bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direction‐ and rate‐dependent fractionation during atrial fibrillation persistence: Unmasking cardiac anisotropy?
Authors: Starreveld Roeliene , de Groot Natasja M. S. 
Published: June 2020

AbstractThis human case is the first to illustrate morphological manifestations of direction‐ and rate‐dependent anisotropic conduction in high‐resolution unipolar atrial potentials. Premature impulses induced low‐amplitude, fractionated extracellular potentials with exceptionally prolonged durations in a 76‐year old longstanding persistent patient with atrial fibrillation (AF), demonstrating direction‐dependency of anisotropic conduction. An increased pacing frequency induced presence of similar fractionated potentials, reflecting rate‐dependent anisotropy and inhomogeneous, slow conduction. Pacing with different rates and from different sites could aid in identifying nonuniform anisotropic tissue and thus the substrate of AF.
AMPH1 functions as a tumour suppressor in ovarian cancer via the inactivation of PI3K/AKT pathway
Authors: Chen Yajun , Cao Wenjiao , Wang Lihua , Zhong Tianying 
Published: June 2020

AbstractAMPH1, an abundant protein in nerve terminals, plays a critical role in the recruitment of dynamin to sites of clathrin‐mediated endocytosis. Recently, it is reported to be involved in breast cancer and lung cancer. However, the impact of AMPH1 on ovarian cancer is unclear. In this study, we used gain‐of‐function and loss‐of‐function methods to explore the role of AMPH1 in ovarian cancer cells. AMPH1 inhibited ovarian cancer cell growth and cell migration, and promoted caspase‐3 activity, resulting in the increase of cell apoptosis. In xenograft mice model, AMPH1 prevented tumour progression. The anti‐oncogene effects of AMPH1 on ovarian cancer might be partially due to the inhibition of PI3K/AKT signalling pathway after overexpression of AMPH1. Immunohistochemistry analysis showed that the staining of AMPH1 was remarkably reduced in ovarian cancer tissues compared with normal ovarian tissues. In conclusion, our study identifies AMPH1 as a tumour suppressor in ovarian cancer in vitro and in vivo. This is the first evidence that AMPH1 inhibited cell growth and migration, and induced apoptosis via the inactivation of PI3K/AKT signalling pathway on ovarian cancer, which may be used as an effective strategy.
Equivocal Euroscepticism: How Populist Radical Right Parties Can Have Their EU Cake and Eat It
Authors: Heinisch Reinhard , McDonnell Duncan , Werner Annika 
Published: June 2020

AbstractConceptualizations and measurements of Euroscepticism tend to assume that, while parties may change positions from one period to another, they unequivocally espouse hard or soft euroscepticism at a given point in time. However, there are good theoretical reasons for some parties not to do so, in order to speak to different audiences and keep their decision‐making options open. Through an analysis of manifestos and leaders' speeches we show how two populist radical right parties, the Italian Northern League and the Austrian Freedom Party, espoused what we term ‘equivocal euroscepticism’ in the years around the 2014 European Parliament elections. Specifically, these parties articulated a distinct, albeit ambivalent, stance by combining elements of both soft and hard euroscepticism at the same time. We argue that ‘equivocal euroscepticism’ can give these parties strategic advantages, including the freedom to cooperate both with other radical right, hard eurosceptic, parties at European level and more moderate parties at the national one.
A spray containing extracts of oat plantlets and Uncaria tomentosa relieves pain associated with chronic inflammatory skin diseases and dermatological procedures
Authors: Reich A. , Lopez Estebaranz J.L. , Bahadoran P. , Guillot P. , Carballido F. , Saint Aroman M. 
Published: June 2020

