bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Artificial Nutrition on Postoperative Complications
Authors: Sandrucci Sergio , Cotogni Paolo , De Zolt Ponte Beatrice
Published: December 2020

Malnutrition is common in surgical cancer patients and it is widely accepted that it can adversely affect their postoperative outcome. Assessing the nutritional status of every patient, in particular care of elderly and cancer patients, is a crucial feature of the therapeutic pathway in order to optimize every strategy. Evidence exists that the advantages of perioperative nutrition are more significant in malnourished patients submitted to major surgery. For patients recognized as malnourished, preoperative nutrition therapies are indicated; the choice between parenteral and enteral nutrition is still controversial in perioperative malnourished surgical cancer patients, although enteral nutrition seems to have the best risk–benefit ratio. Early oral nutrition after surgery is advisable, when feasible, and should be administered in all the patients undergoing elective major surgery, if compliant. In patients with high risk for postoperative infections, perioperative immunonutrition has been proved in some ways to be effective, even if operations including those for cancer have to be delayed.
Uptake of Health Care Services by Refugees: Modelling a Country Response to a Western Balkan Refugee Crisis
Authors: Santric-Milicevic Milena , Vasic Milena , Vasic Vladimir , Zivkovic-Sulovic Mirjana , Cirovic Dragana , Lackovic Milan , Boskovic Nikolina
Published: December 2020

Planning and adjusting health capacities to meet the needs of refugees is a constant issue for transit and destination countries following the 2015/2016 Western Balkans refugee crisis. Understanding this crisis is important for taking the right steps in the future. The study informs about the prediction of the refugees’ health needs and demands for services in correspondence to political decision-making during 2015/2016 Western Balkan Refugee Crisis. Time series analysis, linear regression, and correlation analyses modelled the weekly flux of arrivals of more than half a million refugees to Serbia and the European Union, changes in the utilization of health care services, and disease diagnoses. With strategic planning, in the event of a recurrence of the refugee crises, the demand for health care services in the transit country could increase by 63 (95% CI: 21–105) for every additional 1000 refugees.
Barriers to and Facilitators of Adherence to Clinical Practice Guidelines in the Middle East and North Africa Region: A Systematic Review
Authors: Almazrou Saja H. , Alfaifi Sarah I. , Alfaifi Sumayyah H. , Hakami Lamees E. , Al-Aqeel Sinaa A.
Published: December 2020

The current review aims to investigate the barriers to and facilitators of the adherence to clinical practice guidelines (CPGs) in the Middle East and North Africa (MENA) region. English language studies published between January 2010 and May 2019 were searched on PubMed, Embase, and EBSCO. The barriers were categorized as clinician-related factors, such as lack of awareness of familiarity with the CPGs, and external factors, such as patients, guidelines, and environmental factors. The search identified 295 titles, out of which 15 were included. Environmental factors, specifically lack of time, resources, incentives, availability, and costs of treatment or diagnostic tests, training, and dissemination plans were the most commonly identified barriers. The familiarity with or awareness of healthcare professionals about the guideline, guideline characteristics, lack of agreement with the guidelines and preference in clinical judgment, physician self-efficacy, and motivation were reported to a lesser extent. Few studies reported on the compliance of facilitators with the guidelines including disseminating and advertising guideline materials, education and training on the guidelines, regulatory and financial incentives, and support from institutions. The review highlights that the studies on barriers to and facilitators of compliance with CPGs in the MENA region are limited in number and quality.
Stimulatory Effect of Seed Priming as Pretreatment Factors on Germination and Yield Performance of Yard Long Bean (Vigna unguiculata)
Authors: Karim Md. Naziul , Sani Md. Nasir Hossain , Uddain Jasim , Azad Md Obyedul Kalam , Kabir Md. Sazzadul , Rahman Mohammed Saifur , Choi Ki Young , Naznin Most Tahera
Published: December 2020

Seed priming is a technique that can potentially facilitate rapid and consistent germination and subsequent plant growth. The present study investigates the effect of different seed priming treatments and processing times on germination and growth efficiency for the effective cultivation of Yard-long bean. Thirteen different primings were used to determine the stimulatory effect on the germination and yield performance of the Yard-long bean. The priming treatments included control (without priming); hydro priming for 12, 18, 24, and 30 h; halo priming (1% CaCl2) for 12, 18, 24, and 30 h; and halo priming (2% KNO3) for 12, 18, 24, and 30 h. Studies showing the highest level of germination (86.66%), germination index (35.69), seedling vigor index (1833.80), number of branches (7.20), and pod yields per plant (1836.00 g) were recorded from halo priming with 1% CaCl2 at 12 h treatment. Halo priming with 1% CaCl2 at 12 h is thus considered to be a compatible priming technique for the germination of seeds and a higher yield of Yard-long bean.
The Effect of Supervisor Identification on Unethical Pro-Supervisor Behavior: The Moderating Role of Employability Perceptions
Authors: Lee Kangmin
Published: December 2020

