bluuebunny/crossref_metadata_2025 huggingface dataset:
The Danish ‘Competition State’: Still Along the Third Way?
Authors: Rasmussen Martin Møller Boje
Published: June 2020

This brief review article addresses the question of whether the so‐called “competition state” was “abandoned” during the recent Danish election of 2019, which brought the Social Democrats back in government under the leadership of Mette Frederiksen. During the prior Social Democratic government of 2011‐2015, led by Helle Thorning‐Schmitt, this concept was introduced as a highly controversial policy concept and came to summarize the government’s program of economic reforms and recovery. The concept was subsequently strongly criticized in broader public political discourse as well as by the Social Democratic party and Mette Frederiksen herself. It is thus worth considering, whether the competition state reform program has been “buried” with the recent election, as this might imply a more radical break or discontinuity away from the “third way” competition state reform program embarked upon by most western European Social democrats since the 1990’s. This article will, first, briefly review the public discussion about the competition state in Denmark, before it, second, will recapitulate the academic debate about the competition state and clarify the concept. Third, it will review central tenets of the economic policy of the Thorning‐Schmitt government of 2011‐2015, as well as, fourth, the announced reform program of the new Social Democratic government. Finally the article will contrast and compare the two programs, and conclude that the “competition state” to a large extent endured the election of 2019, even if the Frederiksen government seems to lead the Danish competition state into reform trajectory towards increasing dis‐universalization of social security and pensions.
A new method of metabarcoding Microsporidia and their hosts reveals high levels of microsporidian infections in mosquitoes (Culicidae)
Authors: Trzebny Artur , Slodkowicz‐Kowalska Anna , Becnel James J. , Sanscrainte Neil , Dabert Miroslawa
Published: June 2020

DNA metabarcoding offers new perspectives, especially with regard to the high‐throughput identification and diagnostics of pathogens. Microsporidia are an example of widely distributed, opportunistic and pathogenic microorganisms in which molecular identification is important for both environmental research and clinical diagnostics. We have developed a method for parallel detection of both microsporidian infection and the host species. We designed new primer sets: one specific for the classical Microsporidia (targeting the hypervariable V5 region of small subunit [ssu] rDNA), and a second one targeting a shortened fragment of the COI gene (standard metazoan DNA‐barcode); both markers are well suited for next generation sequencing. Analysis of the ssu rDNA data set representing 607 microsporidian species (120 genera) indicated that the V5 region enables identification of >98% species in the data set (596/607). To test the method, we used microsporidians that infect mosquitoes in natural populations. Using mini‐COI data, all field‐collected mosquitoes were unambiguously assigned to seven species; among them almost 60% of specimens were positive for at least 11 different microsporidian species, including a new microsporidian ssu rDNA sequence (Microsporidium sp. PL01). Phylogenetic analysis showed that this species belongs to one of the two main clades in the Terresporidia. We found a high rate of microsporidian co‐infections (9.4%). The numbers of sequence reads for the operational taxonomic units suggest that the occurrence of Nosema spp. in co‐infections could benefit them; however, this observation should be retested using a more intensive host sampling. Our results show that DNA barcoding is a rapid and cost‐effective method for deciphering sample diversity in greater resolution, including the hidden biodiversity that may be overlooked using classical methodology.
Effects of electroporation treatment using different concentrations of Cas9 protein with gRNA targeting Myostatin (MSTN) genes on the development and gene editing of porcine zygotes
Authors: Le Quynh A. , Hirata Maki , Nguyen Nhien T. , Takebayashi Koki , Wittayarat Manita , Sato Yoko , Namula Zhao , Nii Masahiro , Tanihara Fuminori , Otoi Takeshige
Published: June 2020

This study was conducted to investigate the effect of seven concentrations of Cas9 protein (0, 25, 50, 100, 200, 500, and 1,000 ng/µl) on the development and gene editing of porcine embryos. This included the target editing and off‐target effect of embryos developed from zygotes that were edited via electroporation of the Cas9 protein with guide RNA targeting Myostatin genes. We found that the development to blastocysts of electroporated zygotes was not affected by the concentration of Cas9 protein. Although the editing rate, which was defined as the ratio of edited blastocysts to total examined blastocysts, did not differ with Cas9 protein concentration, the editing efficiency, which was defined as the frequency of indel mutations in each edited blastocyst, was significantly decreased in the edited blastocysts from zygotes electroporated with 25 ng/µl of Cas9 protein compared with that of blastocysts from zygotes electroporated with higher Cas9 protein concentrations. Moreover the frequency of indel events at the two possible off‐target sites was not significantly different with different concentrations of Cas9 protein. These results indicate that the concentration of Cas9 protein affects gene editing efficiency in embryos but not the embryonic development, gene editing rate, and non‐specific cleavage of off‐target sites.
A case study of improving milking cow performance and milking system performance with using a flow simulator
Authors: Enokidani Masafumi , Kawai Kazuhiro , Shinozuka Yasunori , Kurumisawa Tomomi
Published: June 2020

