bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microfoundations of design sprint: how Johnson & Johnson cultivates innovation in a highly regulated market
Authors: Magistretti Stefano , Allo Luis , Verganti Roberto , Dell’Era Claudio , Reutter Felix 
Published: May 2021

PurposeMastering innovation in highly regulated markets might require companies to overcome significant barriers. Rules, laws and limitations on social, economic and institutional dimensions can hinder the ability of a company to transfer knowledge within and across organizational boundaries. However, as recent research in innovation management increasingly advocates user involvement and early understanding of user needs as best practices, the inability to freely interact with customers due to highly regulated market restrictions can hinder the company’s capability to innovate. Hence, this paper aims to shed light on how an emerging managerial approach, such as Design Sprint, can support companies operating in highly regulated markets to overcome user involvement limitations and boost human-centered innovation.Design/methodology/approachThis paper sheds light on how to boost innovation in a highly regulated market by leveraging an in-depth case study. The study investigates the use of the Design Sprint approach adopted by the pharmaceutical multinational Johnson & Johnson to revise the way its R&D department orchestrates the new product development process, overcoming the user involvement challenges of highly regulated markets.FindingsIn analyzing six different projects undertaken in the past two years, the findings illustrate three microfoundational dimensions of the Design Sprint approach in highly regulated markets, the so-called 3T model: team, time and tools. Indeed, deploying the Design Sprint in a highly regulated market has proven that being able to experiment in the early stages, building rough prototypes in real-time and openly collaborating with partners is crucial to boost innovation and anticipate constraints.Originality/valueThe paper sheds light on the Design Sprint approach by initially grounding an emerging managerial approach on organizational and management theory, leveraging the lens of microfoundations. In doing so, this study suggests how Design Sprint is based on the pillars of experimentation, knowledge transfer and co-creation usually neglected in highly regulated markets where user involvement is challenging. Finally, this study discloses the importance of using a design-based methodology in fostering innovation in highly regulated markets.
Contagion of COVID-19 pandemic between oil and financial assets: the evidence of multivariate Markov switching GARCH models
Authors: Ghorbel Achraf , Jeribi Ahmed 
Published: May 2021

Purpose
In this paper, we investigate empirically the time-frequency co-movement between the recent COVID-19 pandemic, G7stock markets, gold, crude oil price (WTI) and cryptocurrency markets (bitcoin) using both the multivariate MSGARCH models.

Design/methodology/approach
This paper examines the relationship between the volatilities of oil, Chinese stock index and financial assets (cryptocurrency, gold, and G7 stock indexes), for the period January 17th 2020 to December 10th 2020. It tests the presence of regime changes in the GARCH volatility dynamics of bitcoin, gold, Chinese, and G7 stock indexes as well as oil prices by using Markov–Switching GARCH model. Also, the paper estimates the dynamic correlation and volatility spillover between oil, Chinese and financial assets by using the MSBEKK-GARCH and MSDCC-GARCH models.

Findings
Overall, we find that all variables display a strong volatility concentrated in the first four months of Covid-19 outbreak. The paper conducts different backtesting procedures of the 1% and 5% Value-at-Risk forecasts of risk. The results find that gold has the lowest VaR. However, the Canadian and American indices have the highest VaR, for respectively 1% and 5% confidence level. The estimation results of MSBEKK-GARCH prove the volatility spillover between Chinese index, oil and financial assets. Although, the past news about shocks in the Chinese index significantly affects the current conditional volatility of financial assets. Moreover, for the high regime, the correlation increased between Chinese and G7 stock indexes which proving the contagion effect of the COVID-19 pandemic. On the contrary, the correlation decreased between Chinese-gold and Chinese-bitcoin, which confirming that gold and bitcoin can be considered as an alternative hedge for some investors during a crisis. During the COVID-19 pandemic, the correlations for the couples oil-gold and oil-bitcoin peaked. Contrary to gold, bitcoin cannot be considered as a safe haven during the global pandemic when investing in crude oil.

