bluuebunny/crossref_metadata_2025 huggingface dataset:
A reconsideration of the radiocarbon dating of the Marine Isotope Stage 3 fauna from southern Ireland
Authors: Carden Ruth F. , Higham Thomas F. G. , Woodman Peter C.
Published: June 2020

With the improvements in the techniques of radiocarbon dating since the 1990s and the pretreatment of bone samples, it has become apparent that some of the radiocarbon dates from Irish caves such as Castlepook Cave may not be as accurate as previously determined. The faunal remains and sediments within Castlepook Cave are important as this cave is one of only two caves in Ireland in which both pre‐ and post‐Last Glacial Maximum sediments containing faunal remains are found. In this study, samples of identified bones were re‐dated from this cave as well as two others (Foley and Shandon caves) from the same region in the south‐southeast of Ireland. The new dates from Castlepook Cave disclosed results that were significantly older by between c. 5000 and 12 000 radiocarbon years. This was not as apparent in dates obtained from Foley and Shandon caves, where the new dates were older by c. 4000 radiocarbon years on average. The results imply a much older presence of certain mammals during MIS 3 in Ireland and suggest that certain species, notably giant deer and spotted hyaena, may have become locally extirpated before the Last Glacial Maximum, around 40 cal. ka BP.
Digital era open government and democratic governance: The case of Government of Canada Wikipedia editing
Authors: Clarke Amanda , Dubois Elizabeth
Published: June 2020

As digital era open government initiatives are deployed globally, researchers are debating their effects on democratic governance. We develop a framework to evaluate whether these initiatives improve or undermine democratic governance and apply it to the case of Government of Canada Wikipedia editing and an automated Twitter account (@gccaedits) tracking this activity. Through content analysis of edits and analysis of access to information requests we show that while most edits made are useful and non‐partisan, the response of news media and government managers ultimately renders the editing a threat to democratic governance. This complexity highlights the importance of assessing the merits of open government initiatives in their broader socio‐political context. The findings also suggest that more fundamental shifts in contemporary political, media and administrative cultures are necessary before the potential benefits of open government reforms can materialize.
Hypomethylation of Notch1 DNA is associated with the occurrence of uveitis
Authors: Wei H , Yin X , Tang H , Gao Y , Liu B , Wu Q , Tian Q , Hao Y , Bi H , Guo D
Published: June 2020

Uveitis is a serious intra-ocular inflammatory disease that can lead to visual impairment even blindness worldwide. Notch signaling can regulate the differentiation of naive CD4+ T cells, influencing the development of uveitis. DNA methylation is closely related to the autoimmune diseases. In this study, we measured the Notch1 DNA methylation level, determined the Notch1 and related DNA methylases mRNA expression and evaluated the ratio of T helper type 17 regulatory T cell (Th17/Treg) in peripheral blood mononuclear cells (PBMCs) from uveitis patients and normal control subjects; we also tested the levels of relevant inflammatory cytokines in serum from the participants. Results indicated that compared with those in normal control individuals, the expression of ten–eleven translocation 2 (TET2) and Notch1 mRNA is elevated in uveitis patients, whereas the methylation level in Notch1 DNA promotor region [−842 ~ −646 base pairs (bp)] is down-regulated, and is unrelated to anatomical location. Moreover, the Th17/Treg ratio is up-regulated in PBMCs from uveitis patients, accompanied by the elevated levels of proinflammatory cytokines [e.g. interleukin (IL)-2, IL-6, IL-17 and interferon (IFN)-γ] in serum from uveitis patients. These findings suggest that the over-expression of TET2 DNA demethylase may lead to hypomethylation of Notch1, activate the Notch1 signaling, induce naive CD4+ T cells to differentiate the Th17 subset and thus disturb the balance of the Th17/Treg ratio in uveitis patients. Overall, hypomethylation of Notch1 DNA is closely associated with the occurrence of uveitis. Our study preliminarily reveals the underlying mechanism for the occurrence of uveitis related to the hypomethylation of Notch1 DNA, providing a novel therapeutic strategy against uveitis in clinical practice.
Image Morphing With Perceptual Constraints and STN Alignment
Authors: Fish N. , Zhang R. , Perry L. , Cohen‐Or D. , Shechtman E. , Barnes C.
Published: June 2020

