bluuebunny/crossref_metadata_2025 huggingface dataset:
ALPHABETA: a dedicated open‐source tool for calculating TEM stage tilt angles
Authors: CAUTAERTS N. , DELVILLE R. , SCHRYVERS D.
Published: December 2018

This work describes the concepts, the mathematical framework and the implementation of the open source ALPHABETA software, a dedicated tool for calculating α and β tilt angles on any TEM double tilt stage. ALPHABETA provides an intuitive user interface to calibrate the orientation of the region of interest and to subsequently calculate the angle tilts to reach a zone axis, to perform a rotation around a given reflection, or to set up a 2‐beam or weak beam condition. The orientation of the sample on the stage and the tilt range reachable domain can be visualised in a stereographic projection plot. The accuracy of the method to reach a set of zone axis was evaluated and some case studies are presented. The tool significantly reduces time for tilting work as major tilts can be performed in image mode and reachable zones are beforehand indicated in the software. Besides facilitating the tilting to different zone axes, the software can be used for miscellaneous applications such as making dark field tilt series without specialised hardware.

Lay Description

ALPHABETA is an open‐source program we developed to make the life of transmission electron microscope users easier. Work on the transmission electron microscope, or TEM, is done by correctly orienting a thin sample with respect to the electron beam. The orientation determines how images made from the sample will look. Studying a sample may require the user to orient it in multiple different ways. This orienting must be done by adjusting ‘tilt’ parameters of the stage on which the sample sits in the microscope. Correctly adjusting these tilt parameters to obtain the correct orientation is a job that requires practice and experience. Our program should facilitate this step of working with the microscope, because it calculates the tilt parameters to achieve a certain orientation. This paper describes the mathematics behind the software and provides some examples from the work of the authors. We also evaluate how accurate the calculation is. The examples included are orienting to different zone axes, which are special crystal orientations, and making a series of images that provide a 3D effect when played after each other of particles that can only be visualised in particular orientations.
The dependence of brain mitochondria reactive oxygen species production on oxygen level is linear, except when inhibited by antimycin A
Authors: Stepanova Anna , Konrad Csaba , Manfredi Giovanni , Springett Roger , Ten Vadim , Galkin Alexander
Published: December 2018

Reactive oxygen species (ROS) are by‐products of physiological mitochondrial metabolism that are involved in several cellular signaling pathways as well as tissue injury and pathophysiological processes, including brain ischemia/reperfusion injury. The mitochondrial respiratory chain is considered a major source of ROS; however, there is little agreement on how ROS release depends on oxygen concentration. The rate of H2O2 release by intact brain mitochondria was measured with an Amplex UltraRed assay using a high‐resolution respirometer (Oroboros) equipped with a fluorescent optical module and a system of controlled gas flow for varying the oxygen concentration. Three types of substrates were used: malate and pyruvate, succinate and glutamate, succinate alone or glycerol 3‐phosphate. For the first time we determined that, with any substrate used in the absence of inhibitors, H2O2 release by respiring brain mitochondria is linearly dependent on the oxygen concentration. We found that the highest rate of H2O2 release occurs in conditions of reverse electron transfer when mitochondria oxidize succinate or glycerol 3‐phosphate. H2O2 production by complex III is significant only in the presence of antimycin A and, in this case, the oxygen dependence manifested mixed (linear and hyperbolic) kinetics. We also demonstrated that complex II in brain mitochondria could contribute to ROS generation even in the absence of its substrate succinate when the quinone pool is reduced by glycerol 3‐phosphate. Our results underscore the critical importance of reverse electron transfer in the brain, where a significant amount of succinate can be accumulated during ischemia providing a backflow of electrons to complex I at the early stages of reperfusion. Our study also demonstrates that ROS generation in brain mitochondria is lower under hypoxic conditions than in normoxia.

Open science badges

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The relationship between self‐esteem and hair transplantation satisfaction in male androgenetic alopecia patients
Authors: Liu Fang , Miao Yong , Li Xingdong , Qu Qian , Liu Yang , Li Kaitao , Feng Chuanbo , Hu Zhiqi
Published: December 2018

Background

Frustrated with the embarrassing appearance, patients with androgenetic alopecia (AGA) suffer from poor quality of life and low self‐esteem. Moreover, several researches indicate that self‐esteem is an important factor affecting outcomes of cosmetic surgery.

Objective

This retrospective study aims to investigate the impact of hair transplantation on patients’ self‐esteem and satisfaction with appearance, as well as relationship between self‐esteem and patient satisfaction which includes preoperative and postoperative satisfaction.

Methods

The preoperative and 9‐month postoperative self‐esteem were evaluated by Rosenberg Self‐Esteem Scale (RSES), and preoperative satisfaction indicators (satisfaction with appearance, visual age and expected visual age) were assessed by Face‐Q scale. At the same time, postoperative satisfaction indicators (satisfaction with appearance, visual age, satisfaction with decision, psychological well‐being, and social function) were reevaluated as well.