AbstractBackgroundInflammation from skin conditions such as psoriasis, eczema‐like atopic dermatitis (AD) and hand eczema (HE) and following dermatological procedures (post‐acts) can result in intense itching and cutaneous pain. Dermo‐cosmetics containing plant extracts have been shown to reduce or alleviate these symptoms.ObjectivesAssessment of the tolerability and efficacy of a spray containing Rhealba\xAE Oat plantlets and Uncaria tomentosa extracts in adults and children with inflammatory skin diseases and after dermatological procedures.MethodsData from five open label studies were analysed (Study 1: adults with AD; Study 2: children with AD; Study 3: adults with psoriasis; Study 4: adults with HE; Study 5: adults who had undergone a dermatological procedure: laser, intense pulsed light, glycolic acid peeling, photodynamic therapy or cryotherapy procedure). In all studies, subjects could use the test product up to six times per day for symptom relief. Physical and functional signs of inflammation, treatment‐emergent adverse events (TEAEs), soothing effect, changes in quality of life, cutaneous pain and cosmetic acceptability were compared pre‐ and postapplication.ResultsA total of 176 subjects were enrolled across the five studies. Overall, investigators judged the dermatological tolerance of the test product containing Rhealba\xAE Oat plantlets extract and Uncaria tomentosa as good to excellent. All studies showed significant improvements in physical signs, reduction in itching and feeling of pain (P < 0.05). The soothing effect was evident after the first application. TEAEs were mostly mild, transient and occurred within the first few days of treatment. The majority of subjects reported improved QoL across the studies.ConclusionsThe dermo‐cosmetic spray containing Rhealba\xAE Oat plantlets extract and U. tomentosa was well tolerated and efficacious in providing relief of symptoms associated with cutaneous pain from inflammatory skin diseases and following dermatological procedures; however, further studies are needed to rule out alternative explanations of symptom reduction such as natural history and response biases.
Shall I tell my mentor? Exploring the mentor‐student relationship and its impact on students' raising concerns on clinical placement
Authors: Brown Patricia , Jones Aled , Davies Jane 
Published: June 2020

AbstractAimsTo explore student nurses' and nurse mentors' perceptions and experiences of raising concerns on clinical placement and the influence (if any) of their relationship on this process. A secondary aim is to consider the above, from a regulatory perspective in light of current literature and policy developments.BackgroundRaising concerns whilst on clinical placement has been shown to be challenging for student nurses internationally. Registered nurses in the UK (in this case called “nurse mentors”) facilitate learning and assessment in practice. However, limited research exists on the influence of the relationship between the nurse mentor and student nurse on the raising concerns process.DesignA qualitative approach was used to undertake secondary thematic analysis of interview data. The primary data set was generated during a PhD study, focusing on the mentor–student dynamic and the possible influence of this relationship on students' raising concerns.Methods30 individual semi‐structured interviews were subjected to concurrent and thematic analysis. Interviews were undertaken with student nurses (n = 16) and nurse mentors (n = 14) between April 2016–January 2018. The COREQ 32‐item checklist was used during the preparation of this article.FindingsThe following three interrelated analytical themes were generated from the data, “developing a mentor‐student relationship," “keeping your mentor sweet” and “the mentor role in the raising concerns process.”ConclusionOur analysis of participants' experiences and perceptions offers an original contribution to understanding the factors associated with student nurses raising concerns in practice. Student nurses and most mentors believed that students should be encouraged and supported to raise concerns, but students' decisions were strongly influenced by their perceptions of the immediate interpersonal and educational context. Similar barriers to raising concerns have been shown to exist regardless of geographical boundaries, therefore the findings of this study are nationally and internationally relevant.Relevance to clinical practiceThis study provides new insight into the role of the nurse mentor in supporting students who raise concerns on clinical placements. The majority of the mentor participants believed that students should be encouraged and supported to speak up if they witness poor care or unprofessional behaviour. Focusing on the compexities around raising concerns in mentorship training and updates would rovide a forum for open discussion amongst mentors and educators.
Tumour necrosis factor‐α and myoglobin associated with the recovery time of coronary artery lesions in Kawasaki disease patients
Authors: Guo Chun , Tan Chaochao , Xia Xiaohui , Yuan Yonghua , Zhao Menghua , Yuan Zhijie , Wang Yupeng , Deng Zhonghua , Chen Jie , Zhou Yujie , Huang Ying 
Published: June 2020

AimTo assess the relationship between clinical parameters and medium term recovery time of coronary artery lesions (CALs).MethodsIn total, 344 Kawasaki disease patients were screened and 311 Kawasaki disease patients were included and followed‐up for the next 2 years. Clinical records, clinical parameters and inflammatory biomarkers were collected for all subjects.ResultsTumour necrosis factor (TNF)‐α and myoglobin (MYO) levels in patients without recovery from CALs were significantly higher than those without CALs and with recovery from CALs. Kaplan–Meier survival analysis showed that in the high‐TNF‐α group, the estimated median time to recovery (5.0 months, 95% confidence interval (CI) 1.436–8.564) is significantly longer than the low‐TNF‐α group (2.00 months, 95% CI: 0.633–3.367, P = 0.044). Also, the estimated median time (5.0 months, 95% CI: 1.836–8.164) in the high‐MYO group is significantly longer than the low‐MYO group (2.00 months, 95% CI: 0.405–3.595, P = 0.002). Cox regression analysis showed independent factors for recovery of CALs included age, left coronary artery to aortic annulus ratio, TNF‐α and MYO levels.ConclusionsThese findings suggest that clinical parameters such as age, left coronary artery to aortic annulus ratio, TNF‐α and MYO levels associate with medium term recovery time of CALs and could help in the design of a clinical strategy for the surveillance and prevention of late cardiovascular events.
Circadian clock regulates hepatotoxicity of Tripterygium wilfordii through modulation of metabolism
Authors: Zhao Huan , Tong Yongbin , Lu Danyi , Wu Baojian 
Published: June 2020

