bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of Mprofrom COVID-19 virus and discovery of its inhibitors
Authors: Jin Zhenming , Du Xiaoyu , Xu Yechun , Deng Yongqiang , Liu Meiqin , Zhao Yao , Zhang Bing , Li Xiaofeng , Zhang Leike , Peng Chao , Duan Yinkai , Yu Jing , Wang Lin , Yang Kailin , Liu Fengjiang , Jiang Rendi , Yang Xinglou , You Tian , Liu Xiaoce , Yang Xiuna , Bai Fang , Liu Hong , Liu Xiang , Guddat Luke W. , Xu Wenqing , Xiao Gengfu , Qin Chengfeng , Shi Zhengli , Jiang Hualiang , Rao Zihe , Yang Haitao
Published: February 2020

A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1–4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mprois a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mproin complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mprowith IC50values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.
Combinatorial action of transcription factors in open chromatin contributes to early cellular heterogeneity and organizer mesendoderm specification
Authors: Bright Ann Rose , van Genesen Siebe , Li Qingqing , van Heeringen Simon J. , Grasso Alexia , Veenstra Gert Jan C.
Published: February 2020

During gastrulation, mesoderm is induced in pluripotent cells, concomitant with dorsal-ventral patterning and establishing of the dorsal axis. How transcription factors operate within the constraints of chromatin accessibility to mediate these processes is not well-understood. We applied chromatin accessibility and single cell transcriptome analyses to explore the emergence of heterogeneity and underlying gene-regulatory mechanisms during early gastrulation inXenopus. ATAC-sequencing of pluripotent animal cap cells revealed a state of open chromatin of transcriptionally inactive lineage-restricted genes, whereas chromatin accessibility in dorsal marginal zone cells more closely reflected the transcriptional activity of genes. We characterized single cell trajectories in animal cap and dorsal marginal zone in early gastrula embryos, and inferred the activity of transcription factors in single cell clusters by integrating chromatin accessibility and single cell RNA-sequencing. We tested the activity of organizer-expressed transcription factors in mesoderm-competent animal cap cells and found combinatorial effects of these factors on organizer gene expression. In particular the combination of Foxb1 and Eomes induced a gene expression profile that mimicked those observed in head and trunk organizer single cell clusters. In addition, genes induced by Eomes, Otx2 or the Irx3-Otx2 combination, were enriched for promoters with maternally regulated H3K4me3 modifications, whereas promoters selectively induced by Lhx8 were marked more frequently by zygotically controlled H3K4me3. Our results show that combinatorial activity of zygotically expressed transcription factors acts on maternally-regulated accessible chromatin to induce organizer gene expression.
Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+T cells
Authors: Matas-Rico Elisa , Frijlink Elselien , van der Haar Àvila Irene , Menegakis Apostolos , van Zon Maaike , Morris Andrew J. , Koster Jan , Salgado-Polo Fernando , de Kivit Sander , Lança Telma , Mazzocca Antonio , Johnson Zoë , Haanen John , Schumacher Ton N. , Perrakis Anastassis , Verbrugge Inge , van den Berg Joost , Borst Jannie , Moolenaar Wouter H.
Published: February 2020

Autotaxin (ATX) is secreted by diverse cell types to produce lysophosphatidic acid (LPA) that regulates multiple biological functions via G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor cell migration and metastasis mainly via LPAR1; however, its actions in the tumor immune microenvironment remain unclear. Here, we show that ATX secreted by melanoma cells is chemorepulsive for tumor-infiltrating lymphocytes and circulating CD8+T cellsex vivo, with ATX functioning as an LPA-producing chaperone. Mechanistically, T-cell repulsion predominantly involves Gα12/13-coupled LPAR6. Upon anti-cancer vaccination of tumor-bearing mice, ATX does not affect the induction of systemic T-cell responses but suppresses tumor infiltration of cytotoxic CD8+T cells and thereby impairs tumor regression. Moreover, single-cell data from patient samples are consistent with intra-tumor ATX acting as a T-cell repellent. These studies highlight an unexpected role for the pro-metastatic ATX-LPAR axis in suppressing CD8+T-cell infiltration to impede anti-tumor immunity, suggesting new therapeutic opportunities.
Nucleosomal embedding reshapes the dynamics of abasic sites
Authors: Bignon Emmanuelle , Claerbout Victor , Jiang Tao , Morell Christophe , Gillet Natacha , Dumont Elise
Published: February 2020