In image morphing, a sequence of plausible frames are synthesized and composited together to form a smooth transformation between given instances. Intermediates must remain faithful to the input, stand on their own as members of the set and maintain a well‐paced visual transition from one to the next. In this paper, we propose a conditional generative adversarial network (GAN) morphing framework operating on a pair of input images. The network is trained to synthesize frames corresponding to temporal samples along the transformation, and learns a proper shape prior that enhances the plausibility of intermediate frames. While individual frame plausibility is boosted by the adversarial setup, a special training protocol producing sequences of frames, combined with a perceptual similarity loss, promote smooth transformation over time. Explicit stating of correspondences is replaced with a grid‐based freeform deformation spatial transformer that predicts the geometric warp between the inputs, instituting the smooth geometric effect by bringing the shapes into an initial alignment. We provide comparisons to classic as well as latent space morphing techniques, and demonstrate that, given a set of images for self‐supervision, our network learns to generate visually pleasing morphing effects featuring believable in‐betweens, with robustness to changes in shape and texture, requiring no correspondence annotation.
Rewilding in the face of climate change
Authors: Carroll Carlos , Noss Reed F.
Published: June 2020

Expansion of the global protected‐area network has been proposed as a strategy to address threats from accelerating climate change and species extinction. A key step in increasing the effectiveness of such expansion is understanding how novel threats to biodiversity from climate change alter concepts such as rewilding, which have underpinned many proposals for large interconnected reserves. We reviewed potential challenges that climate change poses to rewilding and found that the conservation value of large protected areas persists under climate change. Nevertheless, more attention should be given to protection of microrefugia, macrorefugia, complete environmental gradients, and areas that connect current and future suitable climates and to maintaining ecosystem processes and stabilizing feedbacks via conservation strategies that are resilient to uncertainty regarding climate trends. Because a major element of the threat from climate change stems from its novel geographic patterns, we examined, as an example, the implications for climate‐adaptation planning of latitudinal, longitudinal (continental to maritime), and elevational gradients in climate‐change exposure across the Yellowstone‐to‐Yukon region, the locus of an iconic conservation proposal initially designed to conserve wide‐ranging carnivore species. In addition to a continued emphasis on conserving intact landscapes, restoration of degraded low‐elevation areas within the region is needed to capture sites important for landscape‐level climate resilience. Extreme climate exposure projected for boreal North America suggests the need for ambitious goals for expansion of the protected‐area network there to include refugia created by topography and ecological features, such as peatlands, whose conservation can also reduce emissions from carbon stored in soil. Qualitative understanding of underlying reserve design rules and the geography of climate‐change exposure can strengthen the outcomes of inclusive regional planning processes that identify specific sites for protection.
Positioning sulphonylureas in a modern treatment algorithm for patients with type 2 diabetes: Expert opinion from a European consensus panel
Authors: Consoli Agostino , Czupryniak Leszek , Duarte Rui , Jermendy György , Kautzky‐Willer Alexandra , Mathieu Chantal , Melo Miguel , Mosenzon Ofri , Nobels Frank , Papanas Nikolaos , Roman Gabriela , Schnell Oliver , Sotiropoulos Alexis , Stehouwer Coen D. A. , Tack Cees J. , Woo Vincent , Fadini Gian Paolo , Raz Itamar
Published: June 2020

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second‐line treatment after metformin and are often ranked at the same level as newer glucose‐lowering medications. Strong evidence now shows that sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT‐2is and GLP‐1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT‐2is and/or GLP‐1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second‐line agents continues to be acceptable in resource‐constrained settings.
Sex‐specific associations between cardiovascular risk factors and myocardial infarction in patients with type 2 diabetes: The ADVANCE‐ON study
Authors: Ohkuma Toshiaki , Peters Sanne A. E. , Jun Min , Harrap Stephen , Cooper Mark , Hamet Pavel , Poulter Neil , Chalmers John , Woodward Mark ,   the ADVANCE Collaborative Group
Published: June 2020

Aim

To examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large‐scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales.

Materials and methods

Eleven thousand and sixty‐five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post‐trial follow‐up study, ADVANCE‐ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non‐fatal) by sex, and the women‐to‐men ratio of HRs (RHR).

