bluuebunny/crossref_metadata_2025 huggingface dataset:
Using 87Sr/86Sr LA-MC-ICP-MS Transects within Modern and Ancient Calcite Crystals to Determine Fluid Flow Events in Deep Granite Fractures
Authors: Drake Henrik , Kooijman Ellen , Kielman-Schmitt Melanie
Published: September 2020

The strontium isotope signature (87Sr/86Sr) of calcite precipitated in rock fractures and faults is a frequently used tool to trace paleofluid flow. However, bedrock fracture networks, such as in Precambrian cratons, have often undergone multiple fracture reactivations resulting in complex sequences of fracture mineral infillings. This includes numerous discrete calcite crystal overgrowths. Conventional 87Sr/86Sr analysis of dissolved bulk samples of such crystals is not feasible as they will result in mixed signatures of several growth zonations. In addition, the zonations are too fine-grained for sub-sampling using micro-drilling. Here, we apply high spatial resolution 87Sr/86Sr spot analysis (80 µm) in transects through zoned calcite crystals in deep Paleoproterozoic granitoid fractures using laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) to trace discrete signs of paleofluid flow events. We compare the outermost calcite growth zone with 87Sr/86Sr values of the present-day groundwater sampled in the same boreholes to distinguish potential modern precipitates. We then connect our results to previously reported radiometric dating and C and O isotope signatures to understand the temporal history and physicochemical evolution of fluid flow within the fractures. Comparisons of modern calcite precipitated in a borehole over a period of 17 years with modern waters prove the concept of using 87Sr/86Sr as a marker for fluid origin in this environment and for how 87Sr/86Sr changed during marine water infiltration. Intermittent calcite precipitation over very long time spans is indicated in calcite of the currently open fractures, showing an evolution of 87Sr/86Sr from ~0.705–0.707—a population dated to ~1.43 billion years—to crystal overgrowth values at ~0.715–0.717 that overlap with the present-day groundwater values. This shows that high spatial resolution Sr isotope analysis of fine-scaled growth zonation within single calcite crystals is applicable for tracing episodic fluid flow in fracture networks.
Promotion of Healthy Lifestyles to Teenagers with Mobile Devices: A Case Study in Portugal
Authors: Villasana María Vanessa , Pires Ivan Miguel , Sá Juliana , Garcia Nuno M. , Teixeira Maria Canavarro , Zdravevski Eftim , Chorbev Ivan , Lameski Petre
Published: September 2020

Educating teenagers about nutrition and promoting active lifestyles is essential in reducing the long-term health risks and one idea to achieve this is by using mobile applications. Previous studies showed that the existing mobile applications have similar functionalities, such as intervention with questionnaires, and the use of gamification techniques to improve interactiveness. However, unlike our study, some studies are not validated and verified by healthcare professionals. Additionally, this study intends to promote the interaction between the teenagers and the medical communities. In this study, we analyze the benefits of the proposed mobile application, which features monitoring of physical activity, daily tips and curiosities, questionnaires, and gamification through earning points. Most of the teenagers were satisfied with the physical activity monitoring and found the tips, curiosities, and weekly questionnaires useful. The study started with 26 teenagers from two schools in the center of Portugal that would use the mobile application for five weeks. Still, at the end of the study, only 7 teenagers finalized the study. The decreasing number of teenagers in the study was affected by the lack of social interaction caused by the pandemic situation. During the period, the mobile application would engage the users with notifications on nutrition and physical activity, challenges concerning the number of steps and calories they would have to spend, and questionnaires related to the curiosities and suggestions from the previous week. We used Fisher’s test to investigate the relationship between the assessment obtained in the responses to the questionnaires, and the adoption of healthier eating and sports practices. In summary, participants were satisfied with the mobile application and experienced some improvements in diet and habits.
Children’s Temperament: A Bridge between Mothers’ Parenting and Aggression
Authors: Carrasco Miguel A. , Delgado Begoña , Holgado-Tello Francisco Pablo
Published: September 2020

