bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic ligand-mimicking bioparticles cross the blood-brain barrier and reduce growth of intracranial triple-negative breast cancer using the human epidermal growth factor receptor 3 (HER3) to mediate both routes
Authors: Alonso-Valenteen Felix , Sances Sam , Wang HongQiang , Mikhael Simoun , Sims Jessica , Taguiam Michael , Srinivas Dustin , Serrano Erik , Ondatje Briana , Teh James , Wong Michelle , Nguyenle Kimngan , Miao Tianxin , Benhaghnazar Rebecca , Yu John , Svendsen Clive , Abrol Ravinder , Medina Kauwe LK 
Published: June 2021

ABSTRACTCrossing the blood-brain barrier (BBB) and reaching intracranial tumors is a significant clinical challenge for targeted therapeutics and contributes to the poor prognosis for most patients with brain malignancies. Triple-negative breast cancer (TNBC) has a high propensity for metastasis to the brain and lacks cell surface markers that can be recognized by current targeted therapies used in the clinic, thus limiting therapeutic options. The human epidermal growth factor receptor HER3 (or ErbB3) has emerged as a biomarker of therapeutic resistance and metastasis in a growing range of tumor types and may serve as a possible therapeutic target for TNBC. Accordingly, we have developed HER3-targeted biological particles (bioparticles) that assume polyhedral capsid shapes when encapsulating nucleic acid cargo, forming nano-nucleocapsids (NNCs). The NNCs exhibit systemic homing to resistant and metastatic breast tumors, including TNBC, due to the high cell surface densities of HER3 on these tumors. Here we describe our discovery that HER3 is also prominently expressed on the brain endothelium and can mediate the passage of HER3-targeted NNCs across the BBB and into triple-negative breast tumors localized in the brain. Our findings show that HER3 is present at high levels on the vasculature (but not extravascular parenchyma) of both mouse and human adult brain specimens and associates with the extravasation of systemic HER3-targeted NNCs in mice and in a human model of the BBB (BBB chip). Furthermore, systemically delivered NNCs carrying tumoricidal agents reduced the growth of intracranial TNBC tumors in mice (representing metastatic breast tumors that have established in the brain) and exhibited improved therapeutic profile compared to current therapeutic interventions (liposomal doxorubicin) used in the clinic. This study addresses the major clinical problem of systemically delivering targeted therapeutics across the blood-brain barrier (BBB), and demonstrates a new route for not only accomplishing this but also for reaching tumors localized in the brain.
BSCL2/Seipin Deficiency in Heart Causes Energy Deficit and Heart Failure via Inducing Excessive Lipid Catabolism
Authors: Zhou Hongyi , Li Jie , Su Huabo , Li Ji , Lydic Todd A. , Young Martin E , Chen Weiqin 
Published: June 2021

AbstractHeart failure (HF) is one of the leading causes of death world-wide and is associated with cardiac metabolic perturbations. Human Type 2 Berardinelli-Seip Congenital Lipodystrophy (BSCL2) disease is caused by mutations in the BSCL2 gene. Global lipodystrophic Bscl2−/− mice exhibit hypertrophic cardiomyopathy. Whether BSCL2 plays a direct role in regulating cardiac substrate metabolism and/or contractile function remains unknown. Here we show that mice with cardiac-specific deletion of Bscl2 (Bscl2cKO) developed dilated HF. Myocardial BSCL2 deletion led to elevated ATGL expression and FA oxidation (FAO) along with reduced cardiac lipid contents. Cardiac dysfunction in Bscl2cKO mice was independent of mitochondrial dysfunction and oxidative stress, but associated with decreased metabolic reserve and ATP levels. Importantly, heart failure in Bscl2cKO mice could be partially reversed by pharmacological inhibition of FAO, or prevented by high fat diet (HFD) feeding. Lipidomic analysis further identified markedly reduced glycerolipids, glycerophospholipids, NEFA and acylcarnitines in Bscl2cKO hearts, which were partially normalized by FAO inhibition or HFD. Our study reveals a new form of HF with excessive lipid catabolism, and identifies a crucial cardiomyocyte-specific role of BSCL2 in controlling cardiac lipid catabolism, energy state and contractile function. It also provides novel insights into metabolically treating energy-starved HF using FAO inhibitor or HFD.
Cell-specific chromatin landscape of human coronary artery resolves regulatory mechanisms of disease risk
Authors: Turner Adam W. , Hu Sheng’en , Mosquera Jose Verdezoto , Ma Wei Feng , Hodonsky Chani J. , Wong Doris , Auguste Gaëlle , Sol-Church Katia , Farber Emily , Kundu Soumya , Kundaje Anshul , Lopez Nicolas G. , Ma Lijiang , Ghosh Saikat Kumar B. , Onengut-Gumuscu Suna , Ashley Euan A. , Quertermous Thomas , Finn Aloke V. , Leeper Nicholas J. , Kovacic Jason C. , Björkgren Johan L.M. , Zang Chongzhi , Miller Clint L. 
Published: June 2021

AbstractCoronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell type-specific elements, transcription factors, and prioritized functional CAD risk variants via quantitative trait locus and sequence-based predictive modeling. We identified a number of candidate mechanisms for smooth muscle cell transition states and identified putative binding sites for risk variants. We further employed CRE to gene linkage to nominate disease-associated key driver transcription factors such as PRDM16 and TBX2. This single cell atlas provides a critical step towards interpreting cis-regulatory mechanisms in the vessel wall across the continuum of CAD risk.
Reducing susceptibility distortion related image blurring in diffusion MRI EPI data
Authors: Clark Ian A. , Callaghan Martina F. , Weiskopf Nikolaus , Maguire Eleanor A. , Mohammadi Siawoosh 
Published: June 2021

ABSTRACTDiffusion magnetic resonance imaging (MRI) is an increasingly popular technique in basic and clinical neuroscience. One promising application is to combine diffusion MRI with myelin maps from complementary MRI techniques such as multi-parameter mapping (MPM) to produce g-ratio maps that represent the relative myelination of axons and predict their conduction velocity. Statistical Parametric Mapping (SPM) can process both diffusion data and MPMs, making SPM the only widely accessible software that contains all the processing steps required to perform group analyses of g-ratio data in a common space. However, limitations have been identified in its method for reducing susceptibility-related distortion in diffusion data. More generally, susceptibility-related image distortion is often corrected by combining reverse phase-encoded images (blip-up and blip-down) using the arithmetic mean (AM), however, this can lead to blurred images. In this study we sought to (1) improve the susceptibility-related distortion correction for diffusion MRI data in SPM; (2) deploy an alternative approach to the AM to reduce image blurring in diffusion MRI data when combining blip-up and blip-down EPI data after susceptibility-related distortion correction; and (3) assess the benefits of these changes for g-ratio mapping. We found that the new processing pipeline, called consecutive Hyperelastic Susceptibility Artefact Correction (HySCO) improved distortion correction when compared to the standard approach in the ACID toolbox for SPM. Moreover, using a weighted average (WA) method to combine the distortion corrected data from each phase-encoding polarity achieved greater overlap of diffusion and more anatomically faithful structural white matter probability maps derived from minimally distorted multi-parameter maps as compared to the AM. Third, we showed that the consecutive HySCO WA performed better than the AM method when combined with multi-parameter maps to perform g-ratio mapping. These improvements mean that researchers can conveniently access a wide range of diffusion-related analysis methods within one framework because they are now available within the open-source ACID toolbox as part of SPM, which can be easily combined with other SPM toolboxes, such as the hMRI toolbox, to facilitate computation of myelin biomarkers that are necessary for g-ratio mapping.
A Computational Model of Phosphene Appearance for Epiretinal Prostheses
Authors: Granley Jacob , Beyeler Michael 
Published: June 2021

