bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tripartite Inhibition of SRC-WNT-PKC Signalling Consolidates Human Naïve Pluripotency
Authors: Bayerl Jonathan , Ayyash Muneef , Shani Tom , Manor Yair , Gafni Ohad , Kalma Yael , Aguilera-Castrejon Alejandro , Zerbib Mirie , Amir Hadar , Sheban Daoud , Geula Shay , Mor Nofar , Weinberger Leehee , Krupalnik Vladislav , Oldak Bernardo , Livnat Nir , Tarazi Shadi , Tawil Shadi , Lasman Lior , Hanna Suhair , Novershtern Noa , Ben-Yosef Dalit , Viukov Sergey , Hanna Jacob H. 
Published: May 2020

AbstractDifferent conditions have been devised to isolate MEK/ERK signalling independent human naïve pluripotent stem cells (PSCs) that are distinct from conventional primed PSCs and better correspond to pre-implantation developmental stages. While the naïve conditions described thus far endow human PSCs with different extents of naivety features, isolating human pluripotent cells that retain characteristics of ground state pluripotency while maintaining differentiation potential and genetic integrity, remains a major challenge. Here we engineer reporter systems that allow functional screening for conditions that can endow both the molecular and functional features expected from human naive pluripotency. We establish that simultaneous inhibition of SRC-NFκB, WNT/ßCATENIN and PKC signalling pathways is essential for enabling expansion of teratoma competent fully naïve human PSCs in defined or xeno-free conditions. Divergent signalling and transcriptional requirements for maintaining naïve pluripotency were found between mouse and human. Finally, we establish alternative naïve conditions in which MEK/ERK inhibition is substituted with inhibition for NOTCH/RBPj signalling, which allow obtaining alternative human naïve PSCs with diminished risk for loss of imprinting and deleterious global DNA hypomethylation. Our findings set a framework for the signalling foundations of human naïve pluripotency and may advance its utilization in future translational applications.Highlights of key findingsCombined inhibition of SRC, WNT and PKC signaling consolidates human naïve pluripotencyStable expansion of DNA/RNA methylation-independent and TGF/ACTIVIN-independent human naïve PSCsOpposing roles for ACTIVIN and WNT/ßCATENIN signaling on mouse vs. human naive pluripotency2i and MEK/ERKi independent alternative human naïve PSC conditions via inhibiting NOTCH/RBPj signaling
Construction and application of a revised satisfaction index model for Chinese urban and rural residents basic medical insurance
Authors: Cheng Wenwei , Cheng Jin , Liu Xiaofang , Wu Yanyan , Sun Weichu , Yan Xiaofang , Peng Liai , Liu Xiaoli , Wang Qi , Luo Mingming , Sha Tingting , Shi Jingcheng , Yang Fang 
Published: May 2020

AbstractBackgroundQuality is the most important factor of satisfaction However, the existing URRBMI index model lacks the decomposition of the connotation of perceived quality and cannot provide a reference for quality improvement and satisfaction promotion.ObjectiveThis study aims to construct a Satisfaction Index Model for Chinese Urban and Rural Residents Basic Medical Insurance (SIM-URRBMI) with accurate and detailed measurement of perceived quality and give a feasible and scientific suggestion for URRBMI or insurance for other countries in the world.MethodsBased on the theoretical framework of The American Customer Satisfaction Index (ACSI), the connotation of perceived quality was refined by literature review and expert consultation to form a pool of alternative measurement variables. A three-stage randomized stratified cluster sampling was adopted to select the main decision makers for pupils’ URRBMI in 8 primary schools from Changsha City. Both Classic Test Theory (CTT) and Item Response Theory (IRT) were used for selection of the measurement variables. The model’s reliability and validity were tested using partial least square (PLS) related methods.ResultsA total of 1909 respondents who had insurance for their children were investigated with the initial questionnaire. The revised SIM-URRBMI consists of 11 latent variables and 28 measurement variables with good reliability and validity. Among the three explanatory variables of public satisfaction, perceived quality had the largest total effect (0.737). The variable with greatest effect among the five first-order latent variables on perceived quality was quality of the medical insurance policy (0.472).ConclusionsThe revised SIM-URRBMI consists of 11 latent variables and 28 measurement variables with good reliability and validity. It provides accurate assessment of perceived quality, which will greatly help performance improvement. Perceived quality is crucial to public satisfaction, especially, the most important aspects are policies regarding medical insurance reimbursement (basic coverage scope, coinsurance, deductible).
Visualizing the COVID-19 pandemic in Bangladesh using coxcombs: A tribute to Florence Nightingale
Authors: Khan Hasinur Rahaman , Howlader Tamanna 
Published: May 2020

