bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological characterization of SAGE‐718, a novel positive allosteric modulator of N‐methyl‐d‐aspartate receptors
Authors: Beckley Jacob T. , Aman Teresa K. , Ackley Michael A. , Kazdoba Tatiana M. , Lewis Michael C. , Smith Anne C. , Farley Brandon J. , Dai Jing , Deats Wayne , Hoffmann Ethan , Robichaud Albert J. , Doherty James J. , Quirk Michael C. 
Published: September 2023

Background and PurposeSelect neuroactive steroids tune neural activity by modulating excitatory and inhibitory neurotransmission, including the endogenous cholesterol metabolite 24(S)‐hydroxycholesterol (24(S)‐HC), which is an N‐methyl‐d‐aspartate (NMDA) receptor positive allosteric modulator (PAM). NMDA receptor PAMs are potentially an effective pharmacotherapeutic strategy to treat conditions associated with NMDA receptor hypofunction.Experimental ApproachUsing in vitro and in vivo electrophysiological recording experiments and behavioural approaches, we evaluated the effect of SAGE‐718, a novel neuroactive steroid NMDA receptor PAM currently in clinical development for the treatment of cognitive impairment, on NMDA receptor function and endpoints that are altered by NMDA receptor hypoactivity and assessed its safety profile.Key ResultsSAGE‐718 potentiated GluN1/GluN2A‐D NMDA receptors with equipotency and increased NMDA receptor excitatory postsynaptic potential (EPSP) amplitude without affecting decay kinetics in striatal medium spiny neurons. SAGE‐718 increased the rate of unblock of the NMDA receptor open channel blocker ketamine on GluN1/GluN2A in vitro and accelerated the rate of return on the ketamine‐evoked increase in gamma frequency band power, as measured with electroencephalogram (EEG), suggesting that PAM activity is driven by increased channel open probability. SAGE‐718 ameliorated deficits due to NMDA receptor hypofunction, including social deficits induced by subchronic administration of phencyclidine, and behavioural and electrophysiological deficits from cholesterol and 24(S)‐HC depletion caused by 7‐dehydrocholesterol reductase inhibition. Finally, SAGE‐718 did not produce epileptiform activity in a seizure model or neurodegeneration following chronic dosing.Conclusions and ImplicationsThese findings provide strong evidence that SAGE‐718 is a neuroactive steroid NMDA receptor PAM with a mechanism that is well suited as a treatment for conditions associated with NMDA receptor hypofunction.
Debate: Better use of existing services, not more new pathways, is required for psychosis prevention in young people – Commentary on Salazar de Pablo and Arango: ‘Prevention of psychosis in adolescents: doesCAMHShave a role?’
Authors: Tiffin Paul A. , Northover Guy 
Published: September 2023

BackgroundThere has been much academic interest in ‘the clinical high‐risk state for psychosis’ (CHR‐P) concept. Whilst early intervention in psychosis (EIP) services have offered input to individuals meeting the CHR‐P criteria the involvement of CAMHS clinicians in supporting young people with ideational and perceptual disturbance has been more inconsistent and uncertain.MethodWe bring together our relevant lived experience, empirical evidence and clinical and research expertise to write this commentary.ResultsWe assert that the CHR‐P paradigm needs to be revised. This should reflect the low transition rates to psychosis and the prevalent general, impairing psychopathology in individuals meeting these criteria. Nevertheless, it is clear that both CAMHS and EIP services have potential roles in meeting the needs of young people affected by distressing ideational and perceptual disturbance.ConclusionsWe suggest that new care pathways and services are not required for young people affected by distressing psychosis‐like experiences. Rather more effective joint working between CAMHS, EIP, crisis services and other agencies could meet the needs of these young people more comprehensively.
Local heterogeneity of coral reef diversity and environmental stress provides opportunities for small‐scale conservation
Authors: McClanahan T. R. 
Published: September 2023