Results

Over a median of 9.6 years of follow‐up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05‐2.91) for current smoking, 1.53 (1.00‐2.32) for former smoking, 1.18 (1.02‐1.37) for SBP, and 1.13 (95% CI, 1.003‐1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person‐years) compared with women (5.8 per 1000 person‐years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI.

Conclusions

In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex‐specific approaches and early interventions in women with diabetes.
Preclinical evaluation of tyrosine kinase 2 inhibitors for human beta‐cell protection in type 1 diabetes
Authors: Coomans de Brachène Alexandra , Castela Angela , Op de Beeck Anne , Mirmira Raghavendra G. , Marselli Lorella , Marchetti Piero , Masse Craig , Miao Wenyan , Leit Silvana , Evans‐Molina Carmella , Eizirik Decio L.
Published: June 2020

Aim

Type 1 diabetes (T1D) is a chronic autoimmune disease leading to progressive loss of pancreatic beta cells. Interferon (IFN)‐α plays a critical role in the crosstalk between pancreatic beta cells and the immune system in early insulitis. In human beta cells IFNα signals through JAK1 and TYK2, leading to endoplasmic reticulum stress, inflammation and HLA class I overexpression. IFNα, acting synergistically with IL‐1β, induces apoptosis. Polymorphisms in TYK2 that decrease its activity are associated with protection against T1D, and we hypothesized that pharmacological inhibitors that specifically target TYK2 could protect human beta cells against the deleterious effects of IFNα.

Materials and Methods

Two TYK2 inhibitors provided by Nimbus Lakshmi were tested in human insulin‐producing EndoC‐βH1 cells and human islets to evaluate their effect on IFNα signalling, beta‐cell function and susceptibility to viral infection using RT‐qPCR, western blot, immunofluorescence, ELISA and nuclear dyes.

Results

The two TYK2 inhibitors tested prevented IFNα‐induced human beta‐cell gene expression in a dose‐dependent manner. They also protected human islets against IFNα + IL‐1β‐induced apoptosis. Importantly, these inhibitors did not modify beta‐cell function or their survival following infection with the potential diabetogenic coxsackieviruses CVB1 and CVB5.

Conclusions

The two TYK2 inhibitors tested inhibit the IFNα signalling pathway in human beta cells, decreasing its pro‐inflammatory and pro‐apoptotic effects without sensitizing the cells to viral infection. The preclinical findings could pave the way for future clinical trials with TYK2 inhibitors for the prevention and treatment of type 1 diabetes.
WHY DO U.S. PARENTS PREFER PRIVATE TO FOSTER CARE ADOPTIONS? THE ROLE OF ADOPTION SUBSIDIES, GENDER, RACE, AND SPECIAL NEEDS
Authors: Khun Channary , Lahiri Sajal , Lim Sokchea
Published: June 2020

We analyze the demand behavior of adoptive parents in the U.S.A. For the theory, we apply vertical product differentiation to characterize the demand for domestic private, foster care and international adoptions. Then, we use the 2007 U.S. National Survey of Adoptive Parents and apply the control‐function approach to a mixed logit model. We find interesting insights into the relationship between adoption choices and an adoptive parent's preferences over gender, race, and special needs. The government needs to pay an additional $735 ($506) a month to make a parent feel indifferent between international (domestic private) and foster care adoptions. (JEL O12, D10, L13)
Tectonic evolution of the Tethyan region created the Eurasian extratropical biodiversity hotspots: tracing Pireneitega spiders’ diversification history
Authors: Zhao Zhe , Shao Lili , Li Fengyuan , Zhang Xiaoqing , Li Shuqiang
Published: June 2020

