bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection and spatial monitoring of an emerging biological invasion by population genetics and environmental DNA metabarcoding
Authors: Dufresnes Christophe , Déjean Tony , Zumbach Silvia , Schmidt Benedikt R. , Fumagalli Luca , Ramseier Petra , Dubey Sylvain
Published: July 2019

Rapid management responses against invasive species soon after their establishment are the most efficient way to limit their biological and economic impacts. Early detection and reliable monitoring is however challenging when cryptic taxa are involved. Here we show how environmental DNA (eDNA) metabarcoding of water samples efficiently unveiled an emerging invasion of Italian crested newts (Triturus carnifex), one of the most successful amphibian invaders in Europe. We compared and validated an eDNA survey by multilocus population genetics of wild‐caught individuals. Both approaches consistently mapped a localized T. carnifex invasion in northwestern Switzerland, most likely following imports from the Italian Po Plain. We found evidence of gene flow with the indigenous and endangered Triturus cristatus in nearby populations, suggesting a potential expansion. Yet the currently small invasive range should be efficiently contained by future eradication programs. This textbook case emphasizes the implementation of eDNA metabarcoding to screen aquatic communities for exotic species, from which targeted studies can be designed on emerging biological invasions.
‘Outgrowing’ a cerebral palsy diagnosis
Authors: Nelson Karin B
Published: July 2019

This commentary is on the original article by Chen et al. on pages 83‐88 of this issue.
Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children
Authors: Qin Fang , Shi Lingling , Li Qiaochuan , Zhang Zhongming , Liu Lianjin , Li Jing , Yang Gaohui , Lai Yong‐Rong
Published: July 2019

Background

The clinical outcome of hematopoietic stem cell transplantation (HSCT) in those with severe beta‐thalassemia (β‐TM) is closely related to post‐transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce.

Methods

A prospective analysis of the clinical outcome and IR in 47 children with severe β‐TM who underwent in vivo T‐cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. Immune reconstitution, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measured.

Results

In the first year after HSCT, bacterial infections and cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4+ T‐cell recovery was observed. The B cells recovered within 6 months. Natural killer (NK) cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB + BM) group had slower T‐cell recovery, and higher B cells and NK cells in comparison with peripheral blood and bone marrow (PB + BM) group.

Conclusions

The high incidence of infection within 1 year after in vivo T‐cell depletion myeloablative conditioning HSCT in severe β‐TM was consistent with poor IR.
The Impact of Economic Development and National Culture on Management Consulting Expenditures: Evidence from Europe and North America
Authors: Barthélemy Jérôme
Published: July 2019

This study examines the independent and joint effect of economic development and two national culture dimensions (performance orientation and uncertainty avoidance) on management consulting expenditures at the country level. Hypotheses are tested on a sample of 21 European and North American countries over a 20‐year period. Results indicate that economic development and uncertainty avoidance are positively related to country‐level management consulting expenditures. Moreover, the relationship between economic development and management consulting expenditures is stronger in countries high on uncertainty avoidance. On the other hand, performance orientation is neither directly nor indirectly related to country‐level management consulting expenditures.
Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability
Authors: Borlot Felippe , de Almeida Bruno Ivo , Combe Shari L. , Andrade Danielle M. , Filloux Francis M. , Myers Kenneth A.
Published: July 2019

Objective

To determine the diagnostic yield of a commercial epilepsy gene panel in adults with chronic epilepsy and accompanying intellectual disability, given that genetic evaluation is often overlooked in this group of patients.

Methods

This is a cross‐sectional study analyzing the results of epilepsy gene panels including up to 185 genes in adult epilepsy patients with intellectual disability, according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Patients with acquired structural brain abnormalities or known chromosomal abnormalities were excluded.

Results

From approximately 600 patients seen from January 2017 to June 2018 at a single academic epilepsy center, 64 probands and two affected relatives (32 males, mean age = 31 years ± 10) were selected and clinically tested. Fourteen probands (14/64 = 22%; four males, mean age = 32 years ± 10) were found to have pathogenic or likely pathogenic variants in the following genes:SCN1A,GABRB3,UBE3A,KANSL1,SLC2A1,KCNQ2,SLC6A1,HNRNPU,STX1B,SCN2A,PURA,andCHD2. Six variants arose de novo, and the inheritance was not determined in eight. Nine probands (64%) had severe or profound intellectual disability, and five (35%) had autistic features. Eight patients (57%) had a diagnostic change from presumptive clinical diagnosis prior to genetic testing.

