bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Paired-related Homeobox Protein 1 as a key mesenchymal transcription factor in Idiopathic Pulmonary Fibrosis
Authors: Marchal-Duval E. , Homps-Legrand M. , Froidure A. , Jaillet M. , Ghanem M. , Deneuville L. , Justet A. , Maurac A. , Vadel A. , Fortas E. , Cazes A. , Joannes A. , Giersch L. , Mal H. , Mordant P. , Mounier C.M. , Schirduan K. , Korfei M. , Gunther A. , Mari B. , Jaschinski F. , Crestani B. , Mailleux A.A. 
Published: January 2021

ABSTRACTMatrix remodeling is a salient feature of idiopathic pulmonary fibrosis (IPF). Targeting cells driving matrix remodeling could be a promising avenue for IPF treatment. Analysis of transcriptomic database identified the mesenchymal transcription factor PRRX1 as upregulated in IPF.PRRX1, strongly expressed by lung fibroblasts, was regulated by a TGF-β/PGE2 balance in vitro in control and IPF fibroblasts, while IPF fibroblast-derived matrix increasedPRRX1expression in a PDGFR dependent manner in control ones.PRRX1 inhibition decreased fibroblast proliferation by downregulating the expression of S phase cyclins. PRRX1 inhibition also impacted TGF-β driven myofibroblastic differentiation by inhibiting SMAD2/3 phosphorylation through phosphatase PPM1A upregulation and TGFBR2 downregulation, leading to TGF-β response global decrease.Finally, targeted inhibition ofPrrx1attenuated fibrotic remodeling in vivo with intra-tracheal antisense oligonucleotides in bleomycin mouse model of lung fibrosis and ex vivo using precision-cut lung slices.Our results identified PRRX1 as a mesenchymal transcription factor driving lung fibrogenesis.Brief SummaryInhibition of a single fibroblast-associated transcription factor, namely paired-related homeobox protein 1, is sufficient to dampen lung fibrogenesis.
Longitudinal quantitative whole-brain microscopy reveals distinct temporal and spatial efficacies of anti-Aβ therapies
Authors: Kirschenbaum Daniel , Dadgar-Kiani Ehsan , Catto Francesca , Voigt Fabian F. , Trevisan Chiara , Bichsel Oliver , Shirani Hamid , Nilsson K. Peter R. , Frontzek Karl Joachim , Paganetti Paolo , Helmchen Fritjof , Lee Jin Hyung , Aguzzi Adriano 
Published: January 2021

AbstractMany efforts targeting amyloid-β (Aβ) plaques for the treatment of Alzheimer’s Disease thus far have resulted in failures during clinical trials. Regional and temporal heterogeneity of efficacy and dependence on plaque maturity may have contributed to these disappointing outcomes. In this study, we mapped the regional and temporal specificity of various anti-Aβ treatments through high-resolution light-sheet imaging of electrophoretically-cleared brains. We assessed the effect on amyloid plaque formation and growth in Thy1-APP/PS1 mice subjected to β-secretase inhibitors, polythiophenes, or anti-Aβ antibodies. Each treatment showed unique spatiotemporal Aβ clearance, with polythiophenes emerging as a potent anti-Aβ compound. Furthermore, aligning with a spatial-transcriptomic atlas revealed transcripts that correlate with the efficacy of each Aβ therapy. As observed in this study, there is a striking dependence of specific treatments on the location and maturity of Aβ plaques. This may also contribute to the clinical trial failures of Aβ-therapies, suggesting that combinatorial regimens may be significantly more effective in clearing amyloid deposition.
Parallel functional testing identifies enhancers active in early postnatal mouse brain
Authors: Lambert Jason T. , Su-Feher Linda , Cichewicz Karol , Warren Tracy L. , Zdilar Iva , Wang Yurong , Lim Kenneth J. , Haigh Jessica , Morse Sarah J. , Canales Cesar P. , Stradleigh Tyler W. , Castillo Erika , Haghani Viktoria , Moss Spencer , Parolini Hannah , Quintero Diana , Shrestha Diwash , Vogt Daniel , Byrne Leah C. , Nord Alex S. 
Published: January 2021