The withdrawal of the Tethys Sea and the formation of the Alpine‐Himalayan orogenic belt profoundly impacted the distribution and composition of terrestrial biota in Eurasia. However, studies that have explicitly addressed the potential links between the series of tectonic activities in the Tethyan region and the formation of extratropical biodiversity hotspots in the Alpine‐Himalayan belt are rare. Spiders in the genus Pireneitega (Agelenidae) are found throughout Eurasia and show high species richness in these hotspots. Thus, Pireneitega spiders may serve as a model group to shed light on how past tectonic events shaped Eurasian hotspots. To reconstruct the spatial and temporal evolution of Pireneitega spp., we conducted an integrative historical biogeographical analysis using thousands of novel DNA sequences and five novel transcriptome sequences from different species. Species distribution modelling based on complete geographical distribution information was used to assess the ecological preferences and the potential ecological interchangeability of Pireneitega species. Our study suggests that the rapid expansion of Pireneitega in Eurasia benefitted from regression of the Tethys Sea in the early Oligocene. Most Pireneitega species are distributed allopatrically, but in similar niches. The diversification of Pireneitega species relied on invading numerous new isolated habitats created by the uplift of Alpine‐Himalayan mountains during the Miocene (wet valley model). These results imply that the formation of Alpine‐Himalayan hotspots was driven by the series of tectonic events in the Tethyan region during the Oligocene–Miocene.
Trophic control changes with season and nutrient loading in lakes
Authors: Rogers Tanya L. , Munch Stephan B. , Stewart Simon D. , Palkovacs Eric P. , Giron‐Nava Alfredo , Matsuzaki Shin‐ichiro S. , Symons Celia C.
Published: June 2020

Experiments have revealed much about top‐down and bottom‐up control in ecosystems, but manipulative experiments are limited in spatial and temporal scale. To obtain a more nuanced understanding of trophic control over large scales, we explored long‐term time‐series data from 13 globally distributed lakes and used empirical dynamic modelling to quantify interaction strengths between zooplankton and phytoplankton over time within and across lakes. Across all lakes, top‐down effects were associated with nutrients, switching from negative in mesotrophic lakes to positive in oligotrophic lakes. This result suggests that zooplankton nutrient recycling exceeds grazing pressure in nutrient‐limited systems. Within individual lakes, results were consistent with a ‘seasonal reset’ hypothesis in which top‐down and bottom‐up interactions varied seasonally and were both strongest at the beginning of the growing season. Thus, trophic control is not static, but varies with abiotic conditions – dynamics that only become evident when observing changes over large spatial and temporal scales.
Dynamic oxygen changes during status epilepticus and subsequent endogenous kindling
Authors: Wolff Marshal D. , Farrell Jordan S. , Scantlebury Morris H. , Teskey G. Campbell
Published: June 2020

Objective

Brain tissue oxygen (partial oxygen pressure [pO2]) levels are tightly regulated to stay within the normoxic zone, with deviations on either side resulting in impaired brain function. Whereas pathological events such as ischemic attacks and brief seizures have previously been shown to result in pO2 levels well below the normoxic zone, oxygen levels during prolonged status epilepticus (SE) and the subsequent endogenous kindling period are unknown.

Methods

We utilized two models of acquired temporal lobe epilepsy in rats: intrahippocampal kainic acid infusion and prolonged perforant pathway stimulation. Local tissue oxygen was measured in the dorsal hippocampus using an optode during and for several weeks following SE.

Results

We observed hyperoxia in the hippocampus during induced SE in both models. Following termination of SE, 88% of rats initiated focal self‐generated spiking activity in the hippocampus within the first 7 days, which was associated with dynamic oxygen changes. Self‐generated and recurring epileptiform activity subsequently organized into higher‐frequency bursts that became progressively longer and were ultimately associated with behavioral seizures that became more severe with time and led to postictal hypoxia.

Significance

Induced SE and self‐generated recurrent epileptiform activity can have profound and opposing effects on brain tissue oxygenation that may serve as a biomarker for ongoing pathological activity in the brain.
Living Unembodiment: Physicality and Body/Self Discontinuity Among African American Adolescent Girls
Authors: McClure Stephanie
Published: June 2020

Social conditions shape health and health disparities. However, inquiry and intervention in the social determinants of health all too often rests on thin engagement with customary demographic correlates and predictors rather than robust, empirically and theoretically informed engagement with health and health disparity as biocultural phenomena—the integrated product of structure, materiality, and subjectivity. Within‐group variability is neglected. Lived experiences of nonnormative status in multiple, mutually informing cultural systems are undertheorized. This article reports on research addressing these gaps—a study exploring experiences of body/self discontinuity and physical‐activity engagement among African American adolescent girls. Data suggest that experiences of body/self discontinuity, or unembodiment, are common to membership in multiple, nonnormative social categories, vary in degree and quality, and may bear on disposition toward leisure‐time physical activity. Unembodiment shows promise as a means of characterizing variability in physical‐activity engagement within groups evincing low levels of this health behavior.
Next‐generation sequencing identifies novel single nucleotide polymorphisms in high‐risk cutaneous squamous cell carcinoma: A pilot study
Authors: Lobl Marissa B. , Hass Blake , Clarey Dillon , Higgins Shauna , Wysong Ashley
Published: June 2020

Background

Cutaneous squamous cell carcinoma (SCC) causes 1 million cases in the United States annually. There are germline single nucleotide polymorphisms (SNPs) that result in an increased risk of SCC and altered response to therapy.

