bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis
Authors: Huang Yijiang , Chen Daosen , Yan Zijian , Zhan Jingdi , Xue Xinghe , Pan Xiaoyun , Yu Huachen
Published: March 2021

Background

Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammatory changes. This work aims to investigate the protective role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) against the apoptosis of chondrocytes.

Methods

Chondrocyte cell lines, CHON-001, and ATDC5 were treated with different doses of interleukin-1β (IL-1β) to mimic the inflammatory response during OA pathogenesis. Quantitative real-time polymerase chain reaction was performed to measure MEG3, miR-9-5p, and Krüppel-like factor 4 (KLF4) mRNA expression levels. MEG3 and KLF4 overexpression plasmids, MEG3 shRNA, miR-9-5p mimics, and miR-9-5p inhibitors were transfected into the cells. Cell counting kit-8, wound healing assay, and flow cytometry were conducted to determine cell viability, migration, and apoptotic rate. Dual-luciferase reporter assay was adopted to verify the targeting relationships among MEG3, miR-9-5p, and KLF4. Western blot was used to detect KLF4 protein expression. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors.

Results

MEG3 expression in chondrocytes was down-regulated by the stimulation of IL-1β, and MEG3 negatively regulated miR-9-5p expression but positively regulated KLF4 expression. MEG3 overexpression strengthened the viability and migration of CHON-001 and ATDC5 cells but restrained the apoptosis and inflammatory response, while MEG3 knockdown had opposite effects. miR-9-5p inhibition or KLF4 overexpression could counteract the effects of MEG3 knockdown on chondrocytes. Besides that, MEG3 was proved to be a molecular sponge for miR-9-5p, and KLF4 was verified as the target of miR-9-5p.

Conclusion

MEG3 can promote chondrocyte proliferation and migration and inhibit apoptosis and inflammation by sponging miR-9-5p to induce KLF4 expression, which provides a promising therapy target for OA treatment.
Pilates for Overweight or Obesity: A Meta-Analysis
Authors: Wang Yi , Chen Zehua , Wu Zugui , Ye Xiangling , Xu Xuemeng
Published: March 2021

Background: Evidence for the efficacy of Pilates for the modulation of body weight and body composition is unclear.

Objective: This meta-analysis aimed to evaluate the effects of Pilates on body weight and body composition in adults with overweight or obesity.

Data Sources: The PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and EMBASE databases were systematically searched from the inception dates to 12 November 2020 for relevant randomized controlled trials (RCTs).

Study Selection: Randomized controlled trials comparing Pilates with other physical exercises or without any intervention were included.

Data Extraction and Synthesis: Three reviewers independently performed the data extraction and assessed study quality. The mean differences (MDs) and 95% confidence intervals (CIs) for pooled data were calculated.

Main Outcomes and Measures: Outcome measures were body weight, body mass index (BMI), body fat percentage, lean body mass, and waist circumference.

Results: Eleven RCTs with 393 subjects were included. This study revealed that Pilates dramatically reduces body weight (MD = −2.40, 95% CI: [−4.04, −0.77], P = 0.004, I2 = 51%), BMI (MD = −1.17, 95% CI: [−1.85, −0.50], P = 0.0006, I2 = 61%), and body fat percentage (MD = −4.22, 95% CI: [−6.44, −2.01], P = 0.0002, I2 = 88%) in adults with overweight or obesity. The reduction in body weight and body fat percentage appears to be more pronounced in studies including participants with obesity only, and the efficacy of Pilates for the improvement of body weight and BMI appears to be more evident in longer intervention duration. However, Pilates has no significant effect on waist circumference (MD = −2.65, 95% CI: [−6.84, 1.55], P = 0.22, I2 = 0%) and lean body mass (MD = −0.00, 95% CI: [−1.40, 1.40], P = 1.00, I2 = 23%).

Conclusions: Pilates dramatically reduces body weight, BMI, and body fat percentage in adults with overweight or obesity. Large-scale and well-designed RCTs with improved methodology and reporting are urgently needed to further confirm these results.
Physiological Disorders and Fruit Quality Attributes in Pomegranate: Effects of Meteorological Parameters, Canopy Position and Acetylsalicylic Acid Foliar Sprays
Authors: Drogoudi Pavlina , Pantelidis Georgios E. , Vekiari Stavroula A.
Published: March 2021