Results

Of the 1106 male AGA patients, 875 completed a 9‐month postoperative questionnaire. Compared with preoperative scores, postoperative scores of self‐esteem and satisfaction with appearance showed an increase of 1.56 and 30.25 respectively (P < 0.05). Subgroup analysis showed that patients with high self‐esteem level trended to have higher scores of postoperative satisfaction with appearance (P = 0.129), psychological well‐being (P = 0.168), social function (P = 0.027), and satisfaction with decision (P = 0.043) compared with patients with low and average self‐esteem level.

Conclusion

Hair transplantation significantly elevated self‐esteem level and increased satisfaction with appearance of AGA patients. Meanwhile, patients with low self‐esteem level trended to have worse postoperative satisfaction. Thus, apart from ensuring the quality of operation, plastic surgeons should offer guidance based on patients’ psychological state to improve postoperative satisfaction.
The importance of local environmental, hydrogeomorphological and spatial variables for beta diversity of macrophyte assemblages in a Neotropical floodplain
Authors: Schneider Berenice , Cunha Eduardo R. , Espínola Luis A. , Marchese Mercedes , Thomaz Sidinei M.
Published: December 2018

Questions

Understanding the processes that determine the variation in community composition (β‐diversity) is a major challenge in ecology, evolution, and conservation. Here we assess the importance of abiotic variables associated with local environmental features, hydrogeomorphology, and space to explain β‐diversity patterns in macrophytes by addressing the following questions: (1) Which are the sets of environmental, hydrogeomorphological, and spatial variables that contribute significantly to the spatial variation of macrophytes? (2) Which are their relative contributions to explaining the total β‐diversity, nestedness and turnover of macrophyte assemblages?

Study Site

Middle Paraná River floodplain, Argentina.

Methods

We sampled 20 lakes at low and high water levels in the Middle Paraná River floodplain. To investigate the relationship of total β‐diversity, turnover and nestedness with explanatory variables, we used the constrained analysis of principal coordinates (CAP). We used variation partitioning to assess the proportion of the variation related to each subset of variables (environmental, hydrogeomorphological and spatial).

Results

Among four alternatives considered to explain the spatial structure, the distance between lakes by watercourses best described the spatial organization of β‐diversity. Species turnover was largely explained by hydrogeomorphological variables, followed by spatial descriptors, whereas nestedness was exclusively related to spatial variables.

Conclusions

In the Middle Paraná River floodplain β‐diversity of macrophyte communities is partly shaped by turnover (mainly driven by the hydrogeomorphology of the floodplain) and nestedness (resulting from dispersal limitation by watercourses), but it also seems to be randomly organized (possibly because of random colonization and extinction, due to disturbances such as floods). Our work indicates that environmental pressures reflect differences between macrophyte communities of lakes with different geomorphological and hydrographical conditions. This suggests that certain ecological processes (such as species sorting) are driven at a higher degree by hydrogeomorphology than by local environment.
LiaR‐independent pathways to daptomycin resistance in Enterococcus faecalis reveal a multilayer defense against cell envelope antibiotics
Authors: Miller William R. , Tran Truc T. , Diaz Lorena , Rios Rafael , Khan Ayesha , Reyes Jinnethe , Prater Amy G. , Panesso Diana , Shamoo Yousif , Arias Cesar A.
Published: December 2018

The lipopeptide antibiotic daptomycin (DAP) is a key drug against serious enterococcal infections, but the emergence of resistance in the clinical setting is a major concern. The LiaFSR system plays a prominent role in the development of DAP resistance (DAP‐R) in enterococci, and blocking this stress response system has been proposed as a novel therapeutic strategy. In this work, we identify LiaR‐independent pathways in Enterococcus faecalis that regulate cell membrane adaptation in response to antibiotics. We adapted E. faecalis OG1RF (a laboratory strain) and S613TM (a clinical strain) lacking liaR to increasing concentrations of DAP, leading to the development of DAP‐R and elevated MICs to bacitracin and ceftriaxone. Whole genome sequencing identified changes in the YxdJK two‐component regulatory system and a putative fatty acid kinase (dak) in both DAP‐R strains. Deletion of the gene encoding the YxdJ response regulator in both the DAP‐R mutant and wild‐type OG1RF decreased MICs to DAP, even when a functional LiaFSR system was present. Mutations in dak were associated with slower growth, decreased membrane fluidity and alterations of cell morphology. These findings suggest that overlapping stress response pathways can provide protection against antimicrobial peptides in E. faecalis at a significant cost in bacterial fitness.
Single transcript unit CRISPR 2.0 systems for robust Cas9 and Cas12a mediated plant genome editing
Authors: Tang Xu , Ren Qiurong , Yang Lijia , Bao Yu , Zhong Zhaohui , He Yao , Liu Shishi , Qi Caiyan , Liu Binglin , Wang Yan , Sretenovic Simon , Zhang Yingxiao , Zheng Xuelian , Zhang Tao , Qi Yiping , Zhang Yong
Published: December 2018

