bluuebunny/crossref_metadata_2025_split huggingface dataset:
A regularized functional regression model enabling transcriptome-wide dosage-dependent association study of cancer drug response
Authors: Koukouli Evanthia , Wang Dennis , Dondelinger Frank , Park Juhyun 
Published: June 2020

AbstractCancer treatments can be highly toxic and frequently only a subset of the patient population will benefit from a given treatment. Tumour genetic makeup plays an important role in cancer drug sensitivity. We suspect that gene expression markers could be used as a decision aid for treatment selection or dosage tuning. Usingin vitrocancer cell line dose-response and gene expression data from the Genomics of Drug Sensitivity in Cancer (GDSC) project, we build a dose-varying regression model. Unlike existing approaches, this allows us to estimate dosage-dependent associations with gene expression. We include the transcriptomic profiles as dose-invariant covariates into the regression model and assume that their effect varies smoothly over the dosage levels. A two-stage variable selection algorithm (variable screening followed by penalised regression) is used to identify genetic factors that are associated with drug response over the varying dosages. We evaluate the effectiveness of our method using simulation studies focusing on the choice of tuning parameters and cross-validation for predictive accuracy assessment. We further apply the model to data from fiveBRAFtargeted compounds applied to different cancer cell lines under different dosage levels. We highlight the dosage-dependent dynamics of the associations between the selected genes and drug response, and we perform pathway enrichment analysis to show that the selected genes play an important role in pathways related to tumourgenesis and DNA damage response.Author SummaryTumour cell lines allow scientists to test anticancer drugs in a laboratory environment. Cells are exposed to the drug in increasing concentrations, and the drug response, or amount of surviving cells, is measured. Generally, drug response is summarized via a single number such as the concentration at which 50% of the cells have died (IC50). To avoid relying on such summary measures, we adopted a functional regression approach that takes the dose-response curves as inputs, and uses them to find biomarkers of drug response. One major advantage of our approach is that it describes how the effect of a biomarker on the drug response changes with the drug dosage. This is useful for determining optimal treatment dosages and predicting drug response curves for unseen drug-cell line combinations. Our method scales to large numbers of biomarkers by using regularisation and, in contrast with existing literature, selects the most informative genes by accounting for drug response at untested dosages. We demonstrate its value using data from the Genomics of Drug Sensitivity in Cancer project to identify genes whose expression is associated with drug response. We show that the selected genes recapitulate prior biological knowledge, and belong to known cancer pathways.
Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243A>G mtDNA mutation
Authors: Chung Chih-Yao , Singh Kritarth , Kotiadis Vassilios N , Valdebenito Gabriel E , Ahn Jee Hwan , Topley Emilie , Tan Joycelyn , Andrews William D , Bilanges Benoit , Pitceathly Robert D S , Szabadkai Gyorgy , Yuneva Mariia , Duchen Michael R 
Published: June 2020

ABSTRACTMutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy – tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient derived cells carrying the most prevalent disease related mtDNA mutation, m.3243A>G. These studies reveal that the mutation promotes changes in metabolites which is associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 activated mitophagy, reduced mtDNA mutant load and rescued cellular bioenergetic function. The rescue was prevented by inhibition of mitophagy. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243A>G mutation.
Use of Scrum in the rehabilitation of a commercial building in Peru
Authors: Ormeño Zender Ysmael , García de Soto Borja 
Published: June 2020

Purpose
This study seeks to break the current paradigm that Scrum, as an agile framework, is only applicable for information technologies (IT) projects and to confirm the feasibility of its application in the construction sector.

Design/methodology/approach
The rehabilitation of a shopping mall in Piura (Peru) is used as a case study to implement Scrum in a construction project. In addition, a thorough literature review is performed to establish the state-of-the-art and practice in this field and set the foundation of the elements applied during the case study.

Findings
The results of this study show the great versatility of Scrum in the construction sector. The key findings include a reduction of the construction duration that provided value to the owner, flexibility for the inclusion of changes (induced by the client or by the complexity of the context in which the project is developed), risk control in high uncertainty scenarios and general satisfaction for all stakeholders.