Under some employment circumstances, individuals in some organizations are willing to engage in unethical behaviors that benefit one’s own supervisors who have a great power to decide the levels of evaluation and compensation for each individual. In this study, two hypotheses were examined. First, based on social identification theory, we hypothesized that individuals’ feeling a sense of oneness with one’s own supervisors promote unethical pro-supervisor behaviors (UPSB). Second, based on a person–situation interactionist model, we hypothesized that this positive relationship is strengthened if the individual perceives lower levels of one’s own employability. Data were collected from 185 individuals of various types of organizations in South Korea. A time-lagged field study supported our hypotheses. In particular, [supervisor identification was positively related to UPSB. Furthermore, for individuals with a weaker employability perception, supervisor identification was positively related to UPSB.
Perceptions of Health Care Use in Germany during the COVID-19 Pandemic
Authors: Hajek André , De Bock Freia , Wieler Lothar H. , Sprengholz Philipp , Kretzler Benedikt , König Hans-Helmut
Published: December 2020

This paper examined the determinants of perceived access to health care use during the COVID-19 pandemic in Germany using data from two waves (8 and 16) of the COVID-19 Snapshot Monitoring (COSMO). Descriptive and regression analysis were used. In wave 8, we found that about 60% of the individuals rather disagreed about having had problems accessing medical care. Furthermore, 73% of the individuals rather disagreed to having experienced health deteriorations due to restrictions on the availability of medical care. Moreover, 85% of the individuals were rather optimistic about future access to healthcare services. Overall, slightly better past and future access to healthcare services has been reported in wave 16. Several determinants were identified in regression analysis. In conclusion, data suggest that perceived past and future access to healthcare services during the COVID-19 pandemic is reasonably good.
“Ashamed, Silent and Stuck in a System”—Applying a Structural Violence Lens to Midwives’ Stories on Social Disadvantage in Pregnancy
Authors: Neely Eva , Raven Briony , Dixon Lesley , Bartle Carol , Timu-Parata Carmen
Published: December 2020

Historical and enduring maternal health inequities and injustices continue to grow in Aotearoa New Zealand, despite attempts to address the problem. Pregnancy increases vulnerability to poverty through a variety of mechanisms. This project qualitatively analysed an open survey response from midwives about their experiences of providing maternity care to women living with social disadvantage. We used a structural violence lens to examine the effects of social disadvantage on pregnant women. The analysis of midwives’ narratives exposed three mechanisms by which women were exposed to structural violence, these included structural disempowerment, inequitable risk and the neoliberal system. Women were structurally disempowered through reduced access to agency, lack of opportunities and inadequate meeting of basic human needs. Disadvantage exacerbated risks inequitably by increasing barriers to care, exacerbating the impact of adverse life circumstances and causing chronic stress. Lastly, the neoliberal system emphasised individual responsibility that perpetuated inequities. Despite the stated aim of equitable access to health care for all in policy documents, the current system and social structure continues to perpetuate systemic disadvantage.
Inclusive Parks across Ages: Multifunction and Urban Open Space Management for Children, Adolescents, and the Elderly
Authors: Sundevall Elin P. , Jansson Märit
Published: December 2020

In urban areas where increased density has caused loss of urban open space (UOS), there is a need for high-quality parks that are inclusive and fit for multiple user groups. To make parks more inclusive, UOS management may need to consider multifunction and the perspectives of various age groups in future development and maintenance activities. Walking interviews were conducted in a park in central Landskrona, Sweden, with children, adolescents, and elderly users, and also with the head park manager of the city. The results revealed different perspectives among the three age groups of users concerning affordances and UOS management. The manager described user-oriented management to support multifunction and inclusion, including user participation. All user groups studied showed an appreciation of liveliness, contact with nature, social places for their own age group, clean and safe parks, and a variety of different atmospheres and activities in the park. Social multifunction can be developed in programmed or non-programmed ways, but some functions interfere with each other. UOS managers can develop parks to suit different age groups, promote user participation within management, and develop social multifunction to create inclusive parks for various age groups.
Changes in Physical Activity, Sitting and Sleep across the COVID-19 National Lockdown Period in Scotland
Authors: Janssen Xanne , Fleming Leanne , Kirk Alison , Rollins Lesley , Young David , Grealy Madeleine , MacDonald Bradley , Flowers Paul , Williams Lynn
Published: December 2020