CRISPR‐Cas9 and Cas12a are two powerful genome editing systems. Expression of CRISPR in plants is typically achieved with a mixed dual promoter system, in which Cas protein is expressed by a Pol II promoter and a guide RNA is expressed by a species‐specific Pol III promoter such as U6 or U3. To achieve coordinated expression and compact vector packaging, it is desirable to express both CRISPR components under a single Pol II promoter. Previously, we demonstrated a first‐generation single transcript unit (STU)‐Cas9 system, STU‐Cas9‐RZ, which is based on hammerhead ribozyme for processing single guide RNAs (sgRNAs). In this study, we developed two new STU‐Cas9 systems and one STU‐Cas12a system for applications in plants, collectively called the STU CRISPR 2.0 systems. We demonstrated these systems for genome editing in rice with both transient expression and stable transgenesis. The two STU‐Cas9 2.0 systems process the sgRNAs with Csy4 ribonuclease and endogenous tRNA processing system respectively. Both STU‐Cas9‐Csy4 and STU‐Cas9‐tRNA systems showed more robust genome editing efficiencies than our first‐generation STU‐Cas9‐RZ system and the conventional mixed dual promoter system. We further applied the STU‐Cas9‐tRNA system to compare two C to T base editing systems based on rAPOBEC1 and PmCDA1 cytidine deaminases. The results suggest STU‐based PmCDA1 base editor system is highly efficient in rice. The STU‐Cas12a system, based on Cas12a’ self‐processing of a CRISPR RNA (crRNA) array, was also developed and demonstrated for expression of a single crRNA and four crRNAs. Altogether, our STU CRISPR 2.0 systems further expanded the CRISPR toolbox for plant genome editing and other applications.
A New Competing Risks Decomposition: Application to the Effect Of Cutting Unemployment Benefit on Unemployment Durations
Authors: O’Neill Donal
Published: December 2018

I propose a competing risks decomposition of the difference in the restricted mean lifetimes of two groups, which distinguishes between the incidence and duration effects of exit states. I use the decomposition to evaluate the effect of a cut in unemployment benefits on unemployment durations in Ireland. Whereas the aggregate effect of the benefit cut is similar for men and women, the decomposition reveals that the channels through which the cut affects unemployment durations differ substantially.
Reviewer Acknowledgements for International Journal of Law and Public Administration, Vol. 1
Authors: Brown Bennett
Published: December 2018

International Journal of Law and Public Administration (IJLPA) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this Volume. Many authors, regardless of whether IJLPA publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this Volume.Reviewers for Volume 1Anca-Iulia Stoian, RomaniaCarmen Garcimartin, SpainElena Atienza-Macias, SpainGeorge Ndi, UKIonel D. BONDOC, ROMANIAJohn Lenon E. Agatep, PhilippinesOyeniyi Abe, NigeriaOzgur DEMIRTAS, TurkeySabina G. Pavlovska-Hilaiel, USATatiana Bachvarova, Bulgaria
Quantitative tests reveal that microtubules tune the healthy heart but underlie arrhythmias in pathology
Authors: Joca Humberto C. , Coleman Andrew K. , Ward Chris W. , Williams George S. B.
Published: December 2018

Key points

Our group previously discovered and characterized the microtubule mechanotransduction pathway linking diastolic stretch to NADPH oxidase 2‐derived reactive oxygen species signals that regulate calcium sparks and calcium influx pathways.

Here we used focused experimental tests to constrain and expand our existing computational models of calcium signalling in heart.

Mechanistic and quantitative modelling revealed new insights in disease including: changes in microtubule network density and properties, elevated NOX2 expression, altered calcium release dynamics, how NADPH oxidase 2 is activated by and responds to stretch, and finally the degree to which normalizing mechano‐activated reactive oxygen species signals can prevent calcium‐dependent arrhythmias.

Microtubule (MT) mechanotransduction links diastolic stretch to generation of NADPH oxidase 2 (NOX2)‐dependent reactive oxygen species (ROS), signals we term X‐ROS. While stretch‐elicited X‐ROS primes intracellular calcium (Ca2+) channels for synchronized activation in the healthy heart, the dysregulated excess in this pathway underscores asynchronous Ca2+ release and arrhythmia. Here, we expanded our existing computational models of Ca2+ signalling in heart to include MT‐dependent mechanotransduction through X‐ROS. Informed by new focused experimental tests to properly constrain our model, we quantify the role of X‐ROS on excitation–contraction coupling in healthy and pathological conditions. This approach allowed for a mechanistic investigation that revealed new insights into X‐ROS signalling in disease including changes in MT network density and post‐translational modifications (PTMs), elevated NOX2 expression, altered Ca2+ release dynamics (i.e. Ca2+ sparks and Ca2+ waves), how NOX2 is activated by and responds to stretch, and finally the degree to which normalizing X‐ROS can prevent Ca2+‐dependent arrhythmias.
Numerical Simulation Study on Fracture Parameter Optimization in Developing Low-Permeability Anisotropic Reservoirs
Authors: Liu Jie , Xu Zhenhua , Yuan Zhe , Bie Hanyu , Liu Pengcheng
Published: December 2018

