bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trends, disease patterns and gender imbalance in the top 100 most cited articles in ophthalmology
Authors: Heng Wong Matthew Yu , Tan Nicholas Y Q , Sabanayagam Charumathi
Published: July 2018

We analysed the 100 top cited articles in ophthalmology to identify and characterise the most influential articles of the past four decades. Two independent investigators searched the Scopus database to determine the 100 most frequently cited articles in ophthalmology (T100-Eye) and general non-ophthalmology journals (T100-Gen) published from 1975 to December 2017. The T100-Eye list consisted of 83 original articles and 17 reviews, and the number of citations ranged from 582 to 2833. Seventy-eight of these articles were published in three journals alone (impact factor (IF): 5.05–8.2), led by the Archives of Ophthalmology. The T100-Gen list consisted of 84 original articles and 16 reviews and the number of citations ranged from 358 to 3272. Forty-five of these articles were published in four journals alone (IF: 9.66–72.41). In both lists, majority of the first authors were from the USA (T100-Eye, n=80; T100-Gen, n=66), and were men (n=76 in T100-Eye; n=72 in T100-Gen). With regard to the article type, in the T100-Eye, among the 83 original research articles, most were randomised controlled trials (n=26) or clinical observational studies related to description of a new condition or new management (n=26). In the T100-Gen, of the 84 original research articles, many were clinical observational studies (n=27) or basic science research (n=26). In both lists, the most frequently examined diseases were age-related macular degeneration, diabetic retinopathy and glaucoma. Our analysis reveals landmark articles, trends and medical advancements in ophthalmology over the past four decades. It also highlights gender disparity and influence of the USA in seminal ophthalmic research.
Discrepancy in current central serous chorioretinopathy classification
Authors: Singh Sumit Randhir , Matet Alexandre , van Dijk Elon H C , Daruich Alejandra , Fauser Sascha , Yzer Suzanne , Peiretti Enrico , Sivaprasad Sobha , Lotery Andrew J , Boon Camiel J F , Behar-Cohen Francine , Freund K Bailey , Chhablani Jay
Published: July 2018

Aim

To report the discordance in central serous chorioretinopathy (CSCR) classification among practising retina specialists.

Methods

The study conducted was a multicentre survey. Multimodal retinal images along with relevant clinical details of 100 cases diagnosed as CSCR (from six centres) were circulated among six retina specialists across the globe. The image sets included colour fundus photographs, fundus autofluorescence images, optical coherence tomography b-scans, fluorescein and indocyanine green angiography of the study and fellow eyes. The graders were asked to classify the disease of study eye, according to their own criteria. The graders were masked to the responses of other graders. The final analysis of the pooled response data was done based on the diagnosis of study eye only. The main outcome measure was degree of agreement between six independent observers using Fleiss Kappa statistics.

Results

Grading for 100 eyes of 100 patients (men, 93%) was included in the analysis. 20 patients had a history of steroid use. The graders provided 36 different terms to classify the disease, with poor agreement among graders (Fleiss Kappa=0.134). The consistency in diagnosing acute CSCR was statistically higher than for either chronic (p=0.012) or recurrent CSCR (p<0.0001). When collapsing descriptors into six main terms, agreement remained poor (Fleiss Kappa=0.218).

Conclusion

The high discordance among experienced retina specialists in describing CSCR clinical subtypes is highlighted. The current work demonstrates the limitations of current empirical CSCR classification methods and the need for a more objective and refined system to bring uniformity in diagnosis and prognostication of the disease.
Feasibility of a postacute structured aerobic exercise intervention following sport concussion in symptomatic adolescents: a randomised controlled study
Authors: Micay Rachel , Richards Doug , Hutchison Michael G
Published: July 2018

Objective

The utility of structured exercise for rehabilitation purposes early in the postacute phase (ie, beyond the initial 24–48 hours of advised rest) following sport-related concussion (SRC) remains largely unexplored. This study examined the feasibility of implementing a standardised aerobic exercise (AE) intervention in the postacute stage of SRC recovery in a sample of adolescent students with SRC compared with usual care.

Methods

Symptomatic adolescents with SRC were randomised to one of two groups: Aerobic Exercise (n=8) or Usual Care (n=7). The AE intervention, beginning on day 6 postinjury, comprised eight sessions with progressive increases in intensity and duration on a cycle ergometer. Usual care consisted of rest followed by physician-advised progressions in activity levels in an unsupervised setting. All participants were evaluated by physician at weeks 1, 2, 3 and 4 postconcussion. Outcome measures included: (1) Intervention feasibility: symptom status pre-post exercise sessions and completion of intervention and (2) Clinical recovery: symptom status at weeks 1, 2, 3 and 4 postinjury and medical clearance date.

Results

All participants completed the exercise sessions as part of the AE intervention and symptom exacerbation was not associated with any exercise session. The AE group experienced greater symptom resolution compared with the Usual Care Group across the recovery timeline.