Significance

We were able to demonstrate that a commercial epilepsy gene panel can be an important resource in clinical practice, identifying the etiology in 22% of adults with epilepsy and intellectual disability. The diagnostic yield is similar to previously reported pediatric cohorts. Larger samples would be required to evaluate the more prevalent genotypes among adult epilepsy patients.
Rational evolution of the cofactor‐binding site of cytochrome P450 reductase yields variants with increased activity towards specific cytochrome P450 enzymes
Authors: Strohmaier Silja J. , Huang Weiliang , Baek Jong‐Min , Hunter Dominic J. B. , Gillam Elizabeth M. J.
Published: July 2019

NADPH‐cytochrome P450 reductase (CPR) is the natural redox partner of microsomal cytochrome P450 enzymes. CPR shows a stringent preference for NADPH over the less expensive cofactor, NADH, economically limiting its use as a biocatalyst. The complexity of cofactor‐linked CPR protein dynamics and the incomplete understanding of the interaction of CPR with both cofactors and electron acceptors present challenges for the successful rational engineering of a CPR with enhanced activity with NADH. Here, we report a rational evolution approach to enhance the activity of CPR with NADH, in which mutations were introduced into the NADPH‐binding flavin adenine dinucleotide (FAD) domain. Multiple CPR mutants that used NADH more effectively than the wild‐type CPR in the reduction of the surrogate electron acceptor, cytochrome c were found. However, most were inactive in supporting P450 activity, arguing against the use of cytochrome c as a surrogate electron acceptor. Unexpectedly, several mutants showed significantly improved activity towards CYP2C9 (mutant 1‐014) and/or CYP2A6 (mutants 1‐014, 1‐015, 1‐053 and 1‐077) using NADPH, even though the mutations were introduced at locations remote from the putative CPR‐P450 interaction face. Therefore, mutations at sites in the FAD domain of CPR may be promising future engineering targets to enhance P450‐mediated substrate turnover.

Enzymes

NADPH‐cytochrome P450 reductase – EC 1.6.2.4; cytochrome P450 – EC 1.14.14.1.
Tiered Information Disclosure: An Empirical Analysis of the Advance Peek into the Michigan Index of Consumer Sentiment
Authors: Wu Weishao , Liu Wenchien , Suardi Sandy , Chang Yuanchen
Published: July 2019

This paper studies market microstructure implications of informed high‐frequency traders (HFTs) from two seconds of advance peek into the Michigan Index of Consumer Sentiment (ICS), provided by Thomson Reuters to its elite customers. Using individual stocks in the NASDAQ data set, we show how HFTs trade around ICS events. We find that liquidity demanders during two seconds of advance peek earn substantive profits, which are consistent with the notion that HFTs’ informational advantages may increase adverse selection costs for other market participants. This evidence elucidates the debate on regulatory oversight and its role in circumventing the potentially adverse effects from an advance peek into ICS.
Increasing the Tick: Examining the Impact of the Tick Size Change on Maker‐Taker and Taker‐Maker Market Models
Authors: Cox Justin , Van Ness Bonnie , Van Ness Robert
Published: July 2019

We investigate the effects of an increase in tick size on order and trading flow across market fee models. Using the pilot firms in the U.S. Securities and Exchange Commission's Tick Size Pilot Program, we document that trade and order volume declines on maker‐taker fee models after the tick size implementation. We find that the inverted fee models (taker‐maker) experience an increase in both trade and order volume. Additionally, we find that a tick size adjustment has a substantial influence on market participation in maker‐taker fee models. We also find that measures of both hidden and algorithmic trading decline with an increasing tick size, which is strongly moderated by the differences in the maker‐taker and taker‐maker fee models.
Recreational sector is the dominant source of fishing mortality for oceanic fishes in the Southeast United States Atlantic Ocean
Authors: Shertzer Kyle W. , Williams Erik H. , Craig Joseph Kevin , Fitzpatrick Eric E. , Klibansky Nikolai , Siegfried Katie I.
Published: July 2019

Recreational fishing is increasingly recognised as an important source of mortality for marine fish populations. In the United States, estimates of marine recreational catch and effort were recently revised for the time period 1981 and beyond, and for many species, the revised estimates were substantially higher than the original values. Here, the proportion of total landings that came from the recreational sector in the Southeast US Atlantic was quantified. The proportions for 22 oceanic species and for all species combined were computed, using a full time series of landings (1981–2016) and a more recent time series (1999–2016). For the full and recent time series, landings of most species (15/22 and 17/22, respectively) were dominated by the recreational sector. For all species combined, 71% of landings in the full time series were from the recreational sector, and 76% in the recent time series. Trend analysis indicated that most species had a stable or increasing proportion of landings from the recreational sector. In addition, stock assessments were conducted on four species, and the catch revisions increased the estimated scale of abundance and, in some cases, affected stock or fishery status. This work underscores the importance of recreational fishing for marine resource management.
A genome‐wide search for local adaptation in a terrestrial‐breeding frog reveals vulnerability to climate change
Authors: Cummins Deanne , Kennington W. Jason , Rudin‐Bitterli Tabitha , Mitchell Nicola J.
Published: July 2019

