bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers
Authors: Lemma Roza Berhanu , Fleischer Thomas , Martinsen Emily , Ledsaak Marit , Kristensen Vessela , Eskeland Ragnhild , Gabrielsen Odd Stokke , Mathelier Anthony 
Published: May 2021

AbstractMethylation of cytosines on DNA is a prominent modification associated with gene expression regulation. Aberrant DNA methylation patterns have recurrently been linked to dysregulation of the regulatory program in cancer cells. To shed light on the underlying molecular mechanism driving this process, we hypothesized that aberrant methylation patterns could be controlled by the binding of specific transcription factors (TFs) across cancer types. By combining DNA methylation arrays and gene expression data with TF binding sites (TFBSs), we explored the interplay between TF binding and DNA methylation in 19 cancer types. We performed emQTL (expression-methylation quantitative trait loci) analyses independently in each cancer type and identified 13 TFs whose expression levels are correlated with local DNA methylation patterns around their binding sites in at least 2 cancer types. The 13 TFs are mainly associated with local demethylation and are enriched for pioneer function, suggesting a specific role for these TFs in modulating chromatin structure and transcription in cancer patients. Furthermore, we confirmed that de novo methylation is precluded across cancers at CpGs lying in genomic regions enriched for TF-binding signatures associated with SP1, CTCF, NRF1, GABPA, KLF9, and/or YY1. The modulation of DNA methylation associated with TF binding was observed at cis-regulatory regions controlling immune- and cancer-associated pathways, corroborating that the emQTL signals were derived from both cancer and tumor-infiltrating cells. As a case example, we experimentally confirmed that FOXA1 knock-down is associated with higher methylation in regions bound by FOXA1 in breast cancer MCF-7 cells. Finally, we reported physical interactions between FOXA1 with TET1 and TET2 both in an in vitro setup and in vivo at physiological levels in MCF-7 cells, adding further support for FOXA1 attracting TET1 and TET2 to induce local demethylation in cancer cells.
Vaccination-induced rapid protection against bacterial pneumonia via training alveolar macrophage in mice
Authors: Gu Hao , Zeng Xi , Peng Liusheng , Xiang Chuanying , Zhou Yangyang , Zhang Xiaomin , Zhang Jixin , Wang Ning , Guo Gang , Li Yan , Liu Kaiyun , Gu Jiang , Zeng Hao , Zhuang Yuan , Li Haibo , Zhang Jinyong , Zhang Weijun , Zou Quanming , Shi Yun 
Published: May 2021

AbstractVaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here we demonstrated a single intranasal immunization of inactivated whole cell (IWC) of Acinetobacter baumannii elicits rapid protection against A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.
A Facile Alternative Sustainable Process for the Extraction and Purification of Microbial Melanin
Authors: Ghadge Vishal , Kumar Pankaj , Maity Tapan K. , Prasad Kamalesh , Shinde Pramod B. 
Published: May 2021

ABSTRACTConventional techniques for the extraction of the melanin encounter several disadvantages such as poor extraction efficiency, excessive use of acid and alkali, and lengthy time duration. To extract melanin in a more sustainable manner, herein suitability of an aqueous solution of quaternary ammonium hydroxide known as tetrabutylammonium hydroxide (40% w/w TBAOH in water) to extract and purify the pigment from the endophyte Streptomyces hyderabadensis 7VPT5-5R was investigated. The solvent could extract 5.54±0.03 g/L of pure melanin against 3.31± 0.02 g/L of pure melanin by conventional method from bacterial culture resulting 66% increase in the yield of the pigment. The quaternary ammonium based solvent was further recycled for 5 consecutive cycles and production of melanin with yield ranging from 5.54±0.03 g/L to 5.47± 0.02 g/L was obtained. The yield of the pigment was 38−40% higher in the recycled solvent in comparison to the melanin yield extracted by conventional method. Considering the efficiency of the solvent for effective extraction and purification of melanin and its recyclability potential, it can be considered as a sustainable solvent for the extraction of the pigments from bacterial culture. Furthermore, the developed method for extraction of melanin from microorganisms as a sustainable source would help in reducing the cost of melanin leading to its efficient utilization in diverse fields.
SARS-CoV-2 receptor ACE2 identifies immuno-hot tumors in breast cancer
Authors: Mei Jie , Cai Yun , Xu Rui , Yu Xinqian , Chen Lingyan , Ma Tao , Gao Tianshu , Gao Fei , Zhu Yichao , Zhang Yan 
Published: May 2021