Conclusion

A structured AE protocol appears to be safe and feasible to administer in the postacute stage of SRC recovery in adolescents and should be explored as part of a full Phase III Clinical Trial.
Preparing for the Practice Standards Scheme medicines assessment: part 2
Authors: Mosedale Pam
Published: July 2018

The medicines module is one of the largest modules of the new‐look Practice Standards Scheme. This article, the second in a two‐part series, discusses how practices should deal with controlled drugs and with the unauthorised use of medicines. It also considers the responsible use of antimicrobials and anthelmintics. The first part, which was published in the June issue of In Practice, considered the storage of medicines, prescribing, dispensing and supply, and record keeping.
Antibiotic usage in rabbits and rodents
Authors: Hedley Joanna
Published: July 2018

Antibiotic usage has been a growing concern in both human and veterinary medicine in recent years as resistant bacteria appear to be an increasingly widespread problem in all species. Conversely, the development of new antibiotics has slowed, leaving both doctors and veterinarians with a finite number of options for treating microbial infections. Particular challenges surround the use of antibiotics in small mammals, such as species‐specific sensitivities to certain drugs and the limited range of licensed products available. This article will outline factors affecting antibiotic selection in small mammals and discuss approaches to common presentations.
A night at the races
Authors: Williams David
Published: July 2018

THIS series gives readers the opportunity to consider and contribute to discussion of some of the ethical dilemmas that can arise in veterinary practice. Each month, a case scenario is presented, followed by discussion of some of the issues involved.

In addition, a possible way forward is suggested; however, there is rarely a cut‐and‐dried answer in such cases, and readers may wish to suggest an alternative approach. This month's dilemma, ‘A night at the races’, was submitted and is discussed by David Williams. Readers with comments to contribute are invited to send them as soon as possible, so that they can be considered for publication in the next issue.

The series is being coordinated by Dr Steven McCulloch, acting director of the Centre for Animal Welfare, University of Winchester. It aims to provide a framework that will help practising veterinarians find solutions when facing similar dilemmas.
Leptospirosis in dogs and cats: new challenges from an old bacteria
Authors: Murphy Kate
Published: July 2018

Leptospirosis is an important bacterial infection which can cause disease in dogs while cats are generally reported to be resistant to clinical signs. Additionally, leptospirosis is a zoonotic disease. Although bivalent vaccination had been effective at controlling disease for many years, leptospirosis appears to be re‐emerging worldwide with other serovars now implicated in causing disease. Traditionally, leptospirosis has been considered as a differential diagnosis in dogs with acute hepatic and kidney disease. The disease should be considered in many other acute disease presentations; such as gastrointestinal disease and respiratory disease. Both chronic infection and carrier status can exist, and treatment is aimed at the reduction of chronic bacterial shedding, which contributes to environmental contamination. This article discusses the common and atypical presentations of leptospirosis, the diagnostic tests available to confirm disease and the recommendations for treatment and prevention.
A review of acute ischemic stroke triage protocol evidence: a context for discussion
Authors: Chartrain Alexander G , Shoirah Hazem , Jauch Edward C , Mocco J
Published: July 2018

Endovascular thrombectomy (EVT) is now the standard of care for eligible patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (ELVO). However, there remains uncertainty in how hospital systems can most efficiently route patients with suspected ELVO for EVT treatment. Given the relative geographic distribution of centers with and without endovascular capabilities, the value of prehospital triage directly to centers with the ability to provide EVT remains debated. While there are no randomized trial data available to date, there is substantial evidence in the literature that may offer guidance on the subject. In this review we examine the available data in the context of improving the existing AIS triage systems and discuss how prehospital triage directly to endovascular-capable centers may confer clinical benefits for patients with suspected ELVO.
Spirulina platensisameliorates arsenic-mediated uterine damage and ovarian steroidogenic disorder
Authors: Khatun Shamima , Maity Moulima , Perveen Hasina , Dash Moumita , Chattopadhyay Sandip
Published: July 2018

Novel, non-invasive, painless oral therapeutic agents are needed to replace the painful conventional treatment of arsenic-associated health hazards with metal chelators. Our aim was to examine the effect of spirulina ( Spirulina platensis ( Geitler, 1925 )) on arsenic-mediated uterine toxicity. Female Wistar rats were divided equally into four experimental treatment groups: control group, sodium arsenite group (1.0 mg/100 g body mass), spirulina placebo group (20 mg/100 g body mass), and sodium arsenite + spirulina group. In contrast with the control group, spectrophotometric and electrozymographic evaluation revealed that rats that ingested arsenic for 8 d showed significant diminution of the activities of superoxide dismutase, catalase, and peroxidase ( p < 0.001). Mutagenic uterine DNA breakage and tissue damage were prominent following arsenic consumption by the rats. Oral delivery of spirulina resulted in a significant amelioration of arsenic-induced adverse oxidative stress and genotoxic state of rats. A significant low-signaling ( p < 0.001) of gonadotropins and estradiol was also noted in the arsenic-treated rats, which was terminated by spirulina; this arsenic-primed adverse effect was significant ( p < 0.05, p < 0.01). The spirulina treatment mechanism could be associated with augmentation of the antioxidant defense system that protects the arsenic-mediated pathological state of the uterus.
Chinese Herbal Medicine for Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Zhang Xia-Wei , Liu Wei , Jiang Hong-Li , Mao Bing
Published: July 2018