Terrestrial‐breeding amphibians are likely to be vulnerable to warming and drying climates, as their embryos require consistent moisture for successful development. Adaptation to environmental change will depend on sufficient genetic variation existing within or between connected populations. Here, we use Single Nucleotide Polymorphism (SNP) data to investigate genome‐wide patterns in genetic diversity, gene flow and local adaptation in a terrestrial‐breeding frog (Pseudophryne guentheri) subject to a rapidly drying climate and recent habitat fragmentation. The species was sampled across 12 central and range‐edge populations (192 samples), and strong genetic structure was apparent, as were high inbreeding coefficients. Populations showed differences in genetic diversity, and one population lost significant genetic diversity in a decade. More than 500 SNP loci were putatively under directional selection, and 413 of these loci were correlated with environmental variables such as temperature, rainfall, evaporation and soil moisture. One locus showed homology to a gene involved in the activation of maturation in Xenopus oocytes, which may facilitate rapid development of embryos in drier climates. The low genetic diversity, strong population structuring and presence of local adaptation revealed in this study shows why management strategies such as targeted gene flow may be necessary to assist isolated populations to adapt to future climates.
Transnational grandparenting: an introduction
Authors: NEDELCU MIHAELA , WYSS MALIKA
Published: July 2019

This first special issue dedicated to grandparenting patterns and their significance within transnational families sheds new light on transnational grandparenting as a phenomenon reflecting the convergence of three major transformations in today's societies – global ageing, diversification of migration and mobility flows, and lifestyle individualization. It contains five articles based on empirical studies conducted in several European countries (Switzerland, Luxembourg, Spain, Romania, and the Czech Republic) focusing on transnational families from both EU and non‐EU countries (Germany, France, Italy, Brazil, Morocco, Algeria, Switzerland, Britain, Portugal, Romania, and Vietnam). These articles portray transnational grandparenting through the prism of three nexuses (mobile/non‐mobile, migrant/non‐migrant, and kin/non‐kin), thus allowing one to understand grandparents' roles in the transnational circulation of care in the light of contemporary family transformations on the one hand, and of the increased transnationalization of everyday ‘doing family’ practices on the other.
Spatial–temporal evolution of the port–hinterland relationship: A case study of the Midstream Yangtze River, China
Authors: He Dan , Sun Zhijing , Gao Peng , Lau Yui‐yip
Published: July 2019

Most scientific attention on port studies centers on deep sea ports, especially container ports. In this paper, in contrast, attention is focused on the spatial–temporal development of inland waterway ports on the Midstream Yangtze River from 2001 to 2013. The aim of this study is to assess two relevant and complementary questions of the hinterland evolution: its geographical extent and the coordination relationship with the inland port. To conduct the study, it was necessary to first identify the boundaries of the ports' hinterlands within the given timeframe. Then, the coupling coordination degree model was introduced to explore the underlying relationship between the port service and hinterland economy. Furthermore, to better depict the intricate economic characteristics of the hinterland, the development stage theory was applied in the models. The results highlight the emergence of a discontinuous hinterland at Wuhan Port and its reinforcement of primacy with respect to fierce hinterland rivalry. It also demonstrates that an interplay between major ports and their corresponding hinterlands evolves from the transitional stage, characterized by lagging port service, to the multi‐stage, wherein the supply of ports partly outstrips hinterland demand.
Clinical efficacy of a new cetylpyridinium chloride‐hyaluronic acid–based mouthrinse compared to chlorhexidine and placebo mouthrinses—A 21‐day randomized clinical trial
Authors: Tadakamadla Santosh Kumar , Bharathwaj Venkata V. , Duraiswamy Prabu , Sforza Chiarella , Tartaglia Gianluca M.
Published: July 2019

Objective

To compare the effectiveness of a novel cetylpyridinium chloride (CPC)‐hyaluronic acid (HA)–based mouthrinse with chlorhexidine (CHX) and placebo mouthrinses in preventing plaque and gingivitis. The secondary outcomes were calculus, extrinsic stains, oral malodour and occurrence of adverse events.

Methods

A 21‐day randomized, double‐blind, three‐arm parallel study with random allocation of young dental students to any of the three mouthrinse groups. Thorough prophylaxis was done at baseline followed by a baseline examination for oral malodour, extrinsic stains, calculus, gingivitis and plaque by a single examiner. All the subjects used the allocated mouthrinse twice daily for 21 days and were examined again at the end of the experimental period. They were also interviewed for adverse events. Change in the scores of clinical indices was calculated and compared between the groups.

Results

A total of 75 subjects were included and completed the experiment. There was a significant difference for change in plaque index scores between the groups (P = .015); subjects in the placebo group experienced higher levels of plaque accumulation than the other groups. Teeth staining increased in the CHX (P < .001) and placebo groups (P = .002), but not in CPC‐HA users (P = .573). No significant differences were found between the three experimental groups for change in the gingival index (P = .08), calculus scores (P = .494), oral malodour (P = .870) and reporting of adverse events (P = .249).