Efforts to improve dairy performance have been focused on increasing milk productivity of cows through improved feeding systems and genetic potential. However, methods for evaluating milking system performance based on milk productivity have not yet been established. Milking system performance was evaluated by measuring the claw vacuum at five flow rates (1.9–8.7 kg/min) produced using a flow simulator for a single eight‐swing milking parlor with a high‐line system. Based on these results, a double eight‐parallel milking parlor with a low‐line system was installed and tested. Farmers can take data obtained from evaluations of milking system performance into account for future management decisions, such as renewing the milking system. By renewing the milking system, average milking productivity, somatic cell linear score (LS) of bulk milk, and LS of each cow were significantly improved in the year after installing the new system (p < .01). In addition to checking conventional milking systems, this novel diagnostic method using a flow simulator can be used for checking new installations and also for proposing renovations.
Use of neomycin as a structured amino‐containing side chain motif for phenanthroline‐based G‐quadruplex ligands and telomerase inhibitors
Authors: Singh Mandeep , Wang Siwen , Joo Hyun , Ye Zhihan , Christison Krege M. , Hekman Ryan , Vierra Craig , Xue Liang
Published: June 2020

In this paper, we report the synthesis of a phenanthroline and neomycin conjugate (7). Compound 7 binds to a human telomeric G‐quadruplex (G1) with a higher affinity compared with its parent compounds (phenanthroline and neomycin), which is determined by several biophysical studies. Compound 7 shows good selectivity for G‐quadruplex (G4) DNA over duplex DNA. The binding of 7 with G1 is predominantly enthalpy‐driven, and the binding stoichiometry of 7 with G1 is one for the tight‐binding event as determined by ESI mass spectrometry. A plausible binding mode is a synergistic effect of end‐stacking and groove interactions, as indicated by docking studies. Compound 7 can inhibit human telomerase activity at low micromolar concentrations, which is more potent than previously reported 5‐substituted phenanthroline derivatives.
LncRNA BBOX1‐AS1 upregulates HOXC6 expression through miR‐361‐3p and HuR to drive cervical cancer progression
Authors: Xu Jun , Yang Baohua , Wang Lifeng , Zhu Yunheng , Zhu Xiuxiang , Xia Ziyin , Zhao Zhen , Xu Ling
Published: June 2020

Objectives

Over the past years, growing attention has been paid to deciphering the pivotal role of long non‐coding RNAs (lncRNAs) in regulating the occurrence and development of human malignancies, cervical cancer (CC) included. Nonetheless, the regulatory role of lncRNA BBOX1 antisense RNA 1 (BBOX1‐AS1) has not been explored as yet.

Material and Methods

The expression of BBOX1‐AS1 was detected by reverse transcription real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell Counting Kit‐8 (CCK‐8), colony formation, TUNEL, Western blot, transwell and immunofluorescence assays testified the critical role of BBOX1‐AS1 in CC. The relationship between RNAs (BBOX1‐AS1, miR‐361‐3p, HOXC6 and HuR) was analysed by luciferase reporter, RNA Immunoprecipitation (RIP) and RNA pull‐down assays.

Results

BBOX1 antisense RNA 1 antisense RNA 1 was revealed to be highly expressed in CC. Decreased expression of BBOX1‐AS1 had suppressive effects on CC cell growth and migration. Molecular mechanism assays verified that BBOX1‐AS1 had negative interaction with miR‐361‐3p in CC. Additionally, homeobox C6 (HOXC6) was validated to be a downstream target of miR‐361‐3p in CC. Furthermore, ELAV‐like RNA‐binding protein 1, also known as HuR, was uncovered to be capable of regulating the mRNA stability of HOXC6 in CC. More importantly, rescue assays delineated that knockdown of HuR after overexpressing miR‐361‐3p could reverse BBOX1‐AS1 upregulation‐mediated effect on CC progression. Similarly, the function induced by BBOX1‐AS1 upregulation on CC progression could be countervailed by HOXC6 depletion.

Conclusions

BBOX1 antisense RNA 1 facilitates CC progression by upregulating HOXC6 expression via miR‐361‐3p and HuR.
The macroecology of reef fish agonistic behaviour
Authors: Fontoura Luisa , Cantor Mauricio , Longo Guilherme O. , Bender Mariana G. , Bonaldo Roberta M. , Floeter Sergio R.
Published: June 2020

Understanding the interplay between processes operating at large and small spatiotemporal scales in shaping biotic interactions remains challenging. Recent studies illustrate how phenotypic specialization, species life‐history traits and/or resource partitioning recurrently underlie the structure of mutualistic interactions in terrestrial ecosystems along large latitudinal gradients of biodiversity. However, we know considerably less about how local processes interact with large‐scale patterns of biodiversity in modulating biotic interactions in the marine realm. Considering agonistic behaviour as a proxy for contest competition, we empirically investigate whether the structure of reef fish agonistic interactions is conserved across a 34 000‐km longitudinal gradient of biodiversity. By sampling coral reefs using standardized remote underwater video, we found recurrent patterns of fish agonistic behaviour in disparate communities distributed across five biogeographic provinces of the Pacific and Atlantic oceans. While the sheer number of species increases with regional richness, the number of aggressive disputes at the habitat scale is similar across communities. We then combined generalized linear models and network theory to reveal that, the emergent structure of local agonistic networks is not modular but instead recurrently display a nested structure, with a core of highly interactive site‐attached herbivores of the Pomacentridae family. Therefore, despite the increase in the number of species involved in agonistic interactions toward speciose communities, the network structure is conserved along the longitudinal richness gradient because local disputes are mostly driven by closely‐related, functionally‐similar species. These findings suggest that evolutionary and local processes interact in modulating reef fish agonistic behaviour and that fine‐scale niche‐partitioning can structure the ecological networks in marine ecosystems.
Dissociating cholinergic influence on alertness and temporal attention in primates in a simple reaction time paradigm
Authors: Oláh Vilmos , Knakker Balázs , Trunk Attila , Lendvai Balázs , Hernádi István
Published: June 2020