Chinese herbal medicine (CHM) has been widely used in the treatment of advanced non-small-cell lung cancer (NSCLC), but their efficacy and safety remain controversial. We sought to comprehensively aggregate and evaluate the available evidence on the efficacy and safety of the combination treatment with CHM and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients. Our exhausted and systematical searching strategy yielded 64 related randomized controlled trials involving 4384 patients. Compared with EGFR-TKIs therapy alone, meta-analysis showed significant differences favoring the combination treatment in progression-free survival ([Formula: see text]), median survival time ([Formula: see text]), one-year survival rate ([Formula: see text]), two-year survival rate ([Formula: see text]), probability of severe toxicities ([Formula: see text]), objective response rate ([Formula: see text]), Karnofsky performance status ([Formula: see text]), and improvement in percentage of CD3[Formula: see text] T lymphocyte ([Formula: see text]) and CD4[Formula: see text] T lymphocyte ([Formula: see text]). Though these results require further confirmation, they are prone to show a potential therapeutic value of CHM in improving the clinical effect, overcoming the drug resistance and toxicities as an adjunctive therapy to EGFR-TKIs.
The (1|1)-Centroid Problem in the Plane with Distance Constraints
Authors: Yu Hung-I , Lin Tien-Ching , Lee D. T.
Published: July 2018

In 1982, Drezner proposed the [Formula: see text]-centroid problem on the plane, in which two players, called the leader and the follower, open facilities to provide service to customers in a competitive manner. The leader opens the first facility, and the follower opens the second. Customers will each patronize the facility closer to them (with ties broken in favor of the first one), thereby deciding the market share of the two facilities. The goal is to find the best position for the leader’s facility so that its market share is maximized. The best algorithm of this problem is an [Formula: see text]-time parametric search approach, which searches over the space of market share values.

In the same paper, Drezner also proposed a generalized version of [Formula: see text]-centroid problem by introducing a minimal distance constraint [Formula: see text], such that the follower’s facility is not allowed to be located within a distance [Formula: see text] from the leader’s. He proposed an [Formula: see text]-time algorithm for this generalized version by identifying [Formula: see text] points as the candidates of the optimal solution and checking the market share for each of them. In this paper, we develop a new parametric search approach searching over the [Formula: see text] candidate points, and present an [Formula: see text]-time algorithm for this generalized version, thereby closing the [Formula: see text] gap between the two bounds.
Approximating Smallest Containers for Packing Three-Dimensional Convex Objects
Authors: Alt Helmut , Scharf Nadja
Published: July 2018

We investigate the problem of computing a minimal-volume container for the non-overlapping packing of a given set of three-dimensional convex objects. Already the simplest versions of the problem are [Formula: see text]-hard so that we cannot expect to find polynomial time algorithms to determine the exact solution. We give constant ratio approximation algorithms for packing axis-parallel (rectangular) cuboids under translation into an axis-parallel (rectangular) cuboid as container, for packing cuboids under rigid motions into an axis-parallel cuboid or into an arbitrary convex container, and for packing convex polyhedra under rigid motions into an axis-parallel cuboid or arbitrary convex container. This work gives the first approximability results for the computation of minimum volume containers for the objects described.
The Grothendieck group of a tower of the Temperley–Lieb algebras
Authors: Wang Pei
Published: July 2018

We provide a diagrammatic approach to compute the algebraic structures on the Grothendieck group of a tower of the Temperley–Lieb algebras.
Can we build a privacy-preserving web browser we all deserve?
Authors: Kerschbaumer Christoph , Crouch Luke , Ritter Tom , Vyas Tanvi
Published: July 2018

The web is the biggest legacy application ever developed or supported by software engineers, but it's also blurring the line between the consumption of data and the leaking of personal details. Browser makers may be the only line of defense.
Environmental Security and the Anthropocene: Law, Criminology, and International Relations
Authors: Holley Cameron , Shearing Clifford , Harrington Cameron , Kennedy Amanda , Mutongwizo Tariro
Published: July 2018

This article analyzes the implications of the Anthropocene for the governance of security. Drawing on environmental law, green criminology, and international relations, the article examines the development of environmental security scholarship over recent decades and shows similarities and differences in perspectives across the three disciplines. It demonstrates that the Anthropocene represents a significant challenge for thinking about and responding to security and the environment. It argues a rethinking is needed, and this can benefit from reaching across the disciplinary divide in three key areas that have become a shared focus of attention and debate regarding security in the Anthropocene. These are, first, examining the implications of the Anthropocene for our understanding of the environment and security; second, addressing and resolving contests between environmental securities; and third, developing new governance responses that mix polycentric and state-backed regulation to bring safety and security to the planet.
High‐ and Low‐Temperature Properties and Thermal Stability of Silica Fume/SBS Composite‐Modified Asphalt Mortar
Authors: Kai Cao , Wenyuan Xu , Dan Chen , Huimin Feng
Published: July 2018