We examine the impact of the COVID-19 outbreak and concomitant restrictions (i.e., lockdown) on 24-hour movement behaviors (i.e., physical activity, sitting, sleep) in a purposive sample of people (n = 3230) reporting change recruited online. Participants’ self-reported time spent in moderate-to-vigorous physical activity (MVPA), walking, sitting and sleep prior to lockdown (T1), during the first national lockdown (T2) and as restrictions initially started to ease (T3). For each 24-hour movement behavior, category-shifts are reported (positive, negative or did not change), as well as the percentage of participants recording positive/negative changes across clusters of behaviors and the percentage of participants recording improvement or maintenance of change across time. From T1 to T2 walking decreased, whereas MVPA, sitting and sleep increased, from T2 to T3 levels returned to pre-lockdown for all but MVPA. Participants who changed one behavior positively were more likely to report a positive change in another and 50% of those who reported positive changes from T1 to T2 maintained or improved further when restrictions started to ease. The current study showed that a large proportion of the sample reported positive changes, most notably those displaying initially poor levels of each behavior. These findings will inform salutogenic intervention development.
Identification of the Knowledge Structure of Cancer Survivors’ Return to Work and Quality of Life: A Text Network Analysis
Authors: Kim Kisook , Lee Ki-Seong
Published: December 2020

This study aimed to understand the trends in research on the quality of life of returning to work (RTW) cancer survivors using text network analysis. Titles and abstracts of each article were examined to extract terms, including “cancer survivors”, “return to work”, and “quality of life”, which were found in 219 articles published between 1990 and June 2020. Python and Gephi software were used to analyze the data and visualize the networks. Keyword ranking was based on the frequency, degree centrality, and betweenness centrality. The keywords commonly ranked at the top included “breast”, “patients”, “rehabilitation”, “intervention”, “treatment”, and “employment”. Clustering results by grouping nodes with high relevance in the network led to four clusters: “participants and method”, “type of research and variables”, “RTW and education in adolescent and young adult cancer survivors”, and “rehabilitation program”. This study provided a visualized overview of the research on cancer survivors’ RTW and quality of life. These findings contribute to the understanding of the flow of the knowledge structure of the existing research and suggest directions for future research.
Religious Attendance in a Secular Country Protects Adolescents from Health-Risk Behavior Only in Combination with Participation in Church Activities
Authors: Buchtova Marie , Malinakova Klara , Kosarkova Alice , Husek Vit , van Dijk Jitse , Tavel Peter
Published: December 2020

Religiosity and spirituality have been considered to be protective factors of adolescent health-risk behavior (HRB). The aim of this study was to assess the relationship between adolescents’ HRB and their religiosity, taking into account their parents’ faith and their own participation in church activities. A nationally representative sample (n = 13377, 13.5 ± 1.7 years, 49.1% boys) of Czech adolescents participated in the 2018 Health Behavior in School-aged Children cross-sectional study. We measured religious attendance (RA), faith importance (FI) (both of respondents and their parents), participation in church activities and adolescent HRB (tobacco, alcohol, and cannabis use and early sexual intercourse). We found that neither RA nor FI of participants or their parents had a significant effect on adolescents’ HRB. Compared to attending respondents who participate in church activities (AP), non-attending respondents who participate in church activities were more likely to report smoking and early sexual intercourse, with odds ratios (ORs) ranging from 3.14 (1.54–6.39) to 3.82 (1.99–7.35). Compared to AP, non-attending respondents who did not participate in church activities were more likely to report early sexual intercourse, with OR = 1.90 (1.14–3.17). Thus, our findings show that RA does not protect adolescents from HRB; they suggest that RA protects adolescents from HRB only in combination with participation in church activities.
Simulation-Based Solutions Reducing Soil and Groundwater Contamination from Fertilizers in Arid and Semi-Arid Regions: Case Study the Eastern Nile Delta, Egypt
Authors: Abd-Elaty Ismail , Pugliese Lorenzo , Zelenakova Martina , Mesaros Peter , Shinawi Abdelaziz El
Published: December 2020

Intensive agriculture requires increasing application of fertilizers in order to sustain food production. Improper use of these substances in combination with increasing seawater intrusion results in long-term and nonpoint soil and groundwater contamination. In this work, a 3-D groundwater and solute transport numerical model was created to simulate the effect of excessive fertilizers application along the Bahr El Baqar drain system, in the eastern Nile Delta, Egypt. The geotechnical properties of the soils, hydrologic parameters, and unconfined compressive strength were determined at different sites and used as input parameters for the model. Model results showed that silty clay soils are able to contain the contaminations and preserve the groundwater quality. Nevertheless, sandy soils primarily located at the beginning of the Bahr El Baqar drain allow leakage of fertilizers to the groundwater. Thus, fertilizer application should be properly managed in the top sandy layers to protect the groundwater and soil, as increasing aquifer by excess irrigation water increased the groundwater contamination in confined layers due to the high value of cumulative salt for the current situation while the unconfined zone decreased groundwater and soil contamination. A mass transport 3-D multi-species (MT3D) model was set to identify the optimal measure to tackle soil and groundwater contamination along the Bahr El-Baqar drain system. A potential increase of the abstraction rates in the study area has a positive impact in reducing the transfer of fertilizer contamination to groundwater while it has a negative impact for soil contamination. The scenario analysis further indicated that the installation of a drainage network decreases the groundwater and soil contamination. Both solutions are potentially effective for protection against nonpoint contamination along the Bahr El Baqar drain system. However, a more sustainable management approach of fertilizer application is needed to adequately protect the receptors located further downstream in the Nile Delta.
The Role of the Foreign Sector in the Spanish Bioeconomy: Two Approaches Based on SAM Linear Models
Authors: Ferreira Valeria , Pié Laia , Terceño Antonio
Published: December 2020