ABSTRACTEnhancers are cis-regulatory elements that play critical regulatory roles in modulating developmental transcription programs and driving cell-type specific and context-dependent gene expression in the brain. The development of massively parallel reporter assays (MPRAs) has enabled high-throughput functional screening of candidate DNA sequences for enhancer activity. Tissue-specific screening ofin vivoenhancer function at scale has the potential to greatly expand our understanding of the role of non-coding sequences in development, evolution, and disease. Here, we adapted a self-transcribing regulatory element MPRA strategy for delivery to early postnatal mouse brain via recombinant adeno-associated virus (rAAV). We identified and validated putative enhancers capable of driving reporter gene expression in mouse forebrain, including regulatory elements within an intronicCACNA1Clinkage disequilibrium block associated with risk in neuropsychiatric disorder genetic studies. Paired screening and single enhancerin vivofunctional testing, as we show here, represents a powerful approach towards characterizing regulatory activity of enhancers and understanding how enhancer sequences organize gene expression in normal and pathogenic brain development.
Structure of Cystathionine β-Synthase from Toxoplasma gondii, a key enzyme in its H2S production machinery
Authors:   In memory of Jan P. Kraus, Fernández-Rodríguez Carmen , Oyenarte Iker , Conter Carolina , González-Recio Irene , Nuñez-Franco Reyes , Gil-Pitarch Claudia , Quintana Iban , Jiménez-Osés Gonzalo , Dominici Paola , Martinez-Chantar Maria Luz , Astegno Alessandra , Martínez-Cruz Luis Alfonso 
Published: January 2021

ABSTRACTCystathionine β-synthase (CBS), the pivotal enzyme of the reverse transsulfuration pathway, catalyzes the pyridoxal-5’-phosphate-dependent condensation of serine with homocysteine to form cystathionine. Additionally, CBS performs alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide (H2S), an important signal transducer in many physiological and pathological processes. Toxoplasma gondii, the causative agent of toxoplasmosis, encodes a functional CBS (TgCBS) that contrary to human CBS, is not allosterically regulated by S-adenosylmethionine and can use both, Ser and O-acetylserine (OAS) as substrates. TgCBS is also strongly implicated in the production of H2S, and thus involved in redox homeostasis of the parasite. Here, we report its crystal structure, the first CBS from a protozoan described so far. Our data reveals a basal-like fold that unexpectedly differs from the active conformations found in other organisms, but structurally similar to the pathogenic activated mutant D444N of the human enzyme.
Establishment and characterization of mammary organoids from non-traditional model organisms
Authors: Bartlett Arianna P. , Van de Walle Gerlinde R. 
Published: January 2021

ABSTRACTMammary organoid (MaO) models are only available for a few traditional model organisms, limiting our ability to investigate mammary gland development and cancer across the diverse taxa of mammals. For example, horses are mammals with a similar mammary anatomy and function as humans, but they have a remarkably low incidence of mammary cancer, making the development of MaOs in non-traditional model organisms attractive, particularly in comparative cancer research. This study established equine mammary organoids (EqMaOs) from mammary gland tissue fragments and evaluated parameters including diameter, budding, and growth stage in non-budding EqMaOs, in cultures with increasing concentrations of epidermal growth factor (EGF), a key growth factor implicated in mammary gland development. Our findings showed that EqMaO diameter is not influenced by EGF concentration, whereas number of EqMaOs with budding and stage in non-budding EqMaOs are positively influenced by increasing EGF concentration. EqMaOs also formed protrusions with putative functions, including organoid fusion and sensory functions. We further characterized EqMaOs by the presence of myoepithelial and luminal cells using immunohistochemistry and used the hormone prolactin to stimulate milk secretion, as illustrated by β-lactoglobulin expression, in these EqMaOs. Additionally, we showed that our method to establish MaOs is widely applicable to additional non-traditional mammalian model organisms such as cat, pig, deer, rabbit, and prairie vole. Collectively, MaO models across species will be a useful tool for comparative developmental and cancer studies.Summary statementMammary organoids can be established from various mammals by embedding mammary tissue fragments into a 3D matrix, providing a high-throughput, physiologically accurate model for comparative studies centered on mammary gland development and cancer.
Development of a novel microfluidic device to study metal geochemistry in situ using X-ray fluorescence microprobe spectroscopy
Authors: Chen Michael A. , Kocar Benjamin D. 
Published: January 2021