AbstractAimStrong social‐ecological trade‐offs between resource extraction and protection have created challenges for large, protected area management in natural resource‐dependent countries. Therefore, local governments and community conservation activities are becoming common and information about low environmental exposure and high biodiversity can provide for planning localized conservation activities.LocationThe western Indian Ocean.MethodsCoral reef sites were evaluated for local‐scale environmental and species richness to elucidate local patterns in spatial heterogeneity. Local coral and fish taxonomic richness and coral community susceptibility to stress were normalized to partially account for common and heterogenous disturbances to coral cover and fish biomass. Residuals of these three response variables were evaluated for local geographic patterns and specific relationships with 21 environmental variables using machine learning methods.ResultsRichness was highly variable at local geographies and had a double‐peaked shape with latitudes. Thirteen of the 21 examined variables were selected and indicated complex, spatially heterogeneous and weak cumulative predictive relationships with specific environmental and human influences. For example, each selected variable contributed 7% to 25% of the variance but with different relationships for the three responses. Coral fish richness and coral community susceptibility correlations were positive but weak and therefore produced different local spatial patterns. Nevertheless, these spatial patterns exhibited some coarse‐scale similarities indicating locations with shared positive community attributes and potential climate refugia. Shared richness variables included depth and wave energy, temperature variables of SST skewness, excess heat and rate of rise. Human influences of distance to shore, human populations and cities were also selected for richness and community susceptibility responses.Main ConclusionsPlanning to include local stress and richness patterns variability could contribute to species persistence. From these specific data, sites in the Pemba Channel between the Tanzanian mainland and Pemba Island, and northern Mozambique and Madagascar fit refugia characteristics.
Export‐platform foreign direct investment and trade policy uncertainty: Evidence from brexit
Authors: Tamberi Nicolò 
Published: September 2023

AbstractThis paper analyses the effect of trade policy uncertainty in a customs union on export‐platform foreign direct investment (FDI). First, I develop a partial equilibrium framework with heterogeneous firms based on the proximity–concentration trade‐off that involves trade policy uncertainty about trade costs inside a customs union. Second, I derive an empirical equation that I test by exploiting the 2016 Brexit referendum as a natural experiment and using data on manufacturing greenfield FDI projects. The results show that trade policy uncertainty impacted negatively the decisions of firms to invest in export‐platform activities in the UK following the Brexit referendum. Moreover, I find that extra‐EU manufacturing firms preferred EU countries as opposed to the UK for new investments after the 2016 referendum.
L‘évolution de l‘écart salarial entre hommes et femmes en Europe: le rôle du prix des compétences professionnelles
Authors: KAYA Ezgi 
Published: September 2023

RésuméDans cette analyse sur l'évolution de l'écart salarial entre hommes et femmes, l'autrice évalue le rôle de la variation du rendement salarial des compé‐tences professionnelles «cérébrales» (cognitives et interpersonnelles) et «physiques» (compétences motrices et force musculaire). Utilisant une série harmonisée sur six pays européens et des données comparables sur les États‐Unis, elle montre que l'effet du prix des compétences professionnelles est très variable selon les pays. Toutefois, dans tous les pays de l'échantillon, une proportion considérable de l'évo‐lution de l'écart de rémunération entre hommes et femmes reste inexpliquée par l'évolution de ce prix.
Tendencias de la brecha salarial de género en Europa. Análisis de factores asociados a los precios de las calificaciones
Authors: KAYA Ezgi 
Published: September 2023

ResumenEn este artículo se examinan las tendencias de la brecha salarial de género desde la perspectiva de la evolución de los rendimientos salariales de las competencias intelectuales (cognitivas e interpersonales) y físicas (fuerza y capa‐cidad motora). Tras analizar datos armonizados de seis países europeos y datos comparables de los Estados Unidos, se observan variaciones sustanciales en cuanto a la influencia de los precios de las calificaciones profesionales en la brecha salarial. Sin embargo, en todos los países de la muestra, una parte considerable de la variación de la disparidad salarial no puede explicarse por la evolución de los precios de las calificaciones.
Sindicatos y desigualdad de ingresos en una selección de países europeos
Authors: MONTEBELLO Roberta , SPITERI Jonathan , VON BROCKDORFF Philip 
Published: September 2023

ResumenLa relación entre la actividad sindical y la creciente desigualdad de ingresos observada en las economías avanzadas, a pesar de su ambigüedad teórica, se ha pasado por alto en los estudios empíricos. En este artículo se estima un modelo empírico para 26 países europeos entre 2005 y 2018, especificando la desigualdad de ingresos como una función de la tasa de densidad sindical, su valor al cuadrado y un conjunto de variables de control. El modelo se amplía con la inclusión de otras instituciones del mercado de trabajo para evaluar los efectos distributivos de la densidad sindical en toda la estructura institucional. Se observa una relación significativa y persistente, en forma de U invertida, entre densidad sindical y desigualdad de ingresos.
Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets
Authors: Liu Liang , Lu Lantian , Qiu Min , Han Ning , Dai Shijie , Shi Shuiping , He Shanshan , Zhang Jing , Yan Qingfeng , Chen Shuqing 
Published: September 2023

AbstractPathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co‐expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non‐fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.
Making Art Explicit: Knowledge, Reason and Art History in the Art and Design Curriculum
Authors: Walton Neil 
Published: September 2023

AbstractDifferent and competing conceptions of knowledge have recently been the focus of debate in education, especially art education. The cognitive science conception of knowledge as information processing and storage in long‐term memory is especially prominent in educational policy. By contrast, within writing that is directly about art education, discussion of knowledge has often been framed in negative, terms, as reductive, as entailing the imposition of rigid subject content and as antithetical to art. Taking issue with both these contrasting views, and using a non‐empirical, philosophical approach, this article puts forward a case for the centrality of knowledge and reasoning within the art and design curriculum. Specifically, the article draws on inferentialism, a theory that has not previously been applied to art education. The argument presented understands art as discursive and rational, as concept using and reason sensitive, as essentially a disjunctive set of historical‐social practices. Art education is then best thought of as a rational‐critical introduction to knowing those practices, as making explicit their proprieties, entailments and contradictions and the choices that are thereby made possible. This view emphasises learning in art and design as developing increasing levels of responsibility and commitment by integrating concepts in practice and theory.
A Green Manifesto for Art, Craft and Design Education
Authors: Hall Emese 
Published: September 2023

AbstractIn the challenging – and frightening – times in which we now live, education is seen as playing a key role in making change for the better. However, the Department for Education's (2022) strategy on education for sustainability and climate change, applicable to schools in England, is lacking in many areas and fails to address students’, teachers’, and teacher educators’ priorities. Crucially, the environment and climate emergency greatly concerns many children and young people and these issues should be addressed across the whole curriculum, not just in geography and science. Further, there needs to be more focus on emotions rather than facts, wellbeing rather than the economy. So, the question is: How can we ‘green’ art, craft and design education to ensure it is both effective and affective? Art can change the world because it is ‘homeless, endless, and edgeless’ – this sounds exciting but does not aid teachers in curriculum design. In this paper I will share an emergent manifesto for an environmentally responsible art, craft and design (ACD) curriculum…
Comparative interaction patterns of groups in an open network environment: The role of facilitators in collaborative learning
Authors: Zhang Wenmei , Wang Cixiao 
Published: September 2023

AbstractBackgroundCollaborative learning can effectively promote the development of higher‐order competencies, where learners collaborate via social interactions to explore and solve complex problems. It has been found that the effective occurrence of collaborative learning requires appropriate external guidance and support. In particular, collaborative interactions in open learning environments are more complex and difficult, which makes it important to provide dynamic interventions for learners according to different collaborative situations. However, the role of facilitators and the characteristics and mechanisms of their interventions have yet to be thoroughly investigated.ObjectivesThe study aims to uncover the characteristics and patterns of interaction among groups with different collaborative performance and facilitator performance in an open learning environment, and to explore the differentiated role of facilitators in this process.MethodGroups are categorised as high or low based on their collaborative performance and facilitator performance. This study used lag sequential analysis (LSA) and content analysis to explore the interaction patterns of groups with different collaborative performance and facilitator performance. Also, the different roles of facilitators were analysed by comparing the differences in interaction patterns of different collaborative performance groups.ResultsThe study found that groups with different collaborative performances and facilitator performances showed significant differences in interaction patterns, and the two had crossover effects. There is also variability in the role of facilitators in groups with different collaborative performance profiles. Patterns of transition between different layers of interaction can indicate the level of groups' collaborative engagement. Specific interaction patterns exist that are conducive to enhancing collaborative learning.ConclusionsThe results of the study pointed out that groups with different collaborative performance and facilitator performance showed different characteristics of interaction patterns. The role of the facilitator in online collaborative learning is characterised by compensatory and merit‐promoting. High‐quality online collaboration is the result of multiple factors, including learners and facilitators working together. This study has practical implications for the design of instructional interventions for group collaboration in online learning communities.
RALF22 promotes plant immunity and amplifies the Pep3 immune signal
Authors: He Yu‐Han , Chen Song‐Yu , Chen Xing‐Yan , Xu You‐Ping , Liang Yan , Cai Xin‐Zhong 
Published: September 2023