Apurinic/apyrimidinic (AP) sites are the most common DNA lesions, which benefit from a most efficient repair by the base excision pathway. The impact of losing a nucleobase on the conformation and dynamics of B-DNA is well characterized. Yet AP sites seem to present an entirely different chemistry in nucleosomal DNA, with lifetimes reduced up to 100-fold, and the much increased formation of covalent DNA-protein cross-links, refractory to repair. We report microsecond range, all-atom molecular dynamics simulations that capture the conformational dynamics of AP sites and their tetrahydrofuran analogs at two symmetrical positions within a nucleosome core particle, starting from a recent crystal structure. Different behaviours between the deoxyribo-based and tetrahydrofuran-type abasic sites are evidenced. The two solvent-exposed lesion sites present contrasted extrahelicities, revealing the crucial role of the position of a defect around the histone core. Our all-atom simulations also identify and quantify the occurrence of several spontaneous, non-covalent interactions between AP and positively-charged residues from the histones H2A and H2B tails that prefigure DNA-protein cross-links. This study paves the way towards an in silico mapping of DNA-protein cross-links.
Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly
Authors: Wioland Hugo , Frémont Stéphane , Guichard Bérengère , Echard Arnaud , Jégou Antoine , Romet-Lemonne Guillaume
Published: February 2020

Proteins of the ADF/cofilin family play a central role in the disassembly of actin filaments, and their activity must be tightly regulated in cells. Recently, the oxidation of actin filaments by the enzyme MICAL1 was found to amplify the severing action of cofilin through unclear mechanisms. Two essential factors normally prevent filament disassembly: the inactivation of cofilin by phosphorylation, and the protection of filaments by tropomyosins, but whether actin oxidation might interfere with these safeguard mechanisms is unknown. Using single filament experimentsin vitro, we found that actin filament oxidation by MICAL1 increases, by several orders of magnitude, both cofilin binding and severing rates, explaining the dramatic synergy between oxidation and cofilin for filament disassembly. Remarkably, we found that actin oxidation bypasses the need for cofilin activation by dephosphorylation. Indeed, non-activated, phosphomimetic S3D-cofilin binds and severs oxidized actin filaments rapidly, in conditions where non-oxidized filaments are unaffected. Finally, tropomyosin Tpm1.8 loses its ability to protect filaments from cofilin severing activity when actin is oxidized by MICAL1. Together, our results show that MICAL1-induced oxidation of actin filaments suppresses their physiological protection from the action of cofilin. We propose that in cells, direct post-translational modification of actin filaments by oxidation is a way to trigger their severing, in spite of being decorated by tropomyosin, and without requiring the activation of cofilin.
Building a Reference Transcriptome for the Hexaploid Hard Fescue Turfgrass (Festuca brevipila) Using a Combination of PacBio Iso-Seq and Illumina Sequencing
Authors: Qiu Yinjie , Yang Ya , Hirsch Cory D. , Watkins Eric
Published: February 2020

Background

Hard fescue (Festuca brevipilaTracey, 2n=6x=42) is a cool season turfgrass with a fine leaf texture that performs well under low-input management. Breeding and genetics studies ofF. brevipilahave been limited due to the complexity of its hexaploid genome. To advance our knowledge ofF. brevipilagenomics, we used PacBio isoform sequencing to develop a reference transcriptome for this species.

Results

Here, we report theF. brevipilareference transcriptome generated from root, crown, leaf, and inflorescence tissues. We obtained 59,510 full-length transcripts, of which 38,556 were non-redundant full-length transcripts. The longest and shortest transcripts were 11,487 and 58 bp, respectively. Distribution of synonymous distances among paralogs withinF. brevipilasuggested highly similar subgenomes that are difficult to distinguish from sequencing errors. To evaluate the phylogenetic relationships amongF. brevipilaand close relatives, we sequenced three additional transcriptomes using closely related species on an Illumina platform. The results of our phylotranscriptomic analysis supported the close relationships amongF. brevipila(6x),Festuca ovina(4x),Festuca ovinasubsp.ovina(2x), andFestuca valesiaca(2x), with high levels of discordance among gene trees.

Conclusions

Overall, theF. brevipilaPacBio Isoseq reference transcriptome provided the foundation for transcriptome studies and allowed breeders a resource for gene discovery in this important turfgrass species.
Gut Microbiome Profiling of a Rural and Urban South African Cohort Reveals Biomarkers of a Population in Lifestyle Transition
Authors: Oduaran OH. , Tamburini FB. , Sahibdeen V. , Brewster R. , Gómez-Olivé FX. , Kahn K. , Norris SA. , Tollman SM. , Twine R. , Wade AN. , Wagner RG. , Lombard Z. , Bhatt AS. , Hazelhurst S.
Published: February 2020

Background

Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most African adults. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To better characterize the microbiome of African adults living in more mainstream lifestyle settings and to investigate associations between the microbiome and obesity, we conducted a pilot study in two South African cohorts that are representative of urban and rural populations. The study was designed collaboratively with community leaders. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data.

Results

We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, our results show a relatively higher than expected abundance of Western gut-associated taxa such as Barnesiella and the presence of Bifidobacteria and Bacteroides together with the more traditionally non-Western gut-associated Prevotella, Treponema and Succinivibrio. Interestingly, we observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in the rural cohort. We also found Prevotella, despite its generally high prevalence relative to all taxa present in the cohort, to be associated with obesity.