Conclusions

CPC‐HA and CHX had similar effectiveness in preventing plaque accumulation, while no differences were observed between the mouthrinses for preventing gingivitis. Dental staining was caused by CHX and the placebo mouthrinses but not by CPC‐HA mouthrinse.
Potentially bioaccessible phenolics, antioxidant capacities and the colour of carrot, pumpkin and apple powders – effect of drying temperature and sample structure
Authors: Bochnak Justyna , Świeca Michał
Published: July 2019

The study aimed to examine carrot, pumpkin and apple powders produced by hot‐air‐drying (50, 60, 70 °C) of samples with different levels of fragmentation (cut, grated, blended). The drying temperatures and sample structure were shown to be important determinants of the quality of the powders. The best colour stability of carrot, pumpkin and apple was found for the grated sample dried at 70 °C, the blended sample dried at 70 °C and the blended sample dried at 70 °C, respectively. The highest antiradical capacity and reducing power were found for powders obtained after drying the cut samples at 70 °C. Total phenolics and free radical quenchers were well bioaccessible in vitro. In turn, the reducing power was markedly reduced after drying at 50 °C. The analysed powders are a valuable source of concentrated bioactive ingredients, which predisposes them to serve as functional food components.
Responses to bullying among individuals with intellectual and developmental disabilities: Support needs and self‐determination
Authors: Griffin Megan M. , Fisher Marisa H. , Lane Laurel A. , Morin Lindsay
Published: July 2019

Background

Compared to the general population, individuals with intellectual and developmental disabilities (IDD) more often experience bullying and its negative social and emotional impacts. Prior studies explored bullying of individuals with IDD primarily through investigations of the perspectives of others and the negative impacts of bullying. The current study examined how individuals with IDD describe their responses to experiences of bullying, with a focus on whether responses included component skills of self‐determination.

Method

Eighteen adults with IDD (50% female) aged 18–63 years were interviewed about their experiences with bullying. Interviews were analysed to determine responses to bullying and the degree to which their responses demonstrated self‐determination.

Results

Data analysis revealed two primary themes, outside support and self‐determination, with additional subthemes.

Conclusions

Findings provide a more nuanced description of the ways in which individuals with IDD respond to bullying, including the demonstration of self‐determination skills. Implications for research and practice are discussed.
Motivational and cognitive benefits of training in immersive virtual reality based on multiple assessments
Authors: Makransky Guido , Borre‐Gude Stefan , Mayer Richard E.
Published: July 2019

The main objective of this study was to examine the effectiveness of immersive virtual reality (VR) as a medium for delivering laboratory safety training. We specifically compare an immersive VR simulation, a desktop VR simulation, and a conventional safety manual. The sample included 105 first year undergraduate engineering students (56 females).  We include five types of learning outcomes including post‐test enjoyment ratings; pre‐ to post‐test changes in intrinsic motivation and self‐efficacy; a post‐test multiple choice retention test; and two behavioral transfer tests. Results indicated that the groups did not differ on the immediate retention test, suggesting that all three media were equivalent in conveying the basic knowledge. However, significant differences were observed favoring the immersive VR group compared to the text group on the two transfer tests involving the solving problems in a physical lab setting (d = 0.54, d = 0.57), as well as enjoyment (d = 1.44) and increases in intrinsic motivation (d = 0.69) and self‐efficacy (d = 0.60). The desktop VR group scored significantly higher than the text group on one transfer test (d = 0.63) but not the other (d= 0.11), as well as enjoyment (d =1.11) and intrinsic motivation (d =0.83).
Long non‐coding RNA LINC01535 promotes cervical cancer progression via targeting the miR‐214/EZH2 feedback loop
Authors: Song Hongjuan , Liu Yuan , Jin Xin , Liu Yang , Yang Yanling , Li Lei , Wang Xuan , Li Guilin
Published: July 2019

Long non‐coding RNAs (lncRNAs) have shown critical roles in multiple cancers via competitively binding common microRNAs. miR‐214 has been proved to play tumour suppressive roles in various cancers, including cervical cancer. In this study, we identified that lncRNA LINC01535 physically binds miR‐214, relieves the repressive roles of miR‐214 on its target EZH2, and therefore up‐regulates EZH2 protein expression. Intriguingly, we also found that EZH2 directly represses the expression of miR‐214. Thus, miR‐214 and EZH2 form double negative regulatory loop. Through up‐regulating EZH2, LINC01535 further represses miR‐214 expression. Functional experiments showed that enhanced expression of LINC01535 promotes cervical cancer cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Reciprocally, LINC01535 knockdown suppresses cervical cancer cell growth, migration and invasion. Activation of the miR‐214/EZH2 regulatory loop by overexpression of miR‐214 or silencing of EZH2 reverses the roles of LINC01535 in promoting cervical canc`er cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Clinically, LINC01535 is significantly up‐regulated in cervical cancer tissues and correlated with advanced clinical stage and poor prognosis. Moreover, the expression of LINC01535 is reversely associated with the expression of miR‐214 and positively associated with the expression of EZH2 in cervical cancer tissues. In conclusion, this study reveals that LINC01535 promotes cervical cancer progression via repressing the miR‐214/EZH2 regulatory loop.
miR‐516a‐3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway
Authors: Chi Yanyan , Wang Feng , Zhang Tengfei , Xu Han , Zhang Yana , Shan Zhengzheng , Wu Shaoxuan , Fan Qingxia , Sun Yan
Published: July 2019