AbstractRetinal neuroprostheses are the only FDA-approved treatment option for blinding degenerative diseases. A major outstanding challenge is to develop a computational model that can accurately predict the elicited visual percepts (phosphenes) across a wide range of electrical stimuli. Here we present a phenomenological model that predicts phosphene appearance as a function of stimulus amplitude, frequency, and pulse duration. The model uses a simulated map of nerve fiber bundles in the retina to produce phosphenes with accurate brightness, size, orientation, and elongation. We validate the model on psychophysical data from two independent studies, showing that it generalizes well to new data, even with different stimuli and on different electrodes. Whereas previous models focused on either spatial or temporal aspects of the elicited phosphenes in isolation, we describe a more comprehensive approach that is able to account for many reported visual effects. The model is designed to be flexible and extensible, and can be fit to data from a specific user. Overall this work is an important first step towards predicting visual outcomes in retinal prosthesis users across a wide range of stimuli.
Adaptive reprogramming during early seed germination requires temporarily enhanced fermentation – a critical role for alternative oxidase (AOX) regulation that concerns also microbiota effectiveness
Authors: Revuru Bharadwaj , Noceda Carlos , Gunasekaran Mohanapriya , Kumar Sarma Rajeev , Lima Thiers Karine Leitão , Costa José Hélio , Macedo Elisete Santos , Kumari Aprajita , Gupta Kapuganti Jagadis , Srivastava Shivani , Adholeya Alok , Oliveira Manuela , Velada Isabel , Sircar Debabrata , Sathishkumar Ramalingam , Arnholdt-Schmitt Birgit 
Published: June 2021

AbstractPlants respond to environmental cues via adaptive cell reprogramming that can affect whole plant and ecosystem functionality. Microbiota constitutes part of plant’s inner and outer environment. This Umwelt underlies steady dynamics, due to complex local and global biotic and abiotic changes. Hence, adaptive plant holobiont responses are crucial for continuous metabolic adjustment at systems levels. Plants require oxygen-dependent respiration for energy-dependent adaptive morphology, such as, germination, root and shoot growth, formation of adventitious, clonal and reproductive organs, fruits and seeds. Fermentative paths can help in acclimation and, to our view the role of alternative oxidase (AOX) in coordinating complex metabolic and physiologic adjustments is underestimated.Cellular level of sucrose is an important sensor of environmental stress. We explored the role of exogenous sucrose and its interplay with AOX during early seed germination. We found that sucrose-dependent initiation of fermentation during the first 12 hours after imbibition (HAI) was beneficial to germination. However, parallel enhanced AOX expression was essential to control negative effects by prolonged sucrose treatment. Early down-regulated AOX activity until 12 HAI improved germination efficiency in the absence of sucrose, but suppressed early germination in its presence. Our results also suggest that seeds-inoculated arbuscular mycorrhizal fungi can buffer sucrose stress during germination to restore normal respiration more efficiently.Following this approach, we propose a simple method to identify organic seeds and low-cost on-farm perspectives for early selection on disease tolerance, predicting plant holobiont behavior and improving germination. Furthermore, our research strengthens the view that AOX can serve as powerful functional marker source for seed hologenomes.
Synergy effect of nutritional labelling on purchase intention of sugar-sweetened beverages
Authors: Teng Hsu-Ju , Lo Chi-Feng , Ni Jia-Jen 
Published: June 2021