Childhood aggression is important to acknowledge due to its social impact and importance in predicting future problems. The temperament of a child and parental socialization have been essential in explaining behavioral problems, particularly in the case of childhood aggression. The aim of this study is to examine—from the parents’ perspective—the role of childhood temperament in the dynamic by which mothers’ reactions socialize their children’s aggression. We also explore how children’s gender and age differences affect these relationships. The sample was composed of 904 participants between 1 and 6 years old. The Early Childhood Behavior Questionnaire and the Children’s Behavior Questionnaire were used to evaluate children’s negative affect and effortful control. The Parent–Child Relationship Inventory Maternal was used to assess maternal communication and discipline, and child aggression was assessed using the Children’s Behavior Checklist. The results supported the mediating role of temperament in the processes by which perceived mothers’ reactions socialize their children’s aggression and suggested that maternal behaviors may not have the same consequences for girls and boys. Specifically, the aggressiveness of girls is dependent on a negative affect throughout toddlerhood and early childhood, while for boys, the duration of the negative affect’s contribution is shorter, and aggressiveness is more sensitive to the maternal behaviors of discipline and communication.
Get Vigorous with Physical Exercise and Improve Your Well-Being at Work!
Authors: Gil-Beltrán Ester , Meneghel Isabella , Llorens Susana , Salanova Marisa
Published: September 2020

The aim of this study is to investigate whether people who exercise regularly have higher levels of psychological well-being at work. Doing physical exercise is a habit that not only has consequences for physical and mental health, but it can also have positive consequences for organizations because physical exercise makes it easier for the employee to recover from physical, mental, and emotional effort during the workday, thus showing higher levels of engagement the next day. Through the analysis of structural equation models in a sample of 485 workers from different Spanish and Latin American companies, this study shows that subjects who exercise more have higher levels of vigor in physical exercise, which is positively related to high levels of well-being at work. This means that organizations that promote activities related to physical exercise among their employees are building a process of resource recovery, which, through the vigor of these activities, makes workers feel less stressed and more satisfied, thus experiencing greater well-being at work. Therefore, at a practical level, these results suggest that the practice of physical exercise is a tool for organizations that want to promote their employees’ psychological well-being.
Interventional Impacts of Watershed Ecological Compensation on Regional Economic Differences: Evidence from Xin’an River, China
Authors: Yu Bing , Chen Linan
Published: September 2020

Watershed ecological compensation (WEC) is a popular and effective policy instrument for promoting the coordinated development of environment protection and the regional economy in river basin areas. WEC affects the regional economic differences between upstream and downstream regions, as well as between protected areas and areas surrounding upstream regions. Thus, it is necessary to quantify these changes to ensure the balanced development of regions after the implementation of ecological compensation. In the present study, we established two types of Theil indexes for between-group inequalities (THH and THS) and an intervention analysis model in order to evaluate and predict the effects on regional economic differences caused by WEC in the Xin’an River basin. The results showed that the intervention comprising WEC affected regional economic differences, where the economic gap widened between Huangshan City in the upstream region and Hangzhou City in the downstream region, as well as between Huangshan and its surrounding cities. However, the impacts of the intervention gradually decreased in the later pilot period. Considering the fairness of regional social development, we recommend increasing the compensation for protected areas in order to improve the self-development capacity of upstream regions.
Examining Rural Food-Insecure Families’ Perceptions of the Supplemental Nutrition Assistance Program: A Qualitative Study
Authors: Haynes-Maslow Lindsey , Hardison-Moody Annie , Patton-Lopez Megan , Prewitt T. Elaine , Byker Shanks Carmen , Andress Lauri , Osborne Isabel , Jilcott Pitts Stephanie
Published: September 2020

The Supplemental Nutrition Assistance Program (SNAP) is a critical program that helps reduce the risk of food insecurity, yet little is known about how SNAP addresses the needs of rural, food-insecure residents in the United States (U.S.). This study examines how rural, food-insecure residents perceive SNAP. Semi-structured interviews were conducted with 153 individuals living in six diverse rural regions of Arkansas, Montana, North Carolina, Oregon, Texas, and West Virginia. SNAP was described as a crucial stop-gap program, keeping families from experiencing persistent food insecurity, making food dollars stretch when the family budget is tight, and helping them purchase healthier foods. For many rural residents interviewed, SNAP was viewed in a largely positive light. In efforts to continue improving SNAP, particularly in light of its relevance during and post-coronavirus (COVID-19) pandemic, policymakers must be aware of rural families’ perceptions of SNAP. Specific improvements may include increased transparency regarding funding formulas, budgeting and nutrition education for recipients, effective training to improve customer service, connections among social service agencies within a community, and increased availability of automation to streamline application processes.
Effects of the Ionic and Nanoparticle Forms of Cu and Ag on These Metals’ Bioaccumulation in the Eggs and Fry of Rainbow Trout (Oncorhynchus mykiss W.)
Authors: Kowalska-Góralska Monika , Senze Magdalena , Łuczyńska Joanna , Czyż Katarzyna
Published: September 2020