The ability to promptly respond to behaviourally relevant events depends on both general alertness and phasic changes in attentional state driven by temporal expectations. Using a variable foreperiod simple reaction time (RT) task in four adult male rhesus macaques, we investigated the role of the cholinergic system in alertness and temporal expectation. Foreperiod effects on RT reflect temporal expectation, while alertness is quantified as overall response speed. We measured these RT parameters under vehicle treatment and systemic administration of the muscarinic receptor antagonist scopolamine. We also investigated whether and to what extent the effects of scopolamine were reversed by donepezil, a cholinesterase inhibitor widely used for the treatment of dementia. In the control condition, RT showed a continuous decrease as the foreperiod duration increased, which clearly indicated the effect of temporal expectation on RT. This foreperiod effect was mainly detectable on the faster tail of the RT distribution and was eliminated by scopolamine. Furthermore, scopolamine treatment slowed down the average RT. Donepezil treatment was efficient on the slower tail of the RT distribution and improved scopolamine‐induced impairments only on the average RT reflecting a general beneficial effect on alertness without any improvement in temporal expectation. The present results highlight the role of the cholinergic system in temporal expectation and alertness in primates and help delineate the efficacy and scope of donepezil and other cholinomimetic agents as cognitive enhancers in present and future clinical practice.
Objective rest–activity cycle analysis by actigraphy identifies isolated rapid eye movement sleep behavior disorder
Authors: Filardi M. , Stefani A. , Holzknecht E. , Pizza F. , Plazzi G. , Högl B.
Published: June 2020

Background and purpose

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal behaviours during REM sleep. Several studies showed that iRBD is a prodromal stage of synucleinopathies. Therefore, identifying iRBD in the general population is of utmost importance. In this study, we explore whether the assessment of rest–activity rhythm features can distinguish patients with iRBD from patients with disorders characterized by other pathological motor activity during sleep and healthy controls.

Methods

Nineteen patients with video‐polysomnographic diagnosis of iRBD, 39 patients with other disorders with motor activity during sleep [19 with restless leg syndrome (RLS) and 20 with untreated sleep apnea syndrome (SAS)] and 16 healthy controls underwent 2‐week actigraphy and video‐polysomnography, and completed REM sleep behavior disorder screening questionnaires. Non‐parametric analyses were applied to assess the rest–activity rhythm features.

Results

Patients with iRBD showed lower sleep efficiency, increased estimated wake after sleep onset and increased frequency of prolonged activity bouts compared to those with RLS and controls, while no difference emerged compared with SAS patients. Moreover, patients with iRBD presented increased occurrence of estimated nap in comparison to those with RLS, those with SAS and controls. The I < O, a 24‐h measure that expresses the relationship between nocturnal and diurnal motor activity intensity, distinguished patients with iRBD from those with RLS, those with SAS and controls, with an area under the curve greater than that of REM sleep behavior disorder screening questionnaires. An I < O of 98.32 shows the best balance between sensitivity (63.2%) and specificity (89.1%).

Discussion

The I < O index distinguished iRBD patients from those with other pathological motor activity during sleep and controls, confirming its use as an objective measure suitable to screen large at‐risk populations.
Cheetah behaviour at scent‐marking sites indicates differential use by sex and social rank
Authors: Cornhill Kristina L. , Kerley Graham I. H.
Published: June 2020

Scent‐marking is an important form of communication for solitary species, as the information remains for the receiver after the sender has left the area. Individuals of different demographic or dominance classes (ranks) need to provide different information to conspecifics. Therefore, the use of scent‐marking sites is of particular value for solitary species, but their functional role may vary between demographic classes. Using camera traps, we video‐recorded the behaviour of cheetahs at scent‐marking sites, assessing how individuals of different sex and social rank use the sites for different roles. We tested hypotheses that these sites are for territorial marking, reproductive signalling and information gathering. We found that females visit the sites infrequently, apparently to signal oestrous events, while males visit the sites frequently for territorial marking and information gathering. Among males, dominant individuals scent‐marked the most and reacted to female visitation by vocalizing. In contrast, subordinate males, although also visiting the sites, were not recorded scent‐marking nor vocalizing. These differences in the functional use of scent‐marking sites among sex and social rank support the hypotheses that cheetahs use these scent‐marking sites for both territorial and reproductive signalling, as well as to gather information.
The new normal?: A pandemic of task engagement in language learning
Authors: Egbert Joy
Published: June 2020

This article demonstrates how, at a time when learners may be experiencing fear and chaos in other aspects of their lives, a focus on language task engagement is essential across both online and offline language learning contexts. It presents a model of language task engagement and describes why and how teachers can use it to support learner achievement during the current crisis and in the future.
Negotiating displacement, regaining community: The Harvard Language Center's response to the COVID‐19 crisis
Authors: Ross Andrew F. , DiSalvo Mary L.
Published: June 2020

