bluuebunny/crossref_metadata_2025_split huggingface dataset:
TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects
Authors: Ragu Mohana Eswari , Ch’Wan Lim Joanna Mei , Ng Pei-Sze , Yip Cheng-Har , Rajadurai Pathmanathan , Teo Soo-Hwang , Pan Jia-Wern 
Published: April 2022

AbstractRecent genomics studies of breast cancer in Asian cohorts have found a higher prevalence of TP53 mutations in Asian breast cancer patients relative to Caucasian patients. However, the effect of TP53 mutations on Asian breast tumours has not been comprehensively studied. Here, we report an analysis of 492 breast cancer samples from the Malaysian Breast Cancer (MyBrCa) cohort where we examined the impact of TP53 somatic mutations in relation to PAM50 subtypes by comparing whole exome and transcriptome data from tumours with mutant and wild type TP53. We found that the magnitude of impact of TP53 somatic mutations appears to vary between different subtypes. TP53 somatic mutations were associated with larger and more consistent differences in HR deficiency scores as well as transcriptional alterations in the luminal A and luminal B subtypes compared to the basal-like and Her2-enriched subtypes. The only pathways that were consistently dysregulated when comparing tumours with mutant and wild type TP53 across the different subtypes were the mTORC1 signaling and glycolysis pathways. These results suggest that therapies that target TP53 or other downstream pathways may be more effective against luminal A and B tumours in the Asian population.
Microgravity enhances the phenotype of Arabidopsis zigzag-1 and reduces the Wortmannin-induced vacuole fusion in root cells
Authors: Wang Mengying , Danz Katherine , Ly Vanessa , Rojas-Pierce Marcela 
Published: April 2022

AbstractThe spaceflight environment of the International Space Station poses a multitude of stresses on plant growth including reduced gravity. Plants exposed to microgravity and other conditions on the ISS display root skewing, changes in gene expression and protein abundance that may result in changes in cell wall composition, antioxidant accumulation and modification of growth anisotropy. Systematic studies that address the effects of microgravity on cellular organelles are lacking but altered numbers and sizes of vacuoles have been detected in previous flights. The prominent size of plant vacuoles makes them ideal models to study organelle dynamics in space. Here, we used Arabidopsis zigzag1 (zig-1) as a sensitized genotype to study the effect of microgravity on plant vacuole fusion. Wortmannin was used to induce vacuole fusion in seedlings and a formaldehyde-based fixation protocol was developed to visualize plant vacuole morphology after sample return, using confocal microscopy. Our results indicate that microgravity enhances the zig-1 phenotype by reducing hypocotyl growth and vacuole fusion in some cells. This study demonstrates the feasibility of chemical inhibitor treatments for plant cell biology experiments in space.
Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway
Authors: Sokoya Tolulope , Parolek Jan , Foged Mads Møller , Danylchuk Dmytro I. , Bozan Manuel , Sarkar Bingshati , Hilderink Angelika , Philippi Michael , Botto Lorenzo D. , Terhal Paulien A. , Mäkitie Outi , Piehler Jacob , Kim Yeongho , Burd Christopher G. , Klymchenko Andrey S. , Maeda Kenji , Holthuis Joost C. M. 
Published: April 2022

ABSTRACTSphingomyelin is a dominant sphingolipid in mammalian cells. Its production in the trans-Golgi traps cholesterol synthesized in the ER to promote formation of a sphingomyelin/sterol gradient along the secretory pathway. This gradient marks a fundamental transition in physical membrane properties that help specify organelle identify and function. We previously identified mutations in sphingomyelin synthase SMS2 that cause osteoporosis and skeletal dysplasia. Here we show that SMS2 variants linked to the most severe bone phenotypes retain full enzymatic activity but fail to leave the ER owing to a defective autonomous ER export signal. Cells harboring pathogenic SMS2 variants accumulate sphingomyelin in the ER and display a disrupted transbilayer sphingomyelin asymmetry. These aberrant sphingomyelin distributions also occur in patient-derived fibroblasts and are accompanied by imbalances in cholesterol organization, glycerophospholipid profiles and lipid order in the secretory pathway. We postulate that pathogenic SMS2 variants undermine the capacity of osteogenic cells to uphold nonrandom lipid distributions that are critical for their bone forming activity.
Engineering a more specific E. coli glyoxylate/hydroxypyruvate reductase for coupled steady state kinetics assays
Authors: Vuksanovic Nemanja , Serrano Dante A. , Patterson Brandon M. , Silvaggi Nicholas R. 
Published: April 2022