The diamond-shape inverted nine-spot well pattern is widely used in developing low-permeability reservoirs with fractures. However, production wells with equal fracture lengths will lead to nonuniform displacement, especially in anisotropic reservoir. Previous researches mainly focused on equal-length fractures, while studies on the unequal-length fractures which can dramatically improve the development efficiency were little. In this paper, a corresponding numerical model with unequal length of fracture designed in the edge and the corner wells was built in a low-permeability anisotropic reservoir. The main objective was to examine and evaluate the effects of anisotropic permeability and fracture parameter on the waterflooding in the diamond-shape inverted nine-spot well pattern. The results indicate that different fractures penetration ratio and anisotropic permeability both result in different development efficiency. Fracture of the edge well are more easily to be water breakthrough, while the increase of penetration ratio of injection well effectively enhance oil recovery. Moreover, the most optimal penetration ratios of production well fractures under different kx : ky are determined. With the increase of kx : ky, the optimized penetration ratio of corner wells fracture decrease, while that of the edge wells increase. Setting unequal length fractures in low-permeability anisotropic reservoirs can effectively improve the oil displacement efficiency in the waterflooding process.
Design and Implementation of 3U CubeSat Platform Architecture
Authors: Song Sua , Kim Hongrae , Chang Young-Keun
Published: December 2018

This paper describes the main concept and development of a standard platform architecture of 3U Cube Satellite, whose design and performance were implemented and verified through the development of KAUSAT-5 3U CubeSat. The 3U standard platform is built in 1.5U size and developed as a modular concept to add and expand payloads and attitude control actuators to meet the user’s needs. In the case of the electrical power system, the solar panel, the battery, and the deployment mechanism are designed to be configured by the user. Mechanical system design maximizes the electrical capability to accommodate various payloads and to integrate and miniaturize EEE (Electrical, Electronic, and Electromechanical) parts and subsystem functions/performance into limited-size PCBs. The performance of KAUSAT-5 adopting standard platform was verified by mounting the VSCMG (Variable Speed Control Moment Gyro), which is one payload for technical demonstration, at the bottom of the platform and the infrared (IR) camera, which is the other payload for science mission, on the top. The 3U CubeSat equipped with the electronic optical camera is under development implementing the standard platform to reduce development cost and schedule by minimizing additional verification.
Optical Coherence Tomography-Guided Transepithelial Phototherapeutic Keratectomy for Central Corneal Opacity in the Pediatric Population
Authors: Rush Sloan W. , Rush Ryan B.
Published: December 2018

Purpose. To report the outcomes of optical coherence tomography- (OCT-) guided transepithelial phototherapeutic keratectomy (PTK) for central corneal opacity in the pediatric population.Methods. The charts of 10 eyes of 8 children aged 9 to 17 with central corneal opacity from various pathologies who underwent a standardized OCT-guided transepithelial PTK technique at a single private practice institution were retrospectively reviewed. The corneal topographic findings, OCT measurements, and visual results with refractive outcomes were analyzed 6 months after the PTK treatment.Results. All 10 eyes tolerated the procedure well without any significant intraoperative or postoperative complications. Uncorrected and best spectacle-corrected visual acuity (BSCVA) significantly improved postoperatively (p<0.0001andp=0.0045, respectively). The absolute value of spherical equivalent on cycloplegic refraction significantly improved postoperatively as well (p=0.0014), but there were no significant changes in topographic measurements. Seven out of the 10 eyes had complete resolution of the central corneal opacity on OCT imaging. None of the subjects lost any lines of BSCVA and developed recurrence of the corneal opacity from the primary disease condition or required keratoplasty during the follow-up period.Conclusions. OCT-guided transepithelial PTK can provide excellent visual outcomes in pediatric patients with central corneal opacities.
Disseminated Mucormycosis with Positive Aspergillus Galactomannan
Authors: Kitmiridou Despoina , Aung Su N. , Farmakiotis Dimitrios
Published: December 2018

We describe a case of disseminated mucormycosis (Apophysomyces elegans) diagnosed on autopsy, in a man who had been working in construction with undiagnosed neutropenia from hairy-cell leukemia, which is rarely associated with invasive mold infections. Galactomannan values in both blood and bronchoalveolar lavage were strongly positive. There is an unmet need for accurate noninvasive fungal diagnostic tests. Detailed history, including occupational exposures, can be more informative than laboratory workup.
Biomass Modification Using Cationic Surfactant Cetyltrimethylammonium Bromide (CTAB) to Remove Palm-Based Cooking Oil
Authors: Mohamed Pauzan Amira Satirawaty , Ahad Normala
Published: December 2018