The COVID‐19 crisis has fundamentally disrupted teaching and learning practices at many post‐secondary institutions with a highly residential population. The present article outlines the situation at Harvard University and details the steps taken by the Language Center to mitigate the effects of the transition to remote teaching and learning. These include changes in communication strategies, support mechanisms for faculty and students, and modifications to the Center's operational policies. The authors provide a number of concrete recommendations for academic support units in transitions of this type.
Corpora as open educational resources for language teaching
Authors: Vyatkina Nina
Published: June 2020

Corpora, large electronic collections of texts, have been used in language teaching for several decades. Also known as Data‐Driven Learning (DDL), this method has been gaining popularity because empirical research has consistently shown its effectiveness for learning. However, corpora are still underutilized, especially with learners of languages other than English, at lower proficiency levels, and in non‐university contexts. This is regrettable because DDL has a great potential for developing modular flipped content, especially for hybrid, remote, and online courses. This article first provides an overview of DDL applications and findings of empirical research. Next, it outlines obstacles to wider DDL implementation as well as available and possible solutions. Corpus user guides and exercise collections tied to specific corpora are discussed as one promising direction, and an example of such new open educational resources for teaching German is presented. The article concludes with a discussion of implications and future directions.
Concurrent shifts in wintering distribution and phenology in migratory swans: Individual and generational effects
Authors: Nuijten Rascha J. M. , Wood Kevin A. , Haitjema Trinus , Rees Eileen C. , Nolet Bart A.
Published: June 2020

Range shifts and phenological change are two processes by which organisms respond to environmental warming. Understanding the mechanisms that drive these changes is key for optimal conservation and management. Here we study both processes in the migratory Bewick's swan (Cygnus columbianus bewickii) using different methods, analysing nearly 50 years of resighting data (1970–2017). In this period the wintering area of the Bewick's swans shifted eastwards (‘short‐stopping’) at a rate of ~13 km/year, thereby shortening individual migration distance on an average by 353 km. Concurrently, the time spent at the wintering grounds has reduced (‘short‐staying’) by ~38 days since 1989. We show that individuals are consistent in their migratory timing in winter, indicating that the frequency of individuals with different migratory schedules has changed over time (a generational shift). In contrast, for short‐stopping we found evidence for both individual plasticity (individuals decrease their migration distances over their lifetime) and generational shift. Additional analysis of swan resightings with temperature data showed that, throughout the winter, Bewick's swans frequent areas where air temperatures are c. 5.5°C. These areas have also shifted eastwards over time, hinting that climate warming is a contributing factor behind the observed changes in the swans' distribution. The occurrence of winter short‐stopping and short‐staying suggests that this species is to some extent able to adjust to climate warming, but benefits or repercussions at other times of the annual cycle need to be assessed. Furthermore, these phenomena could lead to changes in abundance in certain areas, with resulting monitoring and conservation implications. Understanding the processes and driving mechanisms behind population changes therefore is important for population management, both locally and across the species range.
Association of anemia and SRH in older people: the SONIC study
Authors: Noma Tomoko , Kabayama Mai , Gondo Yasuyuki , Yasumoto Saori , Masui Yukie , Sugimoto Ken , Akasaka Hiroshi , Godai Kayo , Higuchi Atsuko , Akagi Yuya , Takami Yoichi , Takeya Yasushi , Yamamoto Koichi , Ikebe Kazunori , Arai Yasumichi , Ishizaki Tatsuro , Rakugi Hiromi , Kamide Kei
Published: June 2020

Aim

The incidence of anemia increases with aging, and it is considered to affect mortality through complex pathophysiological outcomes. Although it has been suggested that self‐rated health may also contribute to the prognosis of anemia in older people, the relationship between anemia and self‐rated health is not well understood. This study thus examined the actual status of anemia in older community‐dwelling Japanese people and clarified the relationship between anemia and self‐rated health.

Methods

We conducted medical interviews, physical measurements and blood testing in 2083 people aged 69–91 years who participated in the long‐term observational Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. Subjects were divided into two groups according to whether they had anemia. Logistic regression analyses were used to assess the relationship between anemia and self‐rated health after adjusting for possible confounding factors.

Results

The prevalence of anemia was 22.3% in all participants, 7.2% in men and 11.6% in women aged 69–71 years, 27.4% in men and 26.3% in women aged 79–81 years, and 55.8% in men and 44.9% in women aged 89–91 years. Multivariate analysis revealed a correlation between the presence of anemia and poor self‐rated health in all (odds ratio 0.67, 95% confidence interval 0.48–0.93) and aged 69–71 years (odds ratio 0.47, 95% confidence interval 0.25–0.86).

Conclusions

Anemia was associated with self‐rated health in older Japanese people, suggesting that careful management of anemia may contribute to health and longevity. Geriatr Gerontol Int 2020; ••: ••–••.
High‐Precision Zinc Isotopic Measurement of Certified Reference Materials Relevant to the Environmental, Earth, Planetary and Biomedical Sciences
Authors: Druce Matthew , Stirling Claudine H. , Rolison John M.
Published: June 2020