The study of in situ microscale biogeochemical processes represents a major challenge in the environmental sciences. The combination of microfluidic devices with X-ray fluorescence microprobe spectroscopy may address this need, but typical materials used in these devices attenuate the X-rays needed to analyze key elements of interest, such as Fe or As. In this work, a method is presented for fabricating an etched silicon microfluidic device that is sealed with a 30 µm thin glass window that is sufficiently transparent for X-ray fluorescence microprobe spectroscopy. The capabilities of these devices for X-ray microprobe spectroscopy are demonstrated using an Fe (hydr)oxide solid that is loaded with As and then infused with sulfide, on beamline 4-BM at NSLS-II, resulting in time-variant Fe precipitation reactions and As sorption. Key results include in situ X-ray fluorescence time-series maps of Fe, As and a Br flow tracer, as well as spot XANES at both the Fe K edge and As K edge. Additionally, multiple energy mapping is used to examine the spatial speciation of As over time. The results of this work clearly demonstrate the capabilities of this novel microfluidic system that can be analyzed using X-ray fluorescence microprobe spectroscopy and can be made to study a wide range of complex microscale geochemical systems.
Rank-dependent preferences, social network and crop insurance uptake: field experimental evidence from rural China
Authors: Zhang Ruojin , Fan Dan , Lai Gene , Wu Junqian , Li Jungong 
Published: January 2021

PurposeAgricultural insurance has become increasingly important to farmers' livelihood and production in rural China. Yet despite the enormous governmental subsidizing efforts, the insurance participation rate remains below expectations. This study revisits the linkage between farmers' risk attitudes and crop insurance utilization by providing a cross-cutting perspective such that the role of risk aversion is re-scrutinized in Chinese “kindred” village economies.Design/methodology/approachThe authors administrated a lottery-based multiple price list (MPL) experiment by recruiting rice farmers from 12 villages in Sichuan province in southwestern China. Using the experimental data, farmers' risk attitudes are assessed and coefficients of risk aversion are estimated within the rank-dependent expected utility (RDEU) framework by maximizing a structured likelihood function.FindingsThis study provides substantiating evidence that rice farmers in southwestern China exhibit relatively high risk aversion. The authors also provide suggestive evidence of the positive relationship between farmers' risk aversion and crop insurance utilization. In addition, findings reveal that kinship network has a negative effect on crop insurance utilization, such that farmers who are connected in higher degree of kinship network have lower likelihood of crop insurance utilization, which suggests that kinship network may be substitute for formal crop insurance. Result also demonstrates that the incentive effect of risk aversion on farmers' crop insurance participation manifests differently depending on the degree of kinship network in rural China.Originality/valueThis study provides a cross-cutting perspective by scrutinizing the effects of farmers' risk attitudes and kinship network on crop insurance participation in rural China, which has received relatively little attention in the literature. Conclusions on the effects of risk aversion on crop insurance participation have been mixed in previous studies. In addition, to the best of our knowledge, little has been done to explicitly examine the influence of social proximity and networks on farmers' insurance uptake. This study attempts to fill both gaps. This study provides new insights which might shed lights on the understanding of farmers' crop insurance participation in rural China.
How does convenience drive consumers' webrooming intention?
Authors: Shankar Amit 
Published: January 2021