Originality/value
In contrast, comparative analysis in terms of responses to US COVID-19 pandemic, the US Covid-19 confirmed cases have relative higher impact on the co-movement in WTI and bitcoin. This paper confirms that gold is a safe haven during the COVID19 pandemic period.
Can adaptive–academic leadership duo make universities ready for change? Evidence from higher education institutions in Pakistan in the light of COVID-19
Authors: Mukaram Aamna Tariq , Rathore Kashif , Khan Mukaram Ali , Danish Rizwan Qaiser , Zubair Syed Sohaib 
Published: May 2021

Purpose
In rapidly changing global village, individuals, organizations and the society are faced with various unforeseen challenges every day, and these challenges continuously trigger and test the instincts for survival, and higher education is of no exception. In the context of today’s most critical uncertainty, i.e. COVID-19, the purpose of this study is to highlight the significance of two leadership styles, i.e. adaptive and academic leadership, and assessing readiness for change among higher education institutions (HEIs) of Punjab, Pakistan.

Design/methodology/approach
An online survey was conducted to collect data from 404 permanent faculty members in the public sector universities identified using stratified random sampling. The hypotheses developed were tested using co-variance-based structural equation modeling.

Findings
As per the findings, both leadership styles as exogenous constructs and the presence of organizational learning capability as mediators contributed positively in crafting organizational readiness for change (ORC) among HEIs in the course of unpredictable circumstances.

Practical implications
The COVID-19 episode globally has reiterated the importance of change, and the role of leadership in this regard cannot be undermined. This study, for that matter, stresses on the importance and benefits of academic and adaptive leadership dealing with uncertainties or change and the readiness of HEIs for change. Several institutions faced challenges in doing so, and the transition was not smooth, except for institutions where leaders were the differentiating factor. On top of it, institutions that had timely invested in digital systems and had enhanced organizations learning capacity survived in these turbulent times.

Originality/value
COVID-19 has placed tremendous challenges on HEIs to adapt with the rapidly changing conditions. Hence, this study is unique in understanding the academic and adaptive leadership styles in context of ORC. This study further helps in understanding that how public sector universities that are already influenced by stringent bureaucratic structures react to change.
Determinants of consumers’ frugal innovation acceptance in a developed country
Authors: Costa Leonor , Teixeira Aurora , Brochado Ana 
Published: May 2021

Purpose
This study aims to understand why young people are interested in buying frugal innovations.

Design/methodology/approach
Data were collected with a survey administered to 534 university students enrolled in various fields of study (e.g. sciences, technology, economics and fine arts). Using the Tata Nano car as an example of frugal innovation, a model based on the unified theory of acceptance and use of technology was developed using partial least squares structural equation modeling.

Findings
The model’s results reveal that effort expectancy, performance expectancy and facilitating conditions are critical factors that explain university students’ intention to buy Tata Nano.

Originality/value
Although frugal innovations are often introduced first in developing countries, frugal innovations could be highly relevant to users in developed nations as these innovations can provide market opportunities in terms of cost-conscious, relatively low-income and sustainability-conscious consumers.
The genetic and epigenetic basis of distinct melanoma types
Authors: Oba Junna , Woodman Scott E. 
Published: May 2021

AbstractMelanoma represents the deadliest skin cancer. Recent therapeutic developments, including targeted and immune therapies have revolutionized clinical management and improved patient outcome. This progress was achieved by rigorous molecular and functional studies followed by robust clinical trials. The identification of key genomic alterations and gene expression profiles have propelled the understanding of distinct characteristics within melanoma subtypes. The aim of this review is to summarize and highlight the main genetic and epigenetic findings of melanomas and highlight their pathological and therapeutic importance.
Effects of different chemical modifications on the structure and biological activities of polysaccharides from Orchis chusua D. Don
Authors: Nuerxiati Rehebati , Mutailipu Paiheerding , Abuduwaili Aytursun , Dou Jun , Aisa Haji Akber , Yili Abulimiti 
Published: May 2021

