bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naringin as a natural bitter tastant promotes proliferation of cultured human bronchial epithelial cells via activation of TAS2R signaling
Authors: Ni Kai , Luo Mingzhi , Bu Bing , Guo Jia , Pan Yan , Li Jingjing , Liu Lei , Deng Linhong 
Published: May 2020

Abstract
Bitter tastants can activate bitter taste receptors (TAS2Rs) and thus initiate the relaxation of airway smooth muscle cells, which have great potential in the development of novel asthma therapy. However, recent study shows that canonical bitter substance denatonium induces apoptosis of bronchial epithelial cells (BECs), indicating the toxic effect of bitter tastants on airways. Considering the diversity of bitter tastants in nature and TAS2Rs expressed in airway cells, it is thus necessary to carefully evaluate the bitter tastant for its effect on the proliferation of BECs, if aimed to treat airway disease. Here we first screened a group of bitter flavonoids, including apignenin, hespretin, kaempferol, naringenin, naringin and quercetin which are commonly used in food and traditional medicine, and then quantitatively evaluated the effects of this group of bitter flavonoids on the proliferation of BECs (i.e. 16HBE14o- cells) cultured in vitro. The results show that five of the six tested bitter tastants inhibited, but only naringin promoted the proliferation of 16HBE14o- BECs in vitro at the dose of a few hundred micromoles. Furthermore, the naringin-promoted cell proliferation was associated with enhanced cell cycle progression, mRNA expression of cyclin E, and evoked calcium signaling/ERK signaling. Inhibition of the TAS2R signaling pathways with specific blockers attenuated the naringin-enhanced cell proliferation, cyclin E expression and calcium signaling/ERK activation. Taken together, these findings indicate that although many bitter flavonoids may inhibit the proliferation of BECs, naringin emerges as one of the kind that promotes the proliferation of BECs via cell cycle progression and TAS2R-activated intracellular signaling. Only such bitter tastant proven to be unharmful to the epithelial structure and function could be further developed as safe and effective TAS2Rs-based bronchodilator in asthma therapy.
Prediction of a potential drug target based on protein druggability for thyroid cancer
Authors: Yang YiFei , Yu Bin , Zhang Xiu-Xia , Zhu Yun-Hua 
Published: May 2020

Abstract
Background: Thyroid cancer is a common endocrine malignancy; however, its treatment is still surgical. With the development and application of targeted therapy in cancer treatment, there are great development prospects in researching targeted drugs for thyroid cancer. Methods: Differentially expressed mRNAs between thyroid cancerous tissue and normal thyroid tissues were screened from The Cancer Genome Atlas (TCGA) database. Using weighted gene coexpression network analysis (WGCNA) to build co-expression modules and combined with differentially methylated gene (DMG) analysis. The druggability was analyzed by PockDrug-Server. Due to drug repositioning to seek targeted drugs to treat thyroid cancer we constructed a protein-protein interaction (PPI) network, and screened out a drug target of thyroid cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) were used to analysis the protein enrichment of PPI network. Results: In the present study, the red module was significantly correlated with thyroid cancer. With DMG analysis, we screened out three genes: HEY2 , TNIK and LRP4 . These three genes were hypomethylation in tumors. The druggability based on PockDrug-Server predicted that only TNIK had protein pocket druggability. With PPI model for TNIK, there were ten genes interacted with TNIK. These genes were enriched in the MAPK and Wnt pathways, which are correlated with tumor proliferation, differentiation, and development. Upon searching for drugs against these 10 genes in Drugbank, it was determined that the targeted drug Binimetinib which is MEK1/2 inhibition. Therefore, we hypothesized that Binimetinib can be used as a targeted drug and TNIK can be regard as drug target for thyroid cancer therapy. Conclusion: Our research provides a bioinformatics method for screening drugs target and provides a theoretical basis for targeted therapy for thyroid cancer.
Development of Prognostic Signature Based on Pan-cancer Proteomics
Authors: Huang Weiguo , Weng Wanqing , Xiang Yukai , Shi Hongqi 
Published: May 2020