Meteorological parameters and occurrences of cracking (CR), russeting (RS), and sun scald (SS) symptoms were monitored in a pomegranate cv. “Wonderful” orchard planted in a W–E orientation, during a 3-year study. Moreover, the efficacy of preharvest foliar sprays with acetylsalicylic acid (ASA; 0.5 mM or 1.0 mM), applied biweekly four to six times, on yield and fruit quality attributes were evaluated in a 2-year study. Fruit from the N-side of the canopy had greater CR and RS, whereas SS symptoms were lower, compared with the S-exposed part of the canopy. The N-side of the canopy had also substantially lower fruit number and yield, suggesting for an important role of light on bisexual flower formation and/or fruit set. Following the occurrences in CR and RS during the fruit maturation period, it was found that temperature fluctuation was the main cause. The presence of RS damages may also be related with increased relative humidity and water movement as symptoms were higher in years with higher values, in the N-side of the canopy and often occurred in the exposed and stylar end of the fruit. The ASA treatment substantially reduced RS by up to 57%, improved the peel red coloration, while anthocyanin, antioxidant capacity, and soluble solid contents in juice were higher. Foliar sprays with ASA did not affect yield, but induced a trend of bigger-sized fruit. In conclusion, planting in a N–S row orientation and selecting an orchard plantation site with a minimum temperature fluctuation and low relative humidity during the fruit-ripening period are measures to control CR and RS in pomegranate. ASA foliar applications proved to have beneficial effects on juice antioxidant contents, but more importantly on fruit appearance.
The Gaze Cueing Effect and Its Enhancement by Facial Expressions Are Impacted by Task Demands: Direct Comparison of Target Localization and Discrimination Tasks
Authors: Chen Zelin , McCrackin Sarah D. , Morgan Alicia , Itier Roxane J.
Published: March 2021

The gaze cueing effect is characterized by faster attentional orienting to a gazed-at than a non-gazed-at target. This effect is often enhanced when the gazing face bears an emotional expression, though this finding is modulated by a number of factors. Here, we tested whether the type of task performed might be one such modulating factor. Target localization and target discrimination tasks are the two most commonly used gaze cueing tasks, and they arguably differ in cognitive resources, which could impact how emotional expression and gaze cues are integrated to orient attention. In a within-subjects design, participants performed both target localization and discrimination gaze cueing tasks with neutral, happy, and fearful faces. The gaze cueing effect for neutral faces was greatly reduced in the discrimination task relative to the localization task, and the emotional enhancement of the gaze cueing effect was only present in the localization task and only when this task was performed first. These results suggest that cognitive resources are needed for gaze cueing and for the integration of emotional expressions and gaze cues. We propose that a shift toward local processing may be the mechanism by which the discrimination task interferes with the emotional modulation of gaze cueing. The results support the idea that gaze cueing can be greatly modulated by top-down influences and cognitive resources and thus taps into endogenous attention. Results are discussed within the context of the recently proposed EyeTune model of social attention.
The Impact of Global Dynamic Capabilities on Governance Structure Choice of Partnership: The Moderating Effect of Ambidexterity
Authors: Ren Guoying , Peng Michael Yao-Ping
Published: March 2021

Research on multinational inter-organizational relationships has demonstrated that the capabilities of small and medium sized enterprises (SMEs) can be developed via partnerships, but at present, we lack studies that relate the development of such capabilities to the management of business governance structure. This study provides a new perspective on internationalized SME marketing strategies in the global context. Using a dynamic capability view of firms, the study develops hierarchical regression models linking global dynamic capabilities and governance structure. This study empirically verifies the research framework from 206 internationalized SME Taiwanese firms. The results confirm previous studies that indicate positive correlations between market orientation, learning orientation, and global dynamic capabilities. The results also indicate that the development of global dynamic capabilities impacts the choice of governance structure in firms. Our study suggests that internationalized SMEs strategically manage their autonomy and strategic options by choosing combinations of different relationship types while they decide to develop global marketing capabilities and global design capability, or both. The study also found that market orientation and learning orientation act as enabling mechanisms for building global dynamic capabilities.
A Study on Traditional Teaching Method Transferring to E-Learning Under the Covid-19 Pandemic: From Chinese Students' Perspectives
Authors: Jin Yuan Qing , Lin Chien-Liang , Zhao Qun , Yu Sung-Wen , Su Yu-Sheng
Published: March 2021

In response to the Covid-19 pandemic, online learning has been carried out in many countries with different types of online learning models being promoted and implemented. In the global pandemic continues, the education environment is forced to change from traditional classroom or blended teaching mode to online learning teaching model. With the outbreak of COVID-19, China was the first to announce that online courses are to be implemented in February 2020. In China, whether online learning can replace traditional offline teaching has become a topic worth discussing. Therefore, this study investigates university students in China by questionnaires and discussions of this topic. The study is based on the Push–Pull Mooring model. Based on 854 valid responses collected from an online survey questionnaire, structural equation modeling was employed to examine the research model. The results show that push effects (Perceived security risk, Learning convenience, and Service quality), pull effects (Usefulness, Ease of use, Teacher's Teaching Attitude, Task-technology Fit), and mooring effects (habit) all significantly influence users' switching intentions from offline to online learning platform. Finally, this study explores whether push–pull–mooring can be a reference for promoting and implementing online learning courses in Chinese colleges and universities in the future after the pandemic.
Testing the Efficacy of the Red-Light Purple-Light Games in Preprimary Classrooms in Kenya
Authors: Willoughby Michael T. , Piper Benjamin , King Katherine Merseth , Nduku Tabitha , Henny Catherine , Zimmermann Sarah
Published: March 2021