AbstractIn this study, an enzyme‐assisted extraction method was used to extract Orchis chusua D. Don (Salep) polysaccharide (SP), which was then modified by sulfation, acetylation, phosphorylation, and carboxymethylation to obtain modified polysaccharides. Furthermore, their degree of substitution, chemical composition, and molecular weight were evaluated. The primary structural features were characterized by UV spectra, FT‐IR spectra, Congo‐red test, and scanning electron microscope. The phosphorylated polysaccharide (SP‐P) was demonstrated the highest scavenging ability on hydroxyl radical and growth‐promoting activity on Lactobacillus Bulgaricus. The carboxymethylated polysaccharide (SP‐C) was exhibited the strongest DPPH and ABTS radical scavenging effects. The acetylated polysaccharide (SP‐A) displayed the best proliferation effects on Bifidobacterium adolescentis, whereas the sulfated polysaccharide (SP‐S) maintained moderately stable antioxidant and probiotic ability. These findings indicate that the modified polysaccharides had their potential significance as new antioxidants and probiotics for the food industry.Practical ApplicationThis article provides a new source for the development of polysaccharide derivatives as new antioxidants and probiotics for the food industry.
Development of dual‐inducible duet‐expression vectors for tunable gene expression control and CRISPR interference‐based gene repression in Pseudomonas putida KT2440
Authors: Gauttam Rahul , Mukhopadhyay Aindrila , Simmons Blake A. , Singer Steven W. 
Published: May 2021

SummaryThe development of P. putida as an industrial host requires a sophisticated molecular toolbox for strain improvement, including vectors for gene expression and repression. To augment existing expression plasmids for metabolic engineering, we developed a series of dual‐inducible duet‐expression vectors for P. putida KT2440. A number of inducible promoters (Plac, Ptac, PtetR/tetA and Pbad) were used in different combinations to differentially regulate the expression of individual genes. Protein expression was evaluated by measuring the fluorescence of reporter proteins (GFP and RFP). Our experiments demonstrated the use of compatible plasmids, a useful approach to coexpress multiple genes in P. putida KT2440. These duet vectors were modified to generate a fully inducible CRISPR interference system using two catalytically inactive Cas9 variants from S. pasteurianus (dCas9) and S. pyogenes (spdCas9). The utility of developed CRISPRi system(s) was demonstrated by repressing the expression of nine conditionally essential genes, resulting in growth impairment and prolonged lag phase for P. putida KT2440 growth on glucose. Furthermore, the system was shown to be tightly regulated, tunable and to provide a simple way to identify essential genes with an observable phenotype.
Evidence for local, regional and interregional exchange networks on Failaka: Some remarks on late Islamic pottery from Kharaib al‐Dasht
Authors: Mierzejewska Marta 
Published: May 2021

AbstractThe site of Kharaib al‐Dasht, located on the northern coast of Failaka, is a late Islamic settlement with an extensive fishing infrastructure. It has been excavated since 2013 by the Kuwaiti‐Polish Archaeological Mission. The ceramic assemblage collected so far exceeds 18,000 fragments. The sherds underwent technological and typological analyses, which demonstrated a wide diversity of local common kitchen wares, consistent with the needs of households specialised in fishing. A considerable percentage of imported vessels was brought to Failaka from the Arabian Gulf and Persia, though Far Eastern luxury tableware was also attested. This paper demonstrates the socioeconomic role of Kharaib al‐Dasht in the context of trade exchange on the microregional (Kuwait) and macroregional (the Gulf, South and Eastern Asia) scales in the eighteenth and nineteenth centuries.
Ordering Diversity: Co‐Producing the Pandemic and the Migrant in Singapore during COVID‐19
Authors: Ye Junjia 
Published: May 2021

AbstractWhat do measures of management during this exceptional and volatile time tell us about the regulation of migrant‐driven diversity and its implications in the arrival city? Using the term “differential diversification” from Singapore, I examine how the socio‐political life of the pandemic is deeply entangled with the management of low‐waged labour migrants. Techno‐political discourses and practices of pandemic management accelerated the state’s attempts to differently include migrant workers, revealing the bare viscerality of biopolitics already in place prior to the pandemic. I argue that diversity is ordered through a striking co‐production of migrant management and pandemic management. This paper draws upon government discourses to demonstrate that measures of pandemic management contribute not only to the spatial regime of migrant management. They also articulate and rationalise the subject transformation of the low‐waged migrant to the extent that, on top of being a moral risk, they are also now a medical risk.
Ocular characteristics and complications in patients with osteogenesis imperfecta: a systematic review
Authors: Treurniet Sanne , Burger Pia , Ghyczy Ebba A.E. , Verbraak Frank D. , Curro‐ Tafili Katie R. , Micha Dimitra , Bravenboer Nathalie , Ralston Stuart H. , de Vries Ralph , Moll Annette C. , Eekhoff Elisabeth Marelise W. 
Published: May 2021