The zinc (Zn) stable isotope system has emerged as a powerful tool for investigating natural and anthropogenic processes of interest to disciplines ranging from the Earth and planetary sciences to biomedical research. In nature, Zn isotopes typically fractionate (66Zn/64Zn) within the range of −1 and +1 permil (‰), and however, analytical limitations restrict the application of the Zn isotope system. Specifically, there is a lack of well‐characterised matrix‐matched reference materials covering most Zn isotope applications that are essential for validating laboratory performance, particularly given the contamination prone nature of Zn. Furthermore, the increasing demand for analysis of size‐limited materials and sample types displaying small, sub‐permil level Zn isotope variations requires improvements in measurement procedures. To address these limitations, the δ66Zn values of two pure Zn solutions and eighteen reference materials including the previously uncharacterised RGM‐2, BCR‐279, DOLT‐4, DOLT‐5, NASS‐7, SBC‐1, SGR‐1b, MESS‐3 and HISS‐1, and the understudied QLO‐1, SDC‐1, BCR‐414, NASS‐6 and COQ‐1 materials are reported. Furthermore, a 70Zn‐67Zn double‐spike design has been implemented that routinely achieves intermediate measurement precision better than ± 0.02‰. This represents at least a two‐fold improvement when compared with other double‐spike designs, providing a robust platform of δ66Zn values required for quality control procedures.
‘Give me my pathway!‘: multinational migration, transnational skills regimes and migrant subjectification
Authors: COLLINS FRANCIS L.
Published: June 2020

In this article, I address the interplay between migration regimes and migrant subjectivities in stepwise multinational migration through a comparative analysis of biographical interviews with migrants in the healthcare and dairy farm work sectors in New Zealand. In both sectors, migrants' trajectories involve movements from Asia to locations in the Middle East, North Africa or Japan before arrival in New Zealand, and in some cases plans for onward migration. The analysis of these migration patterns and the narratives of migrants, reveal an emergent transnational skills regime that involves connected but uncoordinated systems of skills recognition; negotiating this regime occurs through increased attunement to migration on the part of multinational migrants, as well as adaptation to the expectations of authorities and employers. I conclude the article by suggesting that while multinational migration involves new opportunities for people on the move it also entails greater entanglement in the unequal conditioning of transnational migration.
Calcitonin Gene‐Related Peptide Receptor Antagonists (Gepants) for the Acute Treatment of Nausea in Episodic Migraine: A Systematic Review and Meta‐Analysis
Authors: Chan Tommy Lik Hang , Cowan Robert P. , Woldeamanuel Yohannes W.
Published: June 2020

Objective

To synthesize the evidence on the efficacy of calcitonin gene‐related peptide receptor antagonists (gepants) from all clinical trials addressing nausea treatment for episodic migraine.

Introduction

Nausea is one of the most bothersome symptoms in patients with migraine. The most bothersome symptom is part of the outcomes explored in clinical trials.

Methods

Published clinical trials for this project were identified via searches of 4 bibliographic databases: PubMed (includes MEDLINE), Embase, Web of Science, and the Cochrane Library. Individual search strategies included terms related to calcitonin gene‐related peptide, nausea, and vomiting. Random‐effects meta‐analysis was conducted to estimate the overall efficacy of gepants for nausea treatment. Heterogeneity, publication bias, small‐study bias, and potential confounders were explored using Galbraith plot, sensitivity analysis, meta‐regression, and Egger’s regression tests. Cumulative meta‐analysis was done to detect temporal trend from accumulating trials.

Results

The meta‐analysis involved 23,008 participants in 65 clinical trials from 14 published articles; 10,770 subjects participated in gepant treatment arms while 12,238 subjects participated in placebo or non‐gepant arms (85% females, mean age 41 years in both arms). Nearly all studies used a 2‐hour incidence of nausea as an outcome measure. An overall combined effect size with an odds ratio of 1.29 (95% CI 1.18, 1.40, P = .001; I2 = 42.8%) showed the efficacy of gepants for the treatment of nausea in episodic migraine. Galbraith plot demonstrated that 98.4% of studies were within 2 standard deviations from the regression line, indicating lack of significant heterogeneity and outliers. Meta‐analysis results were robust to sensitivity analysis, small‐study bias, and publication bias (Kendall’s Tau −0.09, P = .29; Egger's regression P = .67). Meta‐regression showed that both age and sex ratio were not confounding the meta‐analysis (omnibus P = .69). Cumulative meta‐analysis indicated that the effect size remained stable for studies conducted after 2011, with accumulating evidence continuing to favor efficacy of gepants for the treatment of nausea in episodic migraine.

Conclusion

There is sufficient evidence to support the efficacy of gepants for the treatment of nausea in episodic migraine. Future research may focus on examining this efficacy in under‐represented patient populations (males, older age groups) and in chronic migraine.
UNIVERSAL AND PROFANE: THE HISTORIOGRAPHICAL CONSEQUENCES OF NATURAL RELIGION
Authors: CRIMMINS TIMOTHY
Published: June 2020