PurposeThe aim of this study is to evaluate the impact of convenience on banking consumers' webrooming intention. To fulfil this objective, this study empirically investigates how convenience impacts consumers' webrooming intention, using a comprehensive moderated–mediation framework. The study investigates the mediating effects of perceived hedonic values and perceived utilitarian values and how these mediating effects are moderated by consumers' perceived security concerns.Design/methodology/approachData were collected using a questionnaire-based offline survey from 534 banking users in India, using systematic sampling. The covariance-based structural equation modelling and PROCESS macro were used to examine the hypotheses.FindingsThe results indicated that access convenience, search convenience, benefit convenience and post-benefit convenience have a crucial impact on consumers' webrooming intention. The perceived hedonic values and perceived utilitarian values mediate the effects of convenience dimensions on webrooming intention, and mediation effects varied between high and low levels of consumers' perceived security concern.Research limitations/implicationsThis study was conducted in India using cross-sectional data. The proposed model can be replicated in other countries using longitudinal data for generalising the findings.Practical implicationsThe study's findings will help banks identify how to enhance convenience to manage channel-switching behaviour.Originality/value“Webrooming”, a key channel-switching concern in a multichannel banking context is investigated by examining the impact of convenience dimensions.
ISO-9001 implementation and critical success factors of the Jordanian consulting engineering firms
Authors: Sweis Rateb , AL-Huthaifi Nasser , Alawneh Afnan , Albalkhy Wassim , Suifan Taghrid , Saa'da Raeda 
Published: January 2021

PurposeThis paper aims at studying the level of implementation of ISO 9001 in Jordanian consulting engineering firms and to what extent does the implementation effectiveness affect the success of the construction projects. Moreover, the paper seeks to identify the Critical Success Factors (CSFs) that directly influence the ISO 9001 effectiveness in Jordanian consulting engineering firms.Design/methodology/approachA questionnaire was constructed and distributed to a sample of 125 employees from six ISO 9001-consulting firms. After collecting the data, exploratory factor analysis was utilized to validate the latent constructs (CSFs, ISO 9001 Effectiveness, and Firm Performance).FindingsThe findings suggest that firms experience a high level of ISO 9001 effectiveness. Moreover, among the five identified CSFs; employee attributes, external environmental pressure and quality system attribute had a significant impact on the ISO 9001 effectiveness, while internal motivation and firm attributes were insignificant.Originality/valueThe significance of this study lies in exploring such topic in the developing countries, since most of current studies were focused on developed contexts such as the USA and UK. Therefore, this research acts as a response to calls in the current literature regarding considering different industries and contexts.
Stochastic comparisons of series and parallel systems with independent heterogeneous Gumbel and truncated Gumbel components
Authors: Kızılaslan Fatih 
Published: January 2021

PurposeThe purpose of this paper is to investigate the stochastic comparisons of the parallel system with independent heterogeneous Gumbel components and series and parallel systems with independent heterogeneous truncated Gumbel components in terms of various stochastic orderings.Design/methodology/approachThe obtained results in this paper are obtained by using the vector majorization methods and results. First, the components of series and parallel systems are heterogeneous and having Gumbel or truncated Gumbel distributions. Second, multiple-outlier truncated Gumbel models are discussed for these systems. Then, the relationship between the systems having Gumbel components and Weibull components are considered. Finally, Monte Carlo simulations are performed to illustrate some obtained results.FindingsThe reversed hazard rate and likelihood ratio orderings are obtained for the parallel system of Gumbel components. Using these results, similar new results are derived for the series system of Weibull components. Stochastic comparisons for the series and parallel systems having truncated Gumbel components are established in terms of hazard rate, likelihood ratio and reversed hazard rate orderings. Some new results are also derived for the series and parallel systems of upper-truncated Weibull components.Originality/valueTo the best of our knowledge thus far, stochastic comparisons of series and parallel systems with Gumbel or truncated Gumble components have not been considered in the literature. Moreover, new results for Weibull and upper-truncated Weibull components are presented based on Gumbel case results.
Directive 2014/95/EU: building a research agenda
Authors: Korca Blerita , Costa Ericka 
Published: January 2021