ABSTRACTRapid alkalinization factors (RALFs) in plants have been reported to dampen pathogen‐associated molecular pattern (PAMP)‐triggered immunity via suppressing PAMP‐induced complex formation between the pattern recognition receptor (PRR) and its co‐receptor BAK1. However, the direct and positive role of RALFs in plant immunity remains largely unknown. Herein, we report the direct and positive roles of a typical RALF, RALF22, in plant immunity. RALF22 alone directly elicited a variety of typical immune responses and triggered resistance against the devastating necrotrophic fungal pathogen Sclerotinia sclerotiorum in a FERONIA (FER)‐dependent manner. LORELEI (LRE)‐like glycosylphosphatidylinositol (GPI)‐anchored protein 1 (LLG1) and NADPH oxidase RBOHD were required for RALF22‐elicited reactive oxygen species (ROS) generation. The mutation of cysteines conserved in the C terminus of RALFs abolished, while the constitutive formation of two disulfide bridges between these cysteines promoted the RALF22‐elicited ROS production and resistance against S. sclerotiorum, demonstrating the requirement of these cysteines in the functions of RALF22 in plant immunity. Furthermore, RALF22 amplified the Pep3‐induced immune signal by dramatically increasing the abundance of PROPEP3 transcript and protein. Supply with RALF22 induced resistance against S. sclerotiorum in Brassica crop plants. Collectively, our results reveal that RALF22 triggers immune responses and augments the Pep3‐induced immune signal in a FER‐dependent manner, and exhibits the potential to be exploited as an immune elicitor in crop protection.
Management of Guillain–Barré syndrome in Bangladesh: Clinical practice, limitations and recommendations for low‐ and middle‐income countries
Authors: Papri Nowshin , Islam Zhahirul , Ara Gulshan , Saha Tamal , Leonhard Sonja E. , Endtz Hubert P. , Jacobs Bart C. , Mohammad Quazi D. 
Published: September 2023

AbstractBackground and AimsConsiderable variation in clinical practice for management of Guillain‐Barré syndrome (GBS) has been observed worldwide. Diagnosis and treatment are challenging in low‐ and middle‐income countries (LMIC) due to lack of facilities and treatment availability. We aimed to evaluate current clinical practice and limitations and to provide recommendation for GBS management in low‐resource settings.MethodsWe conducted an explanatory‐sequential mixed‐methods survey among neurologists and internists working in tertiary and secondary government hospitals in Bangladesh. There were two phases: (1) quantitative (cross‐sectional survey to evaluate clinical practice and limitations); (2) qualitative (key informant interview to explain certain clinical practice and provide recommendations for GBS management in LMIC). Data were analyzed by frequencies, χ2 test and thematic analysis.ResultsAmong 159 physicians (65 neurologists and 94 internists), 11% and 8% physicians used Brighton and NINDS criteria respectively to diagnose GBS. Specific treatment protocols of GBS were used by 12% physicians. Overcrowding of patients, inadequate diagnostic facilities, high costs of standard therapy, and inadequate logistics and trained personnel for intensive care unit and rehabilitation services were considered major challenges for GBS management. In qualitative part, respondents recommended regular training for the physicians, development of cost‐effective treatment strategies and appropriate patients' referral and management guideline considering existing limitations in health service delivery and socio‐economic status of the country.InterpretationCurrent study design and recommendations might be applied for other LMIC. Such data can assist policymakers to identify areas requiring urgent attention and take required action to improve GBS management in LMIC.
Explicating narrow and broad conceptualizations of environmental influences on personality
Authors: Weidmann Rebekka , Chopik William J. 
Published: September 2023

AbstractBackgroundA surge of studies aims to identify environmental factors that explain individual differences, personality stability, and personality development. This special issue builds on this large interest and solicited articles on broad and narrow environmental factors of personality.ObjectiveWe provide an overview of the motivations behind the special issue, review each of the articles, and present data on researchers' perceptions of environmental factors contributing to personality expression and development.MethodWe review 16 special issue articles, thematically grouped into seven topics—culture and race, genes and environment, geography and habitat, major/minor life events, social relationships, socioeconomic status and economic inequality, and work. We also present data on researchers' (N = 223) responses and ratings of environmental influences on personality expression and development.ResultsIn the open‐ended responses, the most important environmental influences were family, culture, peers, relationships, and trauma. Among the least important were weather, birth order, geography, climate, and shared environment. Nearly all the environmental influences featured in this special issue were considered at least somewhat important; however, there was considerable heterogeneity in how important researchers found each topic.ConclusionsThere is no perfect consensus among researchers as to which environmental factors contribute most to personality expression and development. We hope that there is a larger surge of studies on personality constructs beyond traits, that contextualize concepts within a cultural and historical framework and develop more stringent theories to hypothesize about the environmental influences on personality.