Conclusions

Altogether, this work identifies putative microbial features associated with host health in a historically understudied community. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research in this regard.
Paired high-throughput, in-situ imaging and high-throughput sequencing illuminate acantharian abundance and vertical distribution
Authors: Mars Brisbin Margaret , Brunner Otis Davey , Grossmann Mary Matilda , Mitarai Satoshi
Published: February 2020

Acantharians are important contributors to surface primary production and to carbon flux to the deep sea, but are often underestimated because their delicate structures are destroyed by plankton nets or dissolved by preservatives. As a result, relatively little is known about acantharian biology, especially regarding their life cycles. Here, we take a paired approach, bringing together high-throughput, in-situ imaging and high-throughput sequencing, to investigate acantharian abundance, vertical distribution, and life-history in the western North Pacific. Observed concentrations of acantharian cells correlated well with sequence abundances from acantharians with known, recognizable morphologies, but not to sequences from those without known morphology (basal environmental clades). These results suggest basal clades may lack characteristic star-shaped skeletons or are much smaller than known acantharians. The decreased size-range of acantharians imaged at depth supports current hypotheses regarding asymbiotic acantharian life cycles: cysts or vegetative cells release reproductive swarmer cells at depth and juvenile cells grow as they ascend towards the surface. Moreover, sequencing data present the possibility that photosymbiotic acantharians also reproduce at depth, like their asymbiotic, encysting relatives, which is counter to previous hypotheses. Finally, in-situ imaging captured a new acantharian behavior that may be a previously undescribed predation strategy.
The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single cell transcriptome study
Authors: Li Mengmeng , Chen Liang , Xiong Chenglong , Li Xiangjie
Published: February 2020

Recent studies have demonstrated that SARS-CoV-2 cell entry depends on both ACE2 and TMPRSS2 genes (DOI: 10.1016/j.cell.2020.02.052), but our current work only focus on ACE2, which is insufficient to support the conclusion of this paper. So the authors have withdrawn their manuscript whilst they perform additional experiments and analysis to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project.
Simultaneous auditory agnosia: Systematic description of a new type of auditory segregation deficit following a right hemisphere lesion
Authors: Holmes Emma , Utoomprurkporn Nattawan , Hoskote Chandrashekar , Warren Jason D. , Bamiou Doris-Eva , Griffiths Timothy D.
Published: February 2020

We investigated auditory processing in a young patient who experienced a single embolus causing an infarct in the right middle cerebral artery territory. This lead to damage to auditory cortex including planum temporale that spared medial Heschl’s gyrus, and included damage to the posterior insula and inferior parietal lobule. She first reported difficulty hearing all sounds, which fully recovered within days, but she subsequently reported chronic difficulties with segregating speech from noise and segregating elements of music. Clinical tests showed no evidence for abnormal cochlear function. Follow-up tests confirmed difficulties with auditory segregation in her left ear that spanned multiple domains, including speech-in-noise and music streaming. Testing with a stochastic figure-ground task—a way of estimating generic acoustic foreground and background segregation—demonstrated that this was also abnormal. This is the first demonstration of an acquired deficit in the segregation of complex acoustic patterns due to cortical damage, which we argue is a causal explanation for the symptomatic deficits in the segregation of speech and music. These symptoms are analogous to the visual symptom of simultaneous agnosia. Consistent with functional imaging studies on normal listeners, the work implicates non-primary auditory cortex. Further, the work demonstrates a (partial) lateralisation of the necessary anatomical substrate for segregation that has not been previously highlighted.

Highlights

Rare case of auditory agnosia in a young patient with a right-hemisphere infarct

Damage affecting non-primary auditory cortex, but sparing primary auditory cortex

Generalised auditory segregation deficit, revealed by auditory figure-ground task

This explains segregation deficits for speech-in-noise and music streaming

The deficit affects stimuli presented on the left
Diversity and Distribution of a Novel Genus of HyperthermophilicAquificaeViruses Encoding a Proof-reading Family-A DNA Polymerase
Authors: Palmer Marike , Hedlund Brian P. , Roux Simon , Tsourkas Philippos K. , Doss Ryan K. , Stamereilers Casey , Mehta Astha , Dodsworth Jeremy A. , Lodes Michael , Monsma Scott , del Rio Tijana Glavina , Schoenfeld Thomas W. , Eloe-Fadrosh Emiley A. , Mead David A.
Published: February 2020

