bluuebunny/crossref_metadata_2025_split huggingface dataset:
GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions
Authors: Izawa Masao , Taniguchi Fuminori , Harada Tasuku 
Published: December 2018

ProblemGenome‐wide profiling of DNA methylation in endometriotic cells has shown a distinct facet of epigenetic backgrounds; however, specific DNA methylation sites responsible for aberrant gene expression in endometriosis were unknown. Are there specific endometriosis‐associated DNA methylations that can be used as molecular markers in endometriosis lesions?Method of studyThis study used endometriotic tissues from the chocolate cyst lining of the ovaries of patients with endometriosis, and endometrial tissues from disease‐free patients. For analysis, stromal cells were collected from endometrial and endometriotic tissues. Using endometrial cells as control, differentially methylated cytosine‐phosphate‐guanine (CpG) characteristic in endometriotic cells was extracted. Among these CpGs, we focused on a stretch of hypomethylated CpGs within GATA6 gene and examined the potential role as enhancer in endometriotic cells and tissues.Result(s)We identified a stretch of hypomethylated CpGs within the GATA6 gene body in endometriotic cells. Because GATA6 mRNA was highly expressed in endometriotic cells but not in endometrial cells, we then hypothesized that the hypomethylated sequence may function as an enhancer in GATA6 gene expression. Chromatin immunoprecipitation analysis predicted the presence of active enhancer within the gene body sequence in endometriotic cells. Immunohistochemistry showed a positive staining of GATA6 in ovarian chocolate cysts, while in endometrial tissues and in some peritoneal tissues with endometriosis, GATA6 staining was at a marginal level.ConclusionThis is the first implication showing a link between an aberrant DNA methylation of cis element and gene expression in endometriosis. GATA6 expression may become a molecular marker to diagnose endometriosis lesions.
Mechanical properties of currently available left atrial appendage occlusion devices: A bench‐testing analysis
Authors: Menne Matthias F. , Schrickel Jan W. , Nickenig Georg , Al‐Kassou Baravan , Nelles Dominik , Schmitz‐Rode Thomas , Steinseifer Ulrich , De Backer Ole , Sedaghat Alexander 
Published: December 2018

AbstractEndoluminal left atrial appendage occlusion is an emerging therapy to treat patients suffering from atrial fibrillation with contraindications against oral anticoagulation. Different occlusion devices have been introduced into the clinical setting while comparative studies between the devices are sparse. This in vitro study compares several endoluminal left atrial appendage occlusion systems regarding 2 mechanical properties: radial (RF) and tug force (TF). Seven different occluder systems of various sizes (24 in total) underwent testing throughout their recommended sizing range. RF was measured in a commercial RF tester. TF was assessed according to a recently published bench test. RF increased with compression of the devices: The LAmbre 2228 device exerted the highest RF (8.6 N) at maximum compression of 16 mm. The lowest RF of 0.1 N was exhibited by the 27 mm Occlutech occluder at minimal compression. The highest TFs were exerted by the WaveCrest devices at maximum compression with 4.6 and 3.6 N for the 22 mm and the 27 mm device, respectively. The lowest TFs were measured for the first‐generation Occlutech devices, particularly for the 24 mm device with 1.1 N at maximum compression and 0.4 N at minimum compression. A strong positive correlation was found between the number of hooks per millimeter circumference of an occluder and its tug force (r = 0.87, P < 0.01). The analysis revealed device stability to be more dependent on anchoring structures than on RF. The wide range of mechanical properties makes comparison of current LAA occluders difficult and emphasizes the need for standardized preclinical testing to prompt clinical compatibility.
Inclusion of memory effects in a dynamic model of electroporation in biological tissues
Authors: Weinert Rodolfo , Pereira Eduardo , Ramos Airton 
Published: December 2018

