bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetic and Thermodynamic Insights on Agonist Interactions with the Parathyroid Hormone Receptor-1 from a New NanoBRET assay
Authors: Yu Zhen , Cary Brian P. , Kim Tae Wook , Nguyen Kevin D. , Gardella Thomas J. , Gellman Samuel H. 
Published: July 2022

AbstractPolypeptides that activate the parathyroid hormone receptor-1 (PTHR1) are important in human physiology and medicine. Most previous studies of peptide binding to this receptor have involved displacement of a radiolabeled ligand. We report a new assay format based on bioluminescence resonance energy transfer (BRET). Fusion of a nanoluciferase (nLuc) unit to the N-terminus of the PTHR1 allows direct detection of binding by an agonist peptide bearing a tetramethylrhodamine (TMR) unit. Affinity measurements from the BRET assay align well with results previously obtained via radioligand displacement. The BRET assay offers substantial operational benefits relative to affinity measurements involving radioactive compounds. The convenience of the new assay allowed us to explore several questions raised by earlier reports. For example, we show that although the first two residues of PTH(1-34) (the drug teriparatide) are critical for PTHR1 activation, these two residues contribute little or nothing to affinity. Comparisons among the well-studied agonists PTH(1-34), PTHrP(1-34) and “long-acting PTH” (LA-PTH) reveal that the high affinity of LA-PTH arises largely from a diminished rate constant for dissociation relative to the other two.
Extrachromosomal DNA in the cancerous transformation of Barrett’s esophagus
Authors: Luebeck Jens , Tian Ng Alvin Wei , Galipeau Patricia C. , Li Xiaohong , Sanchez Carissa A. , Katz-Summercorn Annalise , Kim Hoon , Jammula Sriganesh , He Yudou , Lippman Scott M. , Verhaak Roel , Maley Carlo C. , Alexandrov Ludmil B. , Reid Brian J. , Fitzgerald Rebecca C. , Paulson Thomas G. , Chang Howard Y. , Wu Sihan , Bafna Vineet , Mischel Paul S. 
Published: July 2022

ABSTRACTBACKGROUNDOncogenes are commonly amplified on extrachromosomal DNA (ecDNA) contributing to poor outcomes for patients. Currently, the chronology of ecDNA development is not known. We studied the origination and evolution of ecDNA in patients with Barrett’s esophagus (BE) who progressed to esophageal adenocarcinoma (EAC).METHODSWe analyzed whole-genome sequencing (WGS) data from a BE surveillance cohort and EAC patients at Cambridge University UK (n=206 patients). We also analyzed WGS data from biopsies taken at two time points from multiple sites in the esophagus from 80 patients enrolled in a case-control study at the Fred Hutchinson Cancer Center (FHCC) - 40 BE patients who progressed to EAC and 40 who did not.RESULTSecDNA was detected in 24% and 43% of BE patients with BE-associated early and late-stage EAC, respectively, in the Cambridge cross-sectional cohort. ecDNA was found in 33% of all FHCC BE patients who developed cancer, either prior to, or at EAC diagnosis. ecDNA was strongly associated with patients who developed cancer, in contrast with FHCC BE patients who did not progress (odds ratio, 18.8, CI – 2.3-152, p=3.3×10-4). ecDNAs were enriched for oncogenes and immunomodulatory genes and could be detected early in the transition from high-grade dysplasia to cancer and increased in copy number and complexity over time.CONCLUSIONSecDNAs can develop before a diagnosis of cancer in BE patients and are strongly selected for during the evolution to EAC. ecDNAs promote diverse oncogene and immunomodulatory gene amplification during EAC development and progression.
Neural tracking of speech does not unequivocally reflect intelligibility
Authors: Kösem Anne , Dai Bohan , McQueen James M. , Hagoort Peter 
Published: July 2022

AbstractDuring listening, brain activity tracks the rhythmic structures of speech signals. Here, we directly dissociated the contribution of neural tracking in the processing of speech acoustic cues from that related to linguistic processing. We examined the neural changes associated with the comprehension of Noise-Vocoded (NV) speech using magnetoencephalography (MEG). Participants listened to NV sentences in a 3-phase training paradigm: (1) pre-training, where NV stimuli were barely comprehended, (2) training with exposure of the original clear version of speech stimulus, and (3) post-training, where the same stimuli gained intelligibility from the training phase. Using this paradigm, we tested if the neural responses of a speech signal was modulated by its intelligibility without any change in its acoustic structure. To test the influence of spectral degradation on neural tracking independently of training, participants listened to two types of NV sentences (4-band and 2-band NV speech), but were only trained to understand 4-band NV speech. Significant changes in neural tracking were observed in the delta range in relation to the acoustic degradation of speech. However, we failed to find a direct effect of intelligibility on the neural tracking of speech in both theta and delta ranges. This suggests that acoustics greatly influence the neural tracking response to speech signals, and that caution needs to be taken when choosing the control signals for speech-brain tracking analyses, considering that a slight change in acoustic parameters can have strong effects on the neural tracking response.
Methylation genome wide profiling in lowly and highly efficient adipose somatic cell nuclear transfer in pigs
Authors: Grzybek Maciej , Flisikowski Krzysztof , Giles Tom , Walczak Marta , Ploski Rafal , Gasperowicz Piotr , Emes Richard D. , Lisowski Pawel 
Published: July 2022

