bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-Demographic Factors Involved in a Low-Incidence Phase of SARS-CoV-2 Spread in Sicily, Italy
Authors: Amodio Emanuele , Battisti Michele , Maida Carmelo Massimo , Zarcone Maurizio , Casuccio Alessandra , Vitale Francesco
Published: July 2021

Background: The present study analysed SARS-CoV-2 cases observed in Sicily and investigated social determinants that could have an impact on the virus spread. Methods: SARS-CoV-2 cases observed among Sicilian residents between the 1 February 2020 and 15 October 2020 have been included in the analyses. Age, sex, date of infection detection, residency, clinical outcomes, and exposure route have been evaluated. Each case has been linked to the census section of residency and its socio-demographic data. Results: A total of 10,114 patients (202.3 cases per 100,000 residents; 95% CI = 198.4–206.2) were analysed: 45.4% were asymptomatic and 3.62% were deceased during follow-up. Asymptomatic or mild cases were more frequent among young groups. A multivariable analysis found a reduced risk of SARS-CoV-2 cases was found in census sections with higher male prevalence (adj-OR = 0.99, 95% CI = 0.99–0.99; p < 0.001) and presence of immigrants (adj-OR = 0.89, 95% CI 0.86–0.92; p < 0.001). Proportion of residents aged <15 years, residents with a university degree, residents with secondary education, extra-urban mobility, presence of home for rent, and presence of more than five homes per building were found to increase the risk of SARS-CoV-2 incidence. Conclusion: Routinely collected socio-demographic data can be predictors of SARS-CoV-2 risk infection and they may have a role in mapping high risk micro-areas for virus transmission.
A Model-Based Tool for Assessing the Impact of Land Use Change Scenarios on Flood Risk in Small-Scale River Systems—Part 1: Pre-Processing of Scenario Based Flood Characteristics for the Current State of Land Use
Authors: Kachholz Frauke , Tränckner Jens
Published: July 2021

Land use changes influence the water balance and often increase surface runoff. The resulting impacts on river flow, water level, and flood should be identified beforehand in the phase of spatial planning. In two consecutive papers, we develop a model-based decision support system for quantifying the hydrological and stream hydraulic impacts of land use changes. Part 1 presents the semi-automatic set-up of physically based hydrological and hydraulic models on the basis of geodata analysis for the current state. Appropriate hydrological model parameters for ungauged catchments are derived by a transfer from a calibrated model. In the regarded lowland river basins, parameters of surface and groundwater inflow turned out to be particularly important. While the calibration delivers very good to good model results for flow (Evol =2.4%, R = 0.84, NSE = 0.84), the model performance is good to satisfactory (Evol = −9.6%, R = 0.88, NSE = 0.59) in a different river system parametrized with the transfer procedure. After transferring the concept to a larger area with various small rivers, the current state is analyzed by running simulations based on statistical rainfall scenarios. Results include watercourse section-specific capacities and excess volumes in case of flooding. The developed approach can relatively quickly generate physically reliable and spatially high-resolution results. Part 2 builds on the data generated in part 1 and presents the subsequent approach to assess hydrologic/hydrodynamic impacts of potential land use changes.
Athletic Identity in Youth Athletes: A Systematic Review of the Literature
Authors: Edison Bianca R. , Christino Melissa A. , Rizzone Katherine H.
Published: July 2021

Athletic identity (AI), the degree of personal connection to sport, is well-described in adult research; however, this social trait has been less studied in younger age groups. This systematic review describes epidemiological characteristics of AI in youth athletes. PubMed, Embase and PsycInfo were searched to identify AI studies involving quantitative athlete identity outcomes and cohorts 22 years and younger. The search strategy was developed for each database using the Boolean method. PRISMA guidelines and the Appraisal Tool for Cross-Sectional Studies (AXIS) were utilized. Ten out of ninety-one studies met inclusion criteria. AI scores differed by race/ethnicity. Two studies found increased AI during adolescence compared to later in ones’ training. Mental health-focused studies revealed higher AI levels protect against burnout, but in injured athletes, increased depression risk. Transitioning to a higher level of play during adolescence can correlate with stronger senses of AI. Further research should explore the concept of athletic identity saliency as one moves through an athletic career or training program and how thoughts of perceived success, professional progression, recruitment prospect or injury affect levels of athletic identity.
Adopting the Situation in School Questionnaire to Examine Physical Education Teachers’ Motivating and Demotivating Styles Using a Circumplex Approach
Authors: Escriva-Boulley Géraldine , Guillet-Descas Emma , Aelterman Nathalie , Vansteenkiste Maarten , Van Doren Nele , Lentillon-Kaestner Vanessa , Haerens Leen
Published: July 2021

