bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery and characterization of a first-in-field transcription factor BRN2 inhibitor for the treatment of neuroendocrine prostate cancer
Authors: Thaper Daksh , Munuganti Ravi , Aguda Adeleke , Kim Soojin , Ku Shengyu , Sivak Olena , Kumar Sahil , Vahid Sepideh , Ganguli Dwaipayan , Beltran Himisha , Morrissey Colm , Corey Eva , Zoubeidi Amina 
Published: May 2022

AbstractThe increased incidence of treatment-emergent neuroendocrine prostate cancer (NEPC) is particularly alarming as this diagnosis is associated with poor prognosis. Despite initial responses to platinum-based chemotherapy, relapses are common and there is no effective second line therapy for NEPC. We previously identified that neuronal transcription factor BRN2 (POU3F2) is a potent driver of neuroendocrine differentiation and an attractive target for NEPC. Utilizing a combination of in silico modeling and X-ray crystallography followed by structure-based lead optimization, we have developed the first potent, specific and orally bioavailable BRN2 inhibitor (B18-94), which inhibits the interaction between BRN2 and DNA. This loss of BRN2 on the chromatin drastically reduces its transcriptional output resulting in downregulation of several known targets in NEPC such as SOX2, ASCL1 and PEG10. Additionally, B18-94 reduces specifically cell proliferation specifically in multiple NEPC models with no effect on adenocarcinoma and other BRN2 negative prostate cancer models. Importantly, the consistency in the transcriptomic changes driven by B18-94 and or CRISPR/Cas9 mediated BRN2 knockout confirmed the on-target specificity, with both methods of BRN2 inhibition downregulating pathways involved in cellular plasticity and proliferation. Finally, we have demonstrated that B18-94, the first-in-field POU-domain transcription factor inhibitor, significantly reduced tumor growth in several NEPC xenograft models with no observable toxicity, suggesting potential for therapeutic intervention of NEPC.
Role of Rab5 early endosomes in regulatingDrosophilagut antibacterial response
Authors: Joshi Manish , Viallat-Lieutaud Annelise , Royet Julien 
Published: May 2022

AbstractInteractions between prokaryotes and eukaryotes require a dialogue between MAMPs and PRRs. InDrosophila, bacterial peptidoglycan is detected by PGRP receptors. While the components of the signaling cascades activated upon PGN/PGRP interactions are well characterized, little is known about the subcellular events that translate these early signaling steps into target gene transcription. Using aDrosophilaenteric infection model, we show that gut-associated bacteria can induce the formation of intracellular PGRP-LE aggregates which colocalized with the early endosome marker Rab5. Combining microscopic and RNA-seq analysis, we demonstrate that RNAi inactivation of the endocytosis pathway in theDrosophilagut affects the expression of essential regulators of the NF-κB response leading not only to a disruption of the immune response locally in the gut but also at the systemic level. This work sheds new light on the involvement of the endocytosis pathway in the control of the gut response to intestinal bacterial infectionGraphical abstract
Expression of GDNF Receptors Within Nucleus Ambiguus During Rat Development
Authors: Blount Quinton , Hernandez-Morato Ignacio , Moayedi Yalda , Pitman Michael J 
Published: May 2022