Nanotechnology is a rapidly growing field of science, and an increasing number of nanoproducts, including nanometals, can be found on the market. Various nanometals and the products that are manufactured based on them can help to fight bacteria and fungi, but they can also penetrate organisms and accumulate in them. This study aimed to compare the effects of two metals, silver (Ag) and copper (Cu), with known antibacterial and fungicidal properties in their ionic (AgNO3, CuSO4·5H2O) and nanoparticle (AgNPs, CuNPs) forms on rainbow trout eggs and fry. Concentrations of metals ranging from 0 to 16 mg/L were used during egg swelling for 2 h. The swelling of eggs in Cu solutions resulted in an increase in Cu content in the eggs (just like in the case of Ag); however, the changes in fry were not significant in the case of both Ag and Cu. The concentrations of these metals in eggs was greatly affected by the applied form of Ag and Cu. Because CuNPs penetrated the embryo in fish eggs at lower concentrations compared to AgNPs, it would be worth considering them for antibacterial applications during egg incubation.
Do Physicians’ Attitudes towards Patient-Centered Communication Promote Physicians’ Intention and Behavior of Involving Patients in Medical Decisions?
Authors: Wang Dan , Liu Chenxi , Zhang Xinping
Published: September 2020

Promoting patient-centered communication among physicians is one core strategy for improving physician–patient relationships and patient outcomes. Our study aims to understand the physicians’ attitudes towards patient-centered communication and its effects on physicians’ intention and behavior of involving patients in medical decisions in primary care in China. One cross-sectional study was conducted in primary facilities in Hubei province, China, from December 2019 to January 2020, where physicians’ attitudes towards patient-centered communication were measured by the Chinese-revised patient–practitioner orientation scale. Multilevel ordinal logistic regression was conducted for estimating the effects of physicians’ attitudes on their intention and behavior of patient involvement in medical decisions. Six hundred and seventeen physicians were investigated for the main study. Physicians had a medium score of patient-centered communication (3.78, SD = 0.56), with relatively high caring subscale score (4.59, SD = 0.64), and low sharing subscale score (3.09, SD = 0.75). After controlling physicians’ covariates, physicians’ attitudes towards patient-centered communication was significantly associated with a higher intention of involving patients in medical decisions (OR > 1, p = 0.020). Physicians’ positive attitudes towards patient-centered communication affected their intention of involving patients in medical decisions, which implies the importance of taking the physicians’ attitudes into account for the accomplishment of patient involvement processes.
Spatial Analysis of the Neighborhood Risk Factors for Respiratory Health in the Australian Capital Territory (ACT): Implications for Emergency Planning
Authors: Davies Sarah , Konings Paul , Lal Aparna
Published: September 2020

The Australian Capital Territory (ACT) experienced the worst air quality in the world for several consecutive days following the 2019–2020 Australian bushfires. With a focus on asthma and Chronic Obstructive Pulmonary Disease (COPD), this retrospective study examined the neighborhood-level risk factors for these diseases from 2011 to 2013, including household distance to hospital emergency departments (ED) and general practices (GP) and area-level socioeconomic disadvantage and demographic characteristics at a high spatial resolution. Poisson and Geographically Weighted Poisson Regression (GWR) were compared to examine the need for spatially explicit models. GWR performed significantly better, with rates of both respiratory diseases positively associated with area-level socioeconomic disadvantage. Asthma rates were positively associated with increasing distance from a hospital. Increasing distance to GP was not associated with asthma or COPD rates. These results suggest that respiratory health improvements could be made by prioritizing areas of socioeconomic disadvantage. The ACT has a relatively high density of GP that is geographically well spaced. This distribution of GP could be leveraged to improve emergency response planning in the future.
Uncovering the Moderating Role of Grit and Gender in the Association between Teacher Autonomy Support and Social Competence among Chinese Undergraduate Students
Authors: Ma Yongfeng , Ma Chunhua , Lan Xiaoyu
Published: September 2020