AbstractThis article presents experimental and computational results of electroporation in rat liver. The experiments were performed using different forms of electrodes and waveforms of applied electric pulses. For the numerical simulation, the electroporation model proposed by Ramos and Weinert in a previous publication was used. Dynamic adjustments were used for obtaining a good modeling of the electric current. A single set of model parameters was obtained to fit the simulated current response for different waveforms and electrodes. These parameters were obtained with the use of a genetic algorithm that minimized the error between the simulated and experimental currents. The electroporation model with dynamic adjustment proved to be an appropriate simulation tool to predict the tissue conductivity during stimulation by intense electrical fields.
Effect of rifampin on enantioselective disposition and anti‐hypertensive effect of benidipine
Authors: Sunwoo Yu Eun , Nguyen Phuong Thi Thu , Chien Chin May , Ryu Ji Young , Shon Jihong , Shin Jae‐Gook 
Published: December 2018

AimsIn vitro study showed that benidipine is exclusively metabolized by cytochrome P450 (CYP) 3A. This study evaluated the effect of rifampin on the enantioselective disposition and anti‐hypertensive effect of benidipine.MethodsBenidipine (8 mg) was administered to healthy subjects with or without repeated rifampin dosing, in a crossover design. Plasma concentrations of (S)‐(S)‐(+)‐α and (R)‐(R)‐(−)‐α isomers of benidipine and blood pressure were measured for up to 24 h after dosing. In addition, CYP3A metabolic capacity was evaluated in each subject using oral clearance of midazolam.ResultsThe exposure of (S)‐(S)‐(+)‐α‐benidipine was greater than that of (R)‐(R)‐(−)‐α‐benidipine by approximately three‐fold following single dose of benidipine. Repeated doses of rifampin significantly decreased the exposure of both isomers. Geometric mean ratios (GMRs) (95% CI) of Cmax and AUC∞ for (S)‐(S)‐(+)‐α‐benidipine were 0.14 (0.10–0.18) and 0.12 (0.08–0.18), respectively. GMRs (95% CI) of Cmax and AUC∞ for (R)‐(R)‐(−)‐α‐benidipine were 0.10 (0.06–0.17) and 0.10 (0.06–0.17), respectively. Oral clearances of both isomers were increased equally by approximately 10‐fold. There were no significant differences in cardiovascular effect following benidipine administration between control and rifampin treatment. CYP3A activity using midazolam did not appear to correlate with oral clearance of benidipine.ConclusionsAfter single administration of racemic benidipine, enantioselective disposition of (S)‐(S)‐(+)‐α‐ and (R)‐(R)‐(−)‐α‐benidipine was observed. Treatments with rifampin significantly decreased the exposure of both isomers but appeared to marginally affect its blood pressure‐lowering effect in healthy subjects. Impact of coadministration of rifampin on the treatment effects of benidipine should be assessed in hypertensive patients.
Cross‐national comparison of paediatric antibiotic use in Norway, Portugal and Hungary
Authors: Benko Ria , Matuz Maria , Silva Ana , Ferreira Joaquina , Machado Maria Céu , Furtado Cláudia , Fungie Galistiani Githa , Bordas Reka , Blix Hege Salvesen 
Published: December 2018

AbstractA cross‐national comparison was performed on paediatric (0‐19 years) antibiotic use in Hungary, Norway and Portugal to explore and compare the scale and pattern of paediatric antibiotic use in these three European countries. Ambulatory care systemic antibiotic use (ATC: J01) was retrieved from national databases for year 2014. The main outcome measure was number of antibacterial packages per child inhabitant per year (packages/child/year) and was further stratified by age groups. Paediatric antibiotic use peaked in Hungary with 1.3 packages/child/year, followed by Portugal (0.8) and Norway (0.3). This ranking was retained and was most prominent in the 5‐ to 9‐year and 10‐ to 14‐year age groups. The pattern of antibiotic use in different paediatric age groups varied also substantially between countries. Narrow‐spectrum penicillins were much commonly used in Norway in all paediatric age subgroups in comparison with Hungary and Portugal. Newer, broad‐spectrum cephalosporins and macrolides were widely prescribed for Hungarian and Portuguese children in all paediatric subgroups in contrast to Norway, while tetracyclines were commonly prescribed for Norwegian adolescents. The scale and pattern of paediatric antibiotic use in Hungary and Portugal were very different compared with Norway. The high antibiotic exposure and the high consumption of broad‐spectrum penicillins begin in childhood in Hungary and Portugal which underpins the responsibility of paediatric GPs.
Educational videos from a film theory perspective: Relating teacher aims to video characteristics
Authors: Wijnker Winnifred , Bakker Arthur , van Gog Tamara , Drijvers Paul 
Published: December 2018