Natural religion in the eighteenth century was seemingly unhistorical or even antihistorical: it “dehistoricized” morality. It posited a morality that was uniform in all ages, not dependent on any particular revelation, watermarked onto the fabric of our nature, and accessible merely by the light of reason. Even so, natural religion played an important role in the secular historiographical turn in eighteenth‐century England. There was in fact an organic relationship between the two, one that historians have failed to articulate. Precisely because natural religion was thought to rest on timeless and universally valid rational foundations, it became possible to treat traditional religion (meaning above all, but not only, Christianity) as a subject of secular historical study, in the sense that it was subject to the same laws of historical knowledge and historical development as all other subjects of historical study, and left no room for miracles. A central figure in this conceptual relationship was Conyers Middleton, a once‐famous, now‐obscure Cambridge librarian. Middleton's account of natural religion has been swamped by the attention lavished on Matthew Tindal, and his turn to secular historiography lies in the shadows cast by Edward Gibbon. Yet Middleton played a crucial and distinctive role in laying historiographical foundations without which Gibbon could not have written as he did. His understanding of natural religion differed from that of other participants in the “deist controversy” in ultimately far‐reaching ways. Those differences explain why he could treat Cicero as a kind of saint in the church of natural religion, reversing, as it were, the elevation of the Bible above Cicero that Augustine had put into effect at the beginning of medieval history. They explain above all why Middleton could approach the history of Christianity in a manner that anticipated both Voltaire and Gibbon and made their historical writings possible.
Potentially inappropriate medications in older adults living with HIV
Authors: López‐Centeno B , Badenes‐Olmedo C , Mataix‐Sanjuan A , Bellón JM , Pérez‐Latorre L , López JC , Benedí J , Khoo S , Marzolini C , Calvo‐Alcántara MJ , Berenguer J
Published: June 2020

Objectives

We assessed the prevalence of potentially inappropriate medication (PIM) among older (≥ 65 years) people living with HIV (O‐PLWH) in the region of Madrid.

Methods

We analysed the dispensation registry of community and hospital pharmacies from the Madrid Regional Health Service (SERMAS) for the period between 1 January and 30 June 2017, looking specifically at PIMs according to the 2019 Beers criteria. Co‐medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system.

Results

A total of 6 636 451 individuals received medications. Of these individuals, 22 945 received antiretrovirals (ARVs), and of these 1292 were O‐PLWH. Overall, 1135 (87.8%) O‐PLWH were taking at least one co‐medication, and polypharmacy (at least five co‐medications) was observed in 852 individuals (65.9%). A PIM was identified in 482 (37.3%) O‐PLWH. Factors independently associated with PIM were polypharmacy [adjusted odds ratio (aOR) 7.08; 95% confidence interval (CI) 5.16–9.72] and female sex (aOR 1.75; 95% CI 1.30–2.35). The distribution of PIMs according to ATC drug class were nervous system drugs (n = 369; 28.6%), musculoskeletal system drugs (n = 140; 10.8%), gastrointestinal and metabolism drugs (n = 72; 5.6%), cardiovascular drugs (n = 61; 4.7%), respiratory system drugs (n = 13; 1.0%), antineoplastic and immunomodulating drugs (n = 10; 0.8%), and systemic anti‐infectives (n = 2; 0.2%). Five drugs accounted for 84.8% of the 482O PLWH with PIMs: lorazepam (38.2%), ibuprofen (18.0%), diazepam (10.2%), metoclopramide (9.9%), and zolpidem (8.5%).

Conclusions

Prescription of PIMs is highly prevalent in O‐PLWH. Consistent with data in uninfected elderly people, the most frequently observed PIMs were benzodiazepines and nonsteroidal anti‐inflammatory drugs . Targeted interventions are warranted to reduce inappropriate prescribing and polypharmacy in this vulnerable population.
House Wrens Troglodytes aedon reduce repertoire size and change song element frequencies in response to anthropogenic noise
Authors: Juárez Roselvy , Araya‐Ajoy Yimen G. , Barrantes Gilbert , Sandoval Luis
Published: June 2020

Anthropogenic noise (≤ 3 kHz) can affect key features of birds’ acoustic communication via two different processes: (1) song‐learning, because songbirds need to hear themselves and other birds to crystallize their song, and (2) avoidance of song elements that overlap with anthropogenic noise. In this study we tested whether anthropogenic noise reduces the number of song elements in the repertoire of House Wren Troglodytes aedon, an urban species. Additionally, we tested whether the proportion of high‐frequency elements (i.e. elements where the minimum frequency is above 3 kHz) is related to anthropogenic noise levels, and how the frequencies and duration of shared elements between males change with different levels of anthropogenic noise. We recorded 29 House Wren males exposed to different anthropogenic noise levels (36.50–79.50 dB) during two consecutive breeding seasons from four locations. We recorded each male on 2 days during each season continuously for 50 min (we collected 104 h of recordings) and measured anthropogenic noise levels every 10 min inside each male territory during the recording period. In general, individuals inhabiting noisier territories had smaller repertoires. However, only in two locations with anthropogenic noise levels between 38.60 and 79.50 dB did males inhabiting noisier territories have smaller repertoires. In the other two locations with lower anthropogenic noise (36.50–66.50 dB), the anthropogenic noise inside each territory was not related to the repertoire size. Individuals inhabiting the noisiest location showed a tendency to include more high‐frequency elements in their songs. In 26% of the elements, the anthropogenic noise affected their frequency features. Our results showed that not all House Wrens inhabiting urban environments modify their songs at the highest level of organization (i.e. repertoire) to reduce the masking effect of anthropogenic noise on acoustic communication.
Design of high‐performance curling mascara through utilization of smart thermoresponsive polymer
Authors: Chen S. , Amin S.
Published: June 2020

Objective

In this study, methoxy poly(ethylene glycol)‐b‐poly(D,L‐lactide), or mPEG‐PLA, was used as the smart thermoresponsive polymer in our mascara formulation. The utility of mPEG‐PLA in a mascara formulation was investigated by a stepwise build‐up in an oil in water (O/W) emulsion. The experimental results may pave the way to a strategy of developing more cosmetic formulation with thermoresponsive shape memory polymers (SMPs).