Does teacher autonomy support significantly facilitate the social competence of undergraduate students in a collective cultural context? Does this study association vary by individual characteristics, such as grit and students’ gender? To answer these research questions, we examine the association between teacher autonomy support and social competence. Moreover, we ascertain whether two dimensions of grit (perseverance and consistency) and/or gender may moderate this association. A convenience sample of 1009 Chinese undergraduate students (Mage = 20.66; SD = 1.30, 47.4% female) was involved in this study, and they were asked to complete a set of self-report questionnaires online. Results of linear regression analyses revealed that (a) teacher autonomy support was positively associated with social competence, and (b) when reporting higher levels of consistency, this association was significantly positive for both males and females; by contrast, when reporting lower levels of consistency, this association was only significant for males but not for females. The current study indicates the beneficial role of teacher autonomy support in undergraduate students’ social competence in a collective cultural context. Furthermore, university-based intervention or prevention programs should focus on facilitating teacher autonomy support for all students; it is noteworthy that, for female students, enhancing consistency should also be incorporated into these programs.
Do Older Adults with Parent(s) Alive Experience Higher Psychological Pain and Suicidal Ideation? A Cross-Sectional Study in China
Authors: Yang Ying , Wang Shizhen , Hu Borui , Hao Jinwei , Hu Runhu , Zhou Yinling , Mao Zongfu
Published: September 2020

Elderly mental health promotion is an important task in the current “Healthy China Action”. This study aims to (a) clarify the psychological pain and suicidal ideation of the Chinese elderly with different parental states, (b) examine the associated factors of psychological pain and suicidal ideation, and (c) examine the relationship between psychological pain and suicidal ideation. A sample of 4622 adults aged 60 years and older were included in this study, from the China’s Health-related Quality of Life Survey for Older Adults 2018. Participants with both parents alive demonstrated the heaviest psychological pain, and those with one parent alive observed significantly lowest psychological pain and suicidal ideation. Participants who were single, divorced, or widowed, live in rural areas, had higher education level, had lower family income, suffered from two or more chronic diseases, and had no self-care ability were more likely to experience psychological pain and suicidal ideation. In addition, higher psychological pain significantly associated with the occurrence of suicidal ideation. In China, much more attention should be paid to the mental health condition of the elderly, especially for those with both parents alive. Moreover, the associated factors above should be considered to develop targeted health interventions.
Female Employees’ Perception of Breastfeeding Support in the Workplace, Public Universities in Spain: A Multicentric Comparative Study
Authors: Cervera-Gasch Águeda , Mena-Tudela Desirée , Leon-Larios Fatima , Felip-Galvan Neus , Rochdi-Lahniche Soukaina , Andreu-Pejó Laura , González-Chordá Víctor Manuel
Published: September 2020

Background: Despite scientific recommendations for exclusive breastfeeding until 6 months of age and complementary breastfeeding to 2 years of age, breastfeeding abandonment rates increase with time, and one of the main reasons is that women go back to work. Aim: To analyze the perception of support of breastfeeding workers to continue breastfeeding at two Spanish universities, and associated factors. Methods: A multicenter retrospective cross-sectional comparative study conducted in a population of 777 female workers at the Universidad de Sevilla (US) and the Universitat Jaume I (UJI) in Spain using an online questionnaire. Results: The response rate was 38.74% (n = 301). Of all the participants, 57.8% continued breastfeeding after returning to work. The factors associated with continuing breastfeeding for longer were the university having a breastfeeding support policy and special accommodation (p < 0.001); participating in breastfeeding support groups (p < 0.001); intending to continue breastfeeding after returning to work (p < 0.001); knowing the occupational legislation in force (p = 0.009); having a female supervisor (p = 0.04). Conclusion: Breastfeeding support initiatives and having special accommodation to pump and preserve breast milk after returning to work are associated with a longer duration of female workers’ breastfeeding.
The Relationship between Positive Youth Development and Depressive Symptoms among Chinese Early Adolescents: A Three-Year Cross-Lagged Analysis
Authors: Chi Xinli , Liu Xiaofeng , Huang Qiaomin , Cui Xiumin , Lin Li
Published: September 2020