Adsorption based on natural fibre seems to widely used for oily wastewater recovery due to its low cost, simplicity, feasibility, easy handling, and effectiveness. However, oil sorbent based on natural fibre without modification has low adsorption capacity and selectivity. Thus, this paper proposes chemical modification of sago hampas to improve its adsorbent efficiency for the removal of palm-based cooking oil. The chemical modification was performed using a cationic surfactant, cetyltrimethylammonium bromide (CTAB). The chemical and surface properties of both unmodified and modified sago hampas were characterized by Fourier-Transform Infrared (FTIR) and Scanning Electron Microscopy (SEM). Parameters studied for the removal of cooking oil using modified sago hampas were sorption time, adsorbent dosage, and initial pH. The removal capacity was also compared using unmodified sago hampas. The results showed that additional functional groups were introduced on the surface of modified sago hampas. Modified sago hampas also showed a greater porosity than unmodified sago hampas. These properties enhanced the adsorption of palm-based cooking oil onto the surface of modified sago hampas. Modified sago hampas shows better removal of palm-based cooking oil than unmodified sago hampas, where 84.82% and 68.08% removal were achieved by modified and unmodified sago hampas, respectively. The optimum adsorption of palm-based cooking oil was identified at 45 min sorption time, pH 2, and 0.2 g adsorbent dosage.
A Fast Object Tracker Based on Integrated Multiple Features and Dynamic Learning Rate
Authors: Zhang Jianming , Wu You , Jin Xiaokang , Li Feng , Wang Jin
Published: December 2018

Object tracking is a vital topic in computer vision. Although tracking algorithms have gained great development in recent years, its robustness and accuracy still need to be improved. In this paper, to overcome single feature with poor representation ability in a complex image sequence, we put forward a multifeature integration framework, including the gray features, Histogram of Gradient (HOG), color-naming (CN), and Illumination Invariant Features (IIF), which effectively improve the robustness of object tracking. In addition, we propose a model updating strategy and introduce a skewness to measure the confidence degree of tracking result. Unlike previous tracking algorithms, we judge the relationship of skewness values between two adjacent frames to decide the updating of target appearance model to use a dynamic learning rate. This way makes our tracker further improve the robustness of tracking and effectively prevents the target drifting caused by occlusion and deformation. Extensive experiments on large-scale benchmark containing 50 image sequences show that our tracker is better than most existing excellent trackers in tracking performance and can run at average speed over 43 fps.
Load Transfer Mechanism of Hybrid Pylon Joint with Cells and Bearing Plates
Authors: Li Yongjun , Liu Yuqing , Wang Feihua , Yang Fei
Published: December 2018

To investigate the load transfer mechanism of the steel‐concrete hybrid pylon joint with cells and bearing plates, a theoretical model based on the continuous elastic interlayer method was established. Both the slip effect at the steel‐concrete interface and the local compression effect of the bearing plate were considered in the proposed theoretical model. A segment model test with a 1 : 3 scale was carried out to obtain the strain distribution of the hybrid joint and the relative slip between steel and concrete components. Finite element analysis was implemented on the tested segment model, and the structural performance of the tested hybrid joint was compared with the FEA results. The test and analysis results show that the stress of steel and concrete components is at a lower level, and the relative slip between steel and concrete components is extremely limited. The bearing plates and shear connectors are the two load‐transferring components and could transfer 40% and 60% of the vertical force into the lower concrete pylon, respectively. The vertical force of shear connectors is at a much lower magnitude within 0.6 times the length of the hybrid joint from the bearing plate and will increase gradually within 0.6 to 1.0 times the length of the hybrid joint. The FEA results are in good agreement with the model test results, and the maximum shear force difference between the theoretical analysis results and the FEA results is less than 10%, proving that the proposed theoretical model can reasonably predict the shear force distribution at the steel‐concrete interface of the hybrid joint. In addition, the stiffness of shear connectors has limited effect on the shear force distribution at the steel‐concrete interface.
Two-Stage Assembly Scheduling with Batch Setup Times, Time-Dependent Deterioration, and Preventive Maintenance Activities Using Meta-Heuristic Algorithms
Authors: Jung Sunwoong , Woo Young-Bin , Koh Shiegheun , Kim Byung Soo
Published: December 2018

This article considers a two-stage assembly scheduling problem (TSASP) with batch setup times, time-dependent deterioration, and preventive maintenance activities (PMAs). The objective of this problem is to simultaneously determine the optimal component-manufacturing sequence (CMS), product-assembly sequence (PAS), number of setups, and number and position of PMAs (PPMA). First, to determine the optimal solution, a novel mixed integer linear programming model (MILP) for the proposed problem is derived. Then, a standard genetic algorithm (SGA), hybrid genetic algorithm (HGA), standard harmony search (SHS), hybrid harmony search (HHS), and harmony-search-based evolutionary algorithm (HSEA) were proposed owing to the intractability of the optimal solution for large-scale problems. SGA and SHS provide a chromosome to represent a complete solution including three decisions (CMS, PAS, and PPMA). HGA, HHS, and HSEA provide a chromosome to represent a partial solution including PAS. CMS and PPMA are found by an effective local search heuristic based on the partial solution. A computational experiment is then conducted to evaluate the impacts of the factors on the performance of the proposed algorithms.
Comparison of Oxidative Effects of Two Different Administration Form of Oxybutynin in the Potential Target Tissues
Authors: Kaltalioglu Kaan , Tugcu-Demiroz Fatmanur , Acarturk Fusun , Balabanli Barbaros , Coskun-Cevher Sule
Published: December 2018