Abstract

Objectives
We aimed to determine the diurnal rhythm of Tripterygium wilfordii (TW) hepatotoxicity and to investigate a potential role of metabolism and pharmacokinetics in generating chronotoxicity.

Methods
Hepatotoxicity was determined based on assessment of liver injury after dosing mice with TW at different circadian time points. Circadian clock control of metabolism, pharmacokinetics and hepatotoxicity was investigated using Clock-deficient (Clock−/−) mice.

Key findings
Hepatotoxicity of TW displayed a significant circadian rhythm (the highest level of toxicity was observed at ZT2 and the lowest level at ZT14). Pharmacokinetic experiments showed that oral gavage of TW at ZT2 generated higher plasma concentrations (and systemic exposure) of triptolide (a toxic constituent) compared with ZT14 dosing. This was accompanied by reduced formation of triptolide metabolites at ZT2. Loss of Clock gene sensitized mice to TW-induced hepatotoxicity and abolished the time-dependency of toxicity that was well correlated with altered metabolism and pharmacokinetics of triptolide. Loss of Clock gene also decreased Cyp3a11 expression in mouse liver and blunted its diurnal rhythm.

Conclusions
Tripterygium wilfordii chronotoxicity was associated with diurnal variations in triptolide pharmacokinetics and circadian expression of hepatic Cyp3a11 regulated by circadian clock. Our findings may have implications for improving TW treatment outcome with a chronotherapeutic approach.
An updated Chinese vascular plant tree of life: Phylogenetic diversity hotspots revisited
Authors: Hu Hai‐Hua , Liu Bing , Liang Yi‐Shuo , Ye Jian‐Fei , Saqib Saddam , Meng Zhen , Lu Li‐Min , Chen Zhi‐Duan 
Published: June 2020

AbstractLarge‐scale phylogenies provide a framework for interdisciplinary investigations in taxonomy, evolutionary biology, biogeography, ecology, and conservation. Integration of regional tree of life and species distribution data has greatly promoted spatial phylogenetic studies on biodiversity, floristic assembly, and biogeographic regionalization. In this study, we updated the phylogenetic tree of Chinese vascular plants by integrating data from public databases and sequences newly generated by our laboratory, to facilitate the exploration of floristic and ecological questions at a country scale. A phylogenetic tree with 15 092 tips and 14 878 species was obtained, including 13 663 species (44.0%) and 2953 genera (95.7%) native to China. Only two families (Corsiaceae and Mitrastemonaceae) and 133 genera native to China are not sampled in this study. Low proportion of sampling is detected in orders with high species diversity and those with low species diversity. The Hengduan Mountains, plus the western Qinghai–Tibet Plateau and western Xinjiang, show the greatest gap of target molecular data for angiosperms. Our phylogeny of Chinese vascular plants recovers relationships among and within major lineages that are highly congruent with published phylogenies at a broader scale. Most families (98.7%) are supported as monophyletic, and 573 genera (17.9%) are recognized as non‐monophyletic. Finally, hotspots of phylogenetic diversity for the Chinese angiosperms at both the genus and species levels are identified based on our phylogram, implicating conservation priorities for phylogenetic diversity. The updated phylogeny of Chinese vascular plants is publically available to generate subtrees through our automated phylogeny assembly tool SoTree in the DarwinTree platform (http://www.darwintree.cn/flora-sotree-v2/index.shtml).
Unravelling evolutionary relationships between epifoliar Meliolaceae and angiosperms
Authors: Zeng Xiang‐Yu , Jeewon Rajesh , Hongsanan Sinang , Hyde Kevin D. , Wen Ting‐Chi 
Published: June 2020