Based on the development assets theory and the scar model, the present study examined the relationship between positive youth development (PYD) and depressive symptoms among Chinese early adolescents using a three-year longitudinal study design. Data from three waves were collected from 1301 students (Mean age = 12.46, SD = 0.63 years and 51.2% boys at wave 1) across the junior high school period (Grades 7–9). All participants completed a questionnaire that included the Center for Epidemiologic Studies Depression Scale (CES-D) and the Chinese Positive Youth Development Scale (CPYD) once a year over three years. After controlling for age and gender, this study found that PYD significantly predicted subsequent depressive symptoms. However, depressive symptoms did not significantly predict subsequent PYD. The results indicated a unidirectional relationship between PYD and depressive symptoms, where a reduction in PYD may increase subsequent depressive symptoms, though not vice versa. Besides, the negative cross-sectional correlation between PYD and depressive symptoms remains significant and stable from first year (T1) to third year (T3). These findings suggest that promoting PYD may be a promising approach to preventing/reducing adolescent depressive symptoms.
An Exploration of Family Caregiver Experiences of Burden and Coping While Caring for People with Mental Disorders in Saudi Arabia—A Qualitative Study
Authors: Sharif Loujain , Basri Shimaa , Alsahafi Fidaa , Altaylouni Mashael , Albugumi Shihanah , Banakhar Maram , Mahsoon Alaa , Alasmee Nofaa , Wright Rebecca J.
Published: September 2020

Family caregivers of people with mental disorders face a number of burdens and stressors, such as associative stigma and burnout. These burdens are often a result of their caring role coupled with insufficient support or ineffective coping strategies, which can affect their quality of life and biopsychosocial integrity that, in turn, may affect the care they provide. This study aimed to explore the experiences of family caregivers of people with mental disorders, through examining the burdens that they face and the coping strategies that they use. Using a descriptive qualitative approach, 13 semi-structured interviews were conducted with members of the Saudi public, recruited through popular social media platforms and analyzed using thematic analysis. Five main themes were constructed from the data: Type of care, Challenges, Coping and support, Perceptions of public awareness, and Messages to others. The findings emphasize the different types of burdens that caregivers experience, and their needs that require a range of responses such as educational training on effective coping strategies, and psychological support in the form of counseling or group therapy. This study highlights the voice of caregivers and their message to the public, in order to correct the misconceptions surrounding mental disorders and those associated with them.
Urban Green Plastic Cover Mapping Based on VHR Remote Sensing Images and a Deep Semi-Supervised Learning Framework
Authors: Liu Jiantao , Feng Quanlong , Wang Ying , Batsaikhan Bayartungalag , Gong Jianhua , Li Yi , Liu Chunting , Ma Yin
Published: September 2020

With the rapid process of both urban sprawl and urban renewal, large numbers of old buildings have been demolished in China, leading to wide spread construction sites, which could cause severe dust contamination. To alleviate the accompanied dust pollution, green plastic mulch has been widely used by local governments of China. Therefore, timely and accurate mapping of urban green plastic covered regions is of great significance to both urban environmental management and the understanding of urban growth status. However, the complex spatial patterns of the urban landscape make it challenging to accurately identify these areas of green plastic cover. To tackle this issue, we propose a deep semi-supervised learning framework for green plastic cover mapping using very high resolution (VHR) remote sensing imagery. Specifically, a multi-scale deformable convolution neural network (CNN) was exploited to learn representative and discriminative features under complex urban landscapes. Afterwards, a semi-supervised learning strategy was proposed to integrate the limited labeled data and massive unlabeled data for model co-training. Experimental results indicate that the proposed method could accurately identify green plastic-covered regions in Jinan with an overall accuracy (OA) of 91.63%. An ablation study indicated that, compared with supervised learning, the semi-supervised learning strategy in this study could increase the OA by 6.38%. Moreover, the multi-scale deformable CNN outperforms several classic CNN models in the computer vision field. The proposed method is the first attempt to map urban green plastic-covered regions based on deep learning, which could serve as a baseline and useful reference for future research.
Utilizing Airborne LiDAR and UAV Photogrammetry Techniques in Local Geoid Model Determination and Validation
Authors: Erol Serdar , Özögel Emrah , Kuçak Ramazan Alper , Erol Bihter
Published: September 2020

This investigation evaluates the performance of digital terrain models (DTMs) generated in different vertical datums by aerial LiDAR and unmanned aerial vehicle (UAV) photogrammetry techniques, for the determination and validation of local geoid models. Many engineering projects require the point heights referring to a physical surface, i.e., geoid, rather than an ellipsoid. When a high-accuracy local geoid model is available in the study area, the physical heights are practically obtained with the transformation of global navigation satellite system (GNSS) ellipsoidal heights of the points. Besides the commonly used geodetic methods, this study introduces a novel approach for the determination and validation of the local geoid surface models using photogrammetry. The numeric tests were carried out in the Bergama region, in the west of Turkey. Using direct georeferenced airborne LiDAR and indirect georeferenced UAV photogrammetry-derived point clouds, DTMs were generated in ellipsoidal and geoidal vertical datums, respectively. After this, the local geoid models were calculated as differences between the generated DTMs. Generated local geoid models in the grid and pointwise formats were tested and compared with the regional gravimetric geoid model (TG03) and a high-resolution global geoid model (EIGEN6C4), respectively. In conclusion, the applied approach provided sufficient performance for modeling and validating the geoid heights with centimeter-level accuracy.
An Integrated Spatiotemporal Pattern Analysis Model to Assess and Predict the Degradation of Protected Forest Areas
Authors: Malhi Ramandeep Kaur M. , Anand Akash , Srivastava Prashant K. , Kiran G. Sandhya , P. Petropoulos George , Chalkias Christos
Published: September 2020