AbstractAngiotensin-converting enzyme 2 (ACE2) is known as a host cell receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is identified to be dysregulated in multiple tumors. Although the characterization of abnormal ACE2 expression in malignancies has been preliminarily explored, in-depth analysis of ACE2 in breast cancer (BRCA) has not been elucidated. A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between ACE2 expression immunological characteristics in the BRCA tumor microenvironment (TME) were evaluated. Also, the role of ACE2 in predicting the clinical features and the response to therapeutic options in BRCA was estimated. These findings were subsequently validated in another public transcriptomic cohort as well as a recruited cohort. ACE2 was lowly expressed in most cancers compared with adjacent tissues. ACE2 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB). Besides, high ACE2 levels indicated the triple-negative breast cancer (TNBC) subtype of BRCA, lower response to endocrine therapy and higher response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. To sum up, ACE2 correlates with an inflamed TME and identifies immuno-hot tumors, which may be used as an auxiliary biomarker for the identification of immunological characteristics in BRCA.
Atoh8 is a regulator of intestinal microfold cell (M cell) differentiation
Authors: George Joel Johnson , Martin-Diaz Laura , Ojanen Markus , Viiri Keijo 
Published: May 2021

AbstractIntestinal microfold cells (M cells) are a dynamic lineage of epithelial cells that initiate mucosal immunity in the intestine. They are responsible for the uptake and transcytosis of microorganisms, pathogens and other antigens in the gastrointestinal tract. A mature M cell expresses a receptor Gp2 which binds to pathogens and aids in the uptake. Due to the rarity of these cells in the intestine, its development and differentiation remains yet to be fully understood. We recently demonstrated that polycomb repressive complex 2 (PRC2) is an epigenetic regulator of M cell development and 12 novel transcription factors including Atoh8 were revealed to be regulated by the PRC2. Here, we show that Atoh8 acts as a regulator of M cell differentiation; absence of Atoh8 led to a significant increase in the number of Gp2+ mature M cells and other M cell associated markers. Atoh8 null mice showed an increase in transcytosis capacity of luminal antigens. Increase in M cell population has been previously reported to be detrimental to mucosal immunity because some pathogens like orally acquired prions have been able to exploit the transcytosis capacity of M cells to infect the host; mouse with increased population of M cells are also susceptible to Salmonella infections. Our study here demonstrates that the population density of intestinal M-cell in the Peyer’s patch is regulated by the PRC2 regulated Atoh8.
Innovative GenExpA software for selecting suitable reference genes for reliable normalization of gene expression in melanoma
Authors: Hoja-Łukowicz Dorota , Maciążek Dawid , Kościelniak Piotr , Janik Marcelina E. 
Published: May 2021

AbstractThe algorithms commonly used to select the best stable reference gene in RT-qPCR data analysis have their limitations. We showed that simple selection of the reference gene or pair of genes with the lowest stability value from the pool of potential reference genes - a commonly used approach - is not sufficient to accurately and reliably normalize the target gene transcript and can lead to biologically incorrect conclusions. For reliable assessment of changes in a target gene expression level, we propose our innovative GenExpA software, which works in a manner independent of the experimental model and the normalizer used. GenExpA software selects the best reference by combining the NormFinder algorithm with progressive removal of the least stable gene from the candidate genes in a given experimental model and in the set of daughter models assigned to it. The reliability of references is validated based on the consistency of the statistical analyses of normalized target gene expression levels through all models, described by the coherence score (CS). The use of the CS value imparts a new quality to qPCR analysis because it clarifies how low the stability value of reference must be in order for biologically correct conclusions to be drawn. We tested our method on qPCR data for theB4GALTgenes family in melanoma, which is characterized by a high mutation rate, and in melanocytes. GenExpA is available athttps://github.com/DorotaHojaLukowicz/GenExpAorhttps://www.sciencemarket.pl/baza-programow-open-source#oferty.HighlightsGenExpA – next-generation software for normalizer selection and validationThe GenExpA tool defines how low the stability value of the reference should beThe GenExpA tool determines the level of gene expression analysis robustnessThe GenExpA tool increases the speed of analysis and reduces cost
COVID-19 and the governmentality of emergency food in the City of Turin
Authors: Sargiacomo Massimo , Corazza Laura , D'Andreamatteo Antonio , Dumay John , Guthrie James 
Published: May 2021

PurposeThis paper shows the accounting, accountability and calculative practices associated with emergency food allocations by the City of Turin through a program to feed the vulnerable during COVID-19.Design/methodology/approachThis is a single case study framed by Foucault's governmentality concept. The data was collected through interviews with key institutional actors and triangulated against decrees, circulars, ordinances and other publicly available documents.FindingsThe accounting tools of governmentality are always incomplete. Sometimes unique situations and crises help us to revise and improve the tools we have. Other times, they demand entirely new tools.Research limitations/implicationsAccounting needs both things to count and a context to count them. In the case of food assistance, what is counted is people. In Turin's case, many people had never been counted – either because there was no need or because they were unaccounted for by choice. Now, the government was accountable for the welfare of both. Thus, new classification systems emerged, as did organisational and accounting solutions.Originality/valueAlthough the accounting-for-disasters literature is diverse, studies too often favour the macro social, economic and political issues surrounding crises, neglecting the micro issues associated with governmentality and calculative practices.
Stock price reaction on ISO 9001 certification announcement: evidence from Indonesia
Authors: Kiryanto Kiryanto , Kartika Indri , Zaenudin Zaenudin 
Published: May 2021