Abstract
Background: Utilizing genomic data to predict cancer prognosis was insufficient. Proteomics can improve our understanding of the etiology and progression of cancer and improve the assessment of cancer prognosis. Based on CPTAC (Clinical Proteomic Tumor Analysis Consortium) which has generated extensive proteomics data of the vast majority of tumors, we can perform a proteomic pan-carcinoma analysis.Methods: The proteomics data and clinical features of cancer patients were collected from CPTAC. We screened 69 differentially expressed proteins with R software. GO and KEGG analysis were performed to clarify the function of these proteins. The DEPs-based prognostic model was identified by least absolute shrinkage and selection operator (LASSO)-Cox regression model. The time-dependent receiver operating characteristics analysis was used to evaluate the ability of the prognostic model to predict overall survival.Results: A total of 69 differentially expressed proteins were screened in five different types of cancers: hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), children's brain tumor tissue consortium (CBTTC), clear cell renal cell carcinoma (CCRC) and uterine corpus endometrial carcinoma (UCEC). Furthermore, the differentially expressed proteins were related to cell metabolism, cell proliferation and extracellular matrix. Then 24 DEPs-based classifiers for predicting OS was developed by LASSO-Cox regression model in training cohort, which was validated in validation cohort. Conclusions: In the present study, we identified DEPs-based survival-predictor model to predict most cancers. We are the first group to utilize proteomics to construct a pan-cancer prognosis model, which could accurately and effectively predict the survival rate of most cancers.
Improving communication between the general practitioner and the oncologist: a key role in coordinating care for patients suffering from cancer.
Authors: Druel Vladimir , Gimenez Laetitia , Paricaud Kim , Delord Jean-Pierre , Grosclaude Pascale , Boussier Nathalie , Rougé-Bugat Marie-Eve 
Published: May 2020

Abstract
Background: Patients suffering from cancers are increasingly numerous in general practice consultations. The General Practitioner (GP) should be at the heart of the management of patients. Several studies have examined the perceptions of GPs confronted with the patient suffering from cancer and the relationships of GPs with oncologists, but few studies have focused on the patients’ perspective. We studied the three-way relationship between the oncologist, the GP, and the patient, from the patient’s point of view. Methods: A questionnaire validated by a group consisting of GPs, oncologists, nurses, an epidemiologist and quality analyst, was administered over a three-week period to patients suffering from cancer receiving chemotherapy in a day hospital. Results: The analysis was based on 403 questionnaires. Patients had confidence in the GP’s knowledge of oncology in 88 % of cases; 49 % consulted their GP for pain, 15 % for cancer-related advice, and 44 % in emergencies. Perceived good GP/oncologist communication led patients to turn increasingly to their GP for cancer-related consultations (RR = 1.14; p = 0.01) and gave patients confidence in the GP’s ability to manage cancer-related problems (RR = 1.30; p < 0.01). Mention by the oncologist of the GP’s role increased the consultations for complications (RR = 1.82; p < 0.01) as well as recourse to the GP in an emergency (RR = 1.35; p < 0.01). Conclusion: Patients suffering from cancer considered that the GP was competent, but did not often consult their GP for cancer-related problems. There is a discrepancy between patients’ beliefs and their behaviour. When the oncologist spoke to patients of the GP’s role, patients had recourse to their GP more often. Systematically integrating a GP consultation to conclude cancer diagnosis disclosure, could improve management and care coordination.
The Functional Impacts of the Covid-19 Pandemic: A Rapid Review
Authors: Hitch Danielle , Cramer Emma , Adcock Emily , Sayers Taylah , Nelson Helen , Farley Allison , Browning Laura , Thorpe Matthew 
Published: May 2020