Forest degradation is considered to be one of the major threats to forests over the globe, which has considerably increased in recent decades. Forests are gradually getting fragmented and facing biodiversity losses because of climate change and anthropogenic activities. Future prediction of forest degradation spatiotemporal dynamics and fragmentation is imperative for generating a framework that can aid in prioritizing forest conservation and sustainable management practices. In this study, a random forest algorithm was developed and applied to a series of Landsat images of 1998, 2008, and 2018, to delineate spatiotemporal forest cover status in the sanctuary, along with the predictive model viz. the Cellular Automata Markov Chain for simulating a 2028 forest cover scenario in Shoolpaneshwar Wildlife Sanctuary (SWS), Gujarat, India. The model’s predicting ability was assessed using a series of accuracy indices. Moreover, spatial pattern analysis—with the use of FRAGSTATS 4.2 software—was applied to the generated and predicted forest cover classes, to determine forest fragmentation in SWS. Change detection analysis showed an overall decrease in dense forest and a subsequent increase in the open and degraded forests. Several fragmentation metrics were quantified at patch, class, and landscape level, which showed trends reflecting a decrease in fragmentation in forest areas of SWS for the period 1998 to 2028. The improvement in SWS can be attributed to the enhanced forest management activities led by the government, for the protection and conservation of the sanctuary. To our knowledge, the present study is one of the few focusing on exploring and demonstrating the added value of the synergistic use of the Cellular Automata Markov Chain Model Coupled with Fragmentation Statistics in forest degradation analysis and prediction.
Hepatitis B Virus preS/S Truncation Mutant rtM204I/sW196* Increases Carcinogenesis through Deregulated HIF1A, MGST2, and TGFbi
Authors: Lai Ming-Wei , Liang Kung-Hao , Yeh Chau-Ting
Published: September 2020

Inevitable long-term therapy with nucleos(t)ide analogs in patients with chronic hepatitis B virus (HBV) infection has selected reverse-transcriptase (rt) mutants in a substantial proportion of patients. Some of these mutants introduce premature stop codons in the overlapping surface (s) gene, including rtA181T/sW172*, which has been shown to enhance oncogenicity. The oncogenicity of another drug-resistant mutant, rtM204I/sW196*, has not been studied. We constructed plasmids harboring rtM204I/sW196* and assessed the in vitro cell transformation, endoplasmic reticulum (ER) stress response, and xenograft tumorigenesis of the transformants. Cellular gene expression was analyzed by cDNA microarray and was validated. The rtM204I/sW196* transformants, compared with the control or wild type, showed enhanced transactivation activities for c-fos, increased cell proliferation, decreased apoptosis, more anchorage-independent growth, and enhanced tumor growth in mouse xenografts. X box-binding protein-1 (XBP1) splicing analysis showed no ER stress response. Altered gene expressions, including up-regulated MGST2 and HIF1A, and downregulated transforming growth factor beta-induced (TGFbi), were unveiled by cDNA microarray and validated by RT-qPCR. The TGFbi alteration occurred in transformants with wild type or mutated HBV. The altered MGST2 and HIF1A were found only with mutated HBV. The rtM204I/sW196* preS/S truncation may endorse the cell transformation and tumorigenesis ability via altered host gene expressions, including MGST2, HIF1A, and TGFbi. Downregulated TGFbi may be a common mechanism for oncogenicity in HBV surface truncation mutants.
Developing Electron Microscopy Tools for Profiling Plasma Lipoproteins Using Methyl Cellulose Embedment, Machine Learning and Immunodetection of Apolipoprotein B and Apolipoprotein(a)
Authors: Giesecke Yvonne , Soete Samuel , MacKinnon Katarzyna , Tsiaras Thanasis , Ward Madeline , Althobaiti Mohammed , Suveges Tamas , Lucocq James E. , McKenna Stephen J. , Lucocq John M.
Published: September 2020