Method

mPEG‐PLA was first incorporated in a simple emulsion for rheological evaluation such as shear flow viscosity and small deformation oscillation measurements over the relevant temperature settings to mascara application. Then, wax and pigment were incorporated to complete the basic formulation as an O/W mascara and evaluated rheologically as before. Finally, the formulation was applied by a heated mascara applicator to false lashes to evaluate its curing and lifting effect.

Results

With 0.8% concentration of mPEG‐PLA, the viscosity was able to increase from 0.20 Pas·s to 1.00 Pas·s. At 1.0% concentration of mPEG‐PLA, the emulsion samples with mineral oil were evaluated from 55°C to 25°C for its storage modulus (G’) and were found to have a consistent shear‐thinning characteristic across all temperature range. The sample containing the polymer (M‐1) arrived at a markedly higher elasticity when compared against the sample without (M‐0). The same result holds true for the set of samples formulated with beeswax instead of mineral oil. When the formulations were applied with a heated mascara applicator on false eyelashes, the formulation containing mPEG‐PLA was found to produce a more pronounced and longer‐lasting curl.

Conclusion

This preliminary rheological study of an O/W mascara containing mPEG‐PLA demonstrated that thermoresponsive SMP can be added to enhance the curl and lifting effect of a mascara formulation.
Influence of resveratrol application with pulp‐capping materials on the genetic expression levels of stem cells
Authors: Çelik N. , Işcan Yapar M. , Taghizadehghalehjoughi A. , Nalcı K. A.
Published: June 2020

Aim

To evaluate in a laboratory setting the response of human mesenchymal stem cells (MSCs) to pulp‐capping materials with and without resveratrol (RSV).

Methodology

Five materials, Calcimol LC, Life, TheraCal LC, ProRoot MTA and Biodentine, were prepared according to the manufacturers’ instructions. Human MSCs were then exposed to these materials, with and without RSV, for 24 h (n = 8). Cell viability was evaluated using the MTT assay, and total cell death was quantified by annexin V‐FITC staining with flow cytometry. The expression levels of the IL‐8, IL‐10, HBD‐2 and BCL‐2 genes were investigated using real‐time polymerase chain reaction (RT‐PCR). Data obtained from MTT test were analysed using one‐way anova, and Tukey’s multiple‐comparison test. The paired Student t test was employed to compare the effects of materials on gene expression (significance level of 5%).

Results

The group cell viabilities were Calcimol LC 53%, Life 43%, TheraCal LC 78%, ProRoot MTA 75% and Biodentine 78%. Calcimol LC and Life exhibited significant differences compared with the control groups (P < 0.05). The percentages of necrotic/late apoptotic cells associated with Calcimol LC and TheraCal LC were greater than in the other materials. However, when RSV was added to wells containing materials, cell viability increased to Calcimol LC 63%, Life 52%, TheraCal LC 82%, ProRoot MTA 91% and Biodentine 96%, and the percentages of early apoptotic and late apoptotic/necrotic cells decreased. Calcimol LC + RSV and Life + RSV differed significantly from the control group (P < 0.05). The expression of IL‐8 gene was high for all materials, ProRoot MTA caused significant overexpression, and the addition of RSV reduced the expression of IL‐8 in the Calcimol LC, TheraCal LC and ProRoot MTA groups and led to increased expression of IL‐10 in the Calcimol LC, Life and Biodentine groups. HBD‐2 and BCL‐2 exhibited increased expression in ProRoot MTA with RSV (P < 0.05).

Conclusions

The addition of RSV exerted a protective effect on MSCs and regulated the inflammatory process by altering the expression levels of pro‐ and anti‐inflammatory genes.
Epidemiological analysis of patients with burns in third‐line hospitals in Turkey
Authors: Bahçe Zeynep Şener , Öztaş Tülin
Published: June 2020

Burns are a major health problem worldwide. Burn injury resulting from making contact with hot objects, direct or indirect contact with flame, and exposure to chemical agents or electric current is usually preventable. In this study, epidemiological data of the patients who had been hospitalised in the burn unit was assessed. The records of 1453 patients who were admitted to the burn unit of Diyarbakir Gazi Yaşargil Training and Research Hospital between July 2008 and April 2018 were retrospectively examined. Out of 1453 cases, 81.7% (1187) were children and 18.3% (266) were adults, 58.3% of the cases were male (847) and 41.7% (606) were females. Patients had a mean age of 11 ± 5 years (1‐81 years). The most common cause of burns was contact with hot liquids (82.86%) while other causes were flame burns (12.04%), electrical contact burn (3.02%) contact with chemical substances (2.06%). Most of the cases were found to have burned 10% to 20% of the body surface. Localization was most frequently seen in the lower extremity and less frequently in the upper limb, trunk, head and neck, and perineal regions. The majority of burn injuries are preventable. Therefore, epidemiological studies in the field of burns will provide vital preventive information to develop strategies to reduce injury frequency and spend on health. Because burns are a social problem, prevention efforts require social co‐operation. Promotional meetings in schools are important to increase family‐school cooperation to inform children of school age, to give lectures and first aid measures to rural areas.
A randomized clinical trial of an interactive voice response and text message intervention for individuals with hypertension
Authors: Schroeder Emily B. , Moore Kelly R. , Manson Spero M. , Baldwin Megan A. , Goodrich Glenn K. , Malone Allen S. , Pieper Lisa E. , Xu Stanley , Fort Meredith P. , Son‐Stone Linda , Johnson David , Steiner John F.
Published: June 2020

