bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do not keep it simple: recent advances in the generation of complex organoids
Authors: Wörsdörfer Philipp , I Takashi , Asahina Izumi , Sumita Yoshinori , Ergün Süleyman 
Published: May 2020

Abstract3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.
CDK7 inhibitors as anticancer drugs
Authors: Sava Georgina P. , Fan Hailing , Coombes R. Charles , Buluwela Lakjaya , Ali Simak 
Published: May 2020

AbstractCyclin-dependent kinase 7 (CDK7), along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs progression through the cell cycle via T-loop phosphorylation of cell cycle CDKs. CAK is also a component of the general transcription factor, TFIIH. CDK7-mediated phosphorylation of RNA polymerase II (Pol II) at active gene promoters permits transcription. Cell cycle dysregulation is an established hallmark of cancer, and aberrant control of transcriptional processes, through diverse mechanisms, is also common in many cancers. Furthermore, CDK7 levels are elevated in a number of cancer types and are associated with clinical outcomes, suggestive of greater dependence on CDK7 activity, compared with normal tissues. These findings identify CDK7 as a cancer therapeutic target, and several recent publications report selective CDK7 inhibitors (CDK7i) with activity against diverse cancer types. Preclinical studies have shown that CDK7i cause cell cycle arrest, apoptosis and repression of transcription, particularly of super-enhancer-associated genes in cancer, and have demonstrated their potential for overcoming resistance to cancer treatments. Moreover, combinations of CDK7i with other targeted cancer therapies, including BET inhibitors, BCL2 inhibitors and hormone therapies, have shown efficacy in model systems. Four CDK7i, ICEC0942 (CT7001), SY-1365, SY-5609 and LY3405105, have now progressed to Phase I/II clinical trials. Here we describe the work that has led to the development of selective CDK7i, the current status of the most advanced clinical candidates, and discuss their potential importance as cancer therapeutics, both as monotherapies and in combination settings. ClinicalTrials.gov Identifiers: NCT03363893; NCT03134638; NCT04247126; NCT03770494.
The effect of subacute poisoning with fenpropathrin on mice kidney function and the level of interleukin 1β and tumor necrosis factor α
Authors: Jaremek Maria , Nieradko-Iwanicka Barbara 
Published: May 2020

AbstractFenpropathrin (FEN) is a pyrethroid insecticide. Mammals can be exposed to these compounds with food and water as non-target organisms. Pyrethroids are classified into two types depending on chemical structure and neurotoxic effects. FEN has features of Type I and Type II pyrethroids. There is data that pyrethroids apart from neurotoxic properties, can be also nephrotoxic and immunotoxic. The aim of the study was to assess the influence of FEN on kidney function and concentration of proinflammatory cytokines: tumor necrosis factor alpha (TNFα) and interleukin 1 beta (IL-1β) in mice kidneys. Sixteen female mice were randomly divided into two groups: I—receiving saline and II—receiving FEN at the dose of 11.9 mg/kg ip for 28 consecutive days. On day 29 blood samples were obtained to measure serum creatinine concentration. The animals were killed, and kidneys were obtained in order to measure TNFα and interleukin IL-1β in mice kidneys with use of ELISA assay. The concentration of creatinine was (mean ± SD) in controls 0.2 ± 0.0 mg/dl in the group exposed to FEN 0.225 ± 0.046 mg/dl. TNFα concentration in the kidneys of controls was 6.154 ± 1.597 pg/ml and in the group intoxicated with FEN it was 6.318 ± 1.012 pg/ml. IL-1β concentration in the kidneys of controls was 4.67 ± 1.154 pg/ml while in the group intoxicated with FEN 27.983 ± 26.382 pg/ml (p < 0.05). In conclusion: FEN slightly affects kidney function and increases the concentration of proinflammatory IL-1β in mice kidneys, which supports the hypothesis about nephrotoxic and immunotoxic effect of this insecticide in non target organisms.
Culturally embedded schemata for false belief reasoning
Authors: Berio Leda 
Published: May 2020