Plasma lipoproteins are important carriers of cholesterol and have been linked strongly to cardiovascular disease (CVD). Our study aimed to achieve fine-grained measurements of lipoprotein subpopulations such as low-density lipoprotein (LDL), lipoprotein(a) (Lp(a), or remnant lipoproteins (RLP) using electron microscopy combined with machine learning tools from microliter samples of human plasma. In the reported method, lipoproteins were absorbed onto electron microscopy (EM) support films from diluted plasma and embedded in thin films of methyl cellulose (MC) containing mixed metal stains, providing intense edge contrast. The results show that LPs have a continuous frequency distribution of sizes, extending from LDL (> 15 nm) to intermediate density lipoprotein (IDL) and very low-density lipoproteins (VLDL). Furthermore, mixed metal staining produces striking “positive” contrast of specific antibodies attached to lipoproteins providing quantitative data on apolipoprotein(a)-positive Lp(a) or apolipoprotein B (ApoB)-positive particles. To enable automatic particle characterization, we also demonstrated efficient segmentation of lipoprotein particles using deep learning software characterized by a Mask Region-based Convolutional Neural Networks (R-CNN) architecture with transfer learning. In future, EM and machine learning could be combined with microarray deposition and automated imaging for higher throughput quantitation of lipoproteins associated with CVD risk.
Airway Inflammation and Host Responses in the Era of CFTR Modulators
Authors: Keown Karen , Brown Ryan , Doherty Declan F. , Houston Claire , McKelvey Michael C. , Creane Shannice , Linden Dermot , McAuley Daniel F. , Kidney Joseph C. , Weldon Sinéad , Downey Damian G. , Taggart Clifford C.
Published: September 2020

The arrival of cystic fibrosis transmembrane conductance regulator (CFTR) modulators as a new class of treatment for cystic fibrosis (CF) in 2012 represented a pivotal advance in disease management, as these small molecules directly target the upstream underlying protein defect. Further advancements in the development and scope of these genotype-specific therapies have been transformative for an increasing number of people with CF (PWCF). Despite clear improvements in CFTR function and clinical endpoints such as lung function, body mass index (BMI), and frequency of pulmonary exacerbations, current evidence suggests that CFTR modulators do not prevent continued decline in lung function, halt disease progression, or ameliorate pathogenic organisms in those with established lung disease. Furthermore, it remains unknown whether their restorative effects extend to dysfunctional CFTR expressed in phagocytes and other immune cells, which could modulate airway inflammation. In this review, we explore the effects of CFTR modulators on airway inflammation, infection, and their influence on the impaired pulmonary host defences associated with CF lung disease. We also consider the role of inflammation-directed therapies in light of the widespread clinical use of CFTR modulators and identify key areas for future research.
USP14 Regulates DNA Damage Response and Is a Target for Radiosensitization in Non-Small Cell Lung Cancer
Authors: Sharma Arishya , Almasan Alexandru
Published: September 2020

Non-small cell lung cancer (NSCLC) represents ~85% of the lung cancer cases. Despite recent advances in NSCLC treatment, the five-year survival rate is still around 23%. Radiotherapy is indicated in the treatment of both early and advanced stage NSCLC; however, treatment response in patients is heterogeneous. Thus, identification of new and more effective treatment combinations is warranted. We have identified Ubiquitin-specific protease 14 (USP14) s a regulator of major double-strand break (DSB) repair pathways in response to ionizing radiation (IR) by its impact on both non-homologous end joining (NHEJ) and homologous recombination (HR) in NSCLC. USP14 is a proteasomal deubiquitinase. IR treatment increases levels and DSB recruitment of USP14 in NSCLC cell lines. Genetic knockdown, using shUSP14 expression or pharmacological inhibition of USP14, using IU1, increases radiosensitization in NSCLC cell lines, as determined by a clonogenic survival assay. Moreover, shUSP14-expressing NSCLC cells show increased NHEJ efficiency, as indicated by chromatin recruitment of key NHEJ proteins, NHEJ reporter assay, and increased IR-induced foci formation by 53BP1 and pS2056-DNA-PKcs. Conversely, shUSP14-expressing NSCLC cells show decreased RPA32 and BRCA1 foci formation, suggesting HR-deficiency. These findings identify USP14 as an important determinant of DSB repair in response to radiotherapy and a promising target for NSCLC radiosensitization.
Intraductal Pancreatic Mucinous Neoplasms: A Tumor-Biology Based Approach for Risk Stratification
Authors: Nasca Vincenzo , Chiaravalli Marta , Piro Geny , Esposito Annachiara , Salvatore Lisa , Tortora Giampaolo , Corbo Vincenzo , Carbone Carmine
Published: September 2020