Originality/value
The waterfall or traditional management methodologies are not always effective in construction projects, and their application depends on the features and complexity of the environment in which they are developed. This study provides a case study showing the application of Scrum in the construction industry. The positive results obtained from the application can be used by researchers and practitioners looking to incorporate Scrum (or other agile tools) to enhance the management of construction projects.
Emerging regional innovation policies for industry 4.0: analyzing the digital innovation hub program in European regions
Authors: Hervas-Oliver Jose-Luis , Gonzalez-Alcaide Gregorio , Rojas-Alvarado Ronald , Monto-Mompo Silvia 
Published: June 2020

Purpose
Industry 4.0 or digitization, from a regional innovation system (RIS) and policy perspective to improve regional innovation, is over-looked. Specifically, this paper aims to focus on analyzing the nascent European Commission (EC) digital innovation hub (DIH) program, designed for fostering transition into Industry 4.0 in regions and facilitating new path development.

Design/methodology/approach
Empirically, 10 Spanish DIH is explored through interviews and secondary data analysis.

Findings
The results suggest that DIHs despite their emerging and trial-and-error stage are designed for promoting multi-actor collaborative platforms including non-local actors to stimulate transition into Industry 4.0 by promoting place-based collaboration alliances that respond to local/regional contextual specificities and demands. These regional-based platforms facilitate public-private partnerships that co-design policy initiatives resulting from co-participation and negotiation of spatially-bounded oriented initiatives for digitizing.

Originality/value
The authors answer: what are the key characteristics of emerging European-level regional innovation policies aimed at facilitating Industry 4.0 in regions? This is the first study on the topic.
Public aid for ultra-fast broadband development in archipelagos. The Canary Islands case
Authors: Hernández Pedro Fuentes , Aguilar Chinea Rosa María , Baquero Pérez Pedro 
Published: June 2020

Purpose
This paper aims to study the results of the public aid programmes, through supply-side subsidies, for ultra-fast next generation access (NGA) broadband deployment that have been developed in The Canary Islands since 2013. These findings will, in turn, hopefully help the policymakers of archipelagos define their own ultra-fast broadband development plans.

Design/methodology/approach
An empirical approach has been used, based on the observation of the historical results obtained in the archipelago and the way broadband was diffused throughout the territory.

Findings
Results show that the broadband has developed asymmetrically in the archipelago, which, in turn, has caused the onset of a triple spatial digital divide. It was also observed that some aspects of the current way that such programmes are created and, consequently, the way that public funds are allocated, that could be improved and might help prevent geographical discrimination. Lastly, several insights have been presented for further investigation.

Originality/value
A large amount of scientific research has been carried out studying ultra-fast broadband NGA networks deployment. Less literature can be found on this topic when considering the specificities of fragmented territories like archipelagos. This paper tries to contribute with some empirical insights about such specific scenarios.
How much firms “give” to CSR vs how much they “gain” from it: inequity perceptions and their implications for CSR authenticity
Authors: Tarabashkina Liudmila , Quester Pascale G. , Tarabashkina Olga 
Published: June 2020

PurposeThe purpose of this study is to answer the call for additional detailed research on factors that influence corporate social responsibility (CSR) authenticity by examining how the former is affected by the commonly reported CSR spending allocations expressed as percentages of annual profits. It integrates equity and attribution theories to propose a new construct of inequity perceptions to explain how CSR spending allocations influence CSR authenticity. Inequity perceptions form from smaller allocations that are perceived disproportionate compared to the potential reputational gains from the executed CSR communication, which, in turn, prompts lower authenticity inferences.Design/methodology/approachThree experiments were performed. Study 1 examines how different CSR spending allocations influence inequity perceptions and how the latter relate to CSR authenticity. Study 2 examines how inequity perceptions are affected by firm size. Study 3 examines whether psychological distance (being a customer or non-customer) affects information processing by predisposing customers to forming higher inequity perceptions.FindingsStudy 1 shows that lesser allocations produce higher inequity perceptions. Study 2 demonstrates that inequity perceptions are enhanced when numerically small allocations are reported by a large as opposed to a small firm. Study 3 shows that both customers and non-customers form similar inequity perceptions from smaller percentage allocations without support for the psychological distance effect.Research limitations/implicationsThis study shows that the percentage of profits allocated to CSR, as well as firm size, can affect authenticity inferences via inequity perceptions. These findings point to different implications of CSR communication that features percentage allocations that multiple firms may not be aware of.Practical implicationsMarketers can benefit from the reported findings by understanding when and how CSR communication that features percentage allocations may be counter-productive by generating lesser CSR authenticity.Originality/valueThis study provides a novel perspective on how consumers evaluate CSR authenticity in a marketplace where awareness of firms’ vested interests is increasing.
Crude oil price prediction based on LSTM network and GM (1,1) model
Authors: Yao Tianxiang , Wang Zihan 
Published: June 2020