ABSTRACTObjectiveUpregulation of GDNF and its receptors is observed during laryngeal reinnervation after nerve injury. In contrast, little is known regarding the expression of GDNF receptors in the formation of the nucleus ambiguus (NA) and its innervation of the larynx during embryogenesis. Differences may suggest therapeutic targets after nerve injury.Study DesignLaboratory experiment.MethodsRat brainstems at E14, E16, E18, E20, adult (4 animals/timepoint) were sectioned and stained for GDNF receptors: GFRα-1, GFRα-2, GFRα-3, and Ret. Islet1 and ChAT were used as markers for motoneuron cell bodies. Sections were observed using Zeiss Axio Imager M2 Microscope and quantified using Image J.ResultsExpression of all four GDNF receptors was identified within the nucleus ambiguus, as well as hypoglossal and facial nuclei of the adult rat brainstem. During rat development, GFRα-3 and Ret exhibited upregulation within the nucleus ambiguus at E14 whereas GFRα-1 began showing upregulation at E20. GFRα-2 exhibited no upregulation at embryonic timepoints. Conclusion: Upregulation of the GDNF receptors within the nucleus ambiguus occur after laryngeal muscles innervation during development and may associated with maturation and maintenance of the neuromuscular synapses of the larynx before and after birth. No differences among ambiguus, hypoglossal, and facial nuclei was observed.
The effect of motor-induced shaft dynamics on microtubule stability and length
Authors: Schaer Joël , Andreu-Carbó Mireia , Kruse Karsten , Aumeier Charlotte 
Published: May 2022

ABSTRACTControl of microtubule abundance, stability, and length is crucial to regulate intracellular transport as well as cell polarity and division. How microtubule stability depends on tubulin addition or removal at the dynamic ends is well studied. However, microtubule rescue, the event when a microtubule switches from shrinking to growing, occurs at tubulin exchange sites along the shaft. Molecular motors have recently been shown to promote such exchanges. Using a stochastic theoretical description, we study how microtubule stability and length depends on motor-induced tubulin exchange and thus rescue. Our theoretical description matches our in vitro experiments on microtubule dynamics in presence of kinesin-1 molecular motors. Although the average microtubule dynamics can be captured by an effective rescue rate, the dynamics of individual microtubules differs dramatically when rescue occurs only at exchange sites. Furthermore, we study in detail a transition from bounded to unbounded microtubule growth. Our results provide novel insights into how molecular motors imprint information of microtubule stability on the microtubule network.SIGNIFICANCEThe microtubule network is essential for vital cellular processes like the organization of intracellular transport and division. Although microtubule assembly occurs at its tips, it has recently been reported that tubulin is exchanged along the microtubule shaft. Tubulin exchange plays an essential role in regulating microtubule dynamics and can be induced by molecular motors. Here, we provide the first systematic study of the impact of shaft dynamics on the regulation of rescue events, where a microtubule switches from shrinking to growing. Our results illustrate how the usage of microtubules as tracks for intracellular transport regulates the microtubule network and thus offers a novel perspective on intracellular organization.
Asymptomatic SARS-CoV-2 infection by age: A systematic review and meta-analysis
Authors: Wang Bing , Andraweera Prabha , Elliott Salenna , Mohammed Hassen , Lassi Zohra , Twigger Ashley , Borgas Chloe , Gunasekera Shehani , Ladhani Shamez , Marshall Helen Siobhan 
Published: May 2022

AbstractObjectivesThis systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons by year of age.MethodsWe searched PubMed, Embase, medRxiv and Google Scholar on 10 September 2020 and 1 March 2021. We included studies conducted during January to October 2020, prior to routine vaccination against COVID-19. Since we expected the relationship between the asymptomatic proportion and age to be non-linear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age.ResultsA total of 38 studies were included in the meta-analysis. In total, 6556 out of 14850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14850, 95%CI 43.3%-45.0%). The asymptomatic proportion peaked in adolescents (36.2%, 95%CI 26.0%-46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95%CI 3.4%-12.7%).ConclusionsGiven the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.
Executive alumni and corporate social responsibility in China
Authors: Hu Yuanyuan , Fang Jiali 
Published: May 2022