AbstractTeachers are increasingly using video in their lessons, with various aims (eg, to raise students’ levels of conceptual knowledge or interest). Videos that can be used for educational purposes are numerous, ranging from instruction videos to fiction films. Such videos have different characteristics, for example regarding the amount and structure of information, and the audio‐visual presentation. However, guidelines on which video characteristics can help to achieve specific teacher aims are lacking. As a first step towards composing such guidelines, we added a film theory perspective to educational research on videos. The study included seven science teachers, 13 videos, and 233 students (aged 13–18 years). We used teacher interviews, video analyses, student questionnaires and a cross‐case analysis connecting all the data. Data analysis followed a grounded theory approach, including open and axial coding to structure the data, and the constant comparative method to interconnect them. The results showed that videos that posed questions were associated with an increase in students’ interest, and that highly informative videos with authoritative speakers were associated with an increase in students self‐reported conceptual knowledge gains. Moreover, teachers often did not have explicit aims for using a particular video, and they selected and used videos in their lessons intuitively. Stimulating teachers to use videos in a more aim oriented way may make video usage more effective. From these findings, we developed a framework to assist teachers in selecting or making videos that match their aims, and a model of possible connections between teacher aims and film types as a first step towards guidelines for teachers using educational videos.
Animal prion diseases: the risks to human health
Authors: Houston Fiona , Andréoletti Olivier 
Published: December 2018

AbstractTransmissible spongiform encephalopathies (TSEs) or prion diseases of animals notably include scrapie in small ruminants, chronic wasting disease (CWD) in cervids and classical bovine spongiform encephalopathy (C‐BSE). As the transmission barrier phenomenon naturally limits the propagation of prions from one species to another, and the lack of epidemiological evidence for an association with human prion diseases, the zoonotic potential of these diseases was for a long time considered negligible. However, in 1996, C‐BSE was recognized as the cause of a new human prion disease, variant Creutzfeldt‐Jakob disease (vCJD), which triggered an unprecedented public health crisis in Europe. Large‐scale epidemio‐surveillance programs for scrapie and C‐BSE that were implemented in the EU after the BSE crisis revealed that the distribution and prevalence of prion diseases in the ruminant population had previously been underestimated. They also led to the recognition of new forms of TSEs (named atypical) in cattle and small ruminants and to the recent identification of CWD in Europe. At this stage, the characterization of the strain diversity and zoonotic abilities associated with animal prion diseases remains largely incomplete. However, transmission experiments in nonhuman primates and transgenic mice expressing human PrP clearly indicate that classical scrapie, and certain forms of atypical BSE (L‐BSE) or CWD may have the potential to infect humans. The remaining uncertainties about the origins and relationships between animal prion diseases emphasize the importance of the measures implemented to limit human exposure to these potentially zoonotic agents, and of continued surveillance for both animal and human prion diseases.
Modulation of α‐adrenoceptor signalling protects photoreceptors after retinal detachment by inhibiting oxidative stress and inflammation
Authors: Li Tong , Yang Shiqi , She Xiangjun , Yan Quan , Zhang Pengfei , Zhu Hong , Wang Fenghua , Luo Xueting , Sun Xiaodong 
Published: December 2018