Recently, China has started paying more attention to environmental protection, and the efficient utilization of exhaust gases produced by smelting has emerged as a key problem concern. The silica fume collected from the exhaust gases produced by smelting ferrosilicon or industrial silicon was often used as a cement concrete admixture. Using silica fume as an asphalt modifier can make exhaust gases profitable. In this study, silica fume/SBS composite‐modified asphalt mortar was prepared to improve the performance of asphalt. The effects of the silica fume content, temperature, and ratio of filler asphalt on the composite‐modified asphalt mortar were studied through the cone penetration, softening point, viscosity, dynamic shear rheological (DSR) test, and bending beam rheometer (BBR) test. The thermal stability of composite‐modified asphalt was analyzed through the thermal analysis test. The results showed that with the increase of silica fume content and ratio of filler asphalt, the high‐temperature performance of asphalt mortar was improved; the content of silica fume had a great influence on the low‐temperature performance of asphalt mortar, the optimum silica fume content was 7%; increasing the ratio of filler asphalt reduced the low‐temperature cracking resistance of asphalt mortar; the incorporation of silica fume enhanced the initial decomposition temperature, thermal residual rate, temperature in which the weight loss rate reaches the maximum, and the endothermic peak of maximum temperature and improved the properties of asphalt.
Existence and Approximation of Manifolds for the Swift-Hohenberg Equation with a Parameter
Authors: Guo Yanfeng , Guo Chunxiao , Li Donglong
Published: July 2018

The existence and approximation of manifolds for the Swift-Hohenberg equation with a proper parameter have mainly been studied. Using the backward-forward systems from Swift-Hohenberg equation, the existence and specific representation forms of manifolds for Swift-Hohenberg equation with a parameter have been obtained. Meanwhile, we make use of technique of deposition of lower and higher frequency spaces of solutions and assume the reduced system to obtain the main numeration approximation system of approximation solution for the original system Swift-Hohenberg equation with a proper parameter.
Effects of Tiaozhi Granule on Regulation of Autophagy Levels in HUVECs
Authors: Wu Ying-Ying , Chen Chao , Yu Xiao , Zhao Xiao-Dong , Bao Rong-Qi , Yu Jia-Yu , Zhang Guo-Xing , Chen Jing-Wei
Published: July 2018

Sera from the rats with Tiaozhi granule treatment were collected. Human umbilical vein endothelial cells (HUVECs) were incubated with different dosage of sera with Tiaozhi granule for 48 hours. Rapamycin or angiotensin II was applied to activate autophagy in HUVECs with or without different dosages of sera of Tiaozhi granule. The mRNA expressions of Atg5, Atg7, Beclin‐1, and mammal target of rapamycin (mTOR) were detected by real‐time PCR. Autophagic flux markers (protein expression of LC3, Beclin‐1, and p62) were examined by western blot analyses. The number of autophagosomes was visualized by immunofluorescence analysis with LC3‐II labelling. Results showed that Tiaozhi granule sera increase cell autophagic levels by increase of mRNA of Atg5, Atg7, Beclin‐1, and mTOR and increase of autophagic flux and also number of autophagosomes. However, in response to rapamycin or Ang II stimulation, activated autophagic levels were alleviated by Tiaozhi granule sera by reduction of mRNA of Atg5, Atg7, Beclin‐1, mTOR, autophagic flux, and also number of autophagosomes. Our present data demonstrate that Tiaozhi granule plays a dual role in response to different cell conditions, which is to increase cell autophagy under physiological condition and to suppress cell excessive autophagy under pathological condition.
Mechanical Properties and Acoustic Emission Characteristics of Karst Limestone under Uniaxial Compression
Authors: Chen Jianxun , Wang Qingsong , Guo Jiaqi , Luo Yanbin , Li Yao , Liu Qin , Wang Hongyu
Published: July 2018

Firstly, I‐RPT ultrasonic detector was used to test the wave velocity of karst limestone with different initial microstructure and water content. Then, RMT‐150B rock testing machine and DS2‐16B acoustic emission system were used to test the acoustic emission (AE) under uniaxial compression. Mechanical properties and AE characteristics were obtained during rock failure. The detailed relationship between stress‐strain and AE characteristics was studied in this paper. Research results indicated the following: (1) For samples with many primary fissures and defects, wave velocity in dry state was larger than that in its natural state. From natural state to saturated state, the wave velocity tended to increase. For samples with good integrity, wave velocity increased with increasing of water content. (2) In the dry state, the samples presented tension failure. In saturated state, the samples presented tension‐shear failure. For samples with cracks and good integrity, samples showed brittle failure. For samples with many corrosion pores which showed ductile damage under natural and saturated state, the spalling phenomenon was enhanced under saturated state. (3) With increasing of water content, the peak stress and AE peak reduced dramatically. In brittle failure, AE peak could be considered a sign of failure. In ductile failure, AE activity decreased gradually with the decrease of stress. (4) The mechanical properties and AE characteristics corresponding to four main fracture propagation types were also discussed.
The Effect of Pluchea indica (L.) Less. Tea on Adipogenesis in 3T3‐L1 Adipocytes and Lipase Activity
Authors: Sirichaiwetchakoon Kittipot , Lowe Gordon Matthew , Thumanu Kanjana , Eumkeb Griangsak
Published: July 2018