Premise

There may be biologically relevant SNPs not detected using traditional GWAS studies.

Hypothesis

There are clinically and biologically relevant SNPs in high‐risk SCC that may only be appreciated with next‐generation sequencing.

How to test hypothesis

We performed next‐generation sequencing (NGS) on primary SCCs using a targeted mutation panel with 76 cancer‐associated genes. We analysed the presence of SNPs in a cohort of 20 high‐risk SCCs compared to the American population (AP) (dbSNP).

Relevance and perspectives

Missense rs3822214 was present in significantly more SCC cases versus the AP. While the remainder is synonymous SNPs, there is growing evidence suggesting clinical relevance of these variants. A larger cohort to validate these findings would be useful.
Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars
Authors: Limandjaja Grace C. , Niessen Frank B. , Scheper Rik J. , Gibbs Susan
Published: June 2020

Although hypertrophic scars and keloids both generate excessive scar tissue, keloids are characterized by their extensive growth beyond the borders of the original wound, which is not observed in hypertrophic scars. Whether or not hypertrophic scars and keloids are two sides of the same coin or in fact distinct entities remains a topic of much debate. However, proper comparison between the two ideally occurs within the same study, but this is the exception rather than the rule. For this reason, the goal of this review was to summarize and evaluate all publications in which both hypertrophic scars and keloids were studied and compared to one another within the same study. The presence of horizontal growth is the mainstay of the keloid diagnosis and remains the strongest argument in support of keloids and hypertrophic scars being distinct entities, and the histopathological distinction is less straightforward. Keloidal collagen remains the strongest keloid parameter, but dermal nodules and α‐SMA immunoreactivity are not limited to hypertrophic scars alone. Ultimately, the current hypertrophic scars‐keloid differences are mostly quantitative in nature rather than qualitative, and many similar abnormalities exist in both lesions. Nonetheless, the presence of similarities does not equate the absence of fundamental differences, some of which may not yet have been uncovered given how much we still have to learn about the processes involved in normal wound healing. It therefore seems pertinent to continue treating hypertrophic scars and keloids as separate entities, until such a time as new findings more decisively convinces us otherwise.
A Dyadic Analysis of Depressive Symptoms, Harsh Parenting, and Rejection in Filipino Mothers and Fathers
Authors: Jocson Rosanne M.
Published: June 2020

This study examines within‐person and cross‐person relations between depressive symptoms, harsh parenting, and parental rejection in low‐income Filipino mothers and fathers of adolescents using an actor–partner interdependence model (APIM). Mother and father dyads (N = 81, Mage = 43.48, SD = 8.66) recruited from urban neighborhoods in the Philippines completed orally administered questionnaires on depressive symptoms, harsh parenting, and rejection. Results showed that mothers' scores and fathers' scores on depressive symptoms did not significantly differ and that mothers scored significantly higher than fathers on harsh parenting and rejection. Dyadic analyses using the APIM showed that the actor effect of depressive symptoms on harsh parenting was statistically significant for fathers only and that the actor effects of depressive symptoms on rejection were statistically significant for both mothers and fathers. No partner effects on harsh parenting and rejection were statistically significant. These findings contribute to the robust evidence linking parental depressive symptoms to negative parenting behaviors and highlight the need to attend to both fathers' psychological health and mothers' psychological health in efforts to reduce harsh and rejecting parenting behaviors among Filipino parents.
A continuum damage mechanics method for fracture simulation of quasi‐brittle materials
Authors: Sun Bin
Published: June 2020