PurposeThis study investigates whether corporate executives, who are university alumni, influence each other's firm corporate social responsibility (CSR) performance.Design/methodology/approachDrawing on social network theory, the authors hypothesise that a firm's CSR performance is positively associated with its peer firms' average CSR performance when the executives of the firm and its peer firms are university alumni. The study employs data from 1,685 listed firms and 4,906 executives who graduated from 585 different universities in China and runs multivariate regressions.FindingsThe results reveal a sizeable university peer influence on CSR performance. Such influence is even stronger for executives who graduated from elite universities (e.g. 985 or 211 universities), and universities or programmes that provide more opportunities for alumni reunions or networking (e.g. MBAs/EMBAs). Executives who are more influential in making firm decisions (e.g. CEOs/CFOs), as well as firms that are more likely to mimic the behaviour of others, also show higher degrees of university peer influence.Practical implicationsThe results highlight the role of education in ethical decision-making.Originality/valueThis study documents evidence on a new determinant of firm CSR performance. The study sheds light on the impact of non-institutionalised personal ties, for example, university alumni networks, on CSR performance.
Analysts’ foreign ancestral origins and firms’ information environment
Authors: Wang Kun Tracy , Luo Guqiang , Yu Li 
Published: May 2022

PurposeThe purpose of this study is to examine whether and how analysts’ foreign ancestral origins would have an effect on analysts’ earning forecasts in particular and ultimately on firms’ information environment in general.Design/methodology/approachBy inferring analysts’ ancestral countries based on their surnames, this study empirically examines whether analysts’ ancestral countries affect their earnings forecast errors.FindingsUsing novel data on analysts’ foreign ancestral origins from more than 110 countries, this study finds that relative to analysts with common American surnames, analysts with common foreign surnames tend to have higher earnings forecast errors. The positive relation between analyst foreign surnames and earnings forecast errors is more likely to be observed for African-American analysts and analysts whose ancestry countries are geographically apart from the USA. In contrast, this study finds that when analysts’ foreign countries of ancestry are aligned with that of the CEOs, analysts exhibit lower earnings forecast errors relative to analysts with common American surnames. More importantly, the results show that firms followed by more analysts with foreign surnames tend to exhibit higher earnings forecast errors.Originality/valueTaken together, findings of this study are consistent with the conjecture that geographical, social and ethnical proximity between managers and analysts affect firms’ information environment. Therefore, this study contributes to the determinants of analysts’ earnings forecast errors and adds to the literature on firms’ information environment.
Ownership, capital structure and operating loss of acquiring firms
Authors: Fan Shuangrui , Wang Cong 
Published: May 2022

PurposeThe article aims to investigate the effects of ownership and capital structure on postacquisition operating performance.Design/methodology/approachThe article extends the ongoing literature from an operating loss perspective and provides empirical evidence on the probability of acquirers’ operating loss in relation to ownership and capital structure. The operating performance of publicly listed manufacturing firms in China was tracked up to five years since the completion of the mergers and acquisitions (M&A) during 2003–2014.FindingsThe empirical results show that, in a five-year postacquisition period, state-owned enterprises (SOEs) are more likely to experience operating loss than non-SOEs. The likelihood of the operating loss is negatively associated with ownership concentration, implying that concentrated ownership may serve as an effective corporate governance mechanism in the emerging economy and improve postacquisition performance. The rise in leverage increases the likelihood of postacquisition operating loss, indicating that the costs of debt may outweigh the benefits.Originality/valueThe findings contribute to the literature on ownership, debt governance and post-M&A performance from an emerging economy perspective.
Reconfigurable dual element dual band MIMO antenna for 5G (Sub-6 GHz) and WLAN applications
Authors: Singh Ajit Kumar , Mahto Santosh Kumar , Sinha Rashmi 
Published: May 2022

Purpose
This study aims to present dual band reconfigurable MIMO antenna for 5G (sub-6 GHz) and WLAN applications.

Design/methodology/approach
To achieve optimum bandwidth, radiation pattern and radiation efficiency, the defected ground structure (DGS) and a rectangular stub connected with the DGS are used. To further cover the sub-6 GHz spectrum (3.4–3.6 GHz) for future 5G communications, a two-element multi-input multi-output (MIMO) antenna configuration is designed by using the single element antenna. The proposed reconfigurable MIMO antenna using a PIN diode is designed on an FR4 substrate with a dielectric constant of 4.4 and a loss tangent of 0.02 and a 35 × 20 × 1.6 mm3 dimension.