PurposeThe purpose of this study is to investigate how combined nutrition labelling influences consumer attitudes, subjective norms, perceived behavioural control and purchase intention for sugar-sweetened beverages (SSBs).Design/methodology/approachThis study adopted a mixed method research, quasi-experimental design with 406 valid Taiwanese samples to evaluate the possible effects of combined nutrition labelling on SSB purchase intention; two focus group interviews with four nutritional experts and 12 students were conducted to explain how and why consumers perceived different types of combined nutritional labels.FindingsCombined labels including sugar type/gram with the guideline daily amounts and traffic light display were perceived by consumers as high-quality and reliable, which improved consumer attitude and SSB purchase intention. Consumers perceived the traffic light display and warning claim as a sugar over-consumption message, which reduced SSB purchase intention through subject norms.Practical implicationsGovernments should be aware that concrete nutritional information (NIP) leads to the worst SSB consumption. Moreover, the authors suggest that policymakers emphasise the effectiveness of warning claims on SSB products with “sufficient” sugar information to trigger consumers' concern, remind SSB manufacturers of their moral obligation to consumers.Originality/valueThis study identified that the combined effects of nutritional attributes and parts of meanings might be enhanced, eliminated or even separated from their original meaning. Although the label messages were delivered simultaneously, the consumer's psychological perceptions proved to be more complicated than a single attribute and sequentially affected consumer attitudes, subject norms and SSB purchase intention.
The impact of media on entrepreneurship participation: a cross-country panel data analysis
Authors: Arshad Muhammad , Saleem Sharjeel , Raoof Rabeeya , Sultana Naheed 
Published: June 2021

Purpose
Unlike the previous studies that examined the direct relationship between media attention on entrepreneurship (MAE) and entrepreneurship participation, this paper aims to examine the mediated link through entrepreneurial intention.

Design/methodology/approach
The cognitive theory of media provides the foundation for predictions that primary outcome of MAE is the entrepreneurial intention which in turn affects the different types of entrepreneurship participation (early-stage startup activities, new product development [NPD] activities and informal investment activities). The test of the hypothesized model relies on panel data for 2010–2015 on 40 developing and developed countries taken from the Global Entrepreneurship Monitor report of 2015.

Findings
MAE has an indirect effect on two types of entrepreneurship participation (early-stage startup activities and informal investment activities) via entrepreneurial intention, whereas there is no direct or indirect effect of MAE on NPD activities. The findings also suggest when the entrepreneurial intention is added as a mediator in the model; the direct effect of MAE on early-stage entrepreneurial activities becomes insignificant.

Originality/value
To the best of the authors’ knowledge, this is the first study in its nature which established the relationship between MAE and entrepreneurial intention. In addition, this study also explained the mediation mechanism between the relationship of MAE and entrepreneurship participation by using the panel data.
The bright and dark sides of green customer integration (GCI): evidence from Chinese manufacturers
Authors: Feng Taiwen , Sheng Hongyan , Li Minghui 
Published: June 2021

PurposeBased on resource dependence theory and transaction cost economics this study explores how green customer integration (GCI) affects financial performance via information sharing and opportunistic behavior, and the moderating effects of dependence and trust.Design/methodology/approachThis study develops a theoretical model and tests it using data from two-waved survey data of 206 Chinese manufacturers. The hypotheses were tested using hierarchical linear regression analysis.FindingsThe results show that GCI has a significant and positive impact on information sharing, but its impact on opportunistic behavior is insignificant. Notably, information sharing has a significant and positive impact on financial performance, while opportunistic behavior has an insignificant impact on financial performance. In addition, dependence negatively moderates the impact of GCI on information sharing and positively moderates the impact of GCI on opportunistic behavior. Trust negatively moderates the impact of GCI on opportunistic behavior.Originality/valueAlthough GCI has received widespread attention, how it affects a firm's performance remains unclear. Most previous studies have focused only on its bright side and ignored its dark side. This study highlights how GCI affects financial performance through information sharing and opportunistic behavior, and the moderating effects of dependence and trust. This enriches the understanding of how and under what conditions GCI affects a firm's performance.
Perceived organizational support, graduate research supervision and research completion rate
Authors: Wanyama Seperia Bwadene , Eyamu Samuel 
Published: June 2021