This paper addresses a novel continuum damage‐based method for simulating failure process of quasi‐brittle materials starting from local damage initiation to final fracture. In the developed method, the preset characteristic length field is used to evaluate damage instead of element, which is used to reduce the spurious sensitivity. In addition, damage is only updated in the most dangerous location at a time for considering stress redistribution due to damage evolution, which is used to simulate competitive fracture process. As cases study, representative numerical simulations of two benchmark tests are given to verify the performance of the developed continuum damage‐based method together with a used damage model. The simulation results of the crack paths for two concrete specimens obtained from the developed method matched well with the corresponding experimental results. The results show that the developed continuum damage‐based method is effective and can be used to simulate damage and fracture process of brittle or quasi‐brittle materials. And the simulation results based on the developed method depend only the preset characteristic length field and not grid mesh.
Crack localization in stepped rotors based on Bayesian fusion of multiscale superharmonic characteristic deflection shapes
Authors: Lu Zhiwen , Cao Shancheng , Ouyang Huajiang , Yuan Rui , Lv Yong
Published: June 2020

A crack is one of the most dangerous faults in rotors of key rotating machinery. In order to make reasonable maintenance, crack localization for rotors under operational conditions is very important and full of challenges. Focusing on crack localization in rotating rotors, a new crack localization method for stepped rotors based on Bayesian fusion of multiscale superharmonic characteristic deflection shapes (SCDSs) is proposed. The non‐linearity induced by cracks is utilized to eliminate the interference of stiffness reduction by steps in the rotor, and the noise‐robustness issue is tackled by casting the SCDSs into multiscale SCDSs with multiscale space theory. Moreover, Bayesian fusion is applied to the multiscale SCDSs to derive a new damage index to localize cracks. Numerical and experimental investigations are conducted to validate the proposed method. The results indicate that the proposed method is effective, accurate and robust for single or multiple crack localization in stepped rotors, and thus, it has a great potential in practical applications.
Acquired bleeding disorders
Authors: Tiede Andreas , Zieger Barbara , Lisman Ton
Published: June 2020

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities. This review addresses (a) acquired hemophilia A, an autoimmune disorder characterized by inhibitory autoantibodies against coagulation factor VIII; (b) acquired von Willebrand syndrome in patients with cardiovascular disorders, where shear stress abnormalities result in destruction of von Willebrand factor; and (c) liver function disorders that comprise complex changes in pro‐ and anti‐hemostatic factors, whose clinical implications are often difficult to predict. The article provides an overview on the pathophysiology, diagnostic tests and state‐of‐the‐art treatment strategies.
2‐Hydroxy‐4‐methoxybenzaldehyde inhibits the growth of Aspergillus flavus via damaging cell wall, cell membrane, manipulating respiration thus creating a promising antifungal effect on corn kernels
Authors: Li Qian , Zhu Xiaoman , Xie Yanli , Ren Shilin
Published: June 2020

This study investigated the antifungal activity and the potential antifungal mechanisms of 2‐hydroxy‐4‐methoxybenzaldehyde (HMB) against Aspergillus flavus (A. flavus). The minimum inhibitory concentration (MIC) of HMB in preventing spore germination was 70 μg mL−1. HMB at MIC disrupted cell wall integrity by reducing the number of septa by 86.66% (P < 0.05) in mycelia and increased cell membrane permeability by about 14‐fold (P < 0.05) evidenced by propidium iodide (PI) staining. Furthermore, HMB at MIC inhibited respiration by 33.33%. These results revealed that the antifungal activity of HMB against A. flavus could be attributed to the damaged cell wall integrity, cell membrane permeability and respiration metabolism. What’s more, A. flavus was completely restrained in corn kernels due to HMB. Therefore, HMB could be applied as an effective antifungal agent.
How did subterranean amphipods cross the Adriatic Sea? Phylogenetic evidence for dispersal–vicariance interplay mediated by marine regression–transgression cycles
Authors: Delić Teo , Stoch Fabio , Borko Špela , Flot Jean‐François , Fišer Cene
Published: June 2020

Aim

Freshwater subterranean amphipods with low dispersal abilities are known from both sides of the impermeable barrier, the Adriatic Sea. We tested the hypothesis that historical marine regression–transgression cycles shaped the distribution patterns of subterranean amphipods through repeated cycles of dispersal and vicariance against the hypothesis that subterranean amphipods colonized both sides of the Adriatic Sea independently.