Grounded in SDT, several studies have highlighted the role of teachers’ motivating and demotivating styles for students’ motivation, learning, and physical activity in physical education (PE). However, most of these studies focused on a restricted number of motivating strategies (e.g., offering choice) or dimensions (e.g., autonomy support). Recently, researchers have developed the Situations-in-School (i.e., SIS-Education) questionnaire, which allows one to gain a more integrative and fine-grained insight into teachers’ engagement in autonomy-support, structure, control, and chaos through a circular structure (i.e., a circumplex). Although teaching in PE resembles teaching in academic courses in many ways, some of the items of the original situation-based questionnaire (e.g., regarding homework) are irrelevant to the PE context. In the present study, we therefore sought to develop a modified, PE-friendly version of this earlier validated SIS-questionnaire—the SIS-PE. Findings in a sample of Belgian (N = 136) and French (N = 259) PE teachers, examined together and as independent samples, showed that the variation in PE teachers’ motivating styles in this adapted version is also best captured by a circumplex structure, with four overarching styles and eight subareas differing in their level of need support and directiveness. The SIS-PE possesses excellent convergent and concurrent validity. With the adaptations being successful, great opportunities for future research on PE teachers (de-)motivating styles are created.
Predicting Type 2 Diabetes Using Logistic Regression and Machine Learning Approaches
Authors: Joshi Ram D. , Dhakal Chandra K.
Published: July 2021

Diabetes mellitus is one of the most common human diseases worldwide and may cause several health-related complications. It is responsible for considerable morbidity, mortality, and economic loss. A timely diagnosis and prediction of this disease could provide patients with an opportunity to take the appropriate preventive and treatment strategies. To improve the understanding of risk factors, we predict type 2 diabetes for Pima Indian women utilizing a logistic regression model and decision tree—a machine learning algorithm. Our analysis finds five main predictors of type 2 diabetes: glucose, pregnancy, body mass index (BMI), diabetes pedigree function, and age. We further explore a classification tree to complement and validate our analysis. The six-fold classification tree indicates glucose, BMI, and age are important factors, while the ten-node tree implies glucose, BMI, pregnancy, diabetes pedigree function, and age as the significant predictors. Our preferred specification yields a prediction accuracy of 78.26% and a cross-validation error rate of 21.74%. We argue that our model can be applied to make a reasonable prediction of type 2 diabetes, and could potentially be used to complement existing preventive measures to curb the incidence of diabetes and reduce associated costs.
Comprehensive Assessment and Potential Ecological Risk of Trace Element Pollution (As, Ni, Co and Cr) in Aquatic Environmental Samples from an Industrialized Area
Authors: Díaz-de-Alba M. , Granado-Castro M. D. , Galindo-Riaño M. D. , Casanueva-Marenco M. J.
Published: July 2021

A global assessment of arsenic (As), nickel (Ni), cobalt (Co) and chromium (Cr) was performed in environmental samples from an important industrial bay. Different fractions of water, sediments and tissues from four species of fish were analysed. Samples were collected from selected sampling sites during four consecutive samplings in spring and autumn seasons, in order to evaluate concentrations and their possible correlations among the aquatic compartments. While a higher availability of Cr and Ni was found in water, Co and As were the most available elements in sediments. In fish, the liver was the tissue with the highest proportion of As and Co, and gills showed the highest concentrations of Ni and Cr. Significance differences were observed among sites showing the pollution sources. In sediments, high correlations were found between total Co content and the most available fractions. Total Ni content highly correlated with the oxidisable fraction, while Cr total content tightly correlated with the least available fractions. Quality guideline values for sediments were frequently exceeded. In sediments and biota, concentrations were slightly higher than in other ecosystems, indicating that maritime, industrial and urban activities are affecting this type of ecosystem with great anthropogenic influence.
Associations between Biomarkers of Exposure and Lung Cancer Risk among Exclusive Cigarette Smokers in the Golestan Cohort Study
Authors: Rostron Brian L. , Wang Jia , Etemadi Arash , Thakur Sapna , Chang Joanne T. , Bhandari Deepak , Botelho Julianne Cook , De Jesús Víctor R. , Feng Jun , Gail Mitchell H. , Inoue-Choi Maki , Malekzadeh Reza , Pourshams Akram , Poustchi Hossein , Roshandel Gholamreza , Shiels Meredith S. , Wang Qian , Wang Yuesong , Xia Baoyun , Boffetta Paolo , Brennan Paul , Abnet Christian C. , Calafat Antonia M. , Wang Lanqing , Blount Benjamin C. , Freedman Neal D. , Chang Cindy M.
Published: July 2021