miR‐516a‐3p has been reported to play a suppressive role in several types of human tumours. However, the expression level, biological function and fundamental mechanisms of miR‐516a‐3p in breast cancer remain unclear. In the present study, we found that miR‐516a‐3p expression was down‐regulated and Pygopus2 (Pygo2) expression was up‐regulated in human breast cancer tissues and cells. Through analysing the clinicopathological characteristics, we demonstrated that low miR‐516a‐3p expression or positive Pygo2 expression was a predictor of poor prognosis for patients with breast cancer. The results of a dual luciferase reporter assay and Western blot analysis indicated that Pygo2 was a target gene of miR‐516a‐3p. Moreover, overexpression of miR‐516a‐3p inhibited cell growth, migration and invasion as well as epithelial‐mesenchymal transition (EMT) of breast cancer cells, whereas reduced miR‐516a‐3p expression promoted breast cancer cell growth, migration, invasion and EMT. Furthermore, we showed that miR‐516a‐3p suppressed cell proliferation, metastasis and EMT of breast cancer cells by inhibiting Pygo2 expression. We confirmed that miR‐516a‐3p exerted an anti‐tumour effect by inhibiting the activation of the Wnt/β‐catenin pathway. Finally, xenograft tumour models were used to show that miR‐516a‐3p inhibited breast cancer cell growth and EMT via suppressing the Pygo2/Wnt signalling pathway. Taken together, these results show that miR‐516a‐3p inhibits breast cancer cell growth, metastasis and EMT by blocking the Pygo2/ Wnt/β‐catenin pathway.
Potential competition and quality disclosure
Authors: Oh Frederick Dongchuhl , Park Junghum
Published: July 2019

This study presents a model of quality disclosure in which an incumbent, through its quality and disclosure choices, influences the potential that a new entrant enters the market. In this regard, we consider a sequential framework in which the incumbent chooses its quality and decides whether to disclose it to the market; subsequently, the entrant makes the same decisions, if it enters the market. We show that the potential competition can create strategic incentives for the incumbent to choose nondisclosure, because the availability of information about the incumbent's quality promotes entry by enhancing the entrant's expected profit from the market. In addition, an analysis of the effects of mandatory disclosure laws suggests that they can be effective in encouraging new market entrants and in improving the product quality of established firms.
Aspirin up‐regulates suppressor of cytokine signaling 3 in glial cells via PPARα
Authors: Chakrabarti Sudipta , Roy Avik , Prorok Tim , Patel Dhruv , Dasarathi Sridevi , Pahan Kalipada
Published: July 2019

Neuroinflammation is being recognized as a hallmark of different neurodegenerative disorders, including Alzheimer’s disease. Suppressor of cytokine signaling 3 (SOCS3) is an anti‐inflammatory molecule, which is known to inhibit cytokine signaling and inflammatory gene expression in different cells. However, the pathways by which SOCS3 could be up‐regulated in brain cells are poorly understood. Aspirin is a widely available pain reliever that is showing promise beyond its known pain‐relieving capacity. This study underlines the importance of aspirin in upregulating SOCS3 in astrocytes and microglia. Aspirin increased the expression of Socs3 mRNA and protein in mouse astrocytes and BV‐2 microglial cells in both a time‐ and dose‐dependent manner. While investigating the mechanism, we found that Socs3 gene promoter harbors peroxisome proliferator response element and that aspirin up‐regulated SOCS3 in astrocytes isolated from PPARβ (−/−), but not PPARα (−/−), mice. Accordingly, aspirin increased SOCS3 in vivo in the cortex of wild type and PPARβ (−/−), but not PPARα (−/−), mice. Similarly, aspirin treatment increased astroglial and microglial SOCS3 in the cortex of FAD5X, but not FAD5X/PPARα (−/−), mice. Finally, recruitment of PPARα by aspirin to the proximal, but not distal, peroxisome proliferator response element of the Socs3 promoter suggests that aspirin increases the transcription of Socs3 gene via PPARα. This study describes a novel property of aspirin in elevating SOCS3 in glial cells via PPARα and suggests that aspirin may be further considered for therapeutic application in neuroinflammatory and neurodegenerative disorders.

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Temporospatial effects of acyl‐ghrelin on activation of astrocytes after ischaemic brain injury
Authors: Dong Ruirui , Chen Man , Liu Jing , Kang Jihong , Zhu Shigong
Published: July 2019