The bioeconomy emerges as an opportunity to focus on a more sustainable economy, avoid dependence on non-renewable resources and help to mitigate negative environmental impacts. The bioeconomy is considered a priority for the European Union and for Spain, which launched its strategy in 2016. To promote the Spanish bioeconomy, the impact and variables that may influence its development must be known. While previous works have analyzed the domestic sectors, this paper focuses on analyzing the economic importance of Spanish bioeconomy products and on the influence of and the existing links between the foreign sector and the rest of the economy. For this purpose, we apply two different methodologies based on linear social accounting matrix (SAM) models. The linkages show that many bioeconomy products have the potential to promote the rest of the economy and the values of some product multipliers become more significant due to their import dependence. These results enable us to know the structure of the Spanish bioeconomy and the relationships within its account. This analysis is a useful tool for developing policies focused on fostering the bioeconomy and economic growth.
The Psychological Impact of ‘Mild Lockdown’ in Japan during the COVID-19 Pandemic: A Nationwide Survey under a Declared State of Emergency
Authors: Yamamoto Tetsuya , Uchiumi Chigusa , Suzuki Naho , Yoshimoto Junichiro , Murillo-Rodriguez Eric
Published: December 2020

This study examined the psychological distress caused by non-coercive lockdown (mild lockdown) in Japan. An online survey was conducted with 11,333 people (52.4% females; mean age = 46.3 ± 14.6 years, range = 18–89 years) during the mild lockdown in the seven prefectures most affected by COVID-19 infection. Over one-third (36.6%) of participants experienced mild-to-moderate psychological distress (Kessler Psychological Distress Scale [K6] score 5–12), while 11.5% reported serious psychological distress (K6 score ≥ 13). The estimated prevalence of depression (Patient Health Questionnaire-9 score ≥ 10) was 17.9%. Regarding the distribution of K6 scores, the proportion of those with psychological distress in this study was significantly higher when compared with the previous national survey data from 2010, 2013, 2016, and 2019. Healthcare workers, those with a history of treatment for mental illness, and younger participants (aged 18–19 or 20–39 years) showed particularly high levels of psychological distress. Psychological distress severity was influenced by specific interactional structures of risk factors: high loneliness, poor interpersonal relationships, COVID-19-related sleeplessness and anxiety, deterioration of household economy, and work and academic difficulties. Even when non-coercive lockdowns are implemented, people’s mental health should be considered, and policies to prevent mental health deterioration are needed. Cross-disciplinary public–private sector efforts tailored to each individual’s problem structure are important to address the mental health issues arising from lockdown.
A Virtual Reality Simulation Method for Crowd Evacuation in a Multiexit Indoor Fire Environment
Authors: Guo Yukun , Zhu Jun , Wang Yu , Chai Jinchuan , Li Weilian , Fu Lin , Xu Bingli , Gong Yuhang
Published: December 2020

Evacuation simulations in virtual indoor fire scenes hold great significance for public safety. However, existing evacuation simulation methods are inefficient and provide poor visualized when applied to virtual reality (VR) simulations. Additionally, the influences of the interaction of evacuation processes on the choice of multiple exits have not been fully considered. In the paper, we propose a VR simulation method for crowd evacuation in a multiexit indoor fire environment. An indoor 3D scene model and character model, for studying the environmental factors that affect the multiexit selection of personnel during the fire process, are combined with environmental factors to enhance the evacuation route planning algorithm to improve the efficiency of the VR simulation of evacuation in the scene. In addition, a prototype system that supports multiple experience modes is proposed, and case experiment analyses are performed. The results show that the method described in this paper can effectively support the real-time simulation of indoor fire evacuations in virtual scenes, providing both reliable simulation results and good visualization effects.
Opportunities and Challenges of Geospatial Analysis for Promoting Urban Livability in the Era of Big Data and Machine Learning
Authors: Kovacs-Györi Anna , Ristea Alina , Havas Clemens , Mehaffy Michael , Hochmair Hartwig H. , Resch Bernd , Juhasz Levente , Lehner Arthur , Ramasubramanian Laxmi , Blaschke Thomas
Published: December 2020