Biomarkers of tobacco exposure are known to be associated with disease risk but previous studies are limited in number and restricted to certain regions. We conducted a nested case–control study examining baseline levels and subsequent lung cancer incidence among current male exclusive cigarette smokers in the Golestan Cohort Study in Iran. We calculated geometric mean biomarker concentrations for 28 matched cases and 52 controls for the correlation of biomarker levels among controls and for adjusted odds’ ratios (ORs) for lung cancer incidence by biomarker concentration, accounting for demographic characteristics, smoking quantity and duration, and opium use. Lung cancer cases had higher average levels of most biomarkers including total nicotine equivalents (TNE-2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and 3-hydroxyfluorene (3-FLU). Many biomarkers correlated highly with one another including TNE-2 with NNAL and N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CYEMA), and N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA) with N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (3HMPMA) and N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (4HMBEMA). Lung cancer risk increased with concentration for several biomarkers, including TNE-2 (OR = 2.22, 95% CI = 1.03, 4.78) and NNN (OR = 2.44, 95% CI = 1.13, 5.27), and estimates were significant after further adjustment for demographic and smoking characteristics for 2CYEMA (OR = 2.17, 95% CI = 1.03, 4.55), N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (2CAEMA) (OR = 2.14, 95% CI = 1.01, 4.55), and N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA) (OR = 2.85, 95% CI = 1.04, 7.81). Estimates were not significant with adjustment for opium use. Concentrations of many biomarkers were higher at the baseline for participants who subsequently developed lung cancer than among the matched controls. Odds of lung cancer were higher for several biomarkers including with adjustment for smoking exposure for some but not with adjustment for opium use.
Co-Attendance Communities: A Multilevel Egocentric Network Analysis of American Soccer Supporters’ Groups
Authors: Cocco Adam R. , Katz Matthew , Hambrick Marion E.
Published: July 2021

The growth of professional soccer in the United States is evident through the rapid expansion of franchises and increased game attendance within Major League Soccer (MLS) and the United Soccer League (USL). Coinciding with this growth is the emergence of European-style supporters’ groups filling sections of MLS and USL stadiums. In this study, the authors utilized an egocentric network analysis to explore relationships among supporters’ group members for two professional soccer clubs based in the United States. Egocentric network research focuses on the immediate social environment of individuals and is often viewed as an alternative approach to sociocentric (i.e., whole network) analyses. This study employed hierarchical linear modeling as an example of multilevel modeling with egocentric data, using ego- and alter-level variables to explain the strength of co-attendance ties. The results indicate the perceived commitment of fellow fans to the team, shared membership in a supporters’ group, age, and interactions with other fans in team settings related to higher levels of co-attendance. The outcomes of this study are both theoretical, as they advance an understanding of sport consumer behavior within soccer supporters’ groups, and methodological, as they illustrate the unique value of employing egocentric network analysis in sport fan research.
The Adjustment of China’s Grain Planting Structure Reduced the Consumption of Cropland and Water Resources
Authors: Zhang Yu , Wang Jieyong , Dai Chun
Published: July 2021

Driven by technological progress and market demand, the optimization and adjustment of grain planting structure played an important role in increasing grain output. Due to the great difference between the yield per unit area of different types of food crops, the consumption of cropland and water resources has a significant change during the grain growth. From the perspective of structural adjustment, rather than the usual productive factor input, we analyze the process of adjustment for grain planting structure in China and its effect on the consumption of cropland and water resources by using the scenario comparative analysis method. The results show that: (1) From 2003 to 2019, China’s grain output has increased steadily and the planting structure has changed greatly. Rice was replaced by corn to become the grain crop with the maximum proportion of planting area since 2007. The increase of corn planting structure proportion is concentrated in the northern regions. (2) At the national level, according to the adjustment of grain planting structure, the saving of cropland and water resources consumption showed a “cumulative effect” as time went on. (3) The saving effects of structural adjustment in the northern regions on cropland and water resources consumption are better than that in the southern regions, such as Northeast China Plain, Northern arid and semiarid region and Loess Plateau. (4) In reality, although the adjustment of grain planting structure saved lots of cropland and water resources, the continuous growth of grain output has increased the pressure on the ecological environment in the northern regions according to theirs water limits. Therefore, it is necessary to continuously optimize the grain planting structure and restrict land reclamation in northern China. In addition, to ensure food security, it is feasible to encourage the southern regions with abundant water and heat resources to increase the grain planting area and meet its self-sufficiency in grain demand.
Nurses Who Are More Willing to Participate in the Fight against COVID-19: Evidence from China
Authors: Tong Lai-Kun , Zhu Ming-Xia , Wang Si-Chen , Cheong Pak-Leng , Van Iat-Kio
Published: July 2021