AbstractFollowing detection of the first confirmed case of COVID-19 in early December 2019 in Wuhan, China, nearly six months have passed and almost every country in the world is battling against the COVID-19 war. The frontline warriors, namely the doctors, nurses and healthcare staff, have in many countries struggled to care for the sick under conditions of limited resources and protection and the threat of an overwhelmed healthcare system. It is during times such as this, that we draw strength and inspiration from Florence Nightingale - a passionate statistician, social reformer, feminist champion and a pioneer of modern nursing and data visualization. Nightingale’s famed Florence Night-ingle Diagram also known as “coxcomb”, which was created 150 years ago and used to display the causes of death in the British Army hospital barracks, demonstrated how data visualization techniques could be a powerful medium of communication and a force for change. This paper pays tribute to Nightingale’s work by using data from Bangladesh to show that the coxcomb graph is still relevant in the era of COVID-19. The coxcomb graphs that have been produced to display COVID-19 data have provided deeper insights into the trends and relative changes of variables over the course of the pandemic. The paper also describes codes that allow one to easily reproduce the graphs using the statistical programming language R.
Modelling the impact of Plasma Therapy and Immunotherapy for Recovery of COVID-19 Infected Individuals
Authors: Shah Nita H. , Suthar Ankush H. , Jayswal Ekta N. , Shukla Nehal , Shukla Jagdish 
Published: May 2020

AbstractSince the first case of COVID-19 was detected in Wuhan, China in December 2019, COVID-19 has become a pandemic causing a global economic and public health emergency. There is no known treatment or vaccine available for COVID-19 to date. Immunotherapy and plasma therapy has been used with satisfactory efficacy over the past two decades in many viral infections like SARS (Systemic Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), and H1N1. Limited data from China show clinical benefit, radiological resolution, reduction in viral loads, and improved survival. Our aim is to create a mathematical model for COVID-19 transmission and then apply various control parameters to see their effects on recovery from COVID-19 disease. We have formulated a system of non-linear ordinary differential equations, calculated basic reproduction R0, and applied five different controls (self-isolation, quarantine, herd immunity, immunotherapy, plasma therapy) to test the effectiveness of control strategy. Control optimality was checked by Lagrangian functions. Numerical simulations and bifurcation analyses were carried out. The study concludes that the COVID-19 outbreak can be controlled up to a significant level three weeks after applying all the control strategies together. These strategies lead to a reduction in hospitalization and a rise in recovery from infection. Immunotherapy is highly effective initially in hospitalized infected individuals however better results were seen in the long term with plasma therapy.
The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I
Authors: Zhang Yiwen , Zhang Junsong , Chen Yingshi , Luo Baohong , Yuan Yaochang , Huang Feng , Yang Tao , Yu Fei , Liu Jun , Liu Bingfen , Song Zheng , Chen Jingliang , Pan Ting , Zhang Xu , Li Yuzhuang , Li Rong , Huang Wenjing , Xiao Fei , Zhang Hui 
Published: May 2020

SummarySARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls1–4. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS5,6. Especially, it seems that SARS-CoV-2 undergoes vast replicationin vivowithout being effectively monitored by anti-viral immunity7. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs8. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo.
Structural basis of SARS-CoV-2 spike protein induced by ACE2
Authors: Meirson Tomer , Bomze David , Markel Gal 
Published: May 2020

AbstractMotivationThe recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD.ResultsHere, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.
N-type calcium channels control GABAergic transmission in brain areas related to fear and anxiety
Authors: Blazon Maxwell , LaCarubba Brianna , Bunda Alexandra , Czepiel Natalie , Mallat Shayna , Londrigan Laura , Andrade Arturo 
Published: May 2020