Obesity and hyperlipidemia are a major problem in the world. Pluchea indica (L.) Less. tea (PIT) is a beverage that has various indications. This study focused on the effect of the PIT on inhibiting adipogenesis of 3T3‐L1 cells and pancreatic lipase enzyme activity. The viability of 3T3‐L1 cells was not significantly decreased after exposure to 200 to 1000 μg mL−1 PIT compared to controls (p > 0.05). The PIT at 750 to 1000 μg mL−1 exhibited a significantly reduced lipid accumulation compared to the control (p < 0.05). The inhibitory effects of the PIT at 250 to 1000 μg mL−1 on lipase activity were significantly increased compared to control (p < 0.05). The FTIR results showed that the integrated areas of lipids, proteins, nucleic acids, glycogen, and carbohydrates of the PIT‐treated 3T3‐L1 adipocytes were significantly lower than the untreated 3T3‐L1 adipocytes (p < 0.05). These findings may indicate that the PIT is not only capable of inhibiting lipids and carbohydrate accumulation in adipocytes but also has a potential to inhibit pancreatic lipase activity. So, the PIT may be further developed to the novel lipid‐lowering herbal supplement for the management of overweight or obesity.
Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells through the Activation of P38 MAPKs
Authors: Qin Tingyu , Gao Shasha
Published: July 2018

Purpose. As far as we know, during the development of age-related macular degeneration (AMD), the activity of proteasome in retinal pigment epithelium cells (RPE) gradually decreases. And a lot of research has shown that age-related macular degeneration is closely related to inflammation and autoimmune. Moreover, there are many cytokines (CKs) involved in the course of inflammation. In this study, we are going to investigate how the decrease of proteasome activity affects the production of interleukin-6 (IL-6) in human retinal pigment epithelium cells (ARPE-19).Methods. Cultured ARPE-19 was treated with or without MG132, a proteasome inhibitor, and the levels of IL-6 mRNA (messenger ribonucleic acid) in RPE at 1 h, 4 h, 8 h, and IL-6 protein in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were measured by real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunosorbent assay (ELISA). The protein levels of MCP-1 (monocyte chemoattractant protein-1) in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were also measured by ELISA. Then we tested which of cell signal pathways regulating the production of IL-6 were activated when we added MG132 into the medium by Western blot and electrophoretic mobility shift assays (EMSA). After that, we put the inhibitors of these activated cell signal pathways into the medium individually to see which inhibitor can counteract the effect of upregulating the levels of IL-6 in the culture medium of RPE.Results. MG132 decreased the secretion of MCP-1 in the culture medium of RPE, but it increased the expression of IL-6 mRNA in RPE and IL-6 protein level in the culture medium of RPE. MG132 treatment was also found to enhance the level of phosphorylated p38 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal Kinase (JNK) by Western blotting. More importantly, the effect of MG132 on upregulating the levels of IL-6 was inhibited by SB203580, an inhibitor of P38 MAP kinases. But the JNK inhibitor, SP600125, cannot prevent the effect of upregulating the levels of IL-6 by MG132 in the RPE culture medium.Conclusions. We concluded that the proteasome inhibitor, MG132, upregulates IL-6 production in RPE cells through the activation of P38 MAPKs.
Joint X- and S2 Control Charts Optimal Design Using Genetic Algorithm
Authors: Ramadan Saleem Z.
Published: July 2018

A simple and flexible model for economic statistical design of joint X- and S2 control charts was proposed. The design problem was approached by constrained fuzzy multiobjective modeling for three objectives: joint power, joint Type I error, and joint total control cost. Fuzzy membership functions were created to measure the satisfaction levels of the objectives, and the overall satisfaction level of the design was calculated using a weighted-average method. A genetic algorithm was designed to solve this model. The strength of this model lies in its effectiveness in detecting the assignable causes through the joint design and in its simplicity and flexibility in dealing with uncertainties in the design.
An Ecolevel Estimation Method of Individual Driver Performance Based on Driving Simulator Experiment
Authors: Wu Yiping , Zhao Xiaohua , Yao Ying , Rong Jian
Published: July 2018