PurposeCertification information published by a company will be responded by the market. Therefore, the purpose of this study is to examine the impact of ISO 9001 certification on the stock market reaction as indicated by stock returns reaction of companies in Indonesia.Design/methodology/approachThis study used event study method with the period of 13 days. It consists of 6 days before and after ISO 9001 certification announcement and 1 day at the time of the event. It analyzed by using pair sample t-test and one sample t-test. The stock return data is obtained from companies that are ISO 9001 certified and it tested for their stock reactions before and after the certification.FindingsThe results of empirical research showed that the average and companies cumulative abnormal returns in Indonesia react quickly and positively on the first day after ISO 9001 certification announcement. This study proved the differences between abnormal returns before and after the ISO 9001 certification announcement period.Research limitations/implicationsThe company's success in implementing ISO 9001 will have an impact on investment in the capital market with a positive response from stock market players. The implication of this study is the further research can examine directly the impact of ISO 9001 implementation on investor behavior in the capital market.Originality/valueBased on the development of the literature review, this is the first study which examined the impact of ISO 9001 certification announcement on investor reactions in the short term. Therefore, companies in Indonesia need to implement a quality management system for investors in Indonesia.
Exploring how digital kiosk customer experience enhances shopping value, self-mental imagery and behavioral responses
Authors: Lao Aurély , Vlad Mariana , Martin Annabel 
Published: May 2021

PurposeThis research analyzes how the dimensions of the customer experience derived from using a digital kiosk during the store visit influence shopping value, self-mental imagery and the behavioral intentions of buying and word of mouth. Mediation effects of utilitarian, hedonic and social shopping values are examined, as well as the mediating effect of self-mental imagery.Design/methodology/approachTwo empirical studies were conducted to test the research hypotheses. A first analysis was carried out using a sample of 115 customers from several retail sectors. For the second study, 200 customers of one of the largest international sporting goods retailers were interviewed immediately after their store visit.FindingsThe results confirm significant influences of each dimension of the digital kiosk customer experience (sensorial, pragmatic, cognitive, social) on shopping value and self-mental imagery. They highlight strongest effects as well as the quasi-generalized mediating role of these values, and this self-mental imagery in the relations between the components of the experience and the behavioral intentions.Research limitations/implicationsThe studies were carried out in only one country (France). It would be also useful to consider variations in shopping motives and in involvement between retail sectors. Highlighted relationships should be deepened by experiments intended to identify the psychological mechanisms and emotions capable of mediating influences of customer experience on shopping value.Practical implicationsThe results encourage both advice on the design of digital kiosks and the specifications of their content and several recommendations about the widespread introduction of kiosks or similar new technologies.Originality/valueThis research highlights influences of each of components of customer experience when using an interactive kiosk on shopping values and self-mental imagery, and central roles of these in understanding influences of the customer experience on behavioral responses.
The prospects for dark (troubles) tourism in Belfast, NI
Authors: Ironside Greg , James Kieran 
Published: May 2021

Purpose
The purpose of this paper is to investigate the prospects of Belfast as a Tourism City with a special focus on dark (troubles) tourism.

Design/methodology/approach
This paper uses two surveys – one for overseas-based potential tourists and one for Northern Ireland residents; one focus group with potential tourists; and three interviews, one with a Belfast MP and two with tour-guide operators, one from each side of the Northern Ireland divide. This paper is less theoretical than exploratory.

Findings
Generally, there is strong and widespread support for the concept of troubles tourism. Stakeholders must ensure that troubles tourism is intelligently and sensitively handled and builds up communities.

Originality/value
This is a relatively new and under-researched area. Belfast has been rarely looked at in urban-tourism studies. Findings have applicability for other post-conflict and divided countries, such as the countries of the former Yugoslavia.
Financial literacy and awareness of investment scams among university students
Authors: Mohd Padil Hazlina , Kasim Eley Suzana , Muda Salwa , Ismail Norhidayah , Md Zin Norlaila 
Published: May 2021

Purpose
This study aims to examine the relationship between budgeting skills and financial goals and the level of awareness of investment scams among university students.

Design/methodology/approach
An online survey was administered to university students in Malaysia. A total of 211 responses were received. The data was analysed using partial least square method based on structural equation modelling technique by using SmartPLS-3.0 and SPSS-20 statistical software.