PurposeThis paper discusses the current state of research into Directive 2014/95/EU and non-financial disclosure (NFD), with the aim of offering a future research agenda.Design/methodology/approachThe authors have conducted a systematic literature review of 78 studies spanning seven years (2014–2020) that address Directive 2014/95/EU.FindingsThe literature review revealed four main avenues for future research. First, future studies could focus on addressing issues related to the EU Directive's potential impacts, both in terms of NFD and companies' financial performance. Second, because context plays an important role in defining the regulation's impact, future research should consider these contextual factors in NFD. Third, further research should investigate the interplay between the binding requirements of the Directive and the non-binding guidelines suggested to implement it. Finally, future research would do well to employ additional theoretical approaches in order to interpret the Directive's diverse effects for various countries, organisations and timelines.Research limitations/implicationsThis research agenda is intended to help scholars in this field to understand what has yet to be known in order to develop a complete understanding of the EU Directive on non-financial information disclosure.Practical implicationsFocussing on the Directive's implementation across countries and organisations with a longitudinal approach, this paper could indicate whether or not mandatory reporting enhances non-financial information disclosure and consequently, organisational actions. This work could inform both companies' and policymakers' approach to disclosure, whether mandatory or otherwise.Originality/valueTo date, many studies have focussed on specific issues regarding the EU Directive. This paper, however, presents the first systematic literature review considering the current state of research into the EU Directive, thus drawing a future research agenda.
Purchasing behaviour and supplier base evolution – a longitudinal case study
Authors: Dubois Anna , Gadde Lars-Erik , Mattsson Lars-Gunnar 
Published: January 2021

Purpose
The purpose of the paper is to describe and analyse the evolution of the supplier base of a buying firm and the reasons behind these changes.

Design/methodology/approach
The paper is based on a case study of the changes over 52 years in a sub-set of the supplier base of a firm manufacturing fork-lifts.

Findings
The study shows that some relationships feature substantial longevity. However, the duration of one-third of the total relationships is shorter than five years. There was considerable variation over time in the dynamics of the supplier base in terms of entries and exits of suppliers. Owing to this variation, research findings and conclusions in short-term studies are heavily dependent on the specific conditions at the time of the study. Finally, no less than one-fourth of the terminated supplier relationships were reactivated later.

Research limitations/implications
The study was designed in a time when purchasing was considered entirely from the perspective of the buying firm. Further studies, therefore, must increasingly emphasise the role of suppliers and the interaction in the buyer–supplier relationships, as well as the embeddedness in networks.

Originality/value
The findings of the study are unique in two ways. First, they are based on systematic observations over more than 50 years. Second, the study involves the purchases of 11 components representing different technical and economic features. The (few) previous studies are based on much shorter time periods and involves fewer suppliers/components. Moreover, the findings regarding re-activation of terminated relationships represent unique contributions.
Social responsibility approach among universities’ community
Authors: Thanasi-Boçe Marsela , Kurtishi-Kastrati Selma 
Published: January 2021

PurposeThis study aims to explore the extent to which universities in developing countries have adopted social responsibility (SR) and track its implementation.Design/methodology/approachThrough content analysis, the study examined the SR activities in 14 universities in Albania and North Macedonia. A framework for assessing SR in universities was developed based on the ISO 26000/2010 standard and the main SR domains relevant to the university context were identified and analysed. A comparison between public and private universities was made and best practices were highlighted.FindingsThe results showed that the highest scoring domain is organisational governance, while the environment domain scored lowest. No significant differences between public and private universities were identified in the disclosure of the university social responsibility (USR) domains.Research limitations/implicationsDomains were assessed based on the online content the universities disclosed and did not consider any unpublished content.Social implicationsThe best SR practices are promoted to increase other universities’ level of engagement with the USR approach.Originality/valueThe study adds to the contributions in the USR literature by providing a better understanding of the application of USR in developing countries. The developed framework may be used to assess USR engagement in a practical way.