AbstractPurposeOsteogenesis imperfecta (OI) is a rare inherited heterogeneous connective tissue disorder characterized by bone fragility, low bone mineral density, skeletal deformity and blue sclera. The dominantly inherited forms of OI are predominantly caused by mutations in either the COL1A1 or COL1A2 gene. Collagen type I is one of the major structural proteins of the eyes and therefore is the eye theoretically prone to alterations in OI. The aim of this systematic review was to provide an overview of the known ocular problems reported in OI.MethodsA literature search (in PubMed, Embase and Scopus), which included articles from inception to August 2020, was performed in accordance with the PRISMA guidelines.ResultsThe results of this current review show that almost every component of the eye could be affected in OI. Decreased thickness of the cornea and sclera is an important factor causing eye problems in patients with OI such as blue sclera. Findings that stand out are ruptures, lacerations and other eye problems that occur after minor trauma, as well as complications from standard surgical procedures.DiscussionAlterations in collagen type I affect multiple structural components of the eye. It is recommended that OI patients wear protective glasses against accidental eye trauma. Furthermore, when surgery is required, it should be approached with caution. The prevalence of eye problems in different types of OI is still unknown. Additional research is required to obtain a better understanding of the ocular defects that may occur in OI patients and the underlying pathology.
Possibility for avoidance of urgent nighttime operations for acute appendicitis in a regional core university hospital
Authors: Tago Tomoya , Shimoda Mitsugi , Imazato Ryosuke , Udou Ryutaro , Katsumata Kenji , Tsuchida Akihiko , Suzuki Shuji 
Published: May 2021

AbstractIntroductionIn recent years, a shortage of surgeons and anesthesiologists, particularly in regional hospitals, has become a social issue in Japan. In such hospitals, urgent surgery at night has been performed with difficulty. Therefore, we retrospectively assessed the outcomes of appendectomies for the patients visited at nighttime in our hospital categorized as a local university hospital.MethodsA retrospective review was conducted on 82 patients of acute appendicitis presented to our hospital between 5:30 p.m. to 8:30 a.m., between January 2014 and April 2019. We compared patients who underwent urgent nighttime appendectomy (group A) and patients who underwent appendectomy during the daytime, or so‐called short interval appendectomy (group B). The evaluated factors were preoperative characteristics (age, sex, body mass index, cardiopulmonary complications, laboratory data, body temperature, presence of the Blumberg sign, and CT findings), operation characteristics, and postoperative characteristics (surgical‐site infection [SSI], complications, and length of hospital stay).ResultsPatients in group A were significantly younger than patients in group B. Patients in group A were significant more likely to experience an SSI.DiscussionPatients diagnosed with acute appendicitis during the nighttime can undergo short interval appendectomy, which leads to a decreased risk of SSI, has no effect on length of hospital stay after surgery, and lessens medical staff burden.
Application of deep learning to understand resilience to Alzheimer's disease pathology
Authors: Lee Cecilia S. , Latimer Caitlin S. , Henriksen Jonathan C. , Blazes Marian , Larson Eric B. , Crane Paul K. , Keene C. Dirk , Lee Aaron Y. 
Published: May 2021