Oxybutynin is an important anticholinergic agent that prevents uncontrolled contractions in the treatment of overactive bladder (OAB). However, drugs containing oxybutynin have significant side effects such as dry eyes, dry mouth, increased heart rate, constipation, blurred vision, and confusion. In recent years, new delivery methods for this agent are being searched. One of them is vaginal delivery. In this study, we aimed to compare the effects of oxybutynin on oxidative parameters in the potential target tissues of the oral and vaginal delivery. Female New Zealand white rabbits (n=12) were divided into two groups: oral delivery and vaginal delivery. The animals were sacrificed 48 h after administration and nitric oxide (NOx), thiobarbituric acid-reactive substances (TBARs), and glutathione (GSH) levels were determined spectrophotometrically in the aorta, salivary gland, and small intestine tissue samples. Vaginal delivery significantly decreased NOx levels in all tissue samples as compared to oral delivery (p<0.05). Moreover, it reduced TBARs levels in salivary gland and aorta tissue samples (p<0.05). In the light on these findings, it can be said that vaginal delivery may decrease the oxidant-induced side effects of oxybutynin as compared to oral delivery.
A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma
Authors: Chen Shi-Lu , Zhang Chris Zhiyi , Liu Li-Li , Lu Shi-Xun , Pan Ying-Hua , Wang Chun-Hua , He Yang-Fan , Lin Cen-Shan , Yang Xia , Xie Dan , Yun Jing-Ping
Published: December 2018

Hepatocellular carcinogenesis is attributed to the reprogramming of cellular metabolism as a consequence of the alteration in metabolite-related gene regulation. Identifying the mechanism of aberrant metabolism is of great potential to provide novel targets for the treatment of hepatocellular carcinoma (HCC). Here, we demonstrated that glycogen synthase 2 (GYS2) restricted tumor growth in hepatitis B virus–related HCC via a negative feedback loop with p53. Expression of GYS2 was significantly downregulated in HCC and correlated with decreased glycogen content and unfavorable patient outcomes. GYS2 overexpression suppressed, whereas GYS2 knockdown facilitated cell proliferation in vitro and tumor growth in vivo via modulating p53 expression. GYS2 competitively bound to MDM2 to prevent p53 from MDM2-mediated ubiquitination and degradation. Furthermore, GYS2 enhanced the p300-induced acetylation of p53 at K373/382, which in turn inhibited the transcription of GYS2 in the support of HBx/HDAC1 complex. In summary, our findings suggest that GYS2 serves as a prognostic factor and functions as a tumor suppressor in HCC. The newly identified HBx/GYS2/p53 axis is responsible for the deregulation of glycogen metabolism and represents a promising therapeutic target for the clinical management of HCC.

Significance:

We elucidated the clinical significance, biological function, and regulation of the HBx/GYS2/p53 axis, which supplement the understanding of tumor glycogen metabolism and provide potential prognostic and therapeutic targets for HCC treatment.
A Meta-Analysis on the Relationship Between Hair Dye and the Incidence of Non-Hodgkin’s Lymphoma
Authors: Qin Ling  , Deng Hui-Yang  , Chen Sheng-Jiang  , Wei Wei
Published: December 2018

Background: Epidemiologic studies have suggested hair dye to be a risk factor for many cancers. However, previous studies on the association between the personal use of hair dye and risk of non-Hodgkin’s lymphoma (NHL) have been inconclusive. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases, as well as the references cited in included studies, were searched for relevant studies up to February 10, 2015. Odds ratios (OR) with 95% confidence intervals (CI) were applied to assess the strength of the association. Publication bias was evaluated using a funnel plot by Egger’s and Begg’s tests. Results: A total of 16 studies were included in the analysis, including 13 case-control studies and 3 cohort studies. The present meta-analysis results revealed that the risk of NHL in a high population of hair dye users was 14% (OR 1.14, 95% CI 1.01–1.29). Furthermore, individuals who used more than 20 pack-years of hair dye had increased risk of NHL. Conclusion: The outcomes indicate that hair dye use increases the risk of NHL, especially for females. Hence, people who frequently use hair dyes or have been using hair dyes for more than 20 years should minimize their exposure to hair dye products to prevent the risk of NHL.
Role of Corin in Blood Pressure Regulation in Normotensive and Hypertensive Pregnancy
Authors: Badrov Mark B. , Park Sun Young , Yoo Jeung-Ki , Hieda Michinari , Okada Yoshiyuki , Jarvis Sara S. , Stickford Abigail S. , Best Stuart A. , Nelson David B. , Fu Qi
Published: December 2018