This study adapted and tested the efficacy of the Red-Light Purple-Light (RLPL) games for improving executive function (EF) skills in preprimary classrooms in Nairobi, Kenya. A cluster randomized controlled trial was used to evaluate the efficacy of the adapted RLPL intervention. Specifically, 24 centers (including 48 classrooms) were randomized to the RLPL or a wait-list control condition. Consistent with previous studies, participating classrooms delivered 16 lessons across an 8-week intervention period. A total of 479 children were recruited into the study. After exclusions based on child age and data quality, 451 and 404 children (90% retention) had completed computerized assessments of EF skills at pre- and posttest assessments, respectively. Children in the RLPL centers did not demonstrate any improvements in EF skills relative to their peers in the wait-list control condition (Cohen’s ds = −0.14 to 0.03, all ps > 0.20). Exploratory tests of moderators (language of assessment, grade, school type, baseline ability) were also all null. Results are discussed with respect to measurement limitations and contextual factors that may explain the null results of RLPL on EF skills in young children in Kenya.
Relationships Between the Life Satisfaction, Meaning in Life, Hope and COVID-19 Fear for Turkish Adults During the COVID-19 Outbreak
Authors: Karataş Zeynep , Uzun Kıvanç , Tagay Özlem
Published: March 2021

The current study investigated whether there are significant relationships between life satisfaction and meaning in life, hope and COVID-19 fear and the extent to which life satisfaction is predicted by these variables. The study group of this research consists of 1,186 adults with the mean age of 41.04. Study group participants are consists of different cities of different regions of Turkey. As the data collection tools, the life satisfaction scale, the meaning in life scale, the dispositional hope scale and the COVID-19 fear scale were used. The results of the analyses have revealed that meaning in life, hope (actuating thinking and alternative ways thinking) are significant predictors of life satisfaction as positively. Besides, it is seen COVID-19 fear, age, gender and the presence of people infected with COVID-19 around aren’t significant predictors of life satisfaction in adults.
Relationships Among Leaders' and Followers' Work Engagement and Followers' Subjective Career Success: A Multilevel Approach
Authors: Chen Qishan , Yang Shuting , Deng Jiayu , Lu Liuying , He Jingyi
Published: March 2021

Using a sample of 52 work teams (52 work team leaders and their 348 followers) in China, we investigated the influence mechanism of leaders' work engagement on their followers' work engagement and subjective career success. A multilevel structural equation model (MSEM) was applied to analyze the survey data. The results of this study indicated that leaders' work engagement positively influenced their followers' subjective career success, and this relationship was mediated by the followers' work engagement. Implications of these findings, limitations, and directions for future research are discussed in the final section of the paper.
Don't Think That Kids Aren't Noticing: Indirect Pathways to Children's Fear of COVID-19
Authors: Radanović Ana , Micić Isidora , Pavlović Svetlana , Krstić Ksenija
Published: March 2021

The present study is couched within Rachman's three-pathway theory of fear acquisition (Rachman, 1977, 1991). Besides the direct contact with the objects of fear, this model also includes two indirect pathways to fear acquisition: negative information transmission and modeling. The study aims to explore the contribution of these three factors to the level of children's fear of COVID-19. The sample consisted of 376 children (59.6% girls), aged 7–19 (Mage = 12.77, SDage = 3.57), and one of their parents (Mage = 42.88, SDage = 6.00). The survey was conducted online during the COVID-19 national state of emergency in the Republic of Serbia. The children assessed their fear of COVID-19, general fearfulness, negative information transmission, and modeling by their parents, as well as the level of exposure to negative information outside their home. The parents assessed their own fear of COVID-19 and trait anxiety. Parents' anxiety, children's age, and children's general fearfulness were used as covariates. The results of our path analysis provide support for Rachman's notion of indirect pathways. The more the parents were afraid of COVID-19, the more they expressed this (either verbally or through their behavior), which in turn led to an increase in the children's fear of COVID-19. Furthermore, children's exposure to negative information related to COVID-19, provided by their teachers and peers or stemming from the media, directly contributed to the level of children's fear. The results of the study emphasize the importance of caregivers' behavior during global health crises and provide some clues as to what caregivers may do to protect their children's mental health in such circumstances.
Lower Health Literacy of Mania Than Depression Among Older People: A Random Survey of a Community Healthcare Service Center
Authors: Huang Leping , Huang Ruyan , Fei Yue , Liu Taosheng , Mellor David , Xu Weiyun , Xiong Jinxia , Mao Rongjie , Chen Jun , Fang Yiru , Wu Zhiguo , Wang Zuowei
Published: March 2021

Purpose: This study examines health literacy among older outpatients in two Community Healthcare Service Centers in Shanghai, China to facilitate the design of public education programs for the aged population on mood disorders (both depression and mania).