ABSTRACTThe E. coli glyoxylate reductase/hydroxypyruvate reductase A (EcGhrA) was investigated as a coupling enzyme to monitor the transamination of 2-ketoarginine and glycine by the L-enduracididine biosynthetic enzyme MppQ. Surprisingly, 2-ketoarginine proved to be an efficient substrate for EcGhrA. Since the promiscuity of EcGhrA prevented its use as a coupling enzyme to monitor the aminotransferase activity of MppQ, we set about engineering a more specific variant. X-ray crystal structures of EcGhrA were determined in the unliganded state, as well as with glyoxylate and 2-ketoarginine bound. The electron density maps of EcGhrA with 2-ketoarginine bound showed weak electron density for the side chain of this substrate, complicating the choice of active site residues to target for site-directed mutagenesis. The structure of the complex did, however, suggest that the side chain of W45 could interact with the guanidinium group of 2-ketoarginine. We therefore generated the EcGhrAW45F variant and tested it for activity with 2-ketoarginine, glyoxylate, oxaloacetate, α-ketoglutarate, α-oxofuranacetic acid, phenyl pyruvate, 3-mercaptopyruvate and 2-ketobutyric acid. The W45F variant exhibited a ∼10-fold decrease in the specificity constant (kcat/KM) for 2-ketoarginine, while the reaction with glyoxylate was not significantly impaired. The reactions of the W45F variant with the alternative substrates oxaloacetate and α-ketoglutarate were also impaired. Thus, the W45F variant is a less promiscuous enzyme than the wild-type. This engineered EcGhrAW45F variant could be generally useful as a coupling system for enzymes that produce glyoxylate, such as 4-hydroxy-2-oxoglutarate aldolase or isocitrate lyase.
Robustness of the ferret model for influenza risk assessment studies: a cross-laboratory exercise
Authors: Belser Jessica A , Lau Eric HY , Barclay Wendy , Barr Ian G. , Chen Hualan , Fouchier Ron AM , Hatta Masato , Herfst Sander , Kawaoka Yoshihiro , Lakdawala Seema S , Lee Leo Yi Yang , Neumann Gabriele , Peiris Malik , Perez Daniel R , Russell Charles , Subbarao Kanta , Sutton Troy C , Webby Richard J , Yang Huanliang , Yen Hui-Ling ,   Working group on the standardization of the ferret model for influenza risk assessment
Published: April 2022

AbstractFerrets represent the preferred animal model for assessing the transmission potential of newly emerged zoonotic influenza viruses. However, heterogeneity among established experimental protocols and facilities across different laboratories may lead to variable results, complicating interpretation of transmission experimental data. Between 2018-2020, a global exercise was conducted by 11 participating laboratories to assess the range of variation in ferret transmission experiments using two common stock H1N1 influenza viruses that possess different transmission characteristics in ferrets. Inoculation route, dose, and volume were standardized, and all participating laboratories followed the same experimental conditions for respiratory droplet transmission, including a strict 1:1 donor:contact ratio. Additional host and environmental parameters likely to affect influenza transmission kinetics were monitored throughout. Overall transmission outcomes for both viruses across 11 laboratories were concordant, suggesting the robustness of the ferret model for zoonotic influenza risk assessment. To attain high confidence in identifying zoonotic influenza viruses with moderate-to-high or low transmissibility, our analyses support that as few as three but as many as five laboratories, respectively, would need to independently perform viral transmission experiments with concordant results. This exercise facilitates the development of a more homogenous protocol for ferret transmission experiments that are employed for the purposes of risk assessment.
Resilient WASH development for urban poor: the case of Ahmedabad slums
Authors: Thakore Akshat Yaumin , Iyer Mona , Mishra Gargi , Doshi Siddh 
Published: April 2022

Purpose
Climate variability, accompanied by rapid urbanization and rising population disproportionality, impacts urban poor settlements. This paper aims to analyse the climate resilience for the urban poor in Ahmedabad through the lens of WASH development strategies. To assess the adaptive capacities of urban poor communities, a framework in the form of a vulnerability matrix has been used consisting of four key parameters – tenure, basic services, mobilization and partnership and disaster management capacities. The matrix implicitly recommends area-specific interventions to boost adaptive capacities and improve resilience based on WASH services.

Design/methodology/approach
This paper was designed to assess the climate resilience of WASH services in the urban poor settlements of Ahmedabad city. In all, seven slums were selected using a stratified sampling approach considering topography, access to WASH services and urban heat island effect. These slums were then assessed using a theoretical framework having four key parameters – tenure, basic service, mobilization and partnership and disaster management capacities. The data for the analysis was collected from both secondary and primary sources. For the latter, semi-structured interviews with key stakeholders, observational field visits and focused group discussions with the communities were done.