When facing an infectious disease disaster, nurses’ willingness to work is critical. Nurses’ lack of willingness to work during a pandemic may worsen the shortage of health care personnel. The purpose of this study is to assess the willingness of nurses to participate in the fight against COVID-19 in China and to identify factors associated therewith. This cross-sectional study examines nurses working in 11 Chinese cities including Macau, Hong Kong, Shenzhen, Dongguan, Huizhou, Guangzhou, Zhaoqing, Foshan, Jiangmen, Zhongshan, and Zhuhai. Questionnaires were collected from 19 May to 7 August 2020. A total of 8065 questionnaires were received, of which 8030 valid questionnaires were included for analysis. A total of 53.4% of participants reported that they had signed up to support the COVID-19 pandemic response. Multivariate logistic regression analysis revealed that being single (OR = 0.72, 95% CI: 0.60–0.87), having no children (OR = 0.81, 95% CI: 0.68–0.97), possessing higher professional qualifications (OR = 1.25, 95% CI: 1.14–1.37), having a more prestigious professional title (OR = 1.68, 95%CI: 1.50–1.90), being an administrative supervisor (OR = 0.53, 95% CI: 0.45–0.63), having a higher caring dimensions inventory score (OR = 1.01, 95% CI: 1.01–1.01), working in a hospital (OR = 0.53, 95% CI: 0.39–0.72), and receiving employer-provided care training (OR = 0.77, 95% CI: 0.68–0.87) were predictive of nurses’ willingness to participate in the fight against COVID-19. We suggest that unmarried nurses should be given priority when recruiting to fight an epidemic and, for married nurses with children who are recruited to fight an epidemic, supporting measures should be provided for childcare. We suggest strengthening workplace training of caring for nurses in order to better retain and recruit qualified support for an epidemic outbreak of infectious diseases.
Screen Time Parenting Practices and Associations with Preschool Children’s TV Viewing and Weight-Related Outcomes
Authors: Neshteruk Cody D. , Tripicchio Gina L. , Lobaugh Stephanie , Vaughn Amber E. , Luecking Courtney T. , Mazzucca Stephanie , Ward Dianne S.
Published: July 2021

The purpose of this study was to examine associations between screen time (ST) parenting practices and 2–5-year-old children’s TV viewing and weight status. Data were collected from 252 parent–child dyads enrolled in a randomized parent-focused childhood obesity prevention trial from 2009–2012. ST parenting practices were assessed at baseline using a validated parent-reported survey. Parent-reported child TV viewing and objectively measured anthropometrics were assessed at baseline, post-intervention (35 weeks), and follow-up (59 weeks). Marginal effect models were developed to test the association between baseline ST parenting practices and children’s TV viewing, BMI z-score, and waist circumference across all time points. Limiting/monitoring ST was associated with decreased weekly TV viewing (β = −1.79, 95% CI: −2.61; −0.95), while exposure to TV was associated with more weekly TV viewing over 59 weeks (β = 1.23, 95% CI: 0.71; 1.75). Greater parent use of ST as a reward was associated with increased child BMI z-score (β = 0.15, 95% CI: 0.03; 0.27), while limiting/monitoring ST was associated with decreased BMI z-score (β = −0.16, 95% CI: −0.30; −0.01) and smaller waist circumference (β = −0.55, 95% CI: −1.04; −0.06) over the study period. These findings suggest that modifying parent ST practices may be an important strategy to reduce ST and promote healthy weight in young children.
Relational Capital and Post-Traumatic Growth: The Role of Work Meaning
Authors: Nie Ting , Tian Mi , Liang Hengrui
Published: July 2021

Through a statistical survey of 760 front-line medical staff during the COVID-19 epidemic, this study attempts to explore the relationships between relational capital, psychological security, post-traumatic growth and the meaning of work. Data analysis verifies that trust, reciprocity, and identification can promote post-traumatic growth by enhancing the individual’s psychological security. A high level of work meaning can enhance the role of trust, reciprocity and identification in promoting psychological security. Work meaning has a moderated mediating effect when trust and reciprocity affect post-traumatic growth through psychological security, but no moderated mediating effect is found when identification affects post-traumatic growth through psychological security.
Self-Exclusion from Gambling—A Measure of COVID-19 Impact on Gambling in a Highly Online-Based Gambling Market?
Authors: Håkansson Anders , Widinghoff Carolina , Berge Jonas
Published: July 2021

The COVID-19 pandemic, and related changes of the gambling market, have been suspected to affect the risk of problem gambling. Despite media attention and political concern with this risk, study findings hitherto have been mixed. Voluntary self-exclusion from gambling was introduced on a national level in Sweden as a harm reduction tool in 2019, and this self-exclusion service in Sweden is a rare example of such an official, nationwide, multi-operator system. The present study aimed to evaluate whether short-term self-exclusion patterns were affected by different phases of COVID-19-related impacts on gambling markets in 2020. During the lock-down of sports in the spring months of 2020, three-month self-exclusion was unaffected, and one-month self-exclusion appeared to increase, though not more than in a recent period prior to COVID-19. Despite large differences in sports betting practices between women and men, self-exclusion patterns during COVID-19 were not apparently gender-specific. Altogether, self-exclusion from gambling, to date, does not appear to be affected by COVID-19-related changes in society, in contrast with beliefs about such changes producing greater help-seeking behavior in gamblers. Limitations are discussed, including the fact that in a recently introduced system, seasonality aspects and the autocorrelated nature of the data made substantial statistical measures unfeasible.
Evaluation of Screening Tests in Bavarian Healthcare Facilities during the Second Wave of the SARS-CoV-2 Pandemic
Authors: Tischer Christina , Stupp Carolin , Janson Patrick , Willeke Kristina , Hung Chu-Wei , Flöter Jessica , Kirchner Anna , Zink Katharina , Eder Lisa , Hackl Christina , Mühle Ursula , Weidmann Manfred , Nennstiel Uta , Kuhn Joseph , Weidner Christian , Liebl Bernhard , Wildner Manfred , Keil Thomas
Published: July 2021