PurposeAccording to the problem of crude oil price forecasting, the purpose of this paper is to propose a multi-step prediction method based on the empirical mode decomposition, long short-term memory network and GM (1,1) model.Design/methodology/approachFirst, the empirical mode decomposition method is used to decompose the crude oil price series into several components with different frequencies. Then, each subsequence is classified and synthesized based on the specific periodicity and other properties to obtain several components with different significant characteristics. Finally, all components are substituted into a suitable prediction model for fitting. LSTM models with different parameters are constructed for predicting specific components, which approximately and respectively represent short-term market disturbance and long-term influences. Rolling GM (1,1) model is constructed to simulate a series representing the development trend of oil price. Eventually, all results obtained from forecasting models are summarized to evaluate the performance of the model.FindingsThe model is respectively applied to simulate daily, weekly and monthly WTI crude oil price sequences. The results show that the model has high accuracy on the prediction, especially in terms of series representing long-term influences with lower frequency. GM (1,1) model has excellent performance on fitting the trend of crude oil price.Originality/valueThis paper combines GM (1,1) model with LSTM network to forecast WTI crude oil price series. According to the different characteristics of different sequences, suitable forecasting models are constructed to simulate the components.
Too far east is west: tax risk, tax reform and investment timing
Authors: Chen Wanyi 
Published: June 2020

PurposeTax risk refers to the uncertainty of future corporate taxation. Tax reform is a key issue in major current tax system adjustments that seriously affect a firm's tax risk. In response to changes in the economic environment, many countries are actively executing tax reform. Long-term reforms implemented for a smooth transition may instead increase corporate risk. This study examines the relationship among tax risk, tax reform and investment timing.Design/methodology/approachSelecting the Shanghai Stock Exchange and Shenzhen Stock Exchange A-share listed companies' panel data from 2008 to 2017, the paper used survival analysis and the propensity score matching-difference in difference models.FindingsThe results show that a higher corporate tax risk results in more deferred investments, which are further examined using the latest Chinese value-added tax reform as a natural experiment.Originality/valueThe conclusion serves as an important reference for governments to balance reform time and to support enterprises in effectively identifying and managing tax risk under tax reform.
A production recovery plan in manufacturing supply chains for a high-demand item during COVID-19
Authors: Paul Sanjoy Kumar , Chowdhury Priyabrata 
Published: June 2020

PurposeA recent global pandemic, known as coronavirus disease 2019 (COVID-19), affects the manufacturing supply chains most significantly. This effect becomes more challenging for the manufacturers of high-demand and most essential items, such as toilet paper and hand sanitizer. In a pandemic situation, the demand of the essential products increases expressively; on the other hand, the supply of the raw materials decreases considerably with a constraint of production capacity. These dual disruptions impact the production process suddenly, and the process can collapse without immediate and necessary actions. To minimize the impacts of these dual disruptions, we aim to develop a recovery model for making a decision on the revised production plan.Design/methodology/approachIn this paper, the authors use a mathematical modeling approach to develop a production recovery model for a high-demand and essential item during the COVID-19. The authors also analyze the properties of the recovery plan, and optimize the recovery plan to maximize the profit in the recovery window.FindingsThe authors analyze the results using a numerical example. The result shows that the developed recovery model is capable of revising the production plan in the situations of both demand and supply disruptions, and improves the profit for the manufacturers. The authors also discuss the managerial implications, including the roles of digital technologies in the recovery process.Originality/valueThis model, which is a novel contribution to the literature, will help decision-makers of high-demand and essential items to make an accurate and prompt decision in designing the revised production plan to recover during a pandemic, like COVID-19.
What is value? Impact assessment of cultural heritage
Authors: Reher Guillermo S. 
Published: June 2020