Background and PurposeCurrently available treatments do not halt progression of photoreceptor death and subsequent visual impairment related to retinal detachment (RD) which is observed in various retinal disorders. This study investigated the neuroprotective effects of two adrenoceptor ligands, the α1‐adrenoceptor antagonist doxazosin and the α2‐adrenoceptor agonist guanabenz, against photoreceptor cell death in RD.Experimental ApproachWe used a model of experimental RD in Brown‐Norway rats induced by subretinal injection of sodium hyaluronate. Oxidative stress biomarkers and cytokine production were quantified with elisa. Protein expression levels and immunofluorescent labelling were determined in rats with RD and controls for mechanistic elucidation. The effects of systemic (i.p.) administration of doxazosin or guanabenz on photoreceptor apoptosis, retinal histology and electroretinography were evaluated in rats with RD and compared to the effects in vehicle controls.Key ResultsPhotoreceptors were the major source of RD‐induced ROS overproduction in the rat retina through the regulation of NADPH oxidase. Systemic administration of doxazosin or guanabenz decreased the RD‐induced production of ROS and proinflammatory cytokines, including IL‐1β and the chemokine CCL2, and suppressed retinal gliosis, resulting in attenuation of photoreceptor death and preservation of retinal structures and functions in RD.Conclusions and ImplicationsOur findings point to α‐adrenoceptors as novel therapeutic targets to provide photoreceptor protection and suggest that both doxazosin and guanabenz, two FDA‐approved drugs, could be further explored to treat retinal diseases.
Discovery of 2‐(3,4‐dialkoxyphenyl)‐2‐(substituted pyridazin‐3‐yl)acetonitriles as phosphodiesterase 4 inhibitors with anti‐neuroinflammation potential based on three‐dimensional quantitative structure–activity relationship study
Authors: Huang Chang , Zhong Qiu‐Ping , Tang Lv , Wang Hai‐Tao , Xu Jiang‐Ping , Zhou Zhong‐Zhen 
Published: December 2018

AbstractPhosphodiesterase 4 (PDE4) inhibitors with potential activities for CNS disorders provide a new therapeutic strategy for depression. To discover PDE4 inhibitors with anti‐neuroinflammation activities, reliable three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) models on our previous reported catecholic PDE4 inhibitors was built with a statistically significant cross‐validated coefficient (q2), conventional coefficient (r2), and good predictive capabilities based on the molecular docking results, using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods. Based on the analysis of CoMFA and CoMSIA contour maps, a series of 2‐(3,4‐dialkoxyphenyl)‐2‐(substituted pyridazin‐3‐yl) acetonitriles 16a–i was designed and synthesized. Among these compounds, compound 16a exhibited good inhibitory activities toward PDE4B1 and PDE4D7 with mid‐nanomolar IC50 values and potential anti‐neuroinflammation activity in BV‐2 cells. Docking simulation of compound 16a in the PDE4 catalytic domain activity pocket revealed that compound 16a maybe assumed a “V‐shaped” conformation, extending the side chain to S‐pocket.
Factors determining exercise capacity evaluated during cardiopulmonary exercise testing in 6‐month follow‐up after ST elevation myocardial infarction
Authors: Turski Maciej , Kocierz‐Woźnowska Magdalena , Wybraniec Maciej , Grabka Marek , Wita Marcin , Berger‐Kucza Adrianna , Wita Krystian , Mizia‐Stec Katarzyna 
Published: December 2018

SummaryIntroductionST elevation myocardial infarction (STEMI) is one of the main causes of congestive heart failure (CHF). The main symptom of CHF is exercise tolerance impairment. The aim of the study was to evaluate the prevalence and risk factors for impaired exercise tolerance in patients after STEMI.Methods and ResultsA total of 84 patients with STEMI were analysed in the study. Cardiopulmonary exercise test (CPET) was performed 6 months after STEMI. Impaired exercise tolerance defined as peak VO2 < 84% predicted for age and sex was present in 49 (58%) patients and was connected with lack of abciximab administration (91.4 versus 69%, P = 0·02) and the presence of mitral regurgitation (47 versus 23%, P = 0·02). In univariate analysis, the troponin I level at admission (OR 1·89, P = 0·047), the use of abciximab (OR 0·21, P = 0·03), the presence of mitral regurgitation (OR 2·98, P = 0·03) and NT‐proBNP concentration (OR 2·17, P = 0·021) were related to impaired exercise tolerance. The best multivariate model for predicting impaired exercise tolerance included mitral regurgitation and lack of abciximab administration.ConclusionsImpaired exercise tolerance after STEMI is common. Mitral regurgitation and lack of abciximab administration are the best predicting factors of impaired exercise tolerance after STEMI.
Increasing living donation by implementing the Kidney Coach Program
Authors: LaPointe Rudow Dianne , Geatrakas Sara , Armenti Jonathan , Tomback Ariella , Khaim Rafael , Porcello Lisa , Pan Stephanie , Arvelakis Antonios , Shapiro Ron 
Published: December 2018