AbstractSwine is a common model organism for biomedical research. Epigenetic reprogramming in SCNT embryos does not fully recapitulate the natural DNA demethylation events at fertilisation. This study aimed to conduct a genome-wide methylation profiling to detect differentially methylated regions (DMRs) responsible for epigenetic differences in stem cells that displayed high and low efficiency of SCNT and to elucidate the low efficiency of cloning rate in pigs. Adipose tissue mesenchymal stem cells (AMSC)s lines were isolated from adipose tissue of adult male pigs (n=20; high-efficiency cells=10; low efficiency cells= 10). Reduced representation bisulfite sequencing (RRBS) was performed on an Illumina HiSeq1500. Paired-end reads were filtered to remove the adapter contamination, and low-quality reads using TrimGalore!. Filtered reads were mapped to the reference genome using Bismark. MethylKit was used to identify differentially methylated regions (DMRs) (bases and tiles), showing statistically significant differential methylation between two groups: high and low-efficiency AMSCs. Hierarchical cluster analysis according to methylation patterns clearly defined groups with low and high cloning efficiency. We report 3704 bases with statistically significant differences in methylation and 10062 tiles with statistically significant differences in methylation. Most differentially methylated sites are intergenic 62%, 31% are intronic, 4% are located in exons and 4% in promoters. 37% of differentially methylated sites are located in known CpG islands (CGIs) and 4% in CpG island shores (CGSs).
Survivin (BIRC5) peptide vaccine in the 4T1 murine mammary tumor model: a potential neoadjuvant T-cell immunotherapy for triple negative breast cancer
Authors: Burkholz Scott R , Herst Charles V , Carback Richard T , Harris Paul E , Rubsamen Reid M 
Published: July 2022

AbstractA triple negative breast cancer (TNBC) model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin (SVN)-peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but minimal morbidity/mortality within the required study period. Later, in a second cohort of mice, the SVN-peptide microparticle vaccine was administered via intraperitoneal injection at study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3-4 days. Vaccination with SVN peptides was associated with a peptide antigen-specific γIFN Elispot response in the murine splenocyte population but was absent from the control microparticle group. At end of study, we found that vaccination with adjuvanted SVN-peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptide-less vaccination group. These studies suggest that T-cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for TNBC. More pre-clinical studies and clinical trials will be needed to explore this concept further.
Maruti Suzuki India Limited: toward cleaner mobility
Authors: Kumar Santosh , Sahay Arunaditya 
Published: July 2022

Learning outcomes
The case study “Maruti Suzuki – toward cleaner mobility” has been written keeping in view the requirements in the field of strategic management. The key learning objectives are as follows:• Analysis of business environment.• Product development strategy – creating market segment to gain competitive advantage by leveraging available organizational capabilities.• Strategic decision-making – understanding strategic decision-making process in a complex and highly competitive business scenario.

Case overview/synopsis
Maruti Suzuki, a leader in Indian automotive market with around 50% market share in passenger cars, was likely to face intense competition because of disruption by electric vehicles. As electric vehicles adoption was increasing globally in developed countries, automotive companies shaped their strategy accordingly to stay relevant. Maruti Suzuki was yet to be ready with electric vehicles and approached this space differently than other competitors. However, with Indian Government pushing toward cleaner mobility, it was yet to be seen how the company would manage to comply with legislations and compete effectively in marketplace. Indian Auto major, Maruti Suzuki, was on the edge to decide future strategy on electric vehicles to sustain its leadership position. The Indian automotive sector was going through the transformation where auto original equipment manufacturers were bringing electric vehicles and supporting policies from government likely to accelerate its adoption. Maruti Suzuki was striving to counter the competition with available resources to create competitive advantage in changing environment and continue to remain profitable with leadership position in Indian automotive market. The company had successfully maintained its leading position over three decades and transformed the automotive space with its strategies ahead of the curve. Now the company was standing at crossroads with regard to future technology on cleaner mobility. Mr Bhargava had to decide whether to throw the hat in EV ring or wait for other alternate technology disruption.