Abstract
Background: The Covid-19 pandemic is having a severe and unprecedented impact on human functioning, due to its influence on bodily functions and structures, the activities we participate in and the environments in which we live. The aim of this rapid review is to inform health services planning and decision making, by identifying and synthesizing the potential functional impact of the Covid-19 pandemic on human health and wellbeing.Methods: This rapid review was completed within four weeks during April – May 2020. The review focused on primary sources describing and evaluating the functional impact of the SARS, MERS and Covid-19 coronavirus pandemics, published since January 2000 in peer reviewed journal articles. All included sources were evaluated for quality, and the International Classification of Function provided a theoretical structure for synthesizing the available evidence.Results: A total of 65 sources met the inclusion criteria for this review. The majority (n=42, 61.6%) were related to the SARS pandemic, and originated from Asia for North America. Almost half of the reviewed sources (n=32, 49.2%) investigated the impact of coronavirus pandemics on the community, with smaller evidence bases related to people with coronaviruses and their families (n=19, 29.2%) and healthcare workers (n=17, 26.1%). Of the research sources available, the majority utilized descriptive quantitative methods via cross sectional data collection.The functional impact of the Covid-19 pandemic is likely to spread far beyond infected patients, to influence the wellbeing of healthcare workers and the entire community in both positive and negative ways. The findings of this review indicate that health services must engage with the inter-sectionality of pandemic experiences, collaborate with other sectors as part of society-wide responses and prioritize function as a key outcome.Conclusions:Based on the experience of past coronavirus pandemics, and the experience to date of the current Covid-19 outbreak, every health service in all health systems must be prepared to prevent and manage the functional impacts of the Covid-19 pandemic, possibly for decades to come. This review highlights the multitude of avenues available for health service prioritization and planning, and emphasized that a multi-dimensional, multi-service (and ideally multi-systems) approach is needed.
Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate
Authors: Olagnier David P. , Farahani Ensieh , Thyrsted Jacob , Cadanet Julia B. , Herengt Angela , Idorn Manja , Hait Alon , Hernaez Bruno , Knudsen Alice , Iversen Marie Beck , Schilling Mirjam , Jørgensen Sofie E. , Thomsen Michelle , Reinert Line , Lappe Michael , Hoang Huy-Dung , Gilchrist Victoria H. , Hansen Anne Louise , Ottosen Rasmus , Gunderstofte Camilla , Møller Charlotte , Huang Jinrong , Jakobsen Martin , Poulsen Thomas B. , Bartsch Lydia , Thielke Anne L. , Luo Yonglun , Alain Tommy , Rehwinkel Jan , Alcamí Antonio , Hiscott John , Mogensen Trine , Paludan Søren R. , Holm Christian K. 
Published: May 2020

Abstract
Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a potent cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence Summary: NRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses.
Simulation for Enhancement in Sensitivity of Chalcogenide Glasses-Based Fibre Optic Evanescent Absorption Sensor for Malignant Tissue Detection
Authors: Dwivedi Dilip Kumar , Singh Ritesh Kumar , Mishra Adarsh Chandra , Lohia Pooja 
Published: May 2020

Background:
Refractive index determination of biological tissues is a challenging issue.
Many biological species also show vibrational signature in the infrared domain. The chalcogenidebased
glasses can be used to make the fibree optic evanescent wave sensors for the detection of the
analyte.

Objectives:
The primary objective is to study the effect of various parameters on the sensitivity of
chalcogenide glass-based evanescent-wave sensor for biological tissue detection.

Methods:
An evanescent wave sensor has been proposed with collimated source illumination and uniform
tapering. The chalcogenide materials are chosen such that the weakly guiding approximation
could be followed. Complex refractive indices of liver tissue samples have been taken for the analysis
of sensitivity via the method of the evanescent absorption coefficient. Equations for sensitivity have
been solved analytically using MATLAB software.

Results:
The simplification of the formula for sensitivity leads to the inference that the sensitivity is a
function of core radius, refractive indices of sample tissues and wavelength used. Moreover, since the
refractive indices of the materials are also a function of temperature, therefore a change in temperature
results in a change in the profile of guiding mode. Hence, the effect of temperature must also be observed.
The initial simulation parameters are taken; core radius 100 μm, sensing length 4 cm and
wavelength 1.0 μm. In the NIR region, we have a better sensitivity of detection for all the tissue samples
and the risk of photodamage of the bio-samples is reduced to a good extent. It has been found that
sensitivity decreases with wavelength and core radius, whereas increases with temperature. It has also
been shown that sensitivity is found to be better with collimated in comparison with the diffused
source.