Findings
The proposed antenna achieved dual operating bands of 3.4–4.1 GHz (5 G sub-6GHz applications) and 4.99–5.16 GHz (WLAN application) in the D = ON state. For D = OFF state, the proposed antenna achieved 3.55–3.65 GHz and 3.66–4.05 GHz frequency bands for 5G (sub-6GHz) applications. In terms of the envelop correlation coefficient, diversity gain, mean effective gain, total active reflection coefficient and isolation between the ports, the proposed antenna’s diversity performance characteristics are investigated and the obtained values are 0.05, 9.9 dB, ±3dB, −4dB, −15dB, respectively.

Research limitations/implications
The fabricated prototype antenna on FR4 substrate has measurable parameters that are in good agreement with the simulated findings. Due to hardware design limitations, there is a minor difference between software and hardware results.

Originality/value
The proposed MIMO antenna is compact and reconfigurable for 5G (sub-6GHz) and WLAN applications, and from the graph, the measurements and simulations have been found to be in close agreement.
On the road to Industry 4.0 in manufacturing clusters: the role of business support organisations
Authors: Dyba Wojciech , De Marchi Valentina 
Published: May 2022

Purpose
This paper aims to explore the role of business support organisations (BSO) in overcoming barriers to the adoption of Industry 4.0 (I4.0) technologies, especially in disseminating knowledge on such technologies among cluster firms.

Design/methodology/approach
The study is based on in-depth interviews conducted in 2021 with representatives of BSO in three manufacturing clusters (furniture, metal and automotive) in the Wielkopolska region in Poland.

Findings
Companies in clusters face important barriers impeding the adoption of I4.0 technologies, in particular, the unawareness of the characteristics and potential of those technologies. BSO might be particularly helpful in overcoming this barrier by supporting knowledge dissemination among companies. This study’s analyses suggest they can do so in three roles: as knowledge gatekeepers, as brokers of purposeful knowledge transfer and as facilitators of spontaneous knowledge diffusion. Evidence suggests that different types of organisations are more likely to be associated with each of these three roles, despite such a combination of the three often being in one place: public agencies are gatekeeping, selecting and passing on certain knowledge on I4.0; research-oriented organisations (such as technology parks) play a knowledge transfer brokerage role; industry associations and cluster initiatives are actively facilitating spontaneous knowledge diffusion.

Originality/value
This paper is a contribution to the emerging literature on digital transformations of clusters by investigating the difficulties preventing firms from adopting I4.0 technologies and the roles BSO can take on to support overcoming them.
Linking an autonomy-supportive climate and employee creativity: the influence of intrinsic motivation and company support for creativity
Authors: Nili Fatemeh , Tasavori Misagh 
Published: May 2022

PurposeEmployees’ creativity is critical for the growth and survival of firms. Therefore, the purpose of this study is to propose a motivational model of creativity to address the effect of an autonomy-supportive climate on employee creativity. This study investigates whether this effect is mediated by intrinsic motivation in employees and depends on company support for creativity.Design/methodology/approachThis study used a quantitative approach to collect data by conducting a survey in a developing country using paper-based questionnaires. From 220 questionnaires distributed, 151 usable survey responses were gathered for this study. In addition, structural equation modeling was used to test the hypothesis.FindingsThe results suggest a motivational contingent path through which employees’ creativity would be promoted. The findings indicate that employees in autonomy-supportive climates are more intrinsically motivated and more creative only when the company supports creativity.Practical implicationsThe findings suggest that managers should provide employees with an autonomy-supportive climate. Furthermore, rewarding, recognizing and encouraging creativity in employees should be considered by companies.Originality/valueThis research integrates Amabile’s (1996) model of creativity and basic needs theory to empirically shed light on the inconsistent findings of the mediating role of intrinsic motivation in the relation of contextual factors to creativity. This study extends Amabile’s (1988) model to include an autonomy-supportive climate and explain how and when this kind of interpersonal climate contributes to enhanced creativity in employees. This research contributes to the basic needs theory by demonstrating that satisfaction of basic needs can also enhance creativity. The findings also add to the interactionist perspective of creativity because this study examines the interaction effect of company support for creativity and intrinsic motivation.
Soft quality management practices and product innovation ambidexterity: the mediating role of market orientation ambidexterity
Authors: El Manzani Younès , El Idrissi Mostapha , Lissaneddine Zakaria 
Published: May 2022