Despite the high abundance ofAquificaein many geothermal systems, these bacteria are difficult to culture and no viruses infecting members of this phylum have been isolated. Here, we describe the complete, circular dsDNA Uncultivated Virus Genome (UViG) ofThermocrinisOctopus Spring virus (TOSV), derived from metagenomic data, along with eight related UViGs representing three additional species,ThermocrinisGreat Boiling Spring virus (TGBSV),AquificaeJoseph’s Coat Spring Virus (AJCSV), andAquificaeConch Spring Virus (ACSV). Four near-complete UViGs, ranged from 37,256 bp to 41,208 bp and encoded 48 to 53 open reading frames. Despite low overall similarity between viruses from different hot springs, the genomes shared a high degree of synteny, and encoded numerous genes for nucleotide metabolism, including a polyprotein PolA-type polymerase with likely accessory functions, a DNA Pol III beta subunit (sliding clamp), a thymidylate kinase, a DNA gyrase, a helicase, and a DNA methylase. Also present were conserved genes predicted to code for phage capsids, large and small terminases, portal protein, holin, and lytic transglycosylase, all consistent with a distant relatedness to cultivatedCaudovirales. TOSV and TGBSV had the highest coverage in their respective metagenomes and are predicted to infectThermocrinis ruberandThermocrinis jamiesonii, respectively, as multiple CRISPR spacers matching the viral genomes were identified withinThermocrinis ruberOC1/4TandThermocrinis jamiesoniiGBS1T. Based on the predicted, unusual bi-directional replication strategy, low sequence similarity to known viral genomes, and a unique position in gene-sharing networks, we propose a new putative genus, Pyrovirus, in the orderCaudovirales.
[SP-4-2]-(Acetonitrile-κN)chlorido[2-(4,6-diphenylpyridin-2-yl)phenyl-κ2
C
1,N]platinum(II). Corrigendum
Authors: Fang Chengjian , Wang Zhao , Cong Zhongjian , Li Shengli , Li Fei
Published: February 2020

The article by Fang et al. [IUCrData (2019), 4, x191207] is withdrawn.
Autism in black, Asian and minority ethnic communities: a report on the first Autism Voice UK Symposium
Authors: Kandeh Mariama Seray , Kandeh Mariama Korrca , Martin Nicola , Krupa Joanna
Published: February 2020

Purpose

Little is known about the way autism is interpreted and accepted among the black, Asian and minority ethnic (BAME) populations in the UK. This report summarises a Symposium on autism in the UK-BAME community in 2018, organised by Autism Voice UK, Participatory Autism Research Collective and the Critical Autism and Disabilities Studies Research Group at London South Bank University.

Design/methodology/approach

The stance a family or community takes about a condition such as autism is influenced by their cultural background. The aims of the Symposium were to highlight different perspectives about autism in BAME communities and to preserve the cultural dignity of the community in supporting autistic members. Beliefs about autism, its diagnosis and acceptance of and support for autistic people from a specific cultural perspective of BAME communities must be cautiously interpreted by autism professionals because beliefs vary among different cultural groups.

Findings

Thematic analysis of feedback from participants yielded the following foci. Firstly, cultural, ethnic and religious sensitivities were important to participants who felt that these were often ignored by non-BAME professionals. Secondly, the need for collaboration to improve autism awareness within the community and understanding by professionals of the intersectionality between autism and identity in BAME families was prioritised. Thirdly, issues around feelings of stigma were common, but delegates felt that these were not well understood beyond people identifying as BAME.

Originality/value

An action plan was created which highlighted raising public awareness through community engagement, improvement of access to information for parents and culturally aware autism education for professionals and BAME communities.
An analysis of technical information for mechatronics research
Authors: Osorio Nestor L. , Osorio Gabriel E.
Published: February 2020

Purpose

Mechatronics is a very important area of research in industrial applications. The purpose of this study is to find some of the most important components of the literature on this subject.

Design/methodology/approach

The analysis is based on the use of the database Compendex; it was searched in the broadest way for documents related to mechatronics. In addition, subject guides from libraries of universities with mechatronics programs were studied to find resources available in those areas.

Findings

The literature of mechatronics is extensive and multidisciplinary. Based on the results from Compendex, the following data were found: most productive authors, list of leading journals and conference proceedings, publishers and grant organizations, authors’ affiliations and other minor details. Based on the analysis of subject guides, the following types of resources were found: research databases, reference books and ebook collections.

Research limitations/implications

Part of the analysis is based on a search performed in one technical database, Compendex; it was the database that generated the largest number of citations as compared to Inspec and the Web of Science. The results have a strong English language focus. It is possible that by using the results from multiple data bases, some additional sources could be obtained.

Practical implications

Mechatronics is a relatively new technological field comprising a number of scientific and engineering areas. The results obtained summarized a significant amount of bibliographic information.

Originality/value

The work is original; to the best of the authors’ knowledge, no other study has analyzed the literature on this subject.
Exploring role of gratitude in developing teacher leadership in Indian universities
Authors: Garg Naval
Published: February 2020

Purpose

The benefits of teacher leadership have attracted the attention of policymakers, practitioners and researchers. It is increasingly advocated as one of the most crucial and indispensable components of the school, college and university administration. The present study tends to investigate the role of gratitude in developing teacher leadership through examining sufficiency and necessity of thankfulness for educational leadership.