Patients and Methods: A total of 173 outpatients aged 60 years or more with a chronic physical illness were randomly sampled. A health literacy questionnaire was used to assess participants' awareness of depression and mania. Participants were then asked to label two vignettes depicting depression and mania and to give their recommendations for how to seek help for those in the vignettes and how mood disorders should be managed.

Results: In all, 86.1 and 36.4% of participants had heard of depression and mania, respectively, with the most common source of information being relatives and friends. Over half of the participants attributed the possible causes of mood disorders to psychological trauma, pressure or stress in daily life, taking things too hard, and personality problems. Almost two-thirds of participants correctly labeled the depression vignette, but only 26.6% correctly labeled the mania vignette. The most common methods recommended by the participants as being helpful for the individuals portrayed in the vignettes were “traveling” and help-seeking from a psychological therapist/counselor, a psychiatrist, or a close family member or friend.

Conclusion: The older individuals attending community healthcare service settings in Shanghai have good depression literacy but relatively poor mania literacy. However, most participants had a positive attitude toward psychiatric treatment for mood disorders.
A Multi-Site Cross-Sectional Study of Anxiety Symptoms and the Associated Factors Among Chinese Drug Users Undergoing Compulsory Detoxification Treatment
Authors: Yang Xiaoshi , Kovarik Carrie , Wang Yuke , Yu Shenshui
Published: March 2021

Compulsory drug detoxification treatment (CDT) is currently the major drug rehabilitation modality in China, and drug users often suffer from extraordinary levels of stress during CDT, leading to a high prevalence of anxiety symptoms. This study assesses anxiety symptoms of the drug users undergoing CDT and explores the associated factors. A cross-sectional study with cluster sampling was conducted in three cities in Liaoning Province of Northeast China. Nine hundred CDT drug users were interviewed face-to-face with Chinese questionnaires. Hierarchical multiple regression (HMR) analysis was conducted to explore the factors associated with anxiety symptoms. The prevalence of anxiety symptoms among the CDT drug users was substantially high (33.2%). HMR analysis indicated perceived stress and characteristics of drug use such as types of drugs, were the most important contributors to anxiety symptoms. Optimism (LOT-R) played a protective role in reducing anxiety symptoms in this population. Anxiety symptoms of drug users undergoing CDT were present in a significant proportion of the CDT population. Optimism is a protective factor which could attenuate the detrimental effects of perceived stress on anxiety symptoms and potentially improve treatment outcomes.
Use of Connected Technologies to Assess Barriers and Stressors for Age and Disability-Friendly Communities
Authors: Zanwar Preeti , Kim Jinwoo , Kim Jaeyoon , Manser Michael , Ham Youngjib , Chaspari Theodora , Ahn Changbum Ryan
Published: March 2021

Background: The benefits of engaging in outdoor physical activity are numerous for older adults. However, previous work on outdoor monitoring of physical activities did not sufficiently identify how older adults characterize and respond to diverse elements of urban built environments, including structural characteristics, safety attributes, and aesthetics.

Objective: To synthesize emerging multidisciplinary trends on the use of connected technologies to assess environmental barriers and stressors among older adults and for persons with disability.

Methods: A multidisciplinary overview and literature synthesis.

Results: First, we review measurement and monitoring of outdoor physical activity in community environments and during transport using wearable sensing technologies, their contextualization and using smartphone-based applications. We describe physiological responses (e.g., gait patterns, electrodermal activity, brain activity, and heart rate), stressors and physical barriers during outdoor physical activity. Second, we review the use of visual data (e.g., Google street images, Street score) and machine learning algorithms to assess physical (e.g., walkability) and emotional stressors (e.g., stress) in community environments and their impact on human perception. Third, we synthesize the challenges and limitations of using real-time smartphone-based data on driving behavior, incompatibility with software data platforms, and the potential for such data to be confounded by environmental signals in older adults. Lastly, we summarize alternative modes of transport for older adults and for persons with disability.

Conclusion: Environmental design for connected technologies, interventions to promote independence and mobility, and to reduce barriers and stressors, likely requires smart connected age and disability-friendly communities and cities.
Cyberbullying Among Adolescents and Children: A Comprehensive Review of the Global Situation, Risk Factors, and Preventive Measures
Authors: Zhu Chengyan , Huang Shiqing , Evans Richard , Zhang Wei
Published: March 2021

Background: Cyberbullying is well-recognized as a severe public health issue which affects both adolescents and children. Most extant studies have focused on national and regional effects of cyberbullying, with few examining the global perspective of cyberbullying. This systematic review comprehensively examines the global situation, risk factors, and preventive measures taken worldwide to fight cyberbullying among adolescents and children.

Methods: A systematic review of available literature was completed following PRISMA guidelines using the search themes “cyberbullying” and “adolescent or children”; the time frame was from January 1st, 2015 to December 31st, 2019. Eight academic databases pertaining to public health, and communication and psychology were consulted, namely: Web of Science, Science Direct, PubMed, Google Scholar, ProQuest, Communication & Mass Media Complete, CINAHL, and PsycArticles. Additional records identified through other sources included the references of reviews and two websites, Cyberbullying Research Center and United Nations Children's Fund. A total of 63 studies out of 2070 were included in our final review focusing on cyberbullying prevalence and risk factors.