Conclusion:
The comparative study results that one should operate at a shorter NIR region of wavelength
for higher sensitivity. The collimated source illumination should be preferred over diffused one
for launching the light within the fibree to have high sensitivity. Further, the length of the sensing region
should be larger, but the fibree core radius should be smaller. The proposed biosensor is robust
and can also be used many times if the probe (sensing region) is cleaned properly. Moreover, a small
amount of analyte is enough for detection. Thus, the proposed sensor is very useful for biomedical applications
with its high performance, accuracy and robustness.
Az európai klubfutball meghatározó bajnokságainak összehasonlító elemzése
Authors: Bács Bence András 
Published: May 2020

Napjainkban a sport már nemcsak a szórakoztatásról szól, már nemcsak egy társadalmi összetartó erő, hanem komoly gazdasági és üzleti vonatkozásai is vannak. A sportgazdaságról különálló fogalomként, ágazatként beszélhetünk. A sportvállalkozások egy-egy állam nemzeti jövedelméhez egyre nagyobb mértékben járulnak hozzá. A futballvállalkozások rendkívül fontos részei ennek a szerte ágazó és összetett rendszernek, a sportgazdaságnak. Vizsgálatomban az európai futball árbevételének 74%-át adó Big 5 bajnokság gazdasági elemzésére, illetve összehasonlításukra vállalkozok. Az UEFA 2019-es pénzügyi jelentésének elemzése alapján megállapítható, hogy a nagy bajnokságok mindegyikében legalább a klubok 60%-a pozitív eredménnyel zárta a 2017-es évet, de a bevételek összetétele arra figyelmeztet, hogy a jövőben a kluboknak a működésükből származó bevételeikre kell nagyobb figyelmet fordítaniuk. Az adatok alapján nyilvánvaló, hogy az ágazat legmeghatározóbb költségeleme a bérköltség. A top5 ligában az árbevétel 53-68%-át ezek a költségek fedik le. Ezek a megállapítások kijelölik az európai labdarúgás gazdasági fejlődésének irányait, illetve a kiemelkedő labdarúgó klubok gazdálkodása példát adhat a tőlük még elmaradottabbaknak, köztük a magyar futballvállalkozásoknak is.
Twitter-Derived Social Neighborhood Characteristics and Individual-Level Cardiometabolic Outcomes: Cross-Sectional Study in a Nationally Representative Sample
Authors: Huang Dina , Huang Yuru , Khanna Sahil , Dwivedi Pallavi , Slopen Natalie , Green Kerry M , He Xin , Puett Robin , Nguyen Quynh 
Published: May 2020

Background
Social media platforms such as Twitter can serve as a potential data source for public health research to characterize the social neighborhood environment. Few studies have linked Twitter-derived characteristics to individual-level health outcomes.

Objective
This study aims to assess the association between Twitter-derived social neighborhood characteristics, including happiness, food, and physical activity mentions, with individual cardiometabolic outcomes using a nationally representative sample.

Methods
We collected a random 1% of the geotagged tweets from April 2015 to March 2016 using Twitter’s Streaming Application Interface (API). Twitter-derived zip code characteristics on happiness, food, and physical activity were merged to individual outcomes from restricted-use National Health and Nutrition Examination Survey (NHANES) with residential zip codes. Separate regression analyses were performed for each of the neighborhood characteristics using NHANES 2011-2016 and 2007-2016.

Results
Individuals living in the zip codes with the two highest tertiles of happy tweets reported BMI of 0.65 (95% CI –1.10 to –0.20) and 0.85 kg/m2 (95% CI –1.48 to –0.21) lower than those living in zip codes with the lowest frequency of happy tweets. Happy tweets were also associated with a 6%-8% lower prevalence of hypertension. A higher prevalence of healthy food tweets was linked with an 11% (95% CI 2% to 21%) lower prevalence of obesity. Those living in areas with the highest and medium tertiles of physical activity tweets were associated with a lower prevalence of hypertension by 10% (95% CI 4% to 15%) and 8% (95% CI 2% to 14%), respectively.