Urban systems involve a multitude of closely intertwined components, which are more measurable than before due to new sensors, data collection, and spatio-temporal analysis methods. Turning these data into knowledge to facilitate planning efforts in addressing current challenges of urban complex systems requires advanced interdisciplinary analysis methods, such as urban informatics or urban data science. Yet, by applying a purely data-driven approach, it is too easy to get lost in the ‘forest’ of data, and to miss the ‘trees’ of successful, livable cities that are the ultimate aim of urban planning. This paper assesses how geospatial data, and urban analysis, using a mixed methods approach, can help to better understand urban dynamics and human behavior, and how it can assist planning efforts to improve livability. Based on reviewing state-of-the-art research the paper goes one step further and also addresses the potential as well as limitations of new data sources in urban analytics to get a better overview of the whole ‘forest’ of these new data sources and analysis methods. The main discussion revolves around the reliability of using big data from social media platforms or sensors, and how information can be extracted from massive amounts of data through novel analysis methods, such as machine learning, for better-informed decision making aiming at urban livability improvement.
Improving Stability of Tear Film Lipid Layer via Concerted Action of Two Drug Molecules: A Biophysical View
Authors: Eftimov Petar , Olżyńska Agnieszka , Melcrová Adéla , Georgiev Georgi As. , Daull Philippe , Garrigue Jean-Sebastien , Cwiklik Lukasz
Published: December 2020

The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops–tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear–air interface.
Genome-Wide Identification of the Expansin Gene Family and Its Potential Association with Drought Stress in Moso Bamboo
Authors: Jin Kang-Ming , Zhuo Ren-Ying , Xu Dong , Wang Yu-Jun , Fan Hui-Jin , Huang Bi-Yun , Qiao Gui-Rong
Published: December 2020

Expansins, a group of cell wall-loosening proteins, are involved in cell-wall loosening and cell enlargement in a pH-dependent manner. According to previous study, they were involved in plant growth and abiotic stress responses. However, information on the biological function of the expansin gene in moso bamboo is still limited. In this study, we identified a total of 82 expansin genes in moso bamboo, clustered into four subfamilies (α-expansin (EXPA), β-expansin (EXPB), expansin-like A (EXLA) and expansin-like B (EXPB)). Subsequently, the molecular structure, chromosomal location and phylogenetic relationship of the expansin genes of Phyllostachys edulis (PeEXs) were further characterized. A total of 14 pairs of tandem duplication genes and 31 pairs of segmented duplication genes were also identified, which may promote the expansion of the expansin gene family. Promoter analysis found many cis-acting elements related to growth and development and stress response, especially abscisic acid response element (ABRE). Expression pattern revealed that most PeEXs have tissue expression specificity. Meanwhile, the expression of some selected PeEXs was significantly upregulated mostly under abscisic acid (ABA) and polyethylene glycol (PEG) treatment, which implied that these genes actively respond to expression under abiotic stress. This study provided new insights into the structure, evolution and function prediction of the expansin gene family in moso bamboo.
Conformation of the Intermediates in the Reaction Catalyzed by Protoporphyrinogen Oxidase: An In Silico Analysis
Authors: Barker Abigail L. , Barnes Hamlin , Dayan Franck E.
Published: December 2020

Protoporphyrinogen oxidase (PPO) is a critical enzyme across life as the last common step in the synthesis of many metalloporphyrins. The reaction mechanism of PPO was assessed in silico and the unstructured loop near the binding pocket was investigated. The substrate, intermediates, and product were docked in the catalytic domain of PPO using a modified Autodock method, introducing flexibility in the macrocycles. Sixteen PPO protein sequences across phyla were aligned and analyzed with Phyre2 and ProteinPredict to study the unstructured loop from residue 204–210 in the H. sapiens structure. Docking of the substrate, intermediates, and product all resulted in negative binding energies, though the substrate had a lower energy than the others by 40%. The α-H of C10 was found to be 1.4 angstroms closer to FAD than the β-H, explaining previous reports of the reaction occurring on the meso face of the substrate. A lack of homology in sequence or length in the unstructured loop indicates a lack of function for the protein reaction. This docking study supports a reaction mechanism proposed previously whereby all hydride abstractions occur on the C10 of the tetrapyrrole followed by tautomeric rearrangement to prepare the intermediate for the next reaction.
No Easy Way Out for EZH2: Its Pleiotropic, Noncanonical Effects on Gene Regulation and Cellular Function
Authors: Wang Jun , Wang Gang Greg
Published: December 2020