Complexity academic level
Management studies and executive development programs.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy
Framework for entity extraction with verification: application to inference of data set usage in research publications
Authors: Nestorov Svetlozar , Bačić Dinko , Jukić Nenad , Malliaris Mary 
Published: July 2022

Purpose
The purpose of this paper is to propose an extensible framework for extracting data set usage from research articles.

Design/methodology/approach
The framework uses a training set of manually labeled examples to identify word features surrounding data set usage references. Using the word features and general entity identifiers, candidate data sets are extracted and scored separately at the sentence and document levels. Finally, the extracted data set references can be verified by the authors using a web-based verification module.

Findings
This paper successfully addresses a significant gap in entity extraction literature by focusing on data set extraction. In the process, this paper: identified an entity-extraction scenario with specific characteristics that enable a multiphase approach, including a feasible author-verification step; defined the search space for word feature identification; defined scoring functions for sentences and documents; and designed a simple web-based author verification step. The framework is successfully tested on 178 articles authored by researchers from a large research organization.

Originality/value
Whereas previous approaches focused on completely automated large-scale entity recognition from text snippets, the proposed framework is designed for a longer, high-quality text, such as a research publication. The framework includes a verification module that enables the request validation of the discovered entities by the authors of the research publications. This module shares some similarities with general crowdsourcing approaches, but the target scenario increases the likelihood of meaningful author participation.
Flood knowledge management by multiple stakeholders: an example from Malaysia
Authors: Along Nurul Zainab Binti , Ahmed Iftekhar , MacKee Jamie 
Published: July 2022

Purpose
The purpose of this study is to explore multiple stakeholders managing the different type of knowledge in a flood-prone area. Different stakeholders hold different types of knowledge in their area of interest, and both knowledge streams have their intrinsic potentials and limitations. In this paper, the issue of knowledge complementarity is explored in the context of flood hazards. Hazards such as floods may appear messy, unpredictable, with unsorted and unorganised forms of data, information and knowledge on the part of diverse stakeholders.

Design/methodology/approach
Case study design had been used in this study to explore how stakeholders: Orang Asli, Malay, and humanitarian organisations manage the differences in terms of type of knowledge each of them have. To illicit the response from participants from each of the stakeholders, in-depth interviews had been used.

Findings
This research has led to the development of a conceptual framework based on the case study. The lessons learned from the framework is discussed, together with the barriers to their implementation.

Originality/value
This paper presents a research case study on multiple stakeholders in the district of Pekan, the state of Pahang, Malaysia, and how these multiple stakeholders manage flood hazards with their different types of knowledge.
A deep neural network-based approach for fake news detection in regional language
Authors: Katariya Piyush , Gupta Vedika , Arora Rohan , Kumar Adarsh , Dhingra Shreya , Xin Qin , Hemanth Jude 
Published: July 2022

Purpose
The current natural language processing algorithms are still lacking in judgment criteria, and these approaches often require deep knowledge of political or social contexts. Seeing the damage done by the spreading of fake news in various sectors have attracted the attention of several low-level regional communities. However, such methods are widely developed for English language and low-resource languages remain unfocused. This study aims to provide analysis of Hindi fake news and develop a referral system with advanced techniques to identify fake news in Hindi.

Design/methodology/approach
The technique deployed in this model uses bidirectional long short-term memory (B-LSTM) as compared with other models like naïve bayes, logistic regression, random forest, support vector machine, decision tree classifier, kth nearest neighbor, gated recurrent unit and long short-term models.

Findings
The deep learning model such as B-LSTM yields an accuracy of 95.01%.

Originality/value
This study anticipates that this model will be a beneficial resource for building technologies to prevent the spreading of fake news and contribute to research with low resource languages.
Evolutionary philosophical games in strategic management
Authors: Ozkan-Canbolat Ela , Ozkan Gulberk , Beraha Aydin 
Published: July 2022

Purpose
This paper aims to show that evolutionary game theory not only provides a general and unified theory of political philosophy and strategic management theories but also a positive theory of interactive behavior.

Design/methodology/approach
This study suggests a way of the evolutionary game-theoretical model.

Findings
The model presented in this paper demonstrates coopetition is derived from balance points in multi-actor games. As the political–philosophical address of those strategic games will of all becomes convention in this balance point at which common knowledge occurs global optimum.