Design/methodology/approach

The study explores sufficiency and necessity of gratitude for seven dimensions of educational leadership with the help of correlation, regression and necessary condition analysis.

Findings

The paper concludes that gratitude is both sufficient and necessary condition for overall teacher leadership and its seven dimensions.

Originality/value

The paper is based on original data.
Review of the Delphi method in library and information science research
Authors: Lund Brady D.
Published: February 2020

Purpose

This article presents an introduction to the Delphi method and review of Delphi studies published in the literature of library and information science (LIS).

Design/methodology/approach

A review of Delphi studies published between the years of 1971 and 2019 is performed, using studies retrieved from the Library and Information Science Source database. A total of 122 articles were retrieved and evaluated based on the population studied, means of identifying experts, number of participants for each study round, type of Delphi, and type of findings.

Findings

General librarians (any type), academic librarians, and information science researchers are the most common populations in LIS Delphi studies. On average (middle 50 percent of studies), 14–36 experts are used in the first round of LIS Delphi studies (mediann = 23). Employment in a specific role and publications in scholarly journals are the most common means of identifying experts. Variants of the e-Delphi (online survey/email) method are increasingly common, particularly in LIS Delphi studies that focus on general information science, rather than library, topics. Though LIS Delphi studies are relatively few in number, they have a consistent record of being published in some of the most prestigious LIS journals.

Originality/value

This paper provides an introduction to the Delphi method for LIS research and presents an overview of existing literature in LIS that utilizes the research method. No overview of this extent exists in the LIS literature, and, thus, this paper may serve as an important information source about the method for LIS researchers.
Sickness effects on social interactions depend on the type of behaviour and relationship
Authors: Stockmaier Sebastian , Bolnick Daniel I. , Page Rachel A. , Carter Gerald G.
Published: February 2020

Infections can change social behaviour in multiple ways, with profound impacts on pathogen transmission. However, these impacts might depend on the type of behaviour, how sociality as a biological trait is defined (e.g. network degree vs. mean edge strength) and the type of social relationship between the interacting individuals.

We used the highly social common vampire bat Desmodus rotundus to test how an immune challenge by lipopolysaccharide (LPS) injections affects two different social behaviours and three alternate measures of sociality, and whether the LPS effect differs by kinship relationship.

Effects of sickness should be lower for social behaviours that bestow greater benefits to inclusive fitness, such as food sharing. As predicted, immune‐challenged bats experienced a greater reduction in allogrooming received than food sharing received.

Sickness effects might also depend on how a social interaction is defined (e.g. the number of grooming partners vs. the duration of grooming events). We predicted that sickness would impact both the number and duration of social encounters, but we only detected a decrease in the number of grooming partners.

Finally, sickness effects might vary with social relationship type. We predicted that sickness effects should be smaller for interactions among close kin. As expected, the immune challenge had smaller effects on mother–offspring interactions.

In conclusion, our results highlight the need to explicitly consider how the effects of sickness on social network structure can differ depending on the ‘who, what, and how’ of social interactions, because these factors are likely to influence how sickness behaviour alters pathogen transmission.
Europe in the 21st Century: Powerful and Powerless
Authors: Mahbubani Kishore
Published: February 2020

In the dramatically new strategic environment of the 21st century, Europe is, paradoxically, in a position of power and paralysis. It retains many of its great strengths, but now faces very different challenges than it did at the height of its powers in the 20th century. Hence, what Europe needs most is a major strategic reboot. Its main strategic challenge is no longer Russian tanks, but the demographic explosion in Africa. Europe should therefore recalculate the value of its Trans‐Atlantic alliance. It should continue to cooperate with America where it is mutually beneficial. However, it should also cooperate with China to develop Africa and the Middle East to ensure that it deals with its main strategic challenge.
Enhancing Europe’s Global Power in Asia 2030
Authors: Heng Yee‐Kuang
Published: February 2020

As Asia undergoes tectonic power shifts, many states in the region are looking for reassurance and like‐minded partners to help uphold and defend shared common interests. An enhanced European presence could prove welcome, if European power is projected and communicated in the right ways.
Fluctuating Regional (Dis‐)Order in the Post‐Arab Uprising Middle East
Authors: Beck Martin , Richter Thomas
Published: February 2020

The Middle Eastern regional order has been undergoing profound changes in the current decade. These can be traced back to a reconfiguration of international and regional structures. On the one hand, shifts in US foreign policies towards the Middle East corresponded with new regional dynamics. On the other, the monarchies of the Arab Gulf have become more active in regional politics. In this contribution, we scrutinize these two changes and explore their interplay. We argue that a new regional order has emerged that can be characterized as a highly contested multipolar system in flux. Subsequently, three aspects that constitute and reinforce this disorderly regional system of the Middle East are discussed: first, the securitizing of policies by regional and extra‐regional political leaders; second, the increasing disintegration of regional institutions; and third, the emergence of lasting war zones. The paper concludes with a discussion of the meaning of these profound dynamics for future aspects of Middle Eastern regional affairs.
Potentially avoidable issues in urology mortality cases in Australia: identification and improvements
Authors: Gupta Aashray K. , Stewart Sasha K. , Cottell Kimberley , McCulloch Glenn A. J. , Miller John , Babidge Wendy J. , Maddern Guy J.
Published: February 2020

Background

This study aimed to identify the most common potentially avoidable factors in urology deaths, focusing on the lessons that can be learnt.