AbstractEpifoliar fungi are a group of poorly studied fungal symbionts that coinhabit the surface of living plants. Meliolaceae is the largest group of epifoliar fungi and has been considered as obligate parasites. We investigated the taxonomy of Meliolaceae and the coevolutionary events with their host plants using time‐calibrated cophylogeny based on large subunit, small subunit, and internal transcribed spacer (ITS) sequence data obtained from 17 different fungal taxa and rbcL, ITS, and trnH‐psbA sequence data from their corresponding hosts. Nine new fungal species are introduced in this paper and Appendiculella is synonymized under Asteridiella. The dominant coevolutionary events during the Cretaceous and Cenozoic are cospeciation and host shift, respectively. We hypothesize that the evolutionary history of epifoliar fungi can be divided into three major periods: origins of families, formations of genera, and diversification of species. The rise of angiosperms prompted the evolution of modern epifoliar fungi and the diversification of orders of Angiospermae fostered the formation of epifoliar fungal genera. Phylogenetically, epifoliar fungal genera can be delimited according to their coevolutionary patterns and divergent periods.
Self‐care promotion of the intact (non‐circumcised) patient: A review of available recommendations
Authors: Wodwaski Nadine , Munyan Kristen 
Published: June 2020

AbstractPurposeWith routine infant circumcision rates declining in the United States, nurses are likely to encounter more intact (non‐circumcised) male patients requiring genital hygiene, nursing interventions, and education accessing the health system. To date, a little emphasis has been placed on the care of the intact male patient in the nursing literature, resulting in ambiguity in care recommendations. The vagueness is problematic, as improper intact care, particularly in the pediatric patient, can result in forced retraction injuries, bleeding, scarring, and unnecessary intervention. In addition, with nurses conducting many of the tasks of hygiene and education for self‐care, there is potential for impaired patient self‐care and harm if nurses are not knowledgeable in intact care. Utilizing Orem's self‐care theory as a framework, the aim of this effort is to perform a review of current recommendations on intact care to inform nursing practice with this population. As no evidence was found in the scientific literature, readily available consumer website resources were reviewed.ConclusionThemes of hygiene and age of retraction emerged. While recommendations for hygiene practices were variable, all review sources (n = 12) were clear in advising against the premature retraction of the intact foreskin and identified this as a route for injury.Practice ImplicationsWith no current literature available to summarize current nursing clinical or educational practices, dissemination of these recommendations is necessary to prevent patient injury and promote appropriate patient self‐care.
Real‐world utility of HCV core antigen as an alternative to HCV RNA testing: Implications for viral load and genotype
Authors: Pollock Kevin G. , McDonald Scott A. , Gunson Rory , McLeod Allan , Went April , Goldberg David J. , Hutchinson Sharon J. , Barclay Stephen T. 
Published: June 2020

AbstractFollowing positive serology, the gold standard confirmatory test of hepatitis C virus (HCV) infection is detection of HCV RNA by PCR. We assessed the utility of HCV core antigen testing to identify active infection among those positive for anti‐HCV antibodies, when introduced to routine testing. We identified serum samples that were tested at a single laboratory in Scotland from June 2011to December 2017. Serum samples testing positive for HCV antibodies (HCV Ab positive) followed by reflex HCV core antigen (Ag) testing during the study period were identified. Those patients for whom a PCR test was requested on the baseline sample were also identified. For this group, the sensitivity and specificity of HCV Ag as a diagnostic tool were assessed using HCV PCR as gold standard. In our cohort of 744 patients, we demonstrated a sensitivity of 82.1% (95% CI 77.1%‐86.2%) and a specificity of 99.8% (95% CI 98.6%‐100%). Genotype 3 was associated with increased odds of a false‐negative result (OR = 3.59, 95% CI: 1.32‐9.71), and reduced odds of a false negative were associated with older age (odds ratio (OR)=0.92, 95% CI: 0.88‐0.97 per year) and viral load (OR = 0.10, 95% CI: 0.05‐0.21 per log10 IU/ml). While the implementation of HCV core antigen testing for diagnosis could lead to significant cost savings in national screening programmes, our data suggest that a significant proportion of HCV‐infected individuals may be missed. These findings have implications for HCV diagnosis and determination of viral clearance after treatment, particularly in low‐ and middle‐income regions, where genotype 3 is prevalent.
Distinctions in the Acquisition of Vocabulary and Grammar: An Individual Differences Approach
Authors: Walker Neil , Monaghan Padraic , Schoetensack Christine , Rebuschat Patrick 
Published: June 2020