Findings
A ladder form of assessment matrix was derived from a thorough literature review and various pre-existing theories. This matrix consists of four key parameters – tenure, basic service, mobilization and partnership and disaster management capacities. The slums were evaluated by applying this framework, and direct and indirect relationships were established between the said parameters.

Research limitations/implications
This paper was adapted in the light of various obstacles put forward by the Covid-19 pandemic. Some of the interviews with the bureaucrats and external researchers were conducted online, while the engagement with the slum dwellers was in-person, considering appropriate social and/or physical distancing norms. Implications of the Covid-19 second wave restricted the involvement of researchers with the communities at an ethnographic level.

Originality/value
The ladder form of vulnerability assessment framework has been developed and contextualized using the insights from literature review, field visits and multi-stakeholder consultations. It was helpful in identifying aspects that require suitable interventions for improving and imparting resilience among the urban poor settlements. The learnings from this paper are significant for planners and decision-makers in identifying and prioritizing context-specific future projects for a city.
Toward cultural significance awareness in HIS: a data model approach
Authors: Jouan Pierre , Hallot Pierre 
Published: April 2022

PurposeThe purpose of this paper is to address the challenging issue of developing a quantitative approach for the representation of cultural significance data in heritage information systems (HIS). The authors propose to provide experts in the field with a dedicated framework to structure and integrate targeted data about historical objects' significance in such environments.Design/methodology/approachThis research seeks the identification of key indicators which allow to better inform decision-makers about cultural significance. Identified concepts are formalized in a data structure through conceptual data modeling, taking advantage on unified modeling language (HIS). The design science research (DSR) method is implemented to facilitate the development of the data model.FindingsThis paper proposes a practical solution for the formalization of data related to the significance of objects in HIS. The authors end up with a data model which enables multiple knowledge representations through data analysis and information retrieval.Originality/valueThe framework proposed in this article supports a more sustainable vision of heritage preservation as the framework enhances the involvement of all stakeholders in the conservation and management of historical sites. The data model supports explicit communications of the significance of historical objects and strengthens the synergy between the stakeholders involved in different phases of the conservation process.
Sustainable supply chain visibility assessment and proposals for improvements using fuzzy logic
Authors: Apeji Uje Daniel , Sunmola Funlade T. 
Published: April 2022

Purpose
Visibility management is essential to sustainable supply chains (SSCs), allowing the ability to see the chain end-to-end, with opportunities to derive benefits, including competitive advantage. Central to visibility management is visibility assessment and identification of areas for improvement. This paper aims to propose a method of assessing visibility in SSCs and the generation of proposals for improvement.

Design/methodology/approach
A hierarchically structured assessment template is developed that comprises of dimensions, factors and attributes of visibility in SSCs. The template permits the use of linguistic variables. A fuzzy logic approach is adopted to calculate visibility levels and generate improvement areas based on linguistic data captured through the template. An industry-based case study is used to illustrate the process.

Findings
This study reveals that visibility can be measured straightforwardly using the method developed in this paper. It is found that automation and contextual factors can significantly impact visibility levels, so also is sustainability awareness and practices adopted.

Originality/value
This paper describes a visibility assessment model that incorporates linguistic variables, fuzzy logic and the use of an adaptable visibility assessment template. The assessment model can identify potential inhibitors of visibility for SSC under study.
Industry 4.0 enabling manufacturing flexibility: technology contributions to individual resource and shop floor flexibility
Authors: Enrique Daisy Valle , Marcon Érico , Charrua-Santos Fernando , Frank Alejandro G. 
Published: April 2022

PurposeThis paper focuses on understanding the contribution of Industry 4.0 technologies to manufacturing flexibility.Design/methodology/approachA multiple-case study was conducted through interviews and complementary data from 12 adopters of Industry 4.0 technologies from the industrial sector. To enable a broad perspective, cases from 5 industry sectors with different technological intensity levels were studied.FindingsThe findings show that Industry 4.0 technologies are mostly used to improve machine flexibility since there is a major focus on technological approaches rather than on wider flexibility. The results also showed that cloud services, IoT, and data analytics provide the basis for flexible operation, and collaborative robots, ERP/MES/PLM, AGVs, and traceability devices are the most commonly implemented technologies for flexibility. However, inherent contingency factors such as production complexity and product life cycle need to be considered.Originality/valueThis article expands the research on manufacturing flexibility, considering new capabilities introduced by Industry 4.0.
Maintenance practices and overall equipment effectiveness: testing the moderating effect of training
Authors: Duarte André Luís Castro Moura , Santiago Scarpin Marcia Regina Santiago 
Published: April 2022