Results: The prevalence rates of cyberbullying preparation ranged from 6.0 to 46.3%, while the rates of cyberbullying victimization ranged from 13.99 to 57.5%, based on 63 references. Verbal violence was the most common type of cyberbullying. Fourteen risk factors and three protective factors were revealed in this study. At the personal level, variables associated with cyberbullying including age, gender, online behavior, race, health condition, past experience of victimization, and impulsiveness were reviewed as risk factors. Likewise, at the situational level, parent-child relationship, interpersonal relationships, and geographical location were also reviewed in relation to cyberbullying. As for protective factors, empathy and emotional intelligence, parent-child relationship, and school climate were frequently mentioned.

Conclusion: The prevalence rate of cyberbullying has increased significantly in the observed 5-year period, and it is imperative that researchers from low and middle income countries focus sufficient attention on cyberbullying of children and adolescents. Despite a lack of scientific intervention research on cyberbullying, the review also identified several promising strategies for its prevention from the perspectives of youths, parents and schools. More research on cyberbullying is needed, especially on the issue of cross-national cyberbullying. International cooperation, multi-pronged and systematic approaches are highly encouraged to deal with cyberbullying.
Economic Policy Uncertainty in China and Bitcoin Returns: Evidence From the COVID-19 Period
Authors: Chen Tiejun , Lau Chi Keung Marco , Cheema Sadaf , Koo Chun Kwong
Published: March 2021

This paper analyses the effects of the Chinese Economic Policy Uncertainty (CEPU) index on the daily returns of Bitcoin for the period from December 31, 2019 to May 20, 2020. Utilizing the Ordinary Least Squares (OLS) and the Generalized Quantile Regression (GQR) estimation techniques, the paper illustrates that the current CEPU has a positive impact on the returns of Bitcoin. However, the positive impact is statistically significant only at the higher quantiles of the current CEPU. It is concluded that Bitcoin can be used in hedging against policy uncertainties in China since significant rises in uncertainty leads to a higher return in Bitcoin.

JEL Codes: G32; G15; C22
Decolonizing Science Diplomacy: A Case Study of the Dominican Republic’s COVID-19 Response
Authors: Mencía-Ripley Aída , Paulino-Ramírez Robert , Jiménez Juan Ariel , Camilo Odile
Published: March 2021

The COVID-19 pandemic forced healthcare systems globally to handle a dramatic surge in healthcare utilization while also taxing available testing resources. In the context of healthcare systems in Latin America and the Caribbean, COVID-19 added to the existing burden of infectious diseases related to endemic infections such as arboviruses and HIV. In the Dominican Republic, testing is supplied mostly by the private sector and a national public laboratory. The surge in testing demands laid bare a lack of installed capacities both in laboratory facilities and equipment and trained staff in molecular biology laboratory procedures. This article discusses a case of how science diplomacy and a relatively new law fostering public-private partnerships allowed a university to play a major role in public health response while generating knowledge to inform public policy decisions in an unprecedented manner in the country. Science diplomacy is discussed in the context of decolonization and the importance of the local gaze when creating academic partnerships in the context of global health emergencies.
The Untapped Potential of Virtual Reality in Rehabilitation of Balance and Gait in Neurological Disorders
Authors: Keshner Emily A. , Lamontagne Anouk
Published: March 2021

Dynamic systems theory transformed our understanding of motor control by recognizing the continual interaction between the organism and the environment. Movement could no longer be visualized simply as a response to a pattern of stimuli or as a demonstration of prior intent; movement is context dependent and is continuously reshaped by the ongoing dynamics of the world around us. Virtual reality is one methodological variable that allows us to control and manipulate that environmental context. A large body of literature exists to support the impact of visual flow, visual conditions, and visual perception on the planning and execution of movement. In rehabilitative practice, however, this technology has been employed mostly as a tool for motivation and enjoyment of physical exercise. The opportunity to modulate motor behavior through the parameters of the virtual world is often ignored in practice. In this article we present the results of experiments from our laboratories and from others demonstrating that presenting particular characteristics of the virtual world through different sensory modalities will modify balance and locomotor behavior. We will discuss how movement in the virtual world opens a window into the motor planning processes and informs us about the relative weighting of visual and somatosensory signals. Finally, we discuss how these findings should influence future treatment design.
Migrant and Refugee Impact on Well-Being in Rural Areas: Reframing Rural Development Challenges in Greece
Authors: Papadopoulos Apostolos G. , Fratsea Loukia-Maria
Published: March 2021