Due to the lack of data on asymptomatic SARS-CoV-2-positive persons in healthcare institutions, they represent an inestimable risk. Therefore, the aim of the current study was to evaluate the first 1,000,000 reported screening tests of asymptomatic staff, patients, residents, and visitors in hospitals and long-term care (LTC) facilities in the State of Bavaria over a period of seven months. Data were used from the online database BayCoRei (Bavarian Corona Screening Tests), established in July 2020. Descriptive analyses were performed, describing the temporal pattern of persons that tested positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) or antigen tests, stratified by facility. Until 15 March 2021, this database had collected 1,038,146 test results of asymptomatic subjects in healthcare facilities (382,240 by RT-PCR, and 655,906 by antigen tests). Of the RT-PCR tests, 2.2% (n = 8380) were positive: 3.0% in LTC facilities, 2.2% in hospitals, and 1.2% in rehabilitation institutions. Of the antigen tests, 0.4% (n = 2327) were positive: 0.5% in LTC facilities, and 0.3% in both hospitals and rehabilitation institutions, respectively. In LTC facilities and hospitals, infection surveillance using RT-PCR tests, or the less expensive but less sensitive, faster antigen tests, could facilitate the long-term management of the healthcare workforce, patients, and residents.
A Matching Model for Door-to-Door Multimodal Transit by Integrating Taxi-Sharing and Subways
Authors: Wang Rui , Chen Feng , Liu Xiaobin , Liu Xiaobing , Li Zhiqiang , Zhu Yadi
Published: July 2021

We present a sustainable multimodal transit system that integrates taxi-sharing with subways to alleviate traffic congestion and restore the cooperative relationship between taxis and subways. This study proposes a two-phase matching model based on optimization theory, in which pick-up/drop-off sequences for participants, as well as their motivation to shift to a TSS service, were considered. For the transportation system, achieving a reduction in vehicle miles is considered to be the matching objective. We tested the matching model using empirical taxi global positioning system (GPS) data for a typical morning rush hour in Beijing. The optimization model performs well for large-scale data and the optimal solution can be calculated quickly, which is ideal in a dynamic system. Furthermore, several sensitive analysis experiments were conducted to evaluate the performance of the TSS system. We found that approximately 23.13% of taxi users can be served by TSS transit, total taxi mileage can be reduced by 20.17%, and carbon dioxide emissions may be reduced by 15.16%. The proposed model and findings demonstrate that the TSS service considered here is a feasible multimodal transit mode, with the advantages of flexibility and sustainability, and has great potential for improving social benefits.
Creation of a Multimodal Urban Transportation Network through Spatial Data Integration from Authoritative and Crowdsourced Data
Authors: Smarzaro Rodrigo , Davis Clodoveu A. , Quintanilha José Alberto
Published: July 2021

One of the most significant challenges in cities concerns urban mobility. Urban mobility involves the use of different modes of transport, which can be individual or collective, and different organizations can produce their respective datasets that, usually, are used isolated from each other. The lack of an integrated view of the entire multimodal urban transportation network (MUTN) brings difficulties to citizens and urban planning. However, obtaining reliable and up-to-date spatial data is not an easy task. To address this problem, we propose a framework for creating a multimodal urban transportation network by integrating spatial data from heterogeneous sources. The framework standardizes the representation of different datasets through a common conceptual model for spatial data (schema matching), uses topological, geometric, and semantic information to find matches among objects from different datasets (data matching), and consolidated them into a single representation using data fusion techniques in a complementary, redundant and cooperative way. Spatial data integration makes it possible to use reliable data from official sources (possibly outdated and expensive to produce) and crowdsourced data (continuously updated and low cost to use). To evaluate the framework, a MUTN for the Brazilian city of Belo Horizonte was built integrating authoritative and crowdsourced data (OpenStreetMap, Foursquare, Facebook Places, Google Places, and Yelp), and then it was used to compute routes among eighty locations using four transportation possibilities: walk, drive, transit, and drive–walk. The time and distance of each route were compared against their equivalent from Google Maps, and the results point to a great potential for using the framework in urban computing applications that require an integrated view of the entire multimodal urban transportation network.
CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies
Authors: Khare Tripti , Bissonnette Marc , Khare Sharad
Published: July 2021