Methods

This study analysed data from a well‐established and comprehensive peer review audit of surgical deaths in Australian hospitals (excluding New South Wales) from 2009 to 2015, focusing on urology cases with identified areas for improvement in patient management. Of all audited deaths, 11% (79/719) had serious clinical management issues with a total of 109 individual clinical management issues identified. These were categorized based on perioperative stage (preoperative, intraoperative or post‐operative), followed by thematic analysis within each stage.

Results

The study found preoperative issues to be the most common (n = 48), followed by post‐operative issues (n = 32) with intraoperative issues less common (n = 13). Communication issues were seen at all three stages (n = 16). Overall, the most common theme was at the preoperative stage; inadequate preoperative assessment (n = 27). More specifically, the most common preoperative assessment issues involved a failure to order necessary preoperative investigations, or to administer necessary preoperative treatment (e.g. prophylactic antibiotics). The most common communication issue was between teams and at handover, often involving failure by junior medical staff to communicate issues to the responsible surgical consultant.

Conclusion

Urological surgical cases with potentially avoidable mortality constitute a small, but important subset of deaths. The analysis of these cases can inform various stakeholders to improve the quality and safety of urological surgical care.
Development of placental abnormalities in location and anatomy
Authors: Jansen Charlotte H. J. R. , Kastelein Arnoud W. , Kleinrouweler C. Emily , Van Leeuwen Elisabeth , De Jong Kees H. , Pajkrt Eva , Van Noorden Cornelis J. F.
Published: February 2020

Low‐lying placentas, placenta previa and abnormally invasive placentas are the most frequently occurring placental abnormalities in location and anatomy. These conditions can have serious consequences for mother and fetus mainly due to excessive blood loss before, during or after delivery. The incidence of such abnormalities is increasing, but treatment options and preventive strategies are limited. Therefore, it is crucial to understand the etiology of placental abnormalities in location and anatomy. Placental formation already starts at implantation and therefore disorders during implantation may cause these abnormalities. Understanding of the normal placental structure and development is essential to comprehend the etiology of placental abnormalities in location and anatomy, to diagnose the affected women and to guide future research for treatment and preventive strategies. We reviewed the literature on the structure and development of the normal placenta and the placental development resulting in low‐lying placentas, placenta previa and abnormally invasive placentas.
Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic leukemia
Authors: Rathe Mathias , Preiss Birgitte , Marquart Hanne Vibeke , Schmiegelow Kjeld , Wehner Peder Skov
Published: February 2020

Minimal residual disease (MRD) monitoring has a strong prognostic value in childhood lymphoblastic leukemia (ALL) and is currently utilized in all major pediatric ALL protocols. MRD monitoring is done by multiparameter flow cytometry, IG/TCR quantitative PCR or reverse transcriptase quantitative PCR of leukemic fusion transcripts providing a reliable measurement of treatment response. However, occasionally bone marrow (BM) aspirates may not yield representative material or be misinterpreted due to treatment‐induced changes in MRD marker profile, undetected subclones at diagnosis, contamination with peripheral blood or cell adhesion and stroma cell interactions posing a risk for underestimating MRD levels and misclassifying resistant disease that may be detected by traditional BM morphology methods, immunohistochemistry, karyotyping and FISH. We present four cases with high MRD levels where MRD monitoring failed to provide the correct stratification information. Through these cases, we discuss the continued need to consider all available information including BM smears, touch imprints and trephine biopsy preparations not only at diagnosis but throughout remission monitoring in pediatric ALL.
Saving a victim from himself: The rhetoric of the learner’s presence and absence in the Milgram experiments
Authors: Kaposi David
Published: February 2020

This paper contests what has remained a core assumption in social psychological and general understandings of the Milgram experiments. Analysing the learner/victim’s rhetoric in experimental sessions across five conditions (N = 170), it demonstrates that what participants were exposed to was not the black‐and‐white scenario of being pushed towards continuation by the experimental authority and pulled towards discontinuation by the learner/victim. Instead, the traditionally posited explicit collision of ‘forces’ or ‘identities’ was at all points of the experiments undermined by an implicit collusion between them: rendering the learner/victim a divided and contradictory subject, and the experimental process a constantly shifting and paradoxical experiential‐moral field. As a result, the paper concludes that evaluating the participants’ conduct requires an understanding of the experiments where morality and non‐destructive agency were not simple givens to be applied to a transparent case, but had to be re‐created anew – in the face not just of their explicit denial by the experimenter but also of their implicit denial by the victim.
Global warming will affect the maximum potential abundance of boreal plant species
Authors: Villén‐Peréz Sara , Heikkinen Juha , Salemaa Maija , Mäkipää Raisa
Published: February 2020