Accurately acquiring the ecolevel of individual driver performance is the precondition for more targeted ecodriving behavior optimization. Because of obvious advantage in mining hidden relationship, machine learning was adopted to explore the complicated relationship between driver performance and vehicle fuel consumption and thus to predict the ecolevel of individual driver performance in this study. Based on driving simulator tests, data of driver performance and vehicle fuel consumption were collected. The ecolevel was indicated as the ecoscore corresponding to vehicle fuel consumption. The model input was designed as 10 feature indexes of driver performance (e.g., percentage number, mean value, standard deviation, and power of applying acceleration pedal). The output was treated as ecoscore. Taking a number of one hundred of data segments in vehicle starting process as training sample, the optimal structure, functions, and learning rate of a backpropagation neural network model with three layers were obtained, after repeated model simulation experiments. The validation test of 16 sample data items showed that the mean prediction accuracy of our developed model was 92.89%. In addition, comparative analysis displayed that the performance of backpropagation neural network based model was better than linear regression based model and random forest based model, from the aspects of elapsed time and prediction accuracy in estimating the ecolevel of driver performance. The study results provide an effective method to grasp the ecolevel of driver performance and further contribute to driving behavior optimization towards vehicle fuel consumption and emissions reduction.
Syncope: An Atypical Presentation of Pulmonary Embolism Secondary to Occult Uterine Malignancy
Authors: Qutrio Baloch Zulfiqar , Ayyaz Muhammad , Hussain Muhammad , Abbas Shabber Agha , Samreen FNU
Published: July 2018

All syncopal patients who present to the emergency department should be considered for pulmonary embolism (PE) as part of their differential diagnosis. PE presenting as a syncopal episode and associated with occult uterine malignancy is uncommon. Review of the literature indicates that up to 10% of patients with unprovoked venous thromboembolism (VTE) are diagnosed with cancer in the year following that first episode of VTE. In patients suspected of having a PE who do not manifest any source of an embolism require eventual workup to screen for an occult malignancy. Here, we report a 74-year-old female who presented to the emergency department following an unexplained sudden loss of consciousness and eventually was found to have a massive saddle embolus caused by a uterine malignancy-induced VTE.
Antioxidant and Antisenescence Effects of Bergamot Juice
Authors: Da Pozzo Eleonora , De Leo Marinella , Faraone Immacolata , Milella Luigi , Cavallini Chiara , Piragine Eugenia , Testai Lara , Calderone Vincenzo , Pistelli Luisa , Braca Alessandra , Martini Claudia
Published: July 2018

Aging is one of the main risk factor for the onset of cardiovascular diseases; one of the possible explanations could be linked to the age‐associated overproduction of free radicals. This increase of oxidative stress can be overcome with a high intake of food antioxidants. In this context, a number of studies have been addressed to assess the antiaging potential of natural antioxidant compounds. Recently, it has been shown that the juice of bergamot (Citrus bergamia Risso et Poiteau), a fruit mostly produced in the Ionian coastal areas of Southern Italy (Calabria), is a valuable source of health‐promoting constituents with, among other, antioxidant properties. In order to investigate the potential antiaging effects of this Mediterranean natural antioxidant source, bergamot juices of three different cultivars (“fantastico,” “femminello,” and “castagnaro”) were herein characterized by the mean of high‐performance liquid chromatography‐photodiode array‐electrospray ionization‐tandem mass spectrometry. Then, juices were investigated for the evaluation of total polyphenolic and flavonoid contents, cell‐free model antioxidant activities, and in vitro antiaging properties on two different cellular models of induced myocardial senescence. The best performing juice was also assessed in vivo. The phytochemical profiles confirmed that juices were rich in flavonoids, both flavone and flavanone glycosides. In addition, two limonoid glycosides were also identified in all cultivars. Each cultivar showed different phenolic and flavonoid contents. In tube results showed the juice robust antioxidant activities that correlate with their phenolic and flavonoid contents. Moreover, for the first time, the ability of juice to counteract the chemical‐induced senescence was here demonstrated in both cellular models. Lastly, the in vivo data obtained from mouse hearts evidenced an increase in transcription of genes involved in antiaging and antioxidant responses. The overall results suggest that bergamot juice exerts antioxidant and antisenescence effects, making it useful for nutraceutical purposes.
Mitotic Gene Bookmarking: An Epigenetic Program to Maintain Normal and Cancer Phenotypes
Authors: Zaidi Sayyed K. , Nickerson Jeffrey A. , Imbalzano Anthony N. , Lian Jane B. , Stein Janet L. , Stein Gary S.
Published: July 2018