Corin (an atrial natriuretic peptide–converting enzyme) represents a potential biomarker for gestational hypertensive disorders; yet, its role in blood pressure (BP) regulation throughout pregnancy remains unclear. We investigated the time course of change in blood corin content in relation to BP and sympathetic nerve activity throughout pregnancy. Forty-four women (29±0.9 years) participated. Following-term, 23 had low-risk (no personal history of gestational hypertensive disorders) normal pregnancies, 13 had high-risk (personal history of gestational hypertensive disorders) normal pregnancies, and 8 developed gestational hypertension. BP, heart rate, muscle sympathetic nerve activity, and serum corin were measured before pregnancy, during early (4–8 weeks) and late pregnancy (32–36 weeks), and postpartum (6–10 weeks). Overall, compared with prepregnancy, corin remained unchanged during early pregnancy, increased markedly during late pregnancy (
P
<0.001), and returned to prepregnancy levels postpartum. In women who developed gestational hypertension, the change in corin from early to late pregnancy was greater than those with low-risk normal pregnancies (Δ971±134 versus Δ486±79 pg/mL;
P
<0.05). Throughout pregnancy, BP and muscle sympathetic nerve activity were augmented in women with gestational hypertension (all
P
<0.05). Finally, changes in corin from early to late pregnancy were related to all indices of BP (
R
=0.454–0.551; all
P
<0.01) in late pregnancy, whereas burst frequency, burst incidence, and total muscle sympathetic nerve activity (
R
=0.576–0.614; all
P
<0.001) in early pregnancy were related to changes in corin from early to late pregnancy. Corin plays a unique role in BP regulation throughout normotensive and, especially, hypertensive pregnancy and may represent a promising biomarker for determining women at high risk of adverse pregnancy outcome.
Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack
Authors: Kim Joon-Tae , Park Man-Seok , Choi Kang-Ho , Cho Ki-Hyun , Kim Beom Joon , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae-Kwan , Kim Dae-Hyun , Nah Hyun-Wook , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Kim Dong-Eog , Ryu Wi-Sun , Choi Jay Chol , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Yeo Min-Ju , Sohn Sung Il , Hong Jeong-Ho , Lee Ji Sung , Lee Juneyoung , Saver Jeffrey L. , Johnston S. Claiborne , Bae Hee-Joon
Published: December 2018

Background and Purpose—

This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea.

Methods—

CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months.

Results—

Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67–0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63–0.92]) and all stroke events (hazard ratio, 0.74 [0.61–0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (
P
interaction
=0.01) and younger age (<75 years,
P
interaction
=0.07), and absence of benefit associated with small vessel occlusion subtype (
P
interaction
=0.08).

Conclusions—

Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.
Functional Magnetic Resonance Imaging of Inhibitory Control Reveals Decreased Blood Oxygen Level Dependent Effect in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Gavazzi Gioele , Orsolini Stefano , Salvadori Emilia , Bianchi Andrea , Rossi Arianna , Donnini Ida , Rinnoci Valentina , Pescini Francesca , Diciotti Stefano , Viggiano Maria Pia , Mascalchi Mario , Pantoni Leonardo
Published: December 2018

Background and Purpose—

Small-vessel damage in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is associated with impaired vascular constriction and dilation. We used a functional magnetic resonance imaging task with an event-related design of stimulus to explore the anticipated abnormally decreased blood oxygen level dependent effect in CADASIL.

Methods—

Twenty-one CADASIL patients and 16 healthy controls performed a Go/No-go task exploring reactive and proactive phases of inhibition control in a 3-T magnet.

Results—

Error number and reaction times were not different between patients and controls. Analysis of the reactive inhibition (No-go/baseline contrast) did not show clusters of lower or higher blood oxygen level dependent effect in patients or controls. Analysis of the proactive inhibition (alertness contrast) in CADASIL patients revealed a lower blood oxygen level dependent effect in the alerting network (anterior cingulate cortex and insula, thalamus), lower brain stem and left cerebellar hemisphere (crus I) that is involved in executive functions.

Conclusions—

In CADASIL patients, an event-related Go/No-go task reveals a lower blood oxygen level dependent effect in the alerting network and areas involved in executive functions possibly reflecting the altered hemodynamic response secondary to small-vessel changes. Our observation extends the role of MR in demonstrating one of the fundamental pathophysiological changes of CADASIL.
Mobile Technology for Primary Stroke Prevention
Authors: Krishnamurthi Rita , Hale Leigh , Barker-Collo Suzanne , Theadom Alice , Bhattacharjee Rohit , George Ann , Arroll Bruce , Ranta Annamarie , Waters Debra , Wilson Denise , Sandiford Peter , Gall Seana , Parmar Priyakumari , Bennett Derrick , Feigin Valery
Published: December 2018

Background and Purpose—

Feasibility of utilizing the Stroke Riskometer App (App) to improve stroke awareness and modify stroke risk behaviors was assessed to inform a full randomized controlled trial.

Methods—

A parallel, open-label, 2-arm prospective, proof-of-concept pilot randomized controlled trial. Participants were randomized to usual care/control or App intervention group and assessed at baseline, 3, and 6 months. The App measures stroke risk and provides information on management of risk factors. Participants were aged >19 years with at least 2 modifiable stroke risk factors identified, no prior stroke, and owned a smartphone.