AbstractI argue that both language acquisition and cultural and social factors contribute to the formation of schemata that facilitate false belief reasoning. While the proposal for an active role of language acquisition in this sense has been partially advanced by several voices in the mentalizing debate, I argue that other accounts addressing this issue present some shortcomings. Specifically, I analyze the existing proposals distinguishing between “structure-oriented” views (with the most relevant representative in de Villiers and de Villiers in Complements enable representation of the contents of false beliefs: the evolution of a theory of theory of mind. Language Acquisition, Foster-Cohen, 2009; de Villiers in Int Rev Gen Linguistics 117(11):1858–1878, 2007; de Villiers in Why language matters for theory of mind. Oxford University Press, New York, pp 186–219, 2005), that stress the role of language as a set of rules providing syntactic input and providing a representational format, and “cultural/social-oriented views”, that stress the role of social interaction (among others Nelson in Why language matters for theory of mind. Oxford University Press, Oxford, 2005; Hutto in Folk psychological narratives: the sociocultural basis of understanding reasons. Cambridge University Press, Cambridge, 2008b). Starting from the analysis of these views, I defend my own account of the role of language acquisition in aiding false belief reasoning. I argue that language acquisition plays a pivotal role in the formation of schemata used by pre-schoolers to pass the false belief task. I propose a specific learning mechanism for exploiting linguistic information that taps into specific cognitive abilities, thus making a very concrete suggestion about the role of linguistic input in specific cultural contexts for the development of false belief skills.
Development and Application of a Multiplex Marker Assay to Detect PVY Resistance Genes in Solanum tuberosum
Authors: Elison Gregory L. , Hall Darren G. , Novy Richard G. , Whitworth Jonathan L. 
Published: May 2020

AbstractPotato virus Y (PVY) is a major pathogen affecting potato production worldwide. Three independent genes (Ryadg,Rysto,and Rychc) conferring genetic resistance to all known strains of the virus are currently utilized by breeding programs to develop potato varieties containing extreme resistance to infection by PVY. These resistance genes are typically detected using primers specific for the generation of markers closely-linked to the resistance genes. In recent years there have been attempts to develop a multiplex PCR assay for all resistance genes, but all current published methods either omit at least one resistance gene or are unnecessarily complex and therefore difficult to incorporate successfully for marker-assisted selection. We have developed an assay which tests for the presence of all three sources of resistance in a single, easy to use PCR protocol. The multiplex PCR assay was applied to potato varieties, second-field year breeding germplasm, and a selection of test crosses having progeny segregating for multiple resistance genes to validate the methodology for use in marker-assisted selection in potato breeding programs.
Prefrontal Nectin3 Reduction Mediates Adolescent Stress-Induced Deficits of Social Memory, Spatial Working Memory, and Dendritic Structure in Mice
Authors: Wang Hong-Li , Li Ji-Tao , Wang Han , Sun Ya-Xin , Liu Rui , Wang Xiao-Dong , Su Yun-Ai , Si Tian-Mei 
Published: May 2020

AbstractChronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain (especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses, but the underlying molecular mechanisms remain unclear. Here, we investigated how synaptic cell adhesion molecules (e.g., nectin3) are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex (mPFC). Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77. One week later, the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory, simplified dendritic structure, and reduced spine density in the mPFC. Membrane localization of nectin3 was also altered, and was significantly correlated with behavioral performance. Furthermore, knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology. These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
Contribution of women’s fisheries substantial, but overlooked, in Timor-Leste
Authors: Tilley Alexander , Burgos Ariadna , Duarte Agustinha , dos Reis Lopes Joctan , Eriksson Hampus , Mills David 
Published: May 2020

AbstractA greater understanding of gendered roles in fisheries is necessary to value the often-hidden roles that women play in fisheries and households. We examine women’s contributions to household food and income using focus group discussions, market surveys, and landings data in six communities in Timor-Leste. Women were actively fishing more days per month than men. Gleaning was the most frequent activity and 100% of trips returned with catch for food and/or income. Mollusc and crab catches were common and exploitation appeared targeted on a dynamic reappraisal of changing food values and changing estimates of group needs. With as many as 80% of households in coastal areas involved in fishing, and at least 50% of women fishing, this highlights the current lack of women’s engagement as a critical gap in fisheries management approaches. The current androcentric dialogue limits social-ecological understanding of these systems and the potential for their effective stewardship.
Flexibility Grave – Partial Reproduction Focus and Closed System Fetishism in CJEU, Pelham
Authors: Senftleben Martin 
Published: May 2020

AbstractIn the ongoing discussion about the impact of fundamental rights on EU copyright law, thePelhamjudgment of the Court of Justice of the European Union (CJEU) has received much attention. However, the decision also raises important legal-doctrinal issues. The CJEU employs the harmonized right of reproduction as a vehicle to regulate adaptations of pre-existing source material. Moreover, the Court insists on a balancing of interests within the EU matrix of exclusive rights and limitations. The closed list of limitations in EU copyright law, however, can hardly be expected to offer sufficient breathing space for adaptation scenarios. As the Information Society Directive did not harmonize the right of adaptation, there was no need to include indispensable free adaptation rules that have evolved at the national level, such as the German “free use” doctrine. Instead of embracing national rules of equity and fairness to fill the gap, the CJEU is reluctant to borrow from the legal traditions of EU Member States and misses an important opportunity to provide guidance for the regulation of adaptations outside the sound sampling arena. After an introduction to the German “Metall auf Metall” saga that led to thePelhamdecision, the following analysis sheds light on these developments in EU copyright law and discusses problems arising from the approach taken by the CJEU.
Provenance-Aware Knowledge Representation: A Survey of Data Models and Contextualized Knowledge Graphs
Authors: Sikos Leslie F. , Philp Dean 
Published: May 2020

AbstractExpressing machine-interpretable statements in the form of subject-predicate-object triples is a well-established practice for capturing semantics of structured data. However, the standard used for representing these triples, RDF, inherently lacks the mechanism to attach provenance data, which would be crucial to make automatically generated and/or processed data authoritative. This paper is a critical review of data models, annotation frameworks, knowledge organization systems, serialization syntaxes, and algebras that enable provenance-aware RDF statements. The various approaches are assessed in terms of standard compliance, formal semantics, tuple type, vocabulary term usage, blank nodes, provenance granularity, and scalability. This can be used to advance existing solutions and help implementers to select the most suitable approach (or a combination of approaches) for their applications. Moreover, the analysis of the mechanisms and their limitations highlighted in this paper can serve as the basis for novel approaches in RDF-powered applications with increasing provenance needs.
Bildpräsenz
Authors: Grave Johannes 
Published: May 2020

ZusammenfassungIn vielen literarischen Texten umkreist Goethe problematische Effekte von Bildern und Bildpraktiken. Bilder können dazu einladen, das bildlich Dargestellte für einen Teil der Wirklichkeit zu halten, sie können Gegenstand fragwürdiger Projektionen werden oder aber dazu beitragen, die Wirklichkeit selbst bildhaft erstarren zu lassen. Diese Gefahren im Umgang mit Bildern sind nicht zuletzt auf deren spezifische temporale Verfasstheit zurückzuführen, insbesondere wenn die physische Präsenz eines Bildes genutzt wird, um Vergangenes oder Abwesendes zu vergegenwärtigen. Der Beitrag entfaltet diese Problemlage an verschiedenen exemplarischen Texten Goethes. Am Beispiel des Aufsatzes »Ruysdael als Dichter« skizziert er eine alternative Form des Umgangs mit Bildern, die nicht allein auf deren Präsenzeffekt setzt, sondern eine dem Bild eigene Temporalität im Prozess des Sehens und Reflektierens zur Geltung bringt.
Religiöse Identitäten und Vorurteil in Deutschland und der Schweiz – Konzeptionelle Überlegungen und empirische Befunde
Authors: Pickel Gert , Liedhegener Antonius , Jaeckel Yvonne , Odermatt Anastas , Yendell Alexander 
Published: May 2020

ZusammenfassungImmer wieder werden Bezüge zwischen Religion und Vorurteilen hergestellt. Zum einen dienen religiöse Gruppen als Ziel von Vorurteilen, zum anderen wird debattiert, inwieweit der Wahrheitsanspruch von Religionen religiöse Menschen für Vorurteile anfälliger macht. Im Artikel werden mithilfe des aktuellen KONID Survey 2019 beide Fragen empirisch und Ländervergleichend untersucht. Trotz einzelner Abweichungen in Ausprägungen und Bezügen von Vorurteilen, sind die Strukturen der Vorurteile, ihre Erklärung sowie ihre demokratischen Auswirkungen in Deutschland und der Schweiz sehr ähnlich. Religionsgemeinschaften und ihre Mitglieder geraten vor allem aufgrund von Bedrohungsängsten in der Bevölkerung, aber auch Verschwörungstheorien und autoritären Einstellungen in den Fokus von Vorurteilen. Dabei wirkt eine dogmatische, exklusivistisch gedachte und teilweise fundamentalistische religiöse Identität als Vorurteile befördernd, während eine liberale religiöse Identität Antisemitismus, antimuslimischen Rassismus, aber auch Antiziganismus und die Ablehnung von Nichtbinären Geschlechteridentitäten entgegenwirkt.
Trade policy in a “GVC World”: Multinational corporations and trade liberalization
Authors: Anderer Christina , Dür Andreas , Lechner Lisa 
Published: May 2020

AbstractThe globalization of production is changing the political economy of trade policymaking: Traditional supporters of free trade (exporters seeking market access in foreign countries) are joined by new actors (companies needing intermediates from abroad for their production processes) in their lobbying efforts for trade liberalization. Multinational corporations (MNCs) play a crucial role in this new alliance due to their strong involvement in international trade and endowment with resources that can be used to lobby policymakers. We derive an argument from these premises that leads to the expectation of variation in trade policy outcomes across industries depending on their degree of integration in a global network of multinational corporations. Disaggregated data on the level of tariffs and speed of tariff cuts in preferential trade agreements, international mergers and acquisitions at the firm level, and MNC imports of intermediates by sector allow us to test the argument. The findings support our theoretical expectations. The paper sheds light on the processes and outcomes of trade policymaking in a globalized economy by further developing an existing argument about GVCs and trade policy outcomes as well as expanding on it by adding data on international corporate connections.
Respiratory surveillance wards as a strategy to reduce nosocomial transmission of COVID-19 through early detection: The experience of a tertiary-care hospital in Singapore
Authors: Wee Liang En , Hsieh Jenny Yi Chen , Phua Ghee Chee , Tan Yuyang , Conceicao Edwin Philip , Wijaya Limin , Tan Thuan Tong , Tan Ban Hock 
Published: May 2020

AbstractObjectives:Patients with COVID-19 may present with respiratory syndromes indistinguishable from those caused by common viruses. Early isolation and containment is challenging. Although screening all patients with respiratory symptoms for COVID-19 has been recommended, the practicality of such an effort has yet to be assessed.Methods:Over a 6-week period during a SARS-CoV-2 outbreak, our institution introduced a “respiratory surveillance ward” (RSW) to segregate all patients with respiratory symptoms in designated areas, where appropriate personal protective equipment (PPE) could be utilized until SARS-CoV-2 testing was done. Patients could be transferred when SARS-CoV-2 tests were negative on 2 consecutive occasions, 24 hours apart.Results:Over the study period, 1,178 patients were admitted to the RSWs. The mean length-of-stay (LOS) was 1.89 days (SD, 1.23). Among confirmed cases of pneumonia admitted to the RSW, 5 of 310 patients (1.61%) tested positive for SARS-CoV-2. This finding was comparable to the pickup rate from our isolation ward. In total, 126 HCWs were potentially exposed to these cases; however, only 3 (2.38%) required quarantine because most used appropriate PPE. In addition, 13 inpatients overlapped with the index cases during their stay in the RSW; of these 13 exposed inpatients, 1 patient subsequently developed COVID-19 after exposure. No patient–HCW transmission was detected despite intensive surveillance.Conclusions:Our institution successfully utilized the strategy of an RSW over a 6-week period to contain a cluster of COVID-19 cases and to prevent patient–HCW transmission. However, this method was resource-intensive in terms of testing and bed capacity.
The COVID-19 infection control arms race
Authors: Rhee Chanu , Baker Meghan A. , Klompas Michael 
Published: May 2020

AbstractUS hospitals are engaged in an infection control arms race. Hospitals, specialties, and professional groups are spurring one another on to adopt progressively more aggressive measures in response to COVID-19 that often exceed federal and international standards. Examples include universal masking of providers and patients; decreasing thresholds to test asymptomatic patients; using face shields and N95 respirators regardless of symptoms and test results; novel additions to the list of aerosol-generating procedures; and more comprehensive personal protective equipment including hair, shoe, and leg covers. Here, we review the factors underlying this arms race, including fears about personal safety, ongoing uncertainty around how SARS-CoV-2 is transmitted, confusion about what constitutes an aerosol-generating procedure, increasing recognition of the importance of asymptomatic infection, and the limited accuracy of diagnostic tests. We consider the detrimental effects of a maximal infection control approach and the research studies that are needed to eventually de-escalate hospitals and to inform more evidence-based and measured strategies.
The effect of the National Birth Defects Intervention Project on the prevention of congenital disabilities among children in China: a natural experiment
Authors: Guo Chao , Zheng Xiaoying 
Published: May 2020

AbstractMost childhood disabilities are caused by congenital factors such as birth defects. The present study aims to evaluate the effect of periconceptional nutrition intervention on the prevention of congenital disability among Chinese children using the National Birth Defects Intervention Project as a natural experiment. We obtained individual-level data from the Second National Sample Survey on Disability, a nationally representative survey, and 110 365 children born between September 1999 and August 2003 were included for analysis. Difference-in-differences estimates of the project effects on congenital disability were captured by exploiting temporal variation in the timing of project exposure across four birth cohorts along with geographical variation in project category at the province level. The findings contribute to an emerging body of evidence showing that prenatal micronutrient intervention before and during early pregnancy could substantially reduce the risk of congenital disability in childhood (OR 0·73; 95 % CI 0·57, 0·94). The National Birth Defects Intervention Project improved the awareness of reproductive health and disability prevention in the population. It highlights the need for a potential policy change focusing on early-life health investment in China.