PurposeThis paper aims at examining graduate research supervisors' perceptions of organizational and job supervisors' support and their influence on research completion rate. While research supervision has been mainly examined from pedagogical perspectives, little emphasis has been placed on the human resource management (HRM) activity for academics. This review paper draws from organizational support and social exchange theories (SET) to examine the influence of perceived organizational support (POS) and perceived supervisor support (PSS) in research supervision work.Design/methodology/approachThe paper is a narrative literature review of identified relevant readings on organizational support and social exchange, research supervisors' perceived support and their implications for research.FindingsResearch supervisors examine their perceptions of administrative, professional, financial and socio-emotional support from their universities and job supervisors. They in turn feel obligated to reciprocate, for example, through commitment, engagement and performance, towards meeting their goals with the organization, the job supervisor and the student.Research limitations/implicationsThe study relied on a literature review; hence, the findings may not reflect actual expressions of research supervisors' perceptions.Practical implicationsThe paper shows the application of organizational support and social exchange theories in academic work. It emphasizes the importance of support, perception and reciprocation through an exchange relationship. The research support framework is a guide to managing the relationships among the parties involved in research work.Originality/valueThe paper considers research supervisors as key human resources (HRs) that espouse supportive HRM practices from both the organization and the job supervisor. This is unlike most studies that have employed only pedagogical approaches in explaining research. It further develops a research supervision support framework.
The gateway bug to edible insect consumption: interactions between message framing, celebrity endorsement and online social support
Authors: Legendre Tiffany S. , Baker Melissa A. 
Published: June 2021

Purpose
Climate change and global population growth are threatening the sustainability of hospitality food systems. Foodservice organizations are seeking an optimal solution for this problem. The United Nations Food and Agriculture Organization proposed edible insects as a solution, yet the “yuck” factor discourages consumers from actively endorsing this option. Thus, this study aims to find ways to increase consumer acceptance of edible insects.

Design/methodology/approach
A 2 (message framing: hedonic vs utilitarian) × 2 (celebrity endorsement: absence vs presence) × 2 (social support: low vs high) between-subjects factorial design experiment was conducted.

Findings
The significant three-way interaction effects show that when celebrity endorsement is absent, there is no difference in restaurant advocacy (RA) and experience satisfaction between utilitarian and hedonic message framing, regardless of low (vs high) social support. However, when celebrity endorsement is present and social support is not lacking, a hedonic (vs a utilitarian) message had more significant effects on dependent variables. Conversely, when celebrity-endorsed messages receive high social support, utilitarian (vs hedonic) messages had a more substantial effect on the outcome variables.

Originality/value
This study contributes to alternative protein and associated consumer psychology and hospitality marketing literature by introducing marketing strategies for edible insects. By demonstrating the three-way interaction effects of message framing, celebrity, endorsement and social support on RA and experience satisfaction, this study could demonstrate some boundary conditions to consider when applying celebrity endorsement strategies (e.g. message framing and social support). Also, by addressing the effects of social support, this study builds upon the lack of hospitality literature on online social support.
Open innovation and performance in the service sector
Authors: Vincenzi Ticiana Braga De , da Cunha João Carlos 
Published: June 2021

Purpose
Organizations that decide to invest in innovation must define how this will be done: internally, externally or in a hybrid way, developing internal research and establishing partnerships with other agents of the innovation system. This paper aims to analyze whether the service companies’ intensity of openness and innovation efforts are related to their innovative and financial performances. Open innovation assumes that organizations should use external and internal resources as they develop new technologies.

Design/methodology/approach
The study used data from the survey of technological innovation (Pintec). As regards innovations, it was considered the commercial and operational innovation performances and the innovative novelty performance. As regards financial performance, it was considered the overall net sales per employee. The intensity of open innovation was measured by the combination of breadth and depth (diversity and importance of the interfaces). The innovative effort was measured by spending on innovation activities. Regressions were applied to evaluate a set of hypotheses.

Findings
The results indicate that companies with a greater orientation toward open innovation presented better scores. The results also lead to the conclusion that foreign firm ownership structure and being part of a corporate group were the factors that caused the greatest impact on financial performance in the service sector.

Practical implications
The study provides empirical data on the importance of open innovation in improving organizations' performance, especially the breadth of open innovation.

Originality/value
The study contributes to expanding the research field addressing the relationship between service innovation and performance.