PurposeThere are currently various methodologies used for carrying out impact assessments of cultural heritage. This paper aims to critically explore the reasons for this diversity and ascertain their varying consistency.Design/methodology/approachThe paper does a comparative analysis of the methodologies used, exploring how they measure up to the theoretical underpinnings of the ecosystem services approach and the cultural values model, considered to be the most comprehensive strategies for assessing the impact of cultural heritage.FindingsThe study reveals that there are few methodologies, and they only inconsistently work upon the theoretical perspectives mentioned earlier. In addition, from the public policy perspective, surprisingly few areas endowed with cultural heritage have been, in one way or another, assessed for impact, perhaps in part due to the lack of adequate methodologies.Research limitations/implicationsThe methods analysed are those that have been made public, which can be found in English. Also, they may be exploratory themselves, so some of the conclusions reached here may have also been found by the analysts themselves. This research serves to provide some scientific groundings for developing a more comprehensive impact assessment method.Practical implicationsThe results of this paper highlight certain glaring absences from current methodologies which invite the development of more definitive cultural impact assessment models. This is possible given the current state of the art, and further research and practice are necessary to develop a more comprehensive cultural values model–based research assessment.Social implicationsBy focussing on the absence of certain indicators on behalf of impact assessment methodologies, this paper sheds light on the overlooked (or under-measured) benefits derived from cultural heritage. Many of the benefits derived from this type of resource find an opportunity to come out in the open, greatly affecting researchers, cultural heritage planners and local communities.Originality/valueThis paper also serves to substantiate a glaring absence within the ecosystem services framework, which is the lack of practical methodologies for measuring some of these service values.
Transgender sex offenders: gender dysphoria and sexual offending
Authors: Sahota Kirpal Kaur 
Published: June 2020

PurposeTransgender sex offenders are a small, complex and atypical group. The purpose of this paper is to highlight the issues in relationship to the assessment of gender dysphoria in transgender sex offenders and approaches to risk management.Design/methodology/approachClinical and research experience as a Gender Specialist and Consultant Forensic Psychiatrist who has managed sex offender populations has informed this publication.FindingsLittle is known about the relationship between gender dysphoria and criminality. More research is required to develop a typology of transgender sex offenders and develop actuarial risk instruments. Protective factors in relation to gender affirmative care are also important to understand.Research limitations/implicationsThere is little empirical research to guide gender specialists and criminal justice professionals in the management of gender dysphoria and address risk and recidivism in transgender offender populations. The treatment of gender dysphoria could result in improved well-being and better psychosocial adjustment but cannot be relied to reduce future recidivism.Practical implicationsThere is no evidence that treatment of gender dysphoria reduces risk and recidivism in transgender sex offenders and that research is required to identify specific gender related dynamic risk factors.Social implicationsRecommendations are directly relevant to the work of prison and probation staff, community supervisors and gender identity specialists.Originality/valueAs far as the author is aware it is the first paper on the assessment and management of gender diverse sex offenders integrating approaches to gender dysphoria assessment and treatment and risk management. It has implication for gender identity specialists, criminal justice professionals, research and policy.
An impact of simulation labs on engineering students' academic performance: a critical Investigation
Authors: Jasti Naga Vamsi Krishna , Kota Srinivas , P.B. Venkataraman 
Published: June 2020

Purpose
This paper aims to investigate the impact of simulation laboratory on continuing education engineering students’ academic performance.

Design/methodology/approach
The investigation consists of establishing the student learning levels then mapping the student learning levels (knowledge, comprehension, application, analysis, synthesis and evaluation) through program outcomes with appropriate evaluation components. 270 continuing education students enrolled during six years were selected to be observed as part of this study. These students were divided into two subgroups, one with 135 students who were offered simulation lab (G2) and the other 135 students were not offered simulation lab (G1) in this investigation. Subsequently, a comparative analysis was carried out on these two groups to assess the student performance in multiple evaluation components with respect to student learning level and program outcome achievement.

Findings
It was identified that student performance in the application, analysis, synthesis and evaluation learning levels has improved for the group with simulation lab, and no change or minimal change was observed for the group without simulation lab. It was revealed that the simulation lab practice problems needs to be aligned with the theoretical concepts in the course to get a better performance from the students.

Originality/value
The study was conducted in one of the leading institutes with 270 students’ performance observed over a period of six years. It is the comprehensive work done on a complete program with data collated over a period of six years in multiple courses and multiple assessments.