AbstractLearning language requires acquiring the grammatical categories of words in the language, but learning those categories requires understanding the role of words in the syntax. In this study, we examined how this chicken and egg problem is resolved by learners of an artificial language comprising nouns, verbs, adjectives, and case markers following syntactic rules. We also measured individual differences in declarative and procedural memory processing, which have been linked to vocabulary and grammar learning, respectively. The results showed that grammar and vocabulary can be acquired simultaneously, but with distinctive patterns of acquisition: the syntactic role of verbs and their referents first, then other lexical categories, and finally the syntactic function of case markers. Interdependencies in learning were found for word order and verbs, which related to verbal declarative memory, and also for nouns, adjectives, and case markers, which related to procedural memory.
Comparison between the cervical and abdominal vagus nerves in mice, pigs, and humans
Authors: Stakenborg Nathalie , Gomez‐Pinilla Pedro J. , Verlinden Thomas J. M. , Wolthuis Albert M. , D’Hoore Andre , Farré Ricard , Herijgers Paul , Matteoli Gianluca , Boeckxstaens Guy E. 
Published: June 2020

AbstractBackgroundVagus nerve (VN) stimulation is currently evaluated as a novel approach to treat immune‐mediated disorders. The optimal stimulation parameters, however, largely depend on the VN composition potentially impacting on its clinical translation. Hence, we evaluated whether morphological differences exist between the cervical and abdominal VNs across different species.Materials and methodsThe cervical and abdominal VNs of mouse, pig, and humans were stained for major basic protein and neurofilament F to identify the percentage and size of myelinated and non‐myelinated fibers.ResultsThe percentage of myelinated fibers was comparable between species, but was higher in the cervical VN compared with the abdominal VN. The cervical VN contained 54 ± 4%, 47 ± 7%, and 54 ± 7% myelinated fibers in mouse, pig, and humans, respectively. The myelinated fibers consisted of small‐diameter (mouse: 71%, pig: 80%, and humans: 63%), medium‐diameter (mouse: 21%, pig: 18%, and humans: 33%), and large‐diameter fibers (mouse: 7%, pig: 2%, and humans: 4%). The abdominal VN predominantly contained unmyelinated fibers (mouse: 93%, pig: 90%, and humans: 94%). The myelinated fibers mainly consisted of small‐diameter fibers (mouse: 99%, pig: 85%, and humans: 74%) and fewer medium‐diameter (mouse: 1%, pig: 13%, and humans: 23%) and large‐diameter fibers (mouse: 0%, pig: 2%, and humans: 3%).ConclusionThe VN composition was largely similar with respect to myelinated and unmyelinated fibers in the species studied. Human and porcine VNs had a comparable diameter and similar amounts of fibrous tissue and contained multiple fascicles, implying that the porcine VN may be suitable to optimize stimulation parameters for clinical trials.
A plant RNA virus activates selective autophagy in a UPR‐dependent manner to promote virus infection
Authors: Li Fangfang , Zhang Changwei , Tang Ziwei , Zhang Lingrui , Dai Zhaoji , Lyu Shanwu , Li Yinzi , Hou Xilin , Bernards Mark , Wang Aiming 
Published: June 2020

Summary

Autophagy is an evolutionarily conserved pathway in eukaryotes that delivers unwanted cytoplasmic materials to the lysosome/vacuole for degradation/recycling. Stimulated autophagy emerges as an integral part of plant immunity against intracellular pathogens.

In this study, we used turnip mosaic virus (TuMV) as a model to investigate the involvement of autophagy in plant RNA virus infection.

The small integral membrane protein 6K2 of TuMV, known as a marker of the virus replication site and an elicitor of the unfolded protein response (UPR), upregulates the selective autophagy receptor gene NBR1 in a UPR‐dependent manner. NBR1 interacts with TuMV NIb, the RNA‐dependent RNA polymerase of the virus replication complex (VRC), and the autophagy cargo receptor/adaptor protein ATG8f. The NIb/NBR1/ATG8f interaction complexes colocalise with the 6K2‐stained VRC. Overexpression of NBR1 or ATG8f enhances TuMV replication, and deficiency of NBR1 or ATG8f inhibits virus infection. In addition, ATG8f interacts with the tonoplast‐specific protein TIP1 and the NBR1/ATG8f‐containing VRC is enclosed by the TIP1‐labelled tonoplast. In TuMV‐infected cells, numerous membrane‐bound viral particles are evident in the vacuole.

Altogether these results suggest that TuMV activates and manipulates UPR‐dependent NBR1‐ATG8f autophagy to target the VRC to the tonoplast to promote viral replication and virion accumulation.