Chemokines are chemotactic cytokines that promote cancer growth, metastasis, and regulate resistance to chemotherapy. Stromal cell-derived factor 1 (SDF1) also known as C-X-C motif chemokine 12 (CXCL12), a prognostic factor, is an extracellular homeostatic chemokine that is the natural ligand for chemokine receptors C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or cluster of differentiation 184 (CD184) and chemokine receptor type 7 (CXCR7). CXCR4 is the most widely expressed rhodopsin-like G protein coupled chemokine receptor (GPCR). The CXCL12–CXCR4 axis is involved in tumor growth, invasion, angiogenesis, and metastasis in colorectal cancer (CRC). CXCR7, recently termed as atypical chemokine receptor 3 (ACKR3), is amongst the G protein coupled cell surface receptor family that is also commonly expressed in a large variety of cancer cells. CXCR7, like CXCR4, regulates immunity, angiogenesis, stem cell trafficking, cell growth and organ-specific metastases. CXCR4 and CXCR7 are expressed individually or together, depending on the tumor type. When expressed together, CXCR4 and CXCR7 can form homo- or hetero-dimers. Homo- and hetero-dimerization of CXCL12 and its receptors CXCR4 and CXCR7 alter their signaling activity. Only few drugs have been approved for clinical use targeting CXCL12-CXCR4/CXCR7 axis. Several CXCR4 inhibitors are in clinical trials for solid tumor treatment with limited success whereas CXCR7-specific inhibitors are still in preclinical studies for CRC. This review focuses on current knowledge of chemokine CXCL12 and its receptors CXCR4 and CXCR7, with emphasis on targeting the CXCL12–CXCR4/CXCR7 axis as a treatment strategy for CRC.
Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers
Authors: Sen Monokesh K. , Almuslehi Mohammed S. M. , Shortland Peter J. , Mahns David A. , Coorssen Jens R.
Published: July 2021

Multiple Sclerosis (MS) is a demyelinating disease of the human central nervous system having an unconfirmed pathoetiology. Although animal models are used to mimic the pathology and clinical symptoms, no single model successfully replicates the full complexity of MS from its initial clinical identification through disease progression. Most importantly, a lack of preclinical biomarkers is hampering the earliest possible diagnosis and treatment. Notably, the development of rationally targeted therapeutics enabling pre-emptive treatment to halt the disease is also delayed without such biomarkers. Using literature mining and bioinformatic analyses, this review assessed the available proteomic studies of MS patients and animal models to discern (1) whether the models effectively mimic MS; and (2) whether reasonable biomarker candidates have been identified. The implication and necessity of assessing proteoforms and the critical importance of this to identifying rational biomarkers are discussed. Moreover, the challenges of using different proteomic analytical approaches and biological samples are also addressed.
Raman Study on Lipid Droplets in Hepatic Cells Co-Cultured with Fatty Acids
Authors: Paramitha Pradjna N. , Zakaria Riki , Maryani Anisa , Kusaka Yukako , Andriana Bibin B. , Hashimoto Kosuke , Nakazawa Hiromitsu , Kato Satoru , Sato Hidetoshi
Published: July 2021

The purpose of the present study was to investigate molecular compositions of lipid droplets changing in live hepatic cells stimulated with major fatty acids in the human body, i.e., palmitic, stearic, oleic, and linoleic acids. HepG2 cells were used as the model hepatic cells. Morphological changes of lipid droplets were observed by optical microscopy and transmission electron microscopy (TEM) during co-cultivation with fatty acids up to 5 days. The compositional changes in the fatty chains included in the lipid droplets were analyzed via Raman spectroscopy and chemometrics. The growth curves of the cells indicated that palmitic, stearic, and linoleic acids induced cell death in HepG2 cells, but oleic acid did not. Microscopic observations suggested that the rates of fat accumulation were high for oleic and linoleic acids, but low for palmitic and stearic acids. Raman analysis indicated that linoleic fatty chains taken into the cells are modified into oleic fatty chains. These results suggest that the signaling pathway of cell death is independent of fat stimulations. Moreover, these results suggest that hepatic cells have a high affinity for linoleic acid, but linoleic acid induces cell death in these cells. This may be one of the causes of inflammation in nonalcoholic fatty liver disease (NAFLD).
Cisplatin Resistance and Redox-Metabolic Vulnerability: A Second Alteration
Authors: Wangpaichitr Medhi , Theodoropoulos George , Nguyen Dan J. M. , Wu Chunjing , Spector Sydney A. , Feun Lynn G. , Savaraj Niramol
Published: July 2021

The development of drug resistance in tumors is a major obstacle to effective cancer chemotherapy and represents one of the most significant complications to improving long-term patient outcomes. Despite early positive responsiveness to platinum-based chemotherapy, the majority of lung cancer patients develop resistance. The development of a new combination therapy targeting cisplatin-resistant (CR) tumors may mark a major improvement as salvage therapy in these patients. The recent resurgence in research into cellular metabolism has again confirmed that cancer cells utilize aerobic glycolysis (“the Warburg effect”) to produce energy. Hence, this observation still remains a characteristic hallmark of altered metabolism in certain cancer cells. However, recent evidence promotes another concept wherein some tumors that acquire resistance to cisplatin undergo further metabolic alterations that increase tumor reliance on oxidative metabolism (OXMET) instead of glycolysis. Our review focuses on molecular changes that occur in tumors due to the relationship between metabolic demands and the importance of NAD+ in redox (ROS) metabolism and the crosstalk between PARP-1 (Poly (ADP ribose) polymerase-1) and SIRTs (sirtuins) in CR tumors. Finally, we discuss a role for the tumor metabolites of the kynurenine pathway (tryptophan catabolism) as effectors of immune cells in the tumor microenvironment during acquisition of resistance in CR cells. Understanding these concepts will form the basis for future targeting of CR cells by exploiting redox-metabolic changes and their consequences on immune cells in the tumor microenvironment as a new approach to improve overall therapeutic outcomes and survival in patients who fail cisplatin.
G-Quadruplex in Gene Encoding Large Subunit of Plant RNA Polymerase II: A Billion-Year-Old Story
Authors: Volná Adriana , Bartas Martin , Karlický Václav , Nezval Jakub , Kundrátová Kristýna , Pečinka Petr , Špunda Vladimír , Červeň Jiří
Published: July 2021