Reconfiguration of nuclear structure and function during mitosis presents a significant challenge to resume the next cell cycle in the progeny cells without compromising structural and functional identity of the cells. Equally important is the requirement for cancer cells to retain the transformed phenotype, that is, unrestricted proliferative potential, suppression of cell phenotype, and activation of oncogenic pathways. Mitotic gene bookmarking retention of key regulatory proteins that include sequence-specific transcription factors, chromatin-modifying factors, and components of RNA Pol (RNAP) I and II regulatory machineries at gene loci on mitotic chromosomes plays key roles in coordinate control of cell phenotype, growth, and proliferation postmitotically. There is growing recognition that three distinct protein types, mechanistically, play obligatory roles in mitotic gene bookmarking: (i) Retention of phenotypic transcription factors on mitotic chromosomes is essential to sustain lineage commitment; (ii) Select chromatin modifiers and posttranslational histone modifications/variants retain competency of mitotic chromatin for gene reactivation as cells exit mitosis; and (iii) Functional components of RNAP I and II transcription complexes (e.g., UBF and TBP, respectively) are retained on genes poised for reactivation immediately following mitosis. Importantly, recent findings have identified oncogenes that are associated with target genes on mitotic chromosomes in cancer cells. The current review proposes that mitotic gene bookmarking is an extensively utilized epigenetic mechanism for stringent control of proliferation and identity in normal cells and hypothesizes that bookmarking plays a pivotal role in maintenance of tumor phenotypes, that is, unrestricted proliferation and compromised control of differentiation. Mol Cancer Res; 16(11); 1617–24. ©2018 AACR.
Extended Donor Typing by Pooled Capillary Electrophoresis: Impact in a Routine Setting
Authors: Wagner Franz F. , Doescher Andrea , Bittner Rita , Müller Thomas H.
Published: July 2018

Background: PCR with sequence-specific priming using allele-specific fluorescent primers and analysis on a capillary sequencer is a standard technique for DNA typing. We aimed to adapt this method for donor typing in a medium-throughput setting. Methods: Using the Extract-N-Amp PCR system, we devised a set of eight multiplex allele-specific PCR with fluorescent primers for Fya/Fyb, Jka/Jkb, M/N, and S/s. The alleles of a gene were discriminated by the fluorescent color; donor and polymorphism investigated were encoded by product length. Time, cost, and routine performance were collated. Discrepant samples were investigated by sequencing. The association of new alleles with the phenotype was evaluated by a step-wise statistical analysis. Results: On validation using 312 samples, for 1.1% of antigens (in 5.4% of samples) no prediction was obtained. 99.96% of predictions were correct. Consumable cost per donor were below EUR 2.00. In routine use, 92.2% of samples were successfully predicted. Discrepancies were most frequently due to technical reasons. A total of 11 previously unknown alleles were detected in the Kell, Lutheran, and Colton blood group systems. In 2017, more than 20% of the RBC units prepared by our institution were from donors with predicted antigen status. A steady supply of Yt(a-), Co(a-) and Lu(b-) RBC units was ensured. Conclusions: Pooled capillary electrophoresis offers a suitable alternative to other methods for extended donor DNA typing. Establishing a large cohort of typed donors improved transfusion support for patients.
MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis
Authors: Liu Xiaobing , Liu Xin , Wu Yuqi , Fang Zhenqiang , Wu Qingjian , Wu Chao , Hao Yaxing , Yang Xia , Zhao Jiang , Li Jia , Wang Qingqing , Yang Zhenxing , Xu Jie , Hu Xiaoyan , Tan Mingjia , Li Longkun
Published: July 2018

Background/Aims: Chemoresistance is largely responsible for relapses of bladder cancer during clinical therapy. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Growing evidence supports the theory that microRNAs (miRNAs) play an important role in chemotherapeutic drug resistance because they are downregulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. More specifically, the extent and precise mechanism of the involvement of miR-34as in chemoresistance to epirubicin (EPI) in the treatment of bladder cancer remains unclear. Methods: In this study, real-time quantitative polymerase chain reaction (PCR) was used to analyze the expression of miR-34a in bladder cancer cell line BIU87 and its EPI chemoresistant cell line BIU87/ADR. The miR-34a profiles in bladder cancer tissues were obtained from The Cancer Genome Atlas database. The effect of miR-34a on chemosensitivity was evaluated by cell viability assays, colony formation assays, and in vivo experimentation. Apoptosis and the cell cycle were examined by flow cytometry. A luciferase reporter assay was used to assess the target genes of miR-34a. Western blot and qPCR were used to analyze the expression of target proteins and downstream molecules. Results: The downregulation of miR-34a in bladder cancer serves as an independent predictor of reduced patient survival. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to EPI, while miR-34a downregulation resulted in chemoresistance to EPI in vitro. Moreover, it was found that miR-34a increased the sensitivity of BIU87/ADR cells to chemotherapy in vivo. The luciferase reporter assay ascertained that TCF1 and LEF1 are direct target genes of miR-34a. It was found that miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis. Conclusions: The results of this study indicate that miR-34a contributes to the chemosensitivity of BIU87/ADR by inhibiting the TCF1/LEF1 axis. Consequently, miR-34a is a determinant of BIU87 chemosensitivity and may therefore serve as a potential therapeutic target in bladder cancer treatment.
FOXO1 Inhibits Tumor Cell Migration via Regulating Cell Surface Morphology in Non-Small Cell Lung Cancer Cells
Authors: Gao Zhuo , Liu Ruiqi , Ye Na , Liu Chao , Li Xiuli , Guo Xiaodong , Zhang Zhuoran , Li Xiaoxi , Yao Yuanfei , Jiang Xiaofeng
Published: July 2018