Pancreatic ductal adenocarcinoma is one of the most lethal human cancers. Its precursor lesions include pancreatic intra-epithelial neoplasia, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm (IPMN). IPMNs usually present as an incidental finding at imaging in 2.6% of the population and, according to the degree of dysplasia, they are classified as low- or high-grade lesions. Since the risk of malignant transformation is not accurately predictable, the management of these lesions is based on morphological and clinical parameters, such as presence of mural nodule, main pancreatic duct dilation, presence of symptoms, or high-grade dysplasia. Although the main genetic alterations associated to IPMNs have been elucidated, they are still not helpful for disease risk stratification. The growing body of genomic and epigenomic studies along with the more recent development of organotypic cultures provide the opportunity to improve our understanding of the malignant transformation process, which will likely deliver biomarkers to help discriminate between low- and high-risk lesions. Recent insights on the topic are herein summarized.
Current Practices for U.S. Newborn Screening of Pompe Disease and MPSI
Authors: Ames Elizabeth G. , Fisher Rachel , Kleyn Mary , Ahmad Ayesha
Published: September 2020

Two lysosomal storage disorders (LSDs), Pompe disease and Mucopolysaccharidosis type I (MPSI) were added to the Recommended Uniform Screening Panel (RUSP) for newborn screening (NBS) in 2015 and 2016, respectively. These conditions are being screened with variable practice in terms of primary and reflex analytes (either biochemical or molecular testing) as well as collection of short- and long-term follow-up elements. The goal of this study is to evaluate practices of state health departments in regards to screening methods and follow-up data collected. We conducted online surveys and phone questionnaires to determine each U.S. state’s practices for screening and follow-up of positive newborn screens. We report the first snapshot of practices for NBS for the LSDs included on the RUSP. All 50 U.S. states responded to our survey. The majority of U.S. states are not currently screening for Pompe disease and MPSI as of March 2020, but this number will increase to 38 states in the coming 1–3 years based on survey results. Our survey identifies data elements used by state health departments for short-and long-term follow-up that could serve as the basis of common elements for larger, public health-based analyses of the benefits and efficacy of screening for Pompe disease and MPSI.
Perceptions, Attitudes, and Barriers to Obesity Management in Spain: Results from the Spanish Cohort of the International ACTION-IO Observation Study
Authors: Salvador Javier , Vilarrasa Nuria , Poyato Francisco , Rubio Miguel Ángel
Published: September 2020

The prevalence of obesity is rapidly rising in Spain. The Awareness, Care and Treatment in Obesity Management—An International Observation (ACTION-IO) study (NCT03584191) was an international cross-sectional survey conducted to identify the perceptions, attitudes, behaviors, and barriers to obesity management for people with obesity (PwO) and healthcare professionals (HCPs); results from Spain are presented. In Spain, 1500 PwO (body mass index ≥30 kg/m2 based on self-reported height and weight) and 306 HCPs (in direct patient care for ≥2 years) completed the survey. Fewer PwO (59%) than HCPs (93%) agreed that obesity is a chronic disease. Most PwO (80%) assumed complete responsibility for their own weight loss, whilst 19% of HCPs placed the responsibility on PwO. One-fifth of PwO stated they began struggling with weight before age 15. The mean delay in discussing weight for the first time with an HCP was 6 years. Only 24% of HCPs thought their patients were motivated to lose weight, whilst 45% of PwO reported being motivated. Of the 67% of PwO who had discussed their weight with an HCP in the last 5 years, 66% had been formally diagnosed with obesity. Our Spanish dataset reveals discrepancies in the perceptions and attitudes between PwO and HCPs, thus highlighting the need to improve education about obesity and its clinical management.
Drug-Induced Naïve iPS Cells Exhibit Better Performance than Primed iPS Cells with Respect to the Ability to Differentiate into Pancreatic β-Cell Lineage
Authors: Kiyokawa Yuki , Sato Masahiro , Noguchi Hirofumi , Inada Emi , Iwase Yoko , Kubota Naoko , Sawami Tadashi , Terunuma Miho , Maeda Takeyasu , Hayasaki Haruaki