstract
Besides various other privacy concerns with mobile devices, many people suspect their smartphones to be secretly eavesdropping on them. In particular, a large number of reports has emerged in recent years claiming that private conversations conducted in the presence of smartphones seemingly resulted in targeted online advertisements. These rumors have not only attracted media attention, but also the attention of regulatory authorities. With regard to explaining the phenomenon, opinions are divided both in public debate and in research. While one side dismisses the eavesdropping suspicions as unrealistic or even paranoid, many others are fully convinced of the allegations or at least consider them plausible. To help structure the ongoing controversy and dispel misconceptions that may have arisen, this paper provides a holistic overview of the issue, reviewing and analyzing existing arguments and explanatory approaches from both sides. Based on previous research and our own analysis, we challenge the widespread assumption that the spying fears have already been disproved. While confirming a lack of empirical evidence, we cannot rule out the possibility of sophisticated large-scale eavesdropping attacks being successful and remaining undetected. Taking into account existing access control mechanisms, detection methods, and other technical aspects, we point out remaining vulnerabilities and research gaps.
A Cohort Perspective on the Demography of Grandparenthood: Past, Present, and Future Changes in Race and Sex Disparities in the United States
Authors: Margolis Rachel , Verdery Ashton M. 
Published: July 2019

Abstract
How has the demography of grandparenthood changed over the last century? How have racial inequalities in grandparenthood changed, and how are they expected to change in the future? Massive improvements in mortality, increasing childlessness, and fertility postponement have profoundly altered the likelihood that people become grandparents as well as the timing and length of grandparenthood for those that do. The demography of grandparenthood is important to understand for those taking a multigenerational perspective of stratification and racial inequality because these processes define the onset and duration of intergenerational relationships in ways that constrain the forms and levels of intergenerational transfers that can occur within them. In this article, we discuss four measures of the demography of grandparenthood and use simulated data to estimate the broad contours of historical changes in the demography of grandparenthood in the United States for the 1880–1960 birth cohorts. Then we examine race and sex differences in grandparenthood in the past and present, which reveal declining inequality in the demography of grandparenthood and a projection of increasing group convergence in the coming decades.