Conclusions
Twitter-derived social neighborhood characteristics were associated with individual-level obesity and hypertension in a nationally representative sample of US adults. Twitter data could be used for capturing neighborhood sociocultural influences on chronic conditions and may be used as a platform for chronic outcomes prevention.
Becoming European: Strangers Finding a Place in the European Union
Authors: Fischer-Souan Maricia 
Published: May 2020

This article addresses the idea of belonging in Europe from the perspective of postcolonial migrants settling in EU societies. It draws on over one hundred in-depth interviews with Algerian, Ecuadorian, and Indian individuals settled mainly in and around the cities of London, Madrid, and Paris. Rather than investigating migrants’ orientations to Europe through a narrow interest in self-identification (feeling vs. not feeling European), it delves into individual migration narratives for evidence of how Europe is imagined (if it is imagined at all) during the migration process and its relation to other physical and symbolic sites. As a frame for interpreting individual migration narratives, I introduce the concept of ‘migratory rupture’, a dialectical experience of both the disorienting and creative aspects of migration. In excavating some of the reflexive processes involved in constructing symbolic geographies of attachment, I find that regardless of the scales of comparison used to articulate place affiliation across different contexts, e.g. whether small-scale (neighbourhoods or city districts) or larger-scale (supranational or de-territorialized categories), symbolic geographies allow migrants to view their transnational life experience on a single, coherent plane and express a form of global consciousness.
The Effect of Membership in the European Monetary Union on Trade Between Member Countries (An Empirical Study)
Authors: Soroka Ihor 
Published: May 2020

The question of whether or not to adopt the euro is a very important one, not only for the 13 European Union members that do not share the same currency, but also for future EU candidates. Current literature on the effect of the euro on trade is scarce since the European Monetary Union (EMU) was officially created in 1999, and up until recently there has not been enough data to analyze this issue. This paper aims to estimate the effect of the euro on trade between member countries using the standard gravity model of trade. Using data from current 25 EU members over the period from 1997 to 2004, I show that higher trade volumes between EMU members cannot be attributed to the adoption of the euro. I find evidence that the euro adoption has had a short-run effect on bilateral trade and that this effect is eliminated over a short period of time. My findings suggest that members of the EMU trade on average from 8.8% to 47% more compared to non-members depending on the type of regression used, while members of the Free Trade Agreement trade 61.3% more. The effect of the euro on trade is eliminated as soon as I control for country-pair specific effects that include the FTA effect as well as history of trade relations between two countries. I conclude that the adoption of the euro should be seen as a final step in the European economic and monetary integration for countries that already benefit from relatively high volumes of bilateral trade.
Full text availale at: https://doi.org/10.22215/rera.v2i1.166
“Rolling Up the Sleeves”1 How EU policy towards Serbia and Montenegro acts as the glue that holds the State Union together?
Authors: Papic Marko 
Published: May 2020

The most powerful tool of EU foreign policy in dealing with potential candidate countries (and beyond) is that of political conditionality. The successes of this policy, as well as its spectacular failures, have been largely well documented by the political science research community. Far less research, however, goes into explaining the scenarios where the EU goes “beyond conditionality” (Teokarevic 2003) in its dealings with potential candidates for membership in the EU. The goal of this paper is to explain the extremely intensive and pro-active EU involvement in the drafting of the Constitution of Serbia and Montenegro and the subsequent attempts by Brussels to determine the future nature of the union between these neighboring republics. In answering this question the paper looks at the history of EU’s involvement in the region and attempts to provide a theoretical framework that can best provide the explanation for the motivation of EU’s policy makers to utilize such a direct strategy of involvement that goes far “beyond conditionality”.
Full text available: https://doi.org/10.22215/rera.v2i2.170