The protective mechanisms of astrocyte signalling are based on the release of neurotrophic factors and the clearing of toxic substances in the early stages of cerebral ischaemia. However, astrocytes are also responsible for the detrimental effects that occur during the later stages of ischaemia, in which glial scars are formed, thereby impeding neural recovery. Acyl‐ghrelin has been found to be neuroprotective after stroke, although the influence of acyl‐ghrelin on astrocytes after ischaemic injury is yet to be clarified. In the present study, we used permanent middle cerebral arterial occlusion to establish a brain ischaemia model in vivo, as well as oxygen and glucose deprivation (OGD) to mimic ischaemic insults in vitro. We found that acyl‐ghrelin injection significantly increased the number of activated astrocytes in the peri‐infarct area at day 3 after brain ischaemia and decreased the number of activated astrocytes after day 9. Moreover, the expression of fibroblast growth factor 2 (FGF2) in the ischaemic hemisphere increased markedly after day 3, and i.c.v. injection of SU5402, an inhibitor of FGF2 signalling, abolished the suppression effects of acyl‐ghrelin on astrocyte activation in the peri‐infarct region during the later stages of ischaemia. The results from in vitro studies also showed the dual effect of acyl‐ghrelin on astrocyte viability. Acyl‐ghrelin increased the viability of uninjured astrocytes in an indirect way by stimulating the secretion from OGD‐injured astrocytes. It also inhibited the astrocyte viability in the presence of FGF2 in a dose‐dependent manner. Furthermore, the expression of acyl‐ghrelin receptors on astrocytes was increased after acyl‐ghrelin and FGF2 co‐treatment. In conclusion, acyl‐ghrelin promoted astrocyte activation in the early stages of ischaemia but suppressed the activation in later stages of ischaemic injury. These later effects were likely to be triggered by the increased expression of endogenous FGF2 after brain ischaemia.
Nursing Research Literature Production in Terms of the Scope of Country and Health Determinants: A Bibliometric Study
Authors: Kokol Peter , Železnik Danica , Završnik Jernej , Blažun Vošner Helena
Published: July 2019

Purpose

The aim of this paper was to present the results of the first study in which nursing research literature production was studied in the relation to country and health determinants.

Design

Bibliometric analysis was used.

Methods

The corpus of nursing publications was harvested from the Scopus indexing and abstracting database. Using research articles' metadata (funding acknowledgments, publication years, and author affiliations), we analyzed global trends in the nursing research literature production of funded and nonfunded publications. Next, we performed a regression analysis and correlation analysis relating nursing research productivity to health and country determinants.

Findings

The search resulted in 118,870 papers, among which 22.0% were funded (24.7% for G8 countries). Nursing literature production is exhibiting a positive trend. The United States is by far the most productive country in terms of funded and nonfunded literature production, although it is ranked only ninth in per capita production, for which Sweden is the most productive country regarding funded papers. The study also revealed that gross domestic product, human development factor, and gross national income were related to nursing research literature productivity.

Conclusions

The positive trend in nursing research literature production (both funded and nonfunded) reveals a growth in nursing research funding. Regionally centered research literature production shows that the more developed and “rich” countries produce the majority of publications. A positive correlation is evident between country determinants and research literature production, as is a positive correlation between per capita literature research production and well‐being and health determinants.

Clinical Relevance

Substantial growth in terms of nursing research literature production and research funding has been identified. While a limited amount of research in this area exists, this study revealed some interesting relations between nursing literature production and country and health determinants, which might motivate nursing researchers to pursue more intensive research and funders to support further growth of nursing research funding.
Identification of the retrotalar pulley of the Flexor Hallucis Longus tendon
Authors: Tzioupis Chris , Oliveto Anthony , Grabherr Silke , Vallotton Jacques , Riederer Beat M.
Published: July 2019

Functional Hallux Limitus is the expression of the gliding restraint of the Flexor Hallucis Longus (Fhl) tendon, resulting in several painful syndromes. This impingement is located along the tract of the Fhl tendon at the level of its retrotalar tunnel sealed posteriorly by a fibrous pulley. This pulley, although poorly anatomically characterized, has been arthroscopically proven that its presence or resection plays a pivotal clinical role in the biomechanics of the lower leg, being the main restraint to the physiological movement of the Fhl tendon. The aim of our study was to identify and characterize this anatomical structure. Eleven cadaveric lower legs were initially assessed by computer tomography (CT) imaging, subsequently plastinated, dissected and histologically evaluated by use of Mayer's and Hematoxylin stain. We have shown that the retrotalar pulley of the Fhl shares the same histological characteristics with the retinaculum of the long fibularis muscle and the retinaculum of flexor digitorum muscle, thus it constitutes a different entity than the adjacent formations.
Accumulation by and without dispossession: Rural land use, land expropriation, and livelihood implications in China
Authors: Zhan Shaohua
Published: July 2019

Land expropriation and peasant resistance in China have been widely noted, but the many cases in which peasants consent to give up land have drawn less attention. This paper conceptualizes and examines an alternative development practice: accumulation without dispossession (AWD), a concept first developed by Gillian Hart and Giovanni Arrighi. AWD may arise if accumulation takes place without (completely) depriving rural producers of the right to assets and benefits. The paper examines multiple forms of AWD and makes two main arguments. First, land expropriation does not necessarily lead to dispossession if peasants are compensated with valuable flats, commercial venues, and/or secure jobs. Due to its positive effects on social equality and livelihood security, AWD may offer an alternative vision in the era of neoliberal dispossession. Second, the outcome of land expropriation in China has varied substantially across space and time. In general, there has been a shift away from AWD in the 1980s following the neoliberal reform in the 1990s, but in the recent decade, there has been some movement back towards AWD due to peasant protests, though only to a limited degree. Nevertheless, the majority of peasants losing land have not received compensation sufficient to sustain a secure livelihood.
Capitalist development in hostile conjunctures: War, dispossession, and class formation in Turkey
Authors: Karatasli Sahan Savas , Kumral Sefika
Published: July 2019