Interactive voice response and text message (IVR‐T) technology may improve hypertension control in under‐resourced settings. We conducted a randomized clinical trial to determine whether an IVR‐T intervention would improve blood pressure (BP), medication adherence and visit keeping among adults with hypertension from multiple racial and ethnic groups in primary care at an Urban Indian Health Organization in Albuquerque, New Mexico. Two hundred and ninety‐five participants were randomly assigned to IVR‐T (N = 148) or to usual care (N = 147). The IVR‐T arm received reminders for clinic visits, messages to reschedule missed clinic visits, monthly medication refill reminders, weekly motivational messages, and a blood pressure cuff. The usual care arm received no messages. The primary outcome was change in systolic BP (SBP) between baseline and 12 months. Secondary outcomes included change in SBP between baseline and 6 months, change in diastolic BP (DBP) at 6 and 12 months, self‐reported adherence at 6 months, and the proportion of missed primary care clinic appointments. The intervention did not affect SBP or DBP at 6 or 12 months. The 12‐month change in SBP/DBP was 1.66/1.10 mm Hg in usual care and 0.23/1.34 mm Hg in the intervention group (P values = .57 and .88, respectively). Self‐reported medication adherence improved comparably in both groups, and there was no difference in percentage of kept visits. Several features of study design, clinic operations, and data transfer were barriers to demonstrating effectiveness.
Neutrophil extracellular trap inhibition increases inflammation, bacteraemia and mortality in murine necrotizing enterocolitis
Authors: Chaaban Hala , Burge Kathryn , Eckert Jeffrey , Keshari Ravi S. , Silasi Robert , Lupu Cristina , Warner Barbara , Escobedo Marilyn , Caplan Michael , Lupu Florea
Published: June 2020

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease affecting primarily premature infants. The disease is characterized by intestinal inflammation and leucocyte infiltration, often progressing to necrosis, perforation, systemic inflammatory response and death. Neutrophil extracellular traps (NETs), denoting nuclear DNA, histone and antimicrobial protein release, have been suggested to play a role in NEC. This study aimed to determine the role of NETs in NEC and explore the effect of chloramidine, a NET inhibitor, on a murine NEC‐like intestinal injury model. Blood and intestinal tissues were collected from infants diagnosed with ≥ Stage II NEC, and levels of nucleosomes and NETs, respectively, were compared with those of case‐matched controls. In mice, NEC was induced with dithizone/Klebsiella, and mice in the treatment group received 40 mg/kg chloramidine. Bacterial load, intestinal histology, plasma myeloperoxidase and cytokine levels, and immunofluorescent staining were compared with controls. Nucleosomes were significantly elevated in both human and mouse NEC plasma, whereas NET staining was only present in NEC tissue in both species. Chloramidine treatment increased systemic inflammation, bacterial load, organ injury and mortality in murine NEC. Taken together, our findings suggest that NETs are critical in the innate immune defence during NEC in preventing systemic bacteraemia.
Regulation of the EGFR/ErbB signalling by clathrin in response to various ligands in hepatocellular carcinoma cell lines
Authors: Liu Yuanhui , Calmel Claire , Desbois‐Mouthon Christèle , Sobczak‐Thépot Joëlle , Karaiskou Anthi , Praz Françoise
Published: June 2020

Membrane receptor intracellular trafficking and signalling are frequently altered in cancers. Our aim was to investigate whether clathrin‐dependent trafficking modulates signalling of the ErbB receptor family in response to amphiregulin (AR), EGF, heparin‐binding EGF‐like growth factor (HB‐EGF) and heregulin‐1β (HRG). Experiments were performed using three hepatocellular carcinoma (HCC) cell lines, Hep3B, HepG2 and PLC/PRF/5, expressing various levels of EGFR, ErbB2 and ErbB3. Inhibition of clathrin‐mediated endocytosis (CME), by down‐regulating clathrin heavy chain expression, resulted in a cell‐ and ligand‐specific pattern of phosphorylation of the ErbB receptors and their downstream effectors. Clathrin down‐regulation significantly decreased the ratio between phosphorylated EGFR (pEGFR) and total EGFR in all cell lines when stimulated with AR, EGF, HB‐EGF or HRG, except in HRG‐stimulated Hep3B cells in which pEGFR was not detectable. The ratio between phosphorylated ErbB2 and total ErbB2 was significantly decreased in clathrin down‐regulated Hep3B cells stimulated with any of the ligands, and in HRG‐stimulated PLC/PRF/5 cells. The ratio between phosphorylated ErbB3 and total ErbB3 significantly decreased in clathrin down‐regulated cell lines upon stimulation with EGF or HB‐EGF. STAT3 phosphorylation levels significantly increased in all cell lines irrespective of stimulation, while that of AKT remained unchanged, except in AR‐stimulated Hep3B and HepG2 cells in which pAKT was significantly decreased. Finally, ERK phosphorylation was insensitive to clathrin inhibition. Altogether, our observations indicate that clathrin regulation of ErbB signalling in HCC is a complex process that likely depends on the expression of ErbB family members and on the autocrine/paracrine secretion of their ligands in the tumour environment.