PurposeThis study aims to identify the relationship between different maintenance practices and productive efficiency in continuous process productive plants as well as the moderating effect of good training practices.Design/methodology/approachThe empirical data were drawn from a database containing 609 observations of 29 productive units. Scales were validated using the Q-sort method. The panel data technique was used as the analysis methodology, with the inclusion of fixed effects for each productive plant.FindingsMaintenance practices can effectively contribute to increasing the overall equipment effectiveness (OEE) of firms. Application of predictive maintenance practices should be considered as the primary training tool.Research limitations/implicationsThis study used a secondary database, limiting the research design and data manipulation.Practical implicationsThe article provides practitioners with an analysis of maintenance practices by category (predictive, preventive and corrective), and the impact of each practice on the OEE of continuous process productive plants. Moreover, it explores the importance of training for extracting more results from maintenance practices.Social implicationsCompanies are investing in new technologies, but it is also essential to invest in training people. There is a demand for Industry 4.0 through the introduction of upskilling and reskilling programs.Originality/valueThis study used practice-based view (PBV) theory to explain how maintenance practices help firms achieve greater OEE. Furthermore, it introduced training practice as a moderating variable in the relationship between maintenance practices and OEE.
One-year push-off specimens using cocktail and polymeric fibres at elevated temperatures
Authors: Alimrani Naser , Balazs Gyorgy , Abdelmelek Nabil 
Published: April 2022

Purpose This study aims to test push-off specimens at elevated temperatures. This research work is part of the author’s PhD work. The author has published several of the significant findings that were remarkably cited in short time. This research is a continuation of that work, yet it has new findings as well. The author hopes this to be accepted and published.Design/methodology/approachThe approach that was used herein is widely used in the field i.e., the push-off specimen testing. The author has used this approach to investigate the shear performance of concrete exposed to elevated temperatures. In addition, the author has used means of Linear Variable Differential Transformers (LVDTs) to record the displacements of the loading.FindingsResults showed that, at ambient temperature, shear capacity is significantly increased by the virtue of using cocktail fibres, while insignificant increase is noticed using polymeric fibres only. However, significant decrease is noticed when elevated temperatures are included for both mixes.Originality/valueMany of the research findings here were accepted as New Scientific Results in my PhD Thesis. The novelty is remarkable and was appreciated by the committee.
What drives liking different brand-related social media content?
Authors: Ciunova-Shuleska Anita , Palamidovska-Sterjadovska Nikolina , Bogoevska-Gavrilova Irena 
Published: April 2022

PurposeThe purpose of this study is to analyze the interrelationships between incentives and social media users’ intentions to like different brand-related social media content. The study is based on the uses and gratification (U&G) theory and investigates three types of incentives i.e. communal, self-interest, and reward incentives which act as antecedents of customers’ intentions to like three types of brand-related content (commercial messages, personal opinion messages, and lifestyle messages).Design/methodology/approachA data set of 415 effective responses was collected and structural equation modeling (SEM) was used for analyzing the data.FindingsThe obtained results indicate that communal and reward incentives enhance the intentions to like brand-related commercial, personal opinion, and lifestyle content. Self-interest incentives reduce the intentions to like three types of analyzed brand-related content with the strongest negative influence on intentions to like lifestyle content. Regarding the content type, the main drivers for liking lifestyle content and commercial content are reward incentives, whereas liking personal opinion content is mostly motivated by communal incentives.Originality/valueThis study provides valuable insights about users’ motivation to like brand-related content on social media with a focus on different types of brand-related content. The study has strong theoretical contributions as well as practical implications.
Human capital disclosure and the contingency view
Authors: Lajili Kaouthar 
Published: April 2022

PurposeBuilding on an integration of strategic human resource capital management and human capital disclosure literature streams, this paper explores the associations between human resource performance and human resource disclosure in the financial services sector.Design/methodology/approachUsing content analysis and panel regression methods, the paper examines the extent, nature, and information content of human capital disclosures in the financial services sectors in North America during the global financial crisis period.FindingsLabor costs and marginal labor productivity are significantly associated with human resource disclosure and the latter is significantly related to both financial (explicit) and non-financial (implicit or relational) components of the employment relationship. Results show inverted effects between the US and Canadian samples. The findings support a contingency view or “best-fit” approach to human resource capital management.Practical implicationsDifferences in labor market structures and human capital attributes could have significant impacts on human capital disclosure strategies. More transparent and detailed disclosures regarding human resource capital management may provide useful and relevant information for investors and stakeholders in general.Originality/valueThe study provides insights into how labor market structures and human capital attributes jointly affect the extent and nature of corporate disclosures with regards to rents distribution and relational governance between employers and employees.