Location

Western Balkan Peninsula, Adriatic Sea Islands and Apennine Peninsula, Europe.

Taxon

GenusNiphargus, a clade of freshwater subterranean amphipods (Crustacea: Amphipoda).

Methods

The taxonomic structure of the studied clade was revised using unilocus species delimitation methods. The timeframe of cladogenetic events was inferred using a multi‐locus time‐calibrated phylogeny and compared to the main regression–transgression events in the Miocene and Pleistocene. The geographical origin of the studied clade, species range expansions and contractions, as well as vicariance events were assessed through modelling of historical biogeography.

Results

Subterranean amphipods of the genusNiphargus,found on both sides of the Adriatic Sea, form a monophylum. The reconstructions of ancestral ranges suggest that the clade emerged in the Balkan Peninsula, dispersed three times independently to the Apennine Peninsula and once back to the Balkans. Adriatic Islands were colonized multiple times, predominantly from the Balkan Peninsula. The dispersal–vicariance events correspond to historical regression–transgression cycles in Miocene and Pleistocene.

Main conclusions

Marine regression–transgression cycles apparently shaped the distribution patterns of subterranean amphipods while the alternative hypothesis received no support. The actual distribution of subterranean faunas apparently reflects old biogeographical events.
Endo‐epicardial ablation vs endocardial ablation for the management of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta‐analysis
Authors: Romero Jorge , Patel Kavisha , Briceno David , Alviz Isabella , Gabr Mohamed , Diaz Juan Carlos , Trivedi Chintan , Mohanty Sanghamitra , Della Rocca Domenico , Al‐Ahmad Amin , Yang Ruike , Rios Saul , Cerna Luis , Du Xianfeng , Tarantino Nicola , Zhang Xiao‐Dong , Lakkireddy Dhanunjaya , Natale Andrea , Di Biase Luigi
Published: June 2020

Background

The pathologic process of ARVC (arrhythmogenic right ventricular cardiomyopathy) typically originates in the epicardium or subepicardial layers with progression toward endocardium. However, in the most recent ARVC international task force consensus statement, epicardial ventricular tachycardia (VT) ablation is recommended as a Class I indication only in patients with at least one failed endocardial VT ablation attempt.

Objective

The aim of this meta‐analysis is to assess the outcomes of ARVC patients undergoing combined endo‐epicardial VT ablation, as compared to endocardial ablation alone.

Methods

A systematic review of PubMed, Embase, and Cochrane was performed for studies reporting clinical outcomes of endo‐epicardial VT ablation vs endocardial‐only VT ablation in patients with ARVC. Fixed‐Effect model was used if I2 < 25 and the Random‐Effects Model was used if I2 ≥ 25%.

Results

Nine studies consisting of 452 patients were included (mean age 42.3 ± 5.7 years; 70% male). After a mean follow‐up of 48.1 ± 21.5 months, endo‐epicardial ablation was associated with 42% relative risk reduction in VA recurrence as opposed to endocardial ablation alone (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.45‐0.75; P < .0001). No significant differences were noted between endo‐epicardial and endocardial VT ablation groups in terms of all‐cause mortality (RR, 1.19; 95% CI, 0.03‐47.08; P = .93) and acute procedural complications (RR, 5.39; 95% CI, 0.60‐48.74; P = .13).

Conclusions

Our findings suggest that in patients with ARVC, endo‐epicardial VT ablation is associated with a significant reduction in VA recurrence as opposed to endocardial ablation alone, without a significant difference in all‐cause mortality or acute procedural complications.
Direction‐ and rate‐dependent fractionation during atrial fibrillation persistence: Unmasking cardiac anisotropy?
Authors: Starreveld Roeliene , de Groot Natasja M. S.
Published: June 2020

This 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

AMPH1, 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

Conceptualizations 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

Background

Inflammation 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.

Objectives

Assessment 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.

Methods

Data 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.

Results

A 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.

Conclusions

The 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

Aims

To 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.

Background

Raising 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.

Design

A 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.

Methods

30 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.

Findings

The 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.”

Conclusion

Our 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 practice

This 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

Aim

To assess the relationship between clinical parameters and medium term recovery time of coronary artery lesions (CALs).

Methods

In 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.

Results

Tumour 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.

Conclusions

These 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

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.