Forecasting the impact of future global warming on biodiversity requires understanding how temperature limits the distribution of species. Here we rely on Liebig's Law of Minimum to estimate the effect of temperature on the maximum potential abundance that a species can attain at a certain location. We develop 95%‐quantile regressions to model the influence of effective temperature sum on the maximum potential abundance of 25 common understory plant species of Finland, along 868 nationwide plots sampled in 1985. Fifteen of these species showed a significant response to temperature sum that was consistent in temperature‐only models and in all‐predictors models, which also included cumulative precipitation, soil texture, soil fertility, tree species and stand maturity as predictors. For species with significant and consistent responses to temperature, we forecasted potential shifts in abundance for the period 2041–2070 under the IPCC A1B emission scenario using temperature‐only models. We predict major potential changes in abundance and average northward distribution shifts of 6–8 km yr−1. Our results emphasize inter‐specific differences in the impact of global warming on the understory layer of boreal forests. Species in all functional groups from dwarf shrubs, herbs and grasses to bryophytes and lichens showed significant responses to temperature, while temperature did not limit the abundance of 10 species. We discuss the interest of modelling the ‘maximum potential abundance’ to deal with the uncertainty in the predictions of realized abundances associated to the effect of environmental factors not accounted for and to dispersal limitations of species, among others. We believe this concept has a promising and unexplored potential to forecast the impact of specific drivers of global change under future scenarios.
Disability, Quality of Life, and Socioeconomic Burden of Cluster Headache: A Critical Review of Current Evidence and Future Perspectives
Authors: D'Amico Domenico , Raggi Alberto , Grazzi Licia , Lambru Giorgio
Published: February 2020

Objective

To summarize the available evidence on disability, quality of life (QoL), and economic burden on societies of cluster headache (CH), and to present which tools have been used to measure these domains with indications for future research.

Background

CH is a rare and severe primary headache. The focus of research on this disorder has historically been on understanding its complex pathophysiological mechanisms, whereas personal and global healthcare impact, disability, and QoL received little attention.

Methods

We reviewed the available literature published up to 2019, identifying primary research addressing QoL, disability, impact, or impairment in daily life due to episodic CH (ECH) or chronic CH (CCH), and its societal impact.

Results

CH produces a significant impact on sufferers QoL, disability, and work‐related aspects, with a stronger impact on CCH than ECH. The CH‐related disability appears to be greater than is seen in subjects with other primary headache disorders.

Conclusions

Information about patient‐reported outcomes is rarely collected in patients with CH. An effort to improve the amount of information on the lived experience of patients with CH is needed and CH‐specific disability and QoL measures require development.
Ultra–high‐density mapping of conduction gaps and atrial tachycardias: Distinctive patterns following pulmonary vein isolation with cryoballoon or contact–force‐guided radiofrequency current
Authors: Gunawardene Melanie A. , Eickholt Christian , Akbulak Ruken Ö. , Jularic Mario , Klatt Niklas , Hartmann Jens , Schlüter Michael , Meyer Christian , Willems Stephan , Schaeffer Benjamin
Published: February 2020

Introduction

The aim of this study was to investigate electrophysiological findings in patients with arrhythmia recurrence undergoing a repeat ablation procedure using ultra–high‐density (UHDx) mapping following an index procedure using either contact–force (CF)‐guided radiofrequency current (RFC) pulmonary vein isolation (PVI) or second‐generation cryoballoon (CB) PVI for treatment of atrial fibrillation (AF).

Methods and Results

Fifty consecutive patients with recurrence of AF and/or atrial tachycardia (AT) following index CF‐RFC PVI (n = 21) or CB PVI (n = 29) were included. A 64‐pole mini‐basket mapping catheter in combination with an UHDx‐mapping system‐guided ablation was used. RFC was applied using a catheter tip with three incorporated mini‐electrodes. PV reconnection rates were higher after CF‐RFC PVI (CF‐RFC: 2.5 ± 1.3 PVs vs CB: 1.4 ± 0.9 PVs; P = .0025) and left PVs were more frequently reconnected (CF‐RFC: 64% PVs vs CB: 35% PVs; P = .0077). Fractionated signals along the antral index ablation line (FS) were found in 30% of CB‐PVI patients (CF‐RFC: 9.5% vs CB:30%; P = .098) targeted for ablation. In five cases, FS were a critical part of maintaining consecutive AT. The main AT mechanism found during reablation (n = 45 ATs) was macroreentry (80% [36/45], CF‐RFC: 78.9% vs CB: 80.8%; P = 1.0) with a variety of circuits throughout both atria.