ABSTRACTPresynaptic N-type (Cav2.2) calcium channels are key for action potential evoked transmitter release in the peripheral and central nervous system. Previous studies have highlighted the functional relevance of N-type calcium channels at both the peripheral and central level. In the periphery, the N-type calcium channels regulate nociceptive and sympathetic responses. At the central level, N-type calcium channels have been linked to aggression, hyperlocomotion, and anxiety. Among the areas of the brain that are involved in anxiety are the basolateral amygdala, medial prefrontal cortex, and ventral hippocampus. These three areas share similar characteristics in their neuronal circuitry. Pyramidal projection neurons are under the inhibitory control of a wide array of interneurons including those that express the peptide cholecystokinin. This type of interneuron is well-known to rely on N-type calcium channels to release GABA in the hippocampus, however whether these channels control GABA release from cholecystokinin-expressing interneurons in the basolateral amygdala and medial prefrontal cortex is not known. Here using sophisticated mouse models to genetically label cholecystokinin-expressing interneurons, we found that N-type calcium channels control ~50% of GABA release in basolateral amygdala. By contrast, N-type calcium channels are functionally absent in synapses of cholecystokinin-expressing interneurons of medial prefrontal cortex. Our findings provide insights into the precise localization of N-type calcium channels in synapses of brain areas related to anxiety.
Variable Number Tandem Repeats mediate the expression of proximal genes
Authors: Bakhtiari Mehrdad , Park Jonghun , Ding Yuan-Chun , Shleizer-Burko Sharona , Neuhausen Susan L. , Halldórsson Bjarni V. , Stefánsson Kári , Gymrek Melissa , Bafna Vineet 
Published: May 2020

AbstractVariable Number Tandem Repeats (VNTRs) account for a significant amount of human genetic variation. VNTRs have been implicated in both Mendelian and Complex disorders, but are largely ignored by whole genome analysis pipelines due to the complexity of genotyping and the computational expense. We describe adVNTR-NN, a method that uses shallow neural networks for fast read recruitment. On 55X whole genome data, adVNTR-NN genotyped each VNTR in less than 18 cpu-seconds, while maintaining 100% accuracy on 76% of VNTRs.We used adVNTR-NN to genotype 10,264 VNTRs in 652 individuals from the GTEx project and associated VNTR length with gene expression in 46 tissues. We identified 163 ‘eVNTR’ loci that were significantly associated with gene expression. Of the 22 eVNTRs in blood where independent data was available, 21 (95%) were replicated in terms of significance and direction of association. 49% of the eVNTR loci showed a strong and likely causal impact on the expression of genes and 80% had maximum effect size at least 0.3. The impacted genes have important role in complex phenotypes including Alzheimer’s, obesity and familial cancers. Our results point to the importance of studying VNTRs for understanding the genetic basis of complex diseases.
The relationship between professional development and school principals’ leadership practices: the mediating role of self-efficacy
Authors: Gümüş Sedat , Bellibaş Mehmet Şükrü 
Published: May 2020

PurposeThere is an extensive body of contemporary educational literature concerning teachers' professional development (PD), but little attention has been paid to the PD of principals, despite their vital role in improving student learning outcomes. The available literature on principals' PD deals with content and quality while mostly ignoring whether and how PD activities have an impact on leadership practices. In our study, we wanted to examine the extent to which principals perform learning-centred leadership practices and whether and how their practices are influenced by the PD programmes they have engaged in during the past twelve months.Design/methodology/approachA total of 130 Turkish principals participated in the study. Using the SEM model, we examined the direct and indirect links between principals' PD and their self-perceived learning-centred leadership practices, with self-efficacy as the mediating variable.FindingsWe found a positive, statistically significant yet weak relationship between principals' PD and their leadership practices, with self-efficacy playing a considerable mediating role.Originality/valueWe argue that traditional types of PD activities can contribute to the leadership practices of principals, at least in countries where school principals are not adequately prepared for principalship positions. We suggest that such activities can contribute by providing newly appointed school principals with certain basic knowledge regarding effective leadership that many principals in developing countries are missing due to the lack of pre-service training. These activities can also strengthen principals' belief in their ability to overcome school problems and improve student learning. This, in turn, could motivate them to focus more on learning-centred leadership practices.
Autism spectrum disorders and stalking
Authors: Mercer Johanna E. , Allely Clare Sarah 
Published: May 2020