Research limitations/implications
This study explores the connections between several streams in philosophy and strategic management. What does a particular philosophy contribute to strategic management with respect to game theory? When addressing this question in historical or exploratory terms, or in a combination of both, the end result is similar: particular philosophical issues, properly explained, are discussed in relation to important questions in strategic management.

Practical implications
What are the psychological and behavioral underpinnings of strategic decisions of this kind? What type of cognitive frames and managerial mental models, such as the game-theoretical model, might enable or hinder the integration of real-world problems in strategic decision-making?

Social implications
What explains the evolution of such mental models, as well as the development of philosophical ideas, in informing the origins? How does the evolution of social and political contexts influence change in the cognitive and behavioral underpinnings of strategic decision-making?

Originality/value
This study highlights the overt power of strategic management ideas – competition, cooperation and coopetition – which have historically been built on the foundations of organizational theory, while also underlying the potential of philosophies, collective wisdom and Condorcet’s jury theorem and Rousseau’s (1998) correctness theory in games of evaluation. This study investigates whether the many produce better decisions than the wise few.
The IPSAS implementation and the use and usefulness of accounting information: a comparative analysis in the Iberian Peninsula
Authors: Gomes Patrícia , Brusca Isabel , Fernandes Maria J. , Vilhena Estela 
Published: July 2022

PurposeThis paper aims to research the reforms toward International Public Sector Accounting Standards (IPSAS) implementation and the perceptions about the use and usefulness of accounting information in the context of local government in the Iberian Peninsula. The paper focuses on the perspective of chief financial officers (CFOs).Design/methodology/approachThe paper uses a mix of qualitative and quantitative methods. Beyond the study of the context of the reform in both countries through the consultation of legislation and official documents, the authors collected primary data through a survey addressed to the local CFO to catch both countries' perceptions and beliefs toward the topic under research.FindingsThe authors' findings evidence that both countries have made strong efforts to adapt IPSAS to both countries' national standards. The coercive and mimetic isomorphism and the private accounting normative were important determinants in the reform. Looking at perceptions, budget information continues to be perceived as the king information for public management and decision-making. In a comparative way, the Portuguese CFO seems to be more optimistic concerning the use and usefulness of the new accounting system. The strong orientation of CFO to cash-basis and budgeting information is an important explanation of the lower use and usefulness, essentially in the Spanish context. The regression results show that individual perceptions and beliefs on the accounting reform influence the opinion about the usefulness and use of financial information.Research limitations/implicationsThe use of the survey method has some limitations very discussed in the literature that are also applied in this study.Practical implicationsThe paper has the potential to contribute to the academic, political and practitioner discussion of the core purposes of financial accounting information in the public sector and financial accounting information's impacts on the European Public Sector Accounting Standards (EPSAS) framework.Originality/valueThe recent adoption of the new accounting system in local governments of both contexts contributes to knowledge on the public sector accounting reforms toward the transition to accrual accounting and the IPSAS. The innovative character of the paper contributes to better clarify how the perceptions of the accounting reform influence the usage level of public financial information.
Prevention-focused leadership and well-being during the pandemic: mediation by role clarity and workload
Authors: Li Keyao , Griffin Mark A. 
Published: July 2022

PurposeThe global pandemic has required organisational leaders to respond rapidly in a time of uncertainty. A specific challenge for leaders during the global pandemic is the salient and immediate threat to worker health and well-being. Unfortunately, the consequences of different leadership actions in this context are not well understood. By exploring the path from leader behaviour to employee well-being via experienced work characteristics, this study aims to provide a framework for better understanding pandemic threat and corresponding leadership impact.Design/methodology/approachTwo prevention-focused leadership strategies were explored: defend and adapt strategy. Two important work characteristics role clarity and workload were used to help explain the links between leadership strategies and well-being. Potential mediating pathways were tested in path analysis with Mplus (v7.4) based on 515 online survey responses.FindingsDifferent mediating pathways demonstrated complex associations between the constructs. Increases in the both prevention-focused leadership strategies were found associated with positive well-being by increasing employees' perceptions of leadership and by improving role clarity in the workplace. Notably, evidence also supported that increase in defend strategy was linked to reduced worker well-being through intensified workload.Originality/valueIn times of uncertainty amidst the global COVID-19 pandemic, prevention-focused leadership is vital to engage the workforce and ensure compliance with safety procedures to avoid associated risks to worker health and organisational performance. This research focused on the rarely studied topic of prevention-focused leadership, and how prevention strategies were related to employee well-being. Based on the findings for prevention-focused defend and adapt strategies, this study suggested leadership practices that might shape employee well-being in a time of turbulence.