G-quadruplexes have long been perceived as rare and physiologically unimportant nucleic acid structures. However, several studies have revealed their importance in molecular processes, suggesting their possible role in replication and gene expression regulation. Pathways involving G-quadruplexes are intensively studied, especially in the context of human diseases, while their involvement in gene expression regulation in plants remains largely unexplored. Here, we conducted a bioinformatic study and performed a complex circular dichroism measurement to identify a stable G-quadruplex in the gene RPB1, coding for the RNA polymerase II large subunit. We found that this G-quadruplex-forming locus is highly evolutionarily conserved amongst plants sensu lato (Archaeplastida) that share a common ancestor more than one billion years old. Finally, we discussed a new hypothesis regarding G-quadruplexes interacting with UV light in plants to potentially form an additional layer of the regulatory network.
Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)
Authors: Chiang Nancy , Ray Shahla , Lomax Jade , Goertzen Sydney , Komarnytsky Slavko , Ho Chi-Tang , Munafo John P.
Published: July 2021

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.
Physiological Response of Maize Plants (Zea mays L.) to the Use of the Potassium Quercetin Derivative
Authors: Migut Dagmara , Jańczak-Pieniążek Marta , Piechowiak Tomasz , Buczek Jan , Balawejder Maciej
Published: July 2021

Plant production technologies based solely on the improvement of plants themselves face obstacles resulting from the natural limitations of the biological potential of varieties. Therefore, new substances are sought that positively influence the growth and development of plants and increase resistance to various biotic and abiotic stresses, which also translates into an increase in obtained yields. The exogenous application of various phytoprotectants shows great promise in terms of cost effectiveness compared to traditional breeding methods or transgenic approaches in relation to increasing plant tolerance to abiotic stresses. Quercetin is a strong antioxidant among phenolic compounds, and it plays a physiological and biochemical role in plants. As such, the aim of this research was to assess the effect of an aqueous solution of a quercetin derivative with potassium, applied in various concentrations (0.5%, 1.0%, 3.0% and 5.0%), on the efficiency of the photosynthetic apparatus and biochemical properties of maize. Among the tested variants, compared to the control, the most stimulating effect on the course of physiological processes (PN, gs, ci, CCI, Fv/Fm, Fv/F0, PI) in maize leaves was found in 3.0 and 5.0% aqueous solutions of the quercetin derivative. The highest total antioxidant capacity and total content of polyphenolic compounds were found for plants sprayed with 5.0% quercetin derivative solution; therefore, in this study, the optimal concentration could not be clearly selected.
The Impact of Graphite Oxide Nanocomposites on the Antibacterial Activity of Serum
Authors: Morka Katarzyna Dorota , Wernecki Maciej , Kędziora Anna , Książczyk Marta , Dudek Bartłomiej , Gerasymchuk Yuriy , Lukowiak Anna , Bystroń Jarosław , Bugla-Płoskońska Gabriela
Published: July 2021

Nanoparticles can interact with the complement system and modulate the inflammatory response. The effect of these interactions on the complement activity strongly depends on physicochemical properties of nanoparticles. The interactions of silver nanoparticles with serum proteins (particularly with the complement system components) have the potential to significantly affect the antibacterial activity of serum, with serious implications for human health. The aim of the study was to assess the influence of graphite oxide (GO) nanocomposites (GO, GO-PcZr(Lys)2-Ag, GO-Ag, GO-PcZr(Lys)2) on the antibacterial activity of normal human serum (NHS), serum activity against bacteria isolated from alveoli treated with nanocomposites, and nanocomposite sensitivity of bacteria exposed to serum in vitro (using normal human serum). Additionally, the in vivo cytotoxic effect of the GO compounds was determined with application of a Galleria mellonella larvae model. GO-PcZr(Lys)2, without IR irradiation enhance the antimicrobial efficacy of the human serum. IR irradiation enhances bactericidal activity of serum in the case of the GO-PcZr(Lys)2-Ag sample. Bacteria exposed to nanocomposites become more sensitive to the action of serum. Bacteria exposed to serum become more sensitive to the GO-Ag sample. None of the tested GO nanocomposites displayed a cytotoxicity towards larvae.
Influence of Cannabinoid Receptor 1 Genetic Variants on the Subjective Effects of Smoked Cannabis
Authors: Murphy Thomas , Matheson Justin , Mann Robert E. , Brands Bruna , Wickens Christine M. , Tiwari Arun K. , Zai Clement C. , Kennedy James , Le Foll Bernard
Published: July 2021