This article analyses how periods of geopolitical conflict and violence have affected the development of capitalism and class formation in Turkey. We argue that all major episodes of conflict, violence and war—from forced displacement and ethnic cleansing of the non‐Muslims in the late 19th and the early 20th century, to Kurdish secessionist warfare in the 1990s and the Syrian Civil War—have become major historical turning points in the development of historical capitalism in Turkey. These “hostile conjunctures” transformed capitalism through their direct and indirect effects on dispossession, class formation, and capital accumulation. Although each of these conflicts produced a violent dispossession process, none of them resembled the rural dispossession process in England. To make sense of Turkey's experience, we turn our attention to what we call the “Castilian/Spanish road,” and what Lenin called the “Junker/Prussian road” and the “farmers/American road.” Our analysis shows that these differential paths of dispossession, class formation, and capital accumulation have produced highly variegated rather than uniform outcomes. We conclude that we are living in a new “hostile conjuncture,” which is pregnant to a major structural crisis and is generating the preconditions of another historical transformation in the way capitalism operates.
A new strategy for taste masking on bitter drug by other combined drug in fixed-dose combination: bitterness of Amlodipine besylate could be masked efficiently by Valsartan
Authors: Kojima Honami , Nakamura Saki , Haraguchi Tamami , Yoshida Miyako , Habara Masaaki , Ikezaki Hidekazu , Uchida Takahiro
Published: July 2019

Objectives

The aim of this study was to evaluate the bitterness of amlodipine besylate (AML) combined with other five antihypertensive drugs: alacepril, benazepril, hydrochlorothiazide, telmisartan (TEL) and valsartan (VAL), which have possibility of usage as a fixed-dose combination (FDC) drugs.

Methods

The bitterness of individual six drugs and AML combined with each of the five drugs was evaluated using taste sensor SA402B (Intelligent Sensor Technology Inc.). AML combined with TEL or VAL was evaluated by taste sensor and human gustatory sensation tests. The interaction between AML with TEL or VAL was evaluated by 1H-NMR.

Key findings

The bitterness of AML was significantly decreased by addition of VAL, whereas it remained unchanged by the addition of TEL in taste sensor and human gustatory sensation test. In the 1H-NMR spectrum of AML with VAL, signal shifts of protons in AML were observed compared to that in AML alone. On the other hand, in the 1H-NMR spectrum of AML with TEL, signal shifts of protons in AML were not observed.

Conclusions

It was suggested that when VAL was mixed with AML, the electrostatic interactions between positive charged amino group of AML and negative charged tetrazole group of VAL were caused, and thereby led the suppression the bitterness of AML.
Association of A‐FABP gene polymorphism and mRNA expression with intramuscular fat content (IMF) in Baicheng‐You chicken
Authors: Wang Yong , Liu Wenqiang , Hang Chao , Du Yiqiang , Chen Ying , Xing Jinming , Gao Jun , Qiu Dexin
Published: July 2019

This study aims to assess the association of polymorphisms and mRNA expression of adipocyte‐type fatty acid‐binding protein (A‐FABP) with intramuscular fat (IMF) in the breast muscle (BM) and leg muscle (LM) of Baicheng‐You chickens (BYCs). A total of 180 chickens, including sixty black Baicheng‐You chickens (BBYCs), sixty silky Baicheng‐You chickens (SBYCs) and sixty white Baicheng‐You chickens (WBYCs), were reared from 1 to 120 day. A polymerase chain reaction–single‐strand conformation polymorphism strategy (PCR‐SSCP) was used to detect the polymorphism of the A‐FABP gene in the first exon, and the C51T silent mutational site was found. The IMF content with the AA genotype was significantly higher than that with the AG genotype (p = 0.0473) in the LM of WBYC. Thus, this site could be taken as a molecular marker in selecting a higher IMF content of LM in WBYC. A‐FABP gene mRNA expression in the BM and LM of BYCs was detected, and a significant positive correlation was observed in the LM of WBYC. These findings provide fundamental data that might be useful in further study of the role of the A‐FABP gene in IMF content and fatty metabolism in chickens.
Genetic diversity of genotype 6 HCV infections in France: Epidemiology and consequences for treatment strategy
Authors: Pronier Charlotte , Fontaine Hélène , Dorival Céline , Carrat Fabrice , Pol Stanislas , Thibault Vincent ,   the AFEF/ANRS Hepather study group
Published: July 2019