AbstractCandidates for living donor kidney transplantation (LDKT) find it difficult to discuss living donation with people in their social network, and there is a lack of useful interventions to train them. The Kidney Coach Program (KCP) was developed to equip individuals (advocates for candidates and candidate themselves) with the tools needed to find potential donors. The purpose of this pilot study is to evaluate the effects of the KCP on increasing the number of people considering living donation.MethodsCandidates for the KCP were recruited. Data were collected on the number of live donor inquiries in the coach group compared to listed patients (historical controls).ResultsOver a 12‐month period, 20 transplant candidates enrolled in the KCP were compared to 50 controls. Eighty percent of the participants in the KCP had at least one donor inquiry compared to 38% of controls (P = 0.001). Significantly, more Caucasian candidates participated in the KCP compared to other racial groups.ConclusionsThe KCP can be an effective method to increase awareness of a patient's need for LDKT. Existing clinical staff successfully implemented the program. Transplant programs should provide training to candidates and their supports on effective ways to find a living donor.
Standards of diagnostic colonoscopy for early‐stage neoplasia: Recommendations by an Asian private group
Authors: Sano Yasushi , Chiu Han‐Mo , Li Xiao‐bo , Khomvilai Supakij , Pisespongsa Pises , Co Jonard Tan , Kawamura Takuji , Kobayashi Nozomu , Tanaka Shinji , Hewett David G. , Takeuchi Yoji , Imai Kenichiro , Utsumi Takahiro , Teramoto Akira , Hirata Daizen , Iwatate Mineo , Singh Rajvinder , Ng Siew C. , Ho Shiaw‐Hooi , Chiu Philip , Tajiri Hisao 
Published: December 2018

Background and AimIn recent years, the incidence of colorectal cancer has been increasing, and it is now becoming the major cause of cancer death in Asian countries. The aim of the present study was to develop Asian expert‐based consensus to standardize the preparation, detection and characterization for the diagnosis of early‐stage colorectal neoplasia.MethodsA professional group was formed by 36 experts of the Asian Novel Bio‐Imaging and Intervention Group (ANBI2G) members. Representatives from 12 Asia–Pacific countries participated in the meeting. The group organized three consensus meetings focusing on diagnostic endoscopy for gastrointestinal neoplasia. The Delphi method was used to develop the consensus statements.ResultsThrough the three consensus meetings with debating, reviewing the literature and regional data, a consensus was reached at third meeting in 2016. The consensus was reached on a total of 10 statements. Summary of statements is as follows: (i) Adequate bowel preparation for high‐quality colonoscopy; (ii) Antispasmodic agents for lesion detection; (iii) Image‐enhanced endoscopy (IEE) for polyp detection; (iv) Adenoma detection rate for quality indicators; (v) Good documentation of colonoscopy findings; (vi) Complication rates; (vii) Cecal intubation rate; (viii) Cap‐assisted colonoscopy (CAC) for polyp detection; (ix) Macroscopic classification using indigocarmine spray for characterization of colorectal lesions; and (x) IEE and/or magnifying endoscopy for prediction of histology.ConclusionThis consensus provides guidance for carrying out endoscopic diagnosis and characterization for early‐stage colorectal neoplasia based on the evidence. This will enhance the quality of endoscopic diagnosis and improve detection of early‐stage colorectal neoplasia.
Using automated controlled rearing to explore the origins of object permanence
Authors: Prasad Aditya , Wood Samantha M. W. , Wood Justin N. 
Published: December 2018

AbstractWhat are the origins of object permanence? Despite widespread interest in this question, methodological barriers have prevented detailed analysis of how experience shapes the development of object permanence in newborn organisms. Here, we introduce an automated controlled‐rearing method for studying the emergence of object permanence in strictly controlled virtual environments. We used newborn chicks as an animal model and recorded their behavior continuously (24/7) from the onset of vision. Across four experiments, we found that object permanence can develop rapidly, within the first few days of life. This ability developed even when chicks were reared in impoverished visual environments containing no object occlusion events. Object permanence failed to develop, however, when chicks were reared in environments containing temporally non‐smooth objects (objects moving on discontinuous spatiotemporal paths). These results suggest that experience with temporally smooth objects facilitates the development of object permanence, confirming a key prediction of temporal learning models in computational neuroscience.