Enhancer of zeste homolog 2 (EZH2) plays critical roles in a range of biological processes including organ development and homeostasis, epigenomic and transcriptomic regulation, gene repression and imprinting, and DNA damage repair. A widely known function of EZH2 is to serve as an enzymatic subunit of Polycomb repressive complex 2 (PRC2) and catalyze trimethylation of histone H3 lysine 27 (H3K27me3) for repressing target gene expression. However, an increasing body of evidence demonstrates that EZH2 has many “non-conventional” functions that go beyond H3K27 methylation as a Polycomb factor. First, EZH2 can methylate a number of nonhistone proteins, thereby regulating cellular processes in an H3K27me3-independent fashion. Furthermore, EZH2 relies on both methyltransferase-dependent and methyltransferase-independent mechanisms for modulating gene-expression programs and/or epigenomic patterns of cells. Importantly, independent of PRC2, EZH2 also forms physical interactions with a number of DNA-binding factors and transcriptional coactivators to context-dependently influence gene expression. The purpose of this review is to detail the complex, noncanonical roles of EZH2, which are generally less appreciated in gene and (epi)genome regulation. Because EZH2 deregulation is prevalent in human diseases such as cancer, there is increased dependency on its noncanonical function, which shall have important implications in developing more effective therapeutics.
Are There Epigenetic Oxytocin-Mediated Effects on the Mother and Infant during Physiological Childbirth?
Authors: Uvnäs-Moberg Kerstin , Gross Mechthild M. , Agius Andee , Downe Soo , Calleja-Agius Jean
Published: December 2020

Introduction: Studies have shown that long-term positive behavioural and physiological changes are induced in connection with vaginal, physiological birth, and skin-to-skin contact after birth in mothers and babies. Some of these effects are consistent with the effect profile of oxytocin. This scoping review explores whether epigenetic changes of the oxytocin gene and of the oxytocin receptor gene (OTR) are involved in these effects. Methods: We searched Pubmed, Medline, BioMed Central, Cochrane Library, OVID, and Web of Science for evidence of epigenetic changes in connection with childbirth in humans, with a particular focus on the oxytocin system. Results: There were no published studies identified that were related to epigenetic changes of oxytocin and its receptor in connection with labour, birth, and skin-to-skin contact after birth in mothers and babies. However, some studies were identified that showed polymorphisms of the oxytocin receptor influenced the progress of labour. We also identified studies in which the level of global methylation was measured in vaginal birth and caesarean section, with conflicting results. Some studies identified differences in the level of methylation of single genes linked to various effects, for example, immune response, metabolism, and inflammation. In some of these cases, the level of methylation was associated with the duration of labour or mode of birth. We also identified some studies that demonstrated long-term effects of mode of birth and of skin-to-skin contact linked to changes in oxytocin function. Conclusion: There were no studies identified that showed epigenetic changes of the oxytocin system in connection with physiological birth. The lack of evidence, so far, regarding epigenetic changes did not exclude future demonstrations of such effects, as there was a definite role of oxytocin in creating long-term effects during the perinatal period. Such studies may not have been performed. Alternatively, the oxytocin linked effects might be indirectly mediated via other receptors and signalling systems. We conclude that there is a significant lack of research examining long-term changes of oxytocin function and long-term oxytocin mediated adaptive effects induced during physiological birth and skin-to-skin contact after birth in mothers and their infants.
Potential of Bacterial Cellulose Chemisorbed with Anti-Metabolites, 3-Bromopyruvate or Sertraline, to Fight against Helicobacter pylori Lawn Biofilm
Authors: Krzyżek Paweł , Gościniak Grażyna , Fijałkowski Karol , Migdał Paweł , Dziadas Mariusz , Owczarek Artur , Czajkowska Joanna , Aniołek Olga , Junka Adam
Published: December 2020

Helicobacter pylori is a bacterium known mainly of its ability to cause persistent inflammations of the human stomach, resulting in peptic ulcer diseases and gastric cancers. Continuous exposure of this bacterium to antibiotics has resulted in high detection of multidrug-resistant strains and difficulties in obtaining a therapeutic effect. The purpose of the present study was to determine the usability of bacterial cellulose (BC) chemisorbed with 3-bromopyruvate (3-BP) or sertraline (SER) to act against lawn H. pylori biofilms. The characterization of BC carriers was made using a N2 adsorption/desorption analysis, tensile strength test, and scanning electron microscopy (SEM) observations. Determination of an antimicrobial activity was performed using a modified disk-diffusion method and a self-designed method of testing antibacterial activity against biofilm microbial forms. In addition, bacterial morphology was checked by SEM. It was found that BC disks were characterized by a high cross-linking and shear/stretch resistance. Growth inhibition zones for BC disks chemisorbed with 2 mg of SER or 3-BP were equal to 26.5–27.5 mm and 27–30 mm, respectively. The viability of lawn biofilm H. pylori cells after a 4-h incubation with 2 mg SER or 3-BP chemisorbed on BC disks was ≥4 log lower, suggesting their antibacterial effect. SEM observations showed a number of morphostructural changes in H. pylori cells exposed to these substances. Concluding, SER and 3-BP chemisorbed on BC carriers presented a promising antibacterial activity against biofilm H. pylori cells in in vitro conditions.
Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice
Authors: Park Sang Chul , Shim Dahee , Kim Hongmin , Bak Yeeun , Choi Da Yeon , Yoon Joo-Heon , Kim Chang-Hoon , Shin Sung Jae
Published: December 2020