Genotype‐6 hepatitis C virus (GT6‐HCV) exhibits a high genetic diversity. GT6 prevalence, diversity and real‐life response to treatment were studied among 14 603 HCV mono‐infected patients from the French ANRS‐CO22‐Hepather cohort. NS3, NS5A and NS5B‐HCV genes were amplified and sequenced for all GT6‐infections identified in the database. Following phylogenic characterization, resistance‐associated substitution polymorphisms were identified. GT6‐infected patients (n = 36; 0.25%) did not differ from patients infected with other genotypes with regard to gender, age or liver fibrosis. GT6e was the most prevalent (27.8%), followed by 6a (22.2%), 6q (11.1%) and 6o (8.3%). Each subtype p and xc were found in two patients (5.6%) and subtypes f/h/r and t were each detected in one patient. Four strains (11.1%) clustered with unclassified reference sequences. Concordant genotype determination throughout NS3, NS5A and NS5B‐genes is consistent with lack of recombination within this genomic region. All, but three patients were born in Asia, Cambodia (44.4%), Vietnam (38.9%) or Laos (8.3%). GT6a were found in 42.8% of Vietnamese and 6e in 37.5% of Cambodian. GT6q, 6p and 6r were only found in Cambodian patients. Resistance‐associated polymorphisms for each DAA classes were identified in baseline sequences. Twenty‐seven patients were treated with sofosbuvir‐based combinations and 3 with glecaprevir/pibrentasvir. All treated patients, whether naïve or previously treated, achieved a sustained viral response. In conclusion, GT6‐infections are uncommon in France and their genetic diversity likely reflects infection within the country of origin. Despite residue variability at DAA resistance‐associated positions, sustained viral response was obtained in all treated patients.
The ECHO model proved to be a useful tool to increase clinicians' self‐effectiveness for care of patients with Hepatitis C in Argentina
Authors: Mendizabal Manuel , Ridruejo Ezequiel , Ceballos Susana , Sixto Marcela , Billordo Ariel , Gadea Claudia , Mengarelli Silvia , Alonso Cristina , Palazzo Ana , De María Luis , Bruno Andrés , Perez Daniela , Piñero Federico , Deltrozzo Verónica , Mendoza Carlos , Figueroa Sebastián , Manero Estela , Villa Marina , Barreyro Fernando , Moreno Valeria , Vilar José , Murga Dolores , Fernandez Marcelo , O´Flaherty Martin , Arora Sanjeev , Silva Marcelo ,   the Latin American Liver Research, Educational, Awareness Network (LALREAN)
Published: July 2019

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community‐based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct‐acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0‐18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4‐96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7‐98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI −0.24‐0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.
Autism as a Form of Life: Wittgenstein and the Psychological Coherence of Autism
Authors: Chapman Robert
Published: July 2019

Autism is often taken to be a specific kind of mind. The dominant neuro‐cognitivist approach explains this via static processing traits framed in terms of hyper‐systemising and hypo‐empathising. By contrast, Wittgenstein‐inspired commentators argue that the coherence of autism arises relationally, from intersubjective disruption that hinders access to a shared world of linguistic meaning. This paper argues that both camps are unduly reductionistic and conflict with emerging evidence, due in part to unjustifiably assuming a deficit‐based framing of autism. It then develops a new Wittgensteinian account—autism as a different form of life—which avoids these issues. Rather than autistic systemising being the basis of autistic cognition, it is taken to be a reaction to pre‐epistemic and semantic anxieties that come with developing as a minority within a different form of life. This re‐framing can provide a coherent account of the autistic mind, and has significant conceptual, practical, and ethical implications.
Freedom as Non‐Domination and Widespread Prejudice
Authors: Costa M. Victoria
Published: July 2019

This paper offers an answer to an objection to Phillip Pettit’s neo‐republican account of freedom as non‐domination raised by Sharon Krause. The objection is that widespread prejudice, such as systemic racism or sexism, generates significant obstacles to individuals’ free agency but that neo‐republicanism fails to explain why these obstacles reduce freedom. This is because neo‐republicanism defines domination in terms of the capacity for arbitrary interference, but many prejudiced actions do not involve physical coercion, threats, or any other behavior typically described as types of interference. The paper discusses three strategies to account for the impact of widespread prejudice on the domination of groups. It argues that the most plausible strategy redefines domination in terms of behavior that is prima facie wrong and lacks appropriate checks. Such behavior includes interference but also includes prejudiced actions, such as failing to select the most qualified candidate for a job.
A barley stripe mosaic virus‐based guide RNA delivery system for targeted mutagenesis in wheat and maize
Authors: Hu Jiacheng , Li Shaoya , Li Zhaolei , Li Huiyuan , Song Weibin , Zhao Haiming , Lai Jinsheng , Xia Lanqin , Li Dawei , Zhang Yongliang
Published: July 2019

Plant RNA virus‐based guide RNA (gRNA) delivery has substantial advantages compared to that of the conventional constitutive promoter‐driven expression due to the rapid and robust amplification of gRNAs during virus replication and movement. To date, virus‐induced genome editing tools have not been developed for wheat and maize. In this study, we engineered a barley stripe mosaic virus (BSMV)‐based gRNA delivery system for clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9‐mediated targeted mutagenesis in wheat and maize. BSMV‐based delivery of single gRNAs for targeted mutagenesis was first validated in Nicotiana benthamiana. To extend this work, we transformed wheat and maize with the Cas9 nuclease gene and selected the wheat TaGASR7 and maize ZmTMS5 genes as targets to assess the feasibility and efficiency of BSMV‐mediated mutagenesis. Positive targeted mutagenesis of the TaGASR7 and ZmTMS5 genes was achieved for wheat and maize with efficiencies of up to 78% and 48%. Our results provide a useful tool for fast and efficient delivery of gRNAs into economically important crops.