Results—

Fifty participants (24 control, 26 App) were recruited from 148 eligible participants. Retention in the trial was 87%. Mean cardiovascular health (Life’s Simple 7) improved by 0.36 (95% CI, −2.10 to 1.38) in the App group compared with 0.01 (95% CI, −1.34 to 1.32) in controls (
P
=0.6733).

Conclusions—

These findings support a full randomized controlled trial to test the effectiveness of the Stroke Riskometer for primary stroke prevention.

Clinical Trial Registration—

URL:
www.anzctr.org.au
. Unique Identifier: ACTRN12616000376448.
Impact of Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation Classification on Further Course of Arteriopathy and Recurrence of Childhood Stroke
Authors: Böhmer Maik , Niederstadt Thomas , Heindel Walter , Wildgruber Moritz , Sträter Ronald , Hanning Uta , Kemmling André , Sporns Peter B.
Published: December 2018

Background and Purpose—

Arterial ischemic stroke (AIS) in childhood is a severe disease with potentially lifelong restrictions. Apart from cardiac or prothrombotic embolism, arteriopathy has been identified as a major cause and significant target of secondary stroke prevention. The Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation (CASCADE) criteria facilitate a structured tool for categorizing and reporting childhood strokes according to the underlying cause. Our study aims to identify the prognostic value of CASCADE classification on admission for further course of arteriopathy and risk of stroke recurrence. Moreover, we give recommendations for follow-up imaging based on different CASCADE subgroups.

Methods—

Between 2004 and 2017, we identified 86 children with an acute arterial ischemic stroke classified in the 7-basic and 19-expanded subgroups of the acute CASCADE criteria. All included children were diagnosed and followed-up by magnetic resonance imaging. All arteriopathic strokes (basic subgroups 1–4 of acute CASCADE criteria) were further categorized into the chronic CASCADE criteria, including progressive, stable, reversible, and indeterminate course. Outcomes were defined as stroke recurrence and course of arteriopathy according to chronic CASCADE criteria. Associations between acute CASCADE criteria classification and stroke recurrence were assessed by Fisher exact test and between acute CASCADE criteria and chronic CASCADE criteria by Fisher exact test and Mann-Whitney
U
test.

Results—

A total of 86 children were included; of these, 57 presented with arteriopathic stroke (CASCADE 1–4) and 29 as nonarteriopathic. Unilateral cerebral arteriopathy (CASCADE 2;
P
=0.036) and bilateral cerebral arteriopathy (CASCADE 3;
P
=0.016) significantly correlated with stroke recurrence, and progressive arteriopathy significantly correlated with unilateral focal cerebral arteriopathy (
P
<0.001). Time points of progress of arteriopathy differed; whereas patients with unilateral focal cerebral arteriopathy presented with early median progress after 11 days, patients with bilateral cerebral arteriopathy had a significantly later median progress after 124 days (
P
=0.005).

Conclusions—

Initial CASCADE classification is associated with risk of recurrent strokes and progress of arteriopathy. Moreover, time points of arteriopathic progress vary according to the underlying cause.
Highest Lesion Growth Rates in Patients With Hyperacute Stroke
Authors: Broocks Gabriel , Rajput Furqan , Hanning Uta , Faizy Tobias Djamsched , Leischner Hannes , Schön Gerhard , Gellißen Susanne , Sporns Peter , Deb-Chatterji Milani , Thomalla Götz , Kemmling Andre , Fiehler Jens , Flottmann Fabian
Published: December 2018

Background and Purpose—

The early growth of ischemic lesions has been described as being nonlinear, with lesion growth rates at their highest during the earliest period after stroke onset. We hypothesized that the time gap from imaging to revascularization results in higher lesion growth in patients with hyperacute presentation.

Methods—

Fifty-one patients with ischemic stroke with initial multimodal computed tomography (CT), follow-up CT after 24 hours, and successful endovascular recanalization were included and separated into 2 groups according to their median time from symptom onset to imaging (eg, hyperacute versus acute). The difference in Alberta Stroke Program Early CT Score (ASPECTS) between initial CT and follow-up CT was assessed, as well as volumetric lesion growth from early ischemic core in admission perfusion CT and total lesion volume in follow-up CT.

Results—

The median time from onset to imaging was 1.85 hours. There was no significant difference in admission ASPECTS (mean, 8.5 versus 8.2) or time from imaging to recanalization in both groups (median, 2.7 versus 2.4 hours;
P
=0.4). The mean (SD) lesion growth assessed by ASPECTS difference was 2.7 (2.3) in the hyperacute group and 1.6 (1.3) in the acute group (
P
=0.03). The mean (SD) volumetric difference in the hyperacute group was 26.6 mL (43.2 mL) and 17.2 mL (26.3 mL;
P
=0.36) in the acute group, respectively. For every passing hour after onset, ASPECTS lesion growth was reduced by 0.4.

Conclusions—

Patients in the hyperacute phase showed increased ASPECTS lesion growth from imaging to recanalization suggesting a particular benefit of faster recanalization times in this group of patients with stroke.