Conclusion

UHDx mapping is sensitive in detecting conduction gaps along the index ablation line. Left PVs are more frequently reconnected after initial CF‐RFC PVI. FS are a common finding after CB PVI and can maintain certain forms of ATs. ATs after index PVI are mostly macroreentries with a broad spectrum of entities.
Hydrogen exerts neuroprotection by activation of the miR‐21/PI3K/AKT/GSK‐3β pathway in an in vitro model of traumatic brain injury
Authors: Wang Lu , Yin Zhenyu , Wang Feng , Han Zhaoli , Wang Yifeng , Huang Shan , Hu Tianpeng , Guo Mengtian , Lei Ping
Published: February 2020

Few studies have explored the effect of hydrogen on neuronal apoptosis or impaired nerve regeneration after traumatic brain injury, and the mechanisms involved in these processes are unclear. In this study, we explored neuroprotection of hydrogen‐rich medium through activation of the miR‐21/PI3K/AKT/GSK‐3β pathway in an in vitro model of traumatic brain injury. Such model adopted PC12 cells with manual scratching. Then, injured cells were cultured in hydrogen‐rich medium for 48 hours. Expression of miR‐21, p‐PI3K, p‐Akt, p‐GSK‐3β, Bax and Bcl‐2 was measured using RT‐qPCR, Western blot analysis and immunofluorescence staining. Rate of apoptosis was determined using TUNEL staining. Neuronal regeneration was assessed using immunofluorescence staining. The results showed that hydrogen‐rich medium improved neurite regeneration and inhibited apoptosis in the injured cells. Scratch injury was accompanied by up‐regulation of miR‐21, p‐PI3K, p‐Akt and p‐GSK‐3β. A miR‐21 antagomir inhibited the expression of these four molecules, while a PI3K blocker only affected the three proteins and not miR‐21. Both the miR‐21 antagomir and PI3K blocker reversed the protective effect of hydrogen. In conclusion, hydrogen exerted a neuroprotective effect against neuronal apoptosis and impaired nerve regeneration through activation of miR‐21/PI3K/AKT/GSK‐3β signalling in this in vitro model of traumatic brain injury.
The role of socio‐economic status and energy‐density in Australian women of child‐bearing age
Authors: Latter R. , Brown L. J. , Rae K. M. , Rollo M. E. , Schumacher T. L.
Published: February 2020

Introduction

An optimal diet is imperative in preparing women for pregnancy and this may be influenced by socio‐economic status (SES). This research aims to investigate the role of SES on the dietary energy density (ED) in Australian women of preconception age.

Methods

A secondary analysis of the Australian National Nutrition and Physical Activity Survey 2011–12 for females aged 18–39 years (n = 1617) was conducted. Dietary intake was assessed by 24‐hr recalls and dietary ED by dietary energy per weight (kJ.g−1). ED was further categorised as ED of foods and beverages separately. SES was assessed by three variables: Socio‐Economic Indexes for Areas (SEIFA), developed by the Australian Bureau of Statistics; income decile; and level of education. Linear mixed model regressions were used to identify associations between ED and SES.

Results

The median ED for food, beverages and combined food and beverages was 9.38 kJ g−1, 1.02 kJ g−1 and 7.11 kJ g−1, respectively. No significant variation was explained by SES variables when analysing combined ED in the adjusted model or ED from foods. Income decile reduced ED of beverages, although with little effect (coefficient: −0.04, P = 0.002). Significant confounders included inactivity, which increased ED in both combined ED and ED foods (coefficient: 0.51, P = 0.001 and coefficient: 0.78, P < 0.001).

Conclusions

SES explained little variation in dietary ED in women of childbearing age. A large proportion of women had high energy‐dense diets regardless of their SES. These findings suggest that a large proportion of women, who may become pregnant, have diets that exceed the international recommendations for dietary energy density.
Action research: A mechanism for active engagement of clinical nurses in a program of research
Authors: Alomari Albara , Wilson Val , Lewis Joanne
Published: February 2020

This study aimed to explore the outcomes of active participation in an action research project on building the research capacity of clinical nurses. In this qualitative research study, six registered nurses volunteered to participate in the action research team. None of the nurses reported having any prior research experience. This study was part of a larger three‐phase project. The nurses were required to reflect on the data about their medication practice of phase 1, develop and implement a bundle of interventions in phase 2 to improve medication safety, and evaluate the effectiveness of these interventions in phase 3. We report the nurses' participation in Action Research during phase 2. Meeting minutes and six semistructured interviews were thematically analyzed. The results showed that after receiving support to enhance their research skills from the research team, the nurses were empowered to perform and lead clinical nursing research project. Nurses were able to take ownership of the research process and outcomes and were then able to translate their new research knowledge and skills into their clinical practice by building their own research capacity.