The paper aims to exemplify and discuss the changing conditions and challenges posed by the newly arriving populations of migrants and refugees in rural Greece, along with local people’s views on the impact of the new arrivals in their rural places. Its main objective is to understand whether migrants and refugees create threats or opportunities for the local population, and whether movers and non-movers have a shared understanding of well-being in their rural areas. The analysis unveils the connections that are emerging between migrants and refugees and the economy, society and culture in rural receiving areas. Thus, the paper aims at showing the complexity of rural migrant flows and how the interactions between migrants, refugees and locals in the light of the well-being of rural areas may inform rural development in Greece. The paper is structured into five main sections following the introduction. The first section contains a discussion of the main concepts used as building blocks for creating a theoretical framing of well-being in rural areas. The second section develops a brief discussion of international and internal migration to rural areas in Greece, as well as providing some contextual information on the impact of the economic crisis and new developments in response to the recession. The third section includes a short presentation of the methodological approach and a description of the case study area. The fourth section is dedicated to an analysis of the narratives of international migrants, refugees, internal migrants, locals and stakeholders. Finally, the concluding section critically discusses the conceptualisations of rurality and well-being between the various population groups and articulates the challenges connected to well-being and mobilities in contemporary rural Greece.
Using the Nitrification Inhibitor Nitrapyrin in Dairy Farm Effluents Does Not Improve Yield-Scaled Nitrous Oxide and Ammonia Emissions but Reduces Methane Flux
Authors: Pérez-Castillo Ana Gabriela , Arrieta-Méndez Jimmy , Elizondo-Salazar Jorge Alberto , Monge-Muñoz Mayela , Zaman Mohammad , Sanz-Cobena Alberto
Published: March 2021

The application of dairy farm effluents (DFE) without previous treatment in paddocks was intensified due to the approval of this practice in Costa Rican legislation since 2012. Applying DFE instead of synthetic N fertilizer in grasslands is an opportunity to reach a circular economy; however, this practice increases the risk of emissions of nitrous oxide (N2O), methane (CH4), and ammonia (NH3), which contribute to global warming. A field experiment was carried out using a permanent grassland (90% Star grass and 10% Kikuyo grass) to simultaneously assess the effect of nitrapyrin on yield-scaled emissions of NH3, CH4, and N2O. The experiment lasted for 5 months in 2017, based on a randomized complete block design, including three treatments of control (CK) without N application, surface application of DFE with nitrapyrin (SNI), and without nitrapyrin (S). Total N applied was 149 ± 12 kg N ha−1 for both S and SNI treatments split into five applications. CH4 emissions from S, SNI, and CK showed a high temporal variation. Daily fluxes of CH4 from SNI were significantly lower than those of S in August (P < 0.05). Cumulative emissions of CH4, the majority produced in the soil, ranged from 4 to 168 g ha−1 for S, and from −13 to 88 g ha−1 for SNI. The ratio between the N2O cumulative emissions and the N applied as DFE were 1.6 ± 0.5 and 1.7 ± 0.2% for S and SNI, respectively. NH3 volatilization potential was very low (i.e., 0.6 ± 0.2% of the N applied). Under the prevailing experimental conditions, no significant difference between yield-scaled NH3 and N2O emissions were found between S and SNI, suggesting that nitrapyrin may not be a viable mitigation option for gaseous N losses from DFE application in Costa Rican grasslands in rainy season.
Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry
Authors: Huang Richard S. P. , Severson Eric , Haberberger James , Duncan Daniel L. , Hemmerich Amanda , Edgerly Claire , Ferguson N. Lynn , Frampton Garrett , Owens Clarence , Williams Erik , Elvin Julia , Vergilio Jo-Anne , Killian Jonathan Keith , Lin Douglas , Morley Samantha , McEwan Deborah , Holmes Oliver , Danziger Natalie , Cohen Michael B. , Sathyan Pratheesh , McGregor Kimberly , Reddy Prasanth , Venstrom Jeffrey , Anhorn Rachel , Alexander Brian , Brown Charlotte , Ross Jeffrey S. , Ramkissoon Shakti H.
Published: March 2021

Comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) are important biomarker tools used for patients with non-small cell lung cancer (NSCLC) given the expanding number of standard-of-care therapies that require companion diagnostic testing. We examined 9450 NSCLC real-world patient samples that underwent both CGP and programmed death-ligand 1 (PD-L1) IHC to understand the biomarker landscape in this patient cohort. By assessing National Comprehensive Cancer Network (NCCN)-recommended biomarkers including genomic alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (Tumor Proportion Score (TPS) ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results for 70.5% of the 9,450 patients with NSCLC. Among the remaining 29.5% (2,789/9,450) of patients, 86.7% (2,419/2,789) were potentially eligible for another biomarker-associated therapy and/or clinical trial based on their genomic profile. In addition, in the PD-L1TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1TPS<50%, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.
On the Design of Continuously Variable Transmissions with Bidirectional Bridge Structures for Hybrid Vehicles
Authors: Kuo Hsien-Yu , Liu Tyng
Published: March 2021