AbstractPeople who have Alzheimer's disease neuropathologic change (ADNC) typically associated with dementia but not the associated cognitive decline can be considered to be “resilient” to the effects of ADNC. We have previously reported lower neocortical levels of hyperphosphorylated tau (pTau) and less limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) in the resilient participants compared to those with dementia and similar ADNC as determined by current NIA‐AA recommendations using traditional semi‐quantitative assessments of amyloid β and pathological tau burden. To better understand differences between AD‐dementia and resilient participants, we developed and applied a deep learning approach to analyze the neuropathology of 14 brain donors from the Adult Changes in Thought study, including seven stringently defined resilient participants and seven age‐matched AD‐dementia controls. We created two novel, fully automated deep learning algorithms to quantify the level of phosphorylated TDP‐43 (pTDP‐43) and pTau in whole slide imaging. The models performed better than traditional techniques for quantifying pTDP‐43 and pTau. The second model was able to segment lesions staining for pTau into neurofibrillary tangles (NFTs) and tau neurites (neuronal processes positive for pTau). Both groups had similar quantities of pTau localizing to neurites, but the pTau burden associated with NFTs in the resilient group was significantly lower compared to the group with dementia. These results validate use of deep learning approaches to quantify clinically relevant microscopic characteristics from neuropathology workups. These results also suggest that the burden of NFTs is more strongly associated with cognitive impairment than the more diffuse neuritic tau commonly seen with tangle pathology and suggest that additional factors may underlie resilience mechanisms defined by traditional means.
Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer
Authors: Kobayashi Yuta , Masuda Takaaki , Fujii Atsushi , Shimizu Dai , Sato Kuniaki , Kitagawa Akihiro , Tobo Taro , Ozato Yuki , Saito Hideyuki , Kuramitsu Shotaro , Noda Miwa , Otsu Hajime , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi , Mori Masaki , Mimori Koshi 
Published: May 2021

AbstractMicrotubules are among the most successful targets for anticancer therapy because they play important roles in cell proliferation as they constitute the mitotic spindle, which is critical for chromosome segregation during mitosis. Hence, identifying new therapeutic targets encoding proteins that regulate microtubule assembly and function specifically in cancer cells is critical. In the present study, we identified a candidate gene that promotes tumor progression, ribonucleic acid export 1 (RAE1), a mitotic checkpoint regulator, on chromosome 20q through a bioinformatics approach using datasets of colorectal cancer (CRC), including The Cancer Genome Atlas (TCGA). RAE1 was ubiquitously amplified and overexpressed in tumor cells. High expression of RAE1 in tumor tissues was positively associated with distant metastasis and was an independent poor prognostic factor in CRC. In vitro and in vivo analysis showed that RAE1 promoted tumor growth, inhibited apoptosis, and promoted cell cycle progression, possibly with a decreased proportion of multipolar spindle cells in CRC. Furthermore, RAE1 induced chemoresistance through its anti–apoptotic effect. In addition, overexpression of RAE1 and significant effects on survival were observed in various types of cancer, including CRC. In conclusion, we identified RAE1 as a novel gene that facilitates tumor growth in part by inhibiting apoptosis and promoting cell cycle progression through stabilizing spindle bipolarity and facilitating tumor growth. We suggest that it is a potential therapeutic target to overcome therapeutic resistance of CRC.
Detection of von Hippel‐Lindau gene mutation in circulating cell‐free DNA for clear cell renal cell carcinoma
Authors: Sumiyoshi Takayuki , Yamasaki Toshinari , Takeda Masashi , Mizuno Kei , Utsunomiya Noriaki , Sakamoto Hiromasa , Nakamura Eijiro , Ogawa Osamu , Akamatsu Shusuke 
Published: May 2021

AbstractThe therapeutic landscape of metastatic clear cell renal cell carcinoma (ccRCC) has rapidly expanded, and there is an urgent need to develop noninvasive biomarkers that can select an optimal therapy or evaluate the response in real time. To evaluate the clinical utility of circulating tumor DNA (ctDNA) analysis in ccRCC, we established a highly sensitive assay to detect mutations in von Hippel‐Lindau gene (VHL) using a combination of digital PCR and multiplex PCR–based targeted sequencing. The unique assay could detect VHL mutations with a variant allele frequency (VAF) <1.0%. Further, we profiled the mutation status of VHL in 76 cell‐free DNA (cfDNA) and 50 tumor tissues from 56 patients with ccRCC using the assay. Thirteen VHL mutations were identified in cfDNA from 12 (21.4%) patients with a median VAF of 0.78% (range, 0.13%‐4.20%). Of the 28 patients with VHL mutations in matched tumor tissues, eight (28.6%) also had VHL mutation in cfDNA with a median VAF of 0.47% (range, 0.13%‐2.88%). In serial ctDNA analysis from one patient, we confirmed that the VAF of VHL mutation changed consistent with tumor size by radiographic imaging during systemic treatment. In conclusion, VHL mutation in cfDNA was detected only in a small number of patients even using the highly sensitive assay; nevertheless, we showed the potential of ctDNA analysis as a novel biomarker in ccRCC.