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103+ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b+ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.
Comprehensive Analysis Reveals Novel Interactions between Circulating MicroRNAs and Gut Microbiota Composition in Human Obesity
Authors: Assmann Taís Silveira , Cuevas-Sierra Amanda , Riezu-Boj José Ignacio , Milagro Fermín I. , Martínez J. Alfredo
Published: December 2020

Background: The determinants that mediate the interactions between microRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this study was to investigate possible interactions between circulating microRNAs and gut microbiota composition in obesity. Method: The sample comprised 78 subjects with obesity (cases, body mass index (BMI): 30–40 kg/m2) and 25 eutrophic individuals (controls, BMI ≤ 25 kg/m2). The expression of 96 microRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels. Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR correction was used for multiple comparison analyses. Results: A total of 26 circulating microRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p and miR-21-5p) with Bacteroides eggerthi and BMI levels was evidenced (r2 = 0.148, p = 0.004). Moreover, these microRNAs regulate genes that participate in metabolism-related pathways, including fatty acid degradation, insulin signaling and glycerolipid metabolism. Conclusions: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating microRNAs in relation to obesity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts.
Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions
Authors: Fontana Fabrizio , Marzagalli Monica , Montagnani Marelli Marina , Raimondi Michela , Moretti Roberta , Limonta Patrizia
Published: December 2020

Pituitary Gonadotropin-Releasing Hormone receptors (GnRH-R) mediate the activity of the hypothalamic decapeptide GnRH, thus playing a key role in the regulation of the reproductive axis. Early-stage prostate cancer (PCa) is dependent on serum androgen levels, and androgen-deprivation therapy (ADT), based on GnRH agonists and antagonists, represents the standard therapeutic approach for PCa patients. Unfortunately, the tumor often progresses towards the more aggressive castration-resistant prostate cancer (CRPC) stage. GnRH receptors are also expressed in CRPC tissues, where their binding to both GnRH agonists and antagonists is associated with significant antiproliferative/proapoptotic, antimetastatic and antiangiogenic effects, mediated by the Gαi/cAMP signaling cascade. GnRH agonists and antagonists are now considered as an effective therapeutic strategy for CRPC patients with many clinical trials demonstrating that the combined use of these drugs with standard therapies (i.e., docetaxel, enzalutamide, abiraterone) significantly improves disease-free survival. In this context, GnRH-based bioconjugates (cytotoxic drugs covalently linked to a GnRH-based decapeptide) have been recently developed. The rationale of this treatment is that the GnRH peptide selectively binds to its receptors, delivering the cytotoxic drug to CRPC cells while sparing nontumor cells. Some of these compounds have already entered clinical trials.
Epigenetic Regulation of the Hippocampus, with Special Reference to Radiation Exposure
Authors: Saw Genevieve , Tang Feng Ru
Published: December 2020

The hippocampus is crucial in learning, memory and emotion processing, and is involved in the development of different neurological and neuropsychological disorders. Several epigenetic factors, including DNA methylation, histone modifications and non-coding RNAs, have been shown to regulate the development and function of the hippocampus, and the alteration of epigenetic regulation may play important roles in the development of neurocognitive and neurodegenerative diseases. This review summarizes the epigenetic modifications of various cell types and processes within the hippocampus and their resulting effects on cognition, memory and overall hippocampal function. In addition, the effects of exposure to radiation that may induce a myriad of epigenetic changes in the hippocampus are reviewed. By assessing and evaluating the current literature, we hope to prompt a more thorough understanding of the molecular mechanisms that underlie radiation-induced epigenetic changes, an area which can be further explored.
Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia
Authors: Aliotta Alessandro , Krüsi Manuel , Bertaggia Calderara Debora , Zermatten Maxime G. , Gomez Francisco J. , Batista Mesquita Sauvage Ana P. , Alberio Lorenzo
Published: December 2020