To increase the energy efficiency of road vehicles, an ideal transmission system should have a wide ratio coverage, a high torque capacity, and a high mechanical efficiency. Continuously variable units (CVUs) have been successfully implemented due to the smooth ratio variation, sufficient torque capacity, and ratio coverage. Hence, it will be beneficial to develop a hybrid powertrain comprising a CVU. In this paper, a design method called the “basic path diagram” (BPD) is proposed. It provides a simplified schematic of the system and represents the generic connections among the mechanical components. The system configurations synthesized by the BPD can be sorted according to three characteristics: Direction of power flows through the CVU, coupling pattern of the power inputs, and number of transmission paths parallel to the CVU. The first characteristic determines the number of times the CVU ratio coverage can be exploited, the second characteristic determines whether the torque of the power inputs can be independently controlled, and the third characteristic can help reduce the torque loading of the CVU. With the aid of a BPD, one of the possible system configurations is provided as an example. The result shows that the system can exploit twice the ratio coverage of the CVU and reduce the torque and power transmitted by the CVU in combination with planetary gearsets.
Psoas Major Muscle Volume Does Not Affect the Postoperative Thigh Symptoms in XLIF Surgery
Authors: Yingsakmongkol Wicharn , Wathanavasin Waranyoo , Jitpakdee Khanathip , Singhatanadgige Weerasak , Limthongkul Worawat , Kotheeranurak Vit
Published: March 2021

Background: Extreme lateral interbody fusion (XLIF) is a minimally invasive surgery that accesses the lumbar spine through the psoas muscle. This study aimed to evaluate the correlation between the psoas major muscle volume and anterior thigh symptoms after XLIF. Methods: Eighty-one patients (mean age 63 years) with degenerative spine diseases underwent XLIF (total = 94 levels). Thirty-eight patients were female (46.9%), and 24 patients (29.6%) had a history of lumbar surgery. Supplemental pedicle screws were used in 48 patients, and lateral plates were used in 28 patients. Neuromonitoring devices were used in all cases. The patients were classified into two groups (presence of thigh symptoms and no thigh symptoms after the surgery). The psoas major volumes were measured and calculated by CT (computed tomography) scan and compared between the two patient groups. Results: In the first 24 h after surgery, 32 patients (39.5%) had thigh symptoms (20 reported pain, 9 reported numbness, and 18 reported weakness). At one year postoperatively, only 3 of 32 patients (9.4%) had persistent symptoms. Conclusions: As a final observation, no statistically significant difference in the mean psoas major volume was found between the group of patients with new postoperative anterior thigh symptoms and those with no thigh symptoms. Preoperative psoas major muscle volume seems not to correlate with postoperative anterior thigh symptoms after XLIF.
Liposome-Imipramine Blue Inhibits Sonic Hedgehog Medulloblastoma In Vivo
Authors: MacDonald Tobey J. , Liu Jingbo , Yu Bing , Malhotra Anshu , Munson Jenny , Park Jaekeun C. , Wang Kenty , Fei Baowei , Bellamkonda Ravi , Arbiser Jack
Published: March 2021

Sonic hedgehog subtype of medulloblastoma (SHH MB) with metastasis or specific clinical or molecular alteration shas a poor prognosis and current therapy results in long-term cognitive impairment in the majority of survivors. Thus, a great need exists for new targeted therapeutic approaches to more effectively treat SHH MB in children. Imipramine blue (IB), a novel molecule with anti-tumor properties, inhibits the NADPH oxidase (NOX) family of enzymes, which are critical for SHH MB survival and treatment resistance. In this study, IB was encapsulated within a liposome to form a liposomal nanoparticle, Liposome-IB (Lipo-IB). This complex has the ability to cross the blood–brain barrier and be preferentially taken up by tumor cells within the brain. We demonstrated in vitro that Lipo-IB treatment caused a dose-dependent decrease in SHH MB cell viability and migration. Short-term administration of single agent Lipo-IB treatment of SHH MB in vivo significantly inhibited tumor growth, reduced the tumor volume, including a complete tumor response, and improved survival compared to control treated mice, without any observable toxicity. We conclude that Lipo-IB is a potential novel nanoparticle-based therapeutic for the treatment of SHH MB that warrants further preclinical safety and efficacy testing for development towards clinical investigation.
Phase Ib Trial of Copanlisib, A Phosphoinositide-3 Kinase (PI3K) Inhibitor, with Trastuzumab in Advanced Pre-Treated HER2-Positive Breast Cancer “PantHER”
Authors: Keegan Niamh M. , Furney Simon J. , Walshe Janice M. , Gullo Giuseppe , Kennedy M. John , Smith Diarmuid , McCaffrey John , Kelly Catherine M. , Egan Keith , Kerr Jennifer , Given Mark , O’Donovan Peter , Hernando Andres , Teiserskiene Ausra , Parker Imelda , Kay Elaine , Farrelly Angela , Carr Aoife , Calzaferri Giulio , McDermott Ray , Keane Maccon M. , Grogan Liam , Breathnach Oscar , Morris Patrick G. , Toomey Sinead , Hennessy Bryan T.
Published: March 2021