Background/Aims: Cell surface morphology plays pivotal roles in malignant progression and epithelial-mesenchymal transition (EMT). Previous research demonstrated that microvilli play a key role in cell migration of non-small cell lung cancer (NSCLC). In this study, we report that Forkhead box class O1 (FOXO1) is downregulated in human NSCLC and that silencing of FOXO1 is associated with the invasive stage of tumor progression. Methods: The cell proliferation, migration, and invasion were characterized in vitro, and we tested the expression of the Epithelial-mesenchymal transition (EMT) marker by immunofluorescence staining and also identified the effect of FOXO1 on the microvilli by scanning electron microscopy (SEM). Results: Functional analyses revealed that silencing of FOXO1 resulted in an increase in NSCLC cell proliferation, migration, and invasion; whereas overexpression of FOXO1 significantly inhibited the migration and invasive capability of NSCLC cells in vitro. Furthermore, cell morphology imaging showed that FOXO1 maintained the characteristics of epithelial cells. Immunofluorescence staining and western blotting showed that the E-cadherin level was elevated and Vimentin was reduced by FOXO1 overexpression. Conversely, the E-cadherin level was reduced and Vimentin was elevated in cells silenced for FOXO1. Furthermore, scanning electron microscopy (SEM) showed that FOXO1 overexpression increased the length of the microvilli on the cell surface, whereas FOXO1 silencing significantly reduced their length. Conclusions: FOXO1 is involved in human lung carcinogenesis and may serve as a potential therapeutic target in the migration of human lung cancer.
Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death
Authors: Haïssaguerre Michel , Hocini Mélèze , Cheniti Ghassen , Duchateau Josselin , Sacher Frédéric , Puyo Stéphane , Cochet Hubert , Takigawa Masateru , Denis Arnaud , Martin Ruairidh , Derval Nicolas , Bordachar Pierre , Ritter Philippe , Ploux Sylvain , Pambrun Thomas , Klotz Nicolas , Massoullié Gregoire , Pillois Xavier , Dallet Corentin , Schott Jean-Jacques , Scouarnec Solena , Ackerman Michael J. , Tester David , Piot Olivier , Pasquié Jean-Luc , Leclerc Christophe , Hermida Jean-Sylvain , Gandjbakhch Estelle , Maury Philippe , Labrousse Louis , Coronel Ruben , Jais Pierre , Benoist David , Vigmond Edward , Potse Mark , Walton Richard , Nademanee Koonlawee , Bernus Olivier , Dubois Remi
Published: July 2018

Background:

Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported.

Methods:

We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations.

Results:

VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm
2
) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (
P
<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15,
P
=0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up.

Conclusions:

This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.
Dermal Interstitial Alterations in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Nijst Petra , Olinevich Mikhail , Hilkens Petra , Martens Pieter , Dupont Matthias , Tang W.H. Wilson , Lambrichts Ivo , Noben Jean-Paul , Mullens Wilfried
Published: July 2018

Background:

Large networks of interstitial glycosaminoglycans help to regulate water and electrolyte homeostasis. The relation between dermal interstitial alterations and occurrence of edema in heart failure patients with reduced ejection fraction (HFrEF) is unknown. We hypothesize that in HFrEF patients (1) interstitial glycosaminoglycan density is increased, (2) changes in the interstitial glycosaminoglycan network are associated with interstitial fluid accumulation, and (3) there is a link between the interstitial glycosaminoglycan network and the renin-angiotensin-aldosterone system.

Methods and Results:

Two punch biopsies of the skin were obtained in healthy subjects (n=18) and HFrEF patients (n=29). Alcian blue staining and immunostaining for the angiotensin II type 1 receptor was performed. After obtaining tissue water content, total interstitial glycosaminoglycan (uronic acid) and sulfated glycosaminoglycan were quantified. A venous blood sample, clinical examination, and echocardiography were obtained. A significantly higher interstitial glycosaminoglycan content was observed in HFrEF patients compared with healthy subjects (uronic acid: 13.0±4.2 versus 9.6±1.6 μg/mg;
P
=0.002; sulfated glycosaminoglycan: 14.1 [11.7; 18.1] versus 10.0 [9.1; 10.8] μg/mg;
P
<0.001). Uronic acid and sulfated glycosaminoglycan density were strongly associated with tissue water content and peripheral edema (uronic acid: ρ=0.66;
P
<0.0001 and sulfated glycosaminoglycan: τ=0.58;
P
<0.0001). Expression of the angiotensin II type 1 receptor was found on dermal cells, although use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker was associated with significantly lower levels of interstitial glycosaminoglycans in HFrEF patients.

Conclusions:

Interstitial glycosaminoglycan concentration is significantly increased in HFrEF patients compared with healthy subjects and correlated with tissue water content and clinical signs of volume overload. A better appreciation of the interstitial compartment might improve management of volume overload in HF.