As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (CNR1) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (n = 52) were genotyped at the CNR1 rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.
IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis
Authors: Hou Tianheng , Tsang Miranda Sin-Man , Kan Lea Ling-Yu , Li Peiting , Chu Ida Miu-Ting , Lam Christopher Wai-Kei , Wong Chun-Kwok
Published: July 2021

Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture of human basophils and human keratinocyte HaCaT cells and an in vivo MC903-induced AD murine model to investigate the anti-inflammatory mechanism of IL-37. In the in vitro model, IL-37b significantly decreased Der p1-induced thymic stromal lymphopoietin (TSLP) overexpression in HaCaT cells and decreased the expression of TSLP receptor as well as basophil activation marker CD203c on basophils. IL-37 could also reduce Th2 cytokine IL-4 release from TSLP-primed basophils ex vivo. In the in vivo model, alternative depletion of basophils ameliorated AD symptoms and significantly lowered the Th2 cell and eosinophil populations in the ear and spleen of the mice. Blocking TSLP alleviated the AD-like symptoms and reduced the infiltration of basophils in the spleen. In CRISPR/Cas9 human IL-37b knock-in mice or mice with direct treatment by human IL-37b antibody, AD symptoms including ear swelling and itching were significantly alleviated upon MC903 challenge. Notably, IL-37b presence significantly reduced the basophil infiltration in ear lesions. In summary, IL-37b could regulate the TSLP-mediated activation of basophils and reduce the release of IL-4. The results, therefore, suggest that IL-37 may target TSLP-primed basophils to alleviate AD.
Rate and Product Studies with 1-Adamantyl Chlorothioformate under Solvolytic Conditions
Authors: Park Kyoung Ho , Seong Mi Hye , Kyong Jin Burm , Kevill Dennis N.
Published: July 2021

A study was carried out on the solvolysis of 1-adamantyl chlorothioformate (1-AdSCOCl, 1) in hydroxylic solvents. The rate constants of the solvolysis of 1 were well correlated using the Grunwald–Winstein equation in all of the 20 solvents (R = 0.985). The solvolyses of 1 were analyzed as the following two competing reactions: the solvolysis ionization pathway through the intermediate (1-AdSCO)+ (carboxylium ion) stabilized by the loss of chloride ions due to nucleophilic solvation and the solvolysis–decomposition pathway through the intermediate 1-Ad+Cl− ion pairs (carbocation) with the loss of carbonyl sulfide. In addition, the rate constants (kexp) for the solvolysis of 1 were separated into k1-Ad+Cl− and k1-AdSCO+Cl− through a product study and applied to the Grunwald–Winstein equation to obtain the sensitivity (m-value) to change in solvent ionizing power. For binary hydroxylic solvents, the selectivities (S) for the formation of solvolysis products were very similar to those of the 1-adamantyl derivatives discussed previously. The kinetic solvent isotope effects (KSIEs), salt effects and activation parameters for the solvolyses of 1 were also determined. These observations are compared with those previously reported for the solvolyses of 1-adamantyl chloroformate (1-AdOCOCl, 2). The reasons for change in reaction channels are discussed in terms of the gas-phase stabilities of acylium ions calculated using Gaussian 03.
Functional Analyses of Four CYP1A1 Missense Mutations Present in Patients with Atypical Femoral Fractures
Authors: Ugartondo Nerea , Martínez-Gil Núria , Esteve Mònica , Garcia-Giralt Natàlia , Roca-Ayats Neus , Ovejero Diana , Nogués Xavier , Díez-Pérez Adolfo , Rabionet Raquel , Grinberg Daniel , Balcells Susanna
Published: July 2021

Osteoporosis is the most common metabolic bone disorder and nitrogen-containing bisphosphonates (BP) are a first line treatment for it. Yet, atypical femoral fractures (AFF), a rare adverse effect, may appear after prolonged BP administration. Given the low incidence of AFF, an underlying genetic cause that increases the susceptibility to these fractures is suspected. Previous studies uncovered rare CYP1A1 mutations in osteoporosis patients who suffered AFF after long-term BP treatment. CYP1A1 is involved in drug metabolism and steroid catabolism, making it an interesting candidate. However, a functional validation for the AFF-associated CYP1A1 mutations was lacking. Here we tested the enzymatic activity of four such CYP1A1 variants, by transfecting them into Saos-2 cells. We also tested the effect of commonly used BPs on the enzymatic activity of the CYP1A1 forms. We demonstrated that the p.Arg98Trp and p.Arg136His CYP1A1 variants have a significant negative effect on enzymatic activity. Moreover, all the BP treatments decreased CYP1A1 activity, although no specific interaction with CYP1A1 variants was found. Our results provide functional support to the hypothesis that an additive effect between CYP1A1 heterozygous mutations p.Arg98Trp and p.Arg136His, other rare mutations and long-term BP exposure might generate susceptibility to AFF.