Findings
Findings indicated that having adequate budgeting skills can significantly affect awareness of investment scam among students. This implies that early financial management education among students should focus on instilling disciplined budgeting habit to prevent them from becoming victims of investment scams. Nevertheless, when examining financial goals among the respondents, the study found that having a clear financial goal does not significantly contribute to their awareness in identifying investment scams. As such, students need to be properly guided in setting their financial objectives such as avoiding unrealistic goals to lead a luxurious lifestyle using “fast and easy” money.

Social implications
This study recommends that higher education institutions need to work together with relevant regulators and law enforcers in providing necessary financial literacy education as part of the investment scam prevention measures.

Originality/value
This study contributes to the literature gap on the need to focus on financial literacy in creating awareness towards investment scams among university students.
Improving logistics supplier selection process using lean six sigma – an action research case study
Authors: Tay Huay Ling , Aw Hui Sen 
Published: May 2021

Purpose
Outsourcing logistical activities have become a widely used approach for firms to avoid high fixed costs and heavy investment requirements and to achieve competitive advantages. Lean six sigma (LSS) has been accepted globally across sectors as a management strategy for achieving process excellence. The purpose of this paper is to feature the application of LSS for improving the supplier selection process (SSP) of outsourced logistics services in a multinational health-care company.

Design/methodology/approach
This study is based on an action research case study conducted on the SSP of the freight and distribution department in a multinational health-care company. This paper reports on the application of the LSS define-measure-analyze-improve-control (DMAIC) approach for reducing supplier selection lead time.

Findings
The study features a real-world case study of the LSS DMAIC application to improve the supplier selection process of a large health-care company. The key issues that were identified are lack of information visibility, top-down changes and unclear communication lines. To counteract these three root causes, the lean six sigma techniques that are implemented are the 5S, stakeholder analysis and standard operating procedure.

Research limitations/implications
This research provided empirical evidence of how practical challenges in SSP can be managed with the use of LSS. It further proposed plausible solutions for reducing and sustaining improved outcomes. As the study is limited to one case, the validity of the results can be improved by including more organisations and more case studies from other similar organisations.

Originality/value
Research in supplier selection processes rarely links continuous improvement ideology such as LSS to support strategic selection and procurement of logistics services. This paper could serve as a resource for both practitioners to derive useful implications and to academicians as it contributes to the LSS body of knowledge for further theory testing.
Early pregnancy prediction of spontaneous preterm birth before 32 completed weeks of pregnancy using plasma RNA: transcriptome discovery and initial validation of an RNA panel of markers
Authors: Weiner CP , Dong Y , Zhou H , Cuckle H , Ramsey R , Egerman R , Buhimschi I , Buhimschi C 
Published: May 2021

ObjectiveTo compare the second‐trimester plasma cell‐free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation.DesignProspective case–control study.SettingAcademic tertiary care centre.PopulationPregnant women with known outcomes prospectively sampled.MethodsPCF RNAs extracted from women at 22–24 weeks of gestation (five sPTB up to 32 weeks and five at term) were hybridised to gene expression arrays. Differentially regulated RNAs for sPTB up to 32 weeks were initially selected based on P value compared with control (P < 0.01) and fold change (≥1.5×). Potential markers were then reordered by narrowness of distribution. Final marker selection was made by searching the Metacore™ database to determine whether the PCF RNAs interacted with a reported set of myometrial Preterm Initiator genes. RNAs were confirmed by quantitative reverse transcription polymerase chain reaction and tested in a second group of 40 women: 20 with sPTB up to 32 weeks (mean gestation 26.5 weeks, standard deviation ±2.6 weeks), 20 with spontaneous term delivery (40.1 ± 0.9 weeks) sampled at 16–19+5 weeks of gestation.Main outcome measureIdentification of PCF RNAs predictive of sPTB up to 32 weeks.ResultsTwo hundred and ninety‐seven PCR RNAs were differentially expressed in sPTB up to 32 weeks of gestation. Further selection retained 99 RNAs (86 mRNAs and 13 microRNAs) and five of these interacted in silica with seven Preterm Initiator genes. Four of five RNAs were confirmed and tested on the validation group. The expression of each confirmed PCF RNA was significantly higher in sPTB up to 32 weeks of gestation. In vitro study of the four mRNAs revealed higher expression in placentas of women with sPTB up to 32 weeks and the potential to interfere with myometrial quiescence.ConclusionsThe PCF RNA markers are highly associated with sPTB up to 32 weeks by 16 weeks of gestation.Tweetable abstractWomen destined for spontaneous preterm birth can be identified by 16 weeks of gestation with a panel of maternal plasma RNAs.