Background: Activation of the phosphoinositide-3 kinase (PI3K) pathway is a resistance mechanism to anti-human epidermal growth factor receptor 2 (HER2) therapy. This phase Ib trial was conducted to determine the maximum tolerated dose (MTD) of copanlisib, an intravenous (IV) pan-class I PI3K inhibitor, combined with trastuzumab. Methods: Patients with advanced HER2-positive breast cancer and disease progression following at least one prior line of HER2 therapy in the metastatic setting were treated with copanlisib (45 or 60 mg) IV on days 1, 8 and 15 of a 28-day cycle with a fixed dose of trastuzumab 2 mg/kg weekly. Results: Twelve patients were enrolled. The MTD was determined as copanlisib 60 mg plus trastuzumab 2 mg/kg weekly. The most common adverse events of any grade occurring in more than two patients were hyperglycaemia (58%), fatigue (58%), nausea (58%) and hypertension (50%). Stable disease was confirmed at 16 weeks in six participants (50%). PIK3CA mutations were detected in archival tumour of six participants (50%). PIK3CA hotspot mutations, were detectable in pre- and on-treatment plasma of all participants. Pre- and post-treatment tumour biopsies for two patients identified temporal genomic heterogeneity, somatic mutations in the TRRAP gene, which encodes a PI3K-like protein kinase, and emergent somatic mutations related to protein kinase signalling. Conclusion: Copanlisib and trastuzumab can be safely administered with fair overall tolerability. Preliminary evidence of tumour stability was observed in patients with heavily pre-treated, metastatic HER2 positive breast cancer. Several potential biomarkers were identified for further study in the current phase 2 clinical trial. NCT: 02705859.
Measuring Pre- and Post-Copulatory Sexual Selection and Their Interaction in Socially Monogamous Species with Extra-Pair Paternity
Authors: Cramer Emily Rebecca Alison
Published: March 2021

When females copulate with multiple males, pre- and post-copulatory sexual selection may interact synergistically or in opposition. Studying this interaction in wild populations is complex and potentially biased, because copulation and fertilization success are often inferred from offspring parentage rather than being directly measured. Here, I simulated 15 species of socially monogamous birds with varying levels of extra-pair paternity, where I could independently cause a male secondary sexual trait to improve copulation success, and a sperm trait to improve fertilization success. By varying the degree of correlation between the male and sperm traits, I show that several common statistical approaches, including univariate selection gradients and paired t-tests comparing extra-pair males to the within-pair males they cuckolded, can give highly biased results for sperm traits. These tests should therefore be avoided for sperm traits in socially monogamous species with extra-pair paternity, unless the sperm trait is known to be uncorrelated with male trait(s) impacting copulation success. In contrast, multivariate selection analysis and a regression of the proportion of extra-pair brood(s) sired on the sperm trait of the extra-pair male (including only broods where the male sired ≥1 extra-pair offspring) were unbiased, and appear likely to be unbiased under a broad range of conditions for this mating system. In addition, I investigated whether the occurrence of pre-copulatory selection impacted the strength of post-copulatory selection, and vice versa. I found no evidence of an interaction under the conditions simulated, where the male trait impacted only copulation success and the sperm trait impacted only fertilization success. Instead, direct selection on each trait was independent of whether the other trait was under selection. Although pre- and post-copulatory selection strength was independent, selection on the two traits was positively correlated across species because selection on both traits increased with the frequency of extra-pair copulations in these socially monogamous species.
Hydrogen Sulfide—Clues from Evolution and Implication for Neonatal Respiratory Diseases
Authors: Ganguly Abhrajit , Ofman Gaston , Vitiello Peter F
Published: March 2021

Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (H2S) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of H2S signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on H2S for energy. Recent studies have demonstrated an important role of H2S and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the H2S signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease.
Preliminary Analysis of a New Power Train Concept for a City Hybrid Vehicle
Authors: Capata Roberto
Published: March 2021

This research aims to test the feasibility of a prototype of a newly designed thermal engine for a hybrid propulsion vehicle. This study consists of the implementation of an innovative supercharger for city car internal combustion engine ICE (900 cc). The preliminary proposal presented here is to mechanically disconnect the compressor/turbine device, supporting the rotation of the compressor with a dedicated electric motor and connecting a turbine to a generator. Mechanical decoupling will allow both machines to be designed for operating closer to their maximum performance point, for most of the expected real field of operation. Specifically, the turbine is likely to have a lower rotation speed than the original group and will, therefore, be slightly larger. The advantage is that, while in the current supercharger groups the surplus at high regimes is discharged through the waste-gate valve without expanding in a turbine, in the configuration proposed, all the energy of the combustible gases is used by the turbine to generate electrical power that can be used where required. Once the motorization of the vehicle (999 cc) has been fixed, the two turbomachines will have to be studied and designed, looking where possible, for commercial components. Finally, a computational fluid dynamic CFD will be needed to verify the validity of the choice, followed by careful experimentation campaigns.