PurposeThis study empirically analyzes the direct impacts of soft quality management practices (SQMP) and market orientation ambidexterity (MOA) on product innovation ambidexterity (PIA). It also examines the mediating role of MOA in the relationship between SQMP and PIA.Design/methodology/approachFollowing a quantitative research methodology, a well-structured questionnaire is used to collect data from 130 Moroccan certified ISO 9001 firms. The conceptual framework of the study was tested using partial least squares structural equation modeling.FindingsThe results show that SQMP have no significant association with PIA while they positively and significantly impact MOA. The study also revealed that MOA has a positive and significant impact on PIA and fully mediates the relationship between SQMP and PIA.Research limitations/implicationsDue to the conceptualization of MOA and PIA as combined ambidexterity, the results of the study might be different in the case of balanced ambidexterity.Practical implicationsTo achieve PIA, managers need to be aware that implementing SQMP, while important, is not enough. They must invest sufficient resources to properly implement these practices to support MOA. Consequently, MOA will lead their organization to PIA by establishing the significant impact of SQMP on PIA.Originality/valueRegardless of the abundant literature on the relationship between quality management (QM) practices and innovation, this study is among the first to examine the impact of SQMP on PIA. Using MOA as a mediator can give a meaningful answer to the indecisive empirical results of the impact of QM on innovation. Furthermore, this research contributes to the scarce literature on relevant studies conducted in developing countries.
Edgework, institutions and enhanced interrogation
Authors: Balfe Myles 
Published: May 2022

AbstractThe Enhanced Interrogation programme was a medicalised interrogation programme that was designed by the United States in the wake of 9/11. It is now widely recognized that the Enhanced Interrogation programme engaged in some activities that were, at the least, tantamount to torture. The programme was designed by Psychologists and overseen by other professionals, including medical professionals. This article argues that the Enhanced Interrogation programme displayed many of the features of what Sociologists refer to as Edgework. It demonstrated voluntary risk‐taking by health and other professionals; this risk‐taking pressed up against catastrophic outcomes across multiple dimensions; risks were taken for the purposes of escaping a death‐saturated macrosocial context; and the health professionals in the programme were highly skilled. The article argues that a new form of Edgework can be detected by studying the programme, which the article refers to as ‘Institutional Edgework’.
A SHADOWY ‘CITY OF LIGHT’: Private Urbanism, Large‐Scale Land Acquisition and Dispossession in Ghana
Authors: Ablo Austin Dziwornu , Bertelsen Bjørn Enge 
Published: May 2022

AbstractThe rapid expansion of African cities has created both housing deficits and a pluralization of urban orders, including the growth of slum settlements. With an ever‐increasing middle class, urban sub‐Saharan Africa is now also characterized by large‐scale land acquisition processes linked to the construction of wholly private and increasingly enclaved cities. This article maps the impacts of the Appolonia City of Light project—a privately built enclaved city catering to the housing needs of a rapidly growing middle class in Ghana. Building on field research and exploring various dimensions of the development marketed as ‘The City of Light’, we highlight how the project has dramatically altered social relations and resulted in dispossession rippling through nearby local communities. We therefore argue that, instead of merely focusing on the actual physical spaces of private developments or turning attention to often phantasmagoric and utopic visions of the future, research should be directed at changes in the immediate surroundings of urban developments. We highlight the problematic land acquisition inherent to such enclaved developments and demonstrate how these intrinsically constitute assemblages of livelihoods and exemplify dynamics of appropriation, dispossession and commodification.