Patients affected by the rare Glanzmann thrombasthenia (GT) suffer from defective or low levels of the platelet-associated glycoprotein (GP) IIb/IIIa, which acts as a fibrinogen receptor, and have therefore an impaired ability to aggregate platelets. Because the procoagulant activity is a dichotomous facet of platelet activation, diverging from the aggregation endpoint, we were interested in characterizing the ability to generate procoagulant platelets in GT patients. Therefore, we investigated, by flow cytometry analysis, platelet functions in three GT patients as well as their ability to generate procoagulant collagen-and-thrombin (COAT) platelets upon combined activation with convulxin-plus-thrombin. In addition, we further characterized intracellular ion fluxes during the procoagulant response, using specific probes to monitor by flow cytometry kinetics of cytosolic calcium, sodium, and potassium ion fluxes. GT patients generated higher percentages of procoagulant COAT platelets compared to healthy donors. Moreover, they were able to mobilize higher levels of cytosolic calcium following convulxin-plus-thrombin activation, which is congruent with the greater procoagulant activity. Further investigations will dissect the role of GPIIb/IIIa outside-in signalling possibly implicated in the regulation of platelet procoagulant activity.
Mass Spectrometric Imaging of Plasma Membrane Lipid Alteration Correlated with Amperometrically Measured Activity-Dependent Plasticity in Exocytosis
Authors: Gu Chaoyi , Philipsen Mai H. , Ewing Andrew G.
Published: December 2020

The mechanism of synaptic plasticity and its link to memory formation are of interest, yet relatively obscure, especially the initial chemical change in the cell membrane following transmitter release. To understand the chemical mechanism of plasticity, we studied how repetitive stimuli regulate certain membrane lipid species to enhance exocytotic release using mass spectrometric imaging. We found that increasing high-curvature lipid species and decreasing low-curvature lipids in the cell membrane favor the formation of a longer-lasting exocytotic fusion pore, resulting in higher release fraction for individual exocytotic events. The lipid changes observed following repetitive stimuli are similar to those after exposure to the cognitive enhancing drug, methylphenidate, examined in a previous study, and offer an interesting point of view regarding the link between plasticity and memory and cognition.
Elevated Production of Mitochondrial Reactive Oxygen Species via Hyperthermia Enhanced Cytotoxic Effect of Doxorubicin in Human Breast Cancer Cell Lines MDA-MB-453 and MCF-7
Authors: Terasaki Azusa , Kurokawa Hiromi , Ito Hiromu , Komatsu Yoshiki , Matano Daisuke , Terasaki Masahiko , Bando Hiroko , Hara Hisato , Matsui Hirofumi
Published: December 2020

Hyperthermia (HT) treatment is a noninvasive cancer therapy, often used with radiation therapy and chemotherapy. Compared with 37 °C, 42 °C is mild heat stress for cells and produces reactive oxygen species (ROS) from mitochondria. To involve subsequent intracellular accumulation of DOX, we have previously reported that the expression of ATP-binding cassette sub-family G member 2 (ABCG2), an exporter of doxorubicin (DOX), was suppressed by a larger amount of intracellular mitochondrial ROS. We then hypothesized that the additive effect of HT and chemotherapy would be induced by the downregulation of ABCG2 expression via intracellular ROS increase. We used human breast cancer cell lines, MCF-7 and MDA-MB-453, incubated at 37 °C or 42 °C for 1 h to clarify this hypothesis. Intracellular ROS production after HT was detected via electron spin resonance (ESR), and DOX cytotoxicity was calculated. Additionally, ABCG2 expression in whole cells was analyzed using Western blotting. We confirmed that the ESR signal peak with HT became higher than that without HT, indicating that the intracellular ROS level was increased by HT. ABCG2 expression was downregulated by HT, and cells were injured after DOX treatment. DOX cytotoxicity enhancement with HT was considered a result of ABCG2 expression downregulation via the increase of ROS production. HT increased intracellular ROS production and downregulated ABCG2 protein expression, leading to cell damage enhancement via DOX.
EGFR-Binding Peptides: From Computational Design towards Tumor-Targeting of Adeno-Associated Virus Capsids
Authors: Feiner Rebecca C. , Kemker Isabell , Krutzke Lea , Allmendinger Ellen , Mandell Daniel J. , Sewald Norbert , Kochanek Stefan , Müller Kristian M.
Published: December 2020

The epidermal growth factor receptor (EGFR) plays a central role in the progression of many solid tumors. We used this validated target to analyze the de novo design of EGFR-binding peptides and their application for the delivery of complex payloads via rational design of a viral vector. Peptides were computationally designed to interact with the EGFR dimerization interface. Two new peptides and a reference (EDA peptide) were chemically synthesized, and their binding ability characterized. Presentation of these peptides in each of the 60 capsid proteins of recombinant adeno-associated viruses (rAAV) via a genetic based loop insertion enabled targeting of EGFR overexpressing tumor cell lines. Furthermore, tissue distribution and tumor xenograft specificity were analyzed with systemic injection in chicken egg chorioallantoic membrane (CAM) assays. Complex correlations between the targeting of the synthetic peptides and the viral vectors to cells and in ovo were observed. Overall, these data demonstrate the potential of computational design in combination with rational capsid modification for viral vector targeting opening new avenues for viral vector delivery and specifically suicide gene therapy.