PurposeDespite an increasing number of studies that examine sexual offending behaviour in autism spectrum disorder (ASD) individuals, there has been a lack of research investigating stalking and ASD. This study aims to carry out a scoping review following PRISMA guidelines to identify studies which have been carried out exploring stalking behaviour in individuals with threshold or subthreshold ASD.Design/methodology/approachA total of five bibliographic databases were searched to identify studies which explored ASD in relation to stalking and harassment (including case studies as well as empirical studies).FindingsA total of five relevant articles were identified in the present review. One article contained a case study. In a short report, the authors discussed stalking and ASD. One paper explored ASD and stalking behaviour in employment settings and specific interventions that could be used in such environments. Another paper focused on stalking behaviour in those with ASD in school settings. The final paper examined stalking and social and romantic functioning in individuals with ASD. This final paper contained only the empirical study identified in this search.Practical implicationsThe studies identified in this review clearly highlight the need for intensive socio-sexual interventions to improve social interaction skills and romantic functioning in individuals with ASD. There is also a need for schools to provide sex education programs for individuals with ASD.Originality/valueTo the best of the authors’ knowledge, this is the first review looking at ASD and stalking.
A study of the influence of project managers’ signature strengths on project team resilience
Authors: Karlsen Jan Terje , Berg Morten Emil 
Published: May 2020

Purpose
This paper aims to study the influence of project managers’ signature strengths on project team resilience.

Design/methodology/approach
The authors performed a qualitative multiple case study design to explore the research question. Open-ended interviews, site visits, observations and documents were the data sources. The authors used character strengths and virtues within positive psychology as a theoretical framework in the data analysis.

Findings
The main finding of this study is that the project manager’s use of signature strengths influences the resilience of the project team. The cross-case analysis revealed four signature strengths – leadership, open-mindedness, persistence and hope – that influenced team resilience in all three studied cases.

Research limitations/implications
Future research should investigate other organizations, types of projects and countries so that the findings may be generalized.

Practical implications
This paper provides managers and teams with useful insights on signature strengths and team resilience. The findings stress the importance of managers being aware of their signature strengths and knowing how to use them. As the working situation today is often more complex, uncertain and difficult than ever, it is important to have resilient managers and teams.

Originality/value
This study contributes to increased knowledge on signature strengths and team resilience.
Greening of grey infrastructure should not be used as a Trojan horse to facilitate coastal development
Authors: Firth Louise B. , Airoldi Laura , Bulleri Fabio , Challinor Steve , Chee Su‐Yin , Evans Ally J. , Hanley Mick E. , Knights Antony M. , O'Shaughnessy Kathryn , Thompson Richard C. , Hawkins Stephen J. 
Published: May 2020

Abstract

Climate change and coastal urbanization are driving the replacement of natural habitats with artificial structures and reclaimed land globally. These novel habitats are often poor surrogates for natural habitats.

The application of integrated greening of grey infrastructure (IGGI) to artificial shorelines demonstrates how multifunctional structures can provide biodiversity benefits whilst simultaneously serving their primary engineering function. IGGI is being embraced globally, despite many knowledge gaps and limitations. It is a management tool to compensate anthropogenic impacts as part of the Mitigation Hierarchy. There is considerable scope for misuse and ‘greenwashing’ however, by making new developments appear more acceptable, thus facilitating the regulatory process.

We encourage researchers to exercise caution when reporting on small‐scale experimental trials. We advocate that greater attention is paid to when experiments ‘fail’ or yield unintended outcomes. We advise revisiting, repeating and expanding on experiments to test responses over broader spatio‐temporal scales to improve the evidence base.

Synthesis and applications. Where societal and economic demand makes development inevitable, particular attention should be paid to avoiding, minimizing and rehabilitating environmental impacts. Integrated greening of grey infrastructure (IGGI) should be implemented as partial compensation for environmental damage. Mutual benefits for both humans and nature can be achieved when IGGI is implemented retrospectively in previously developed or degraded environments. We caution, however, that any promise of net biodiversity gain from new developments should be scrutinized and any local ecological benefits set in the context of the wider environmental impacts. A ‘greened’ development will always impinge on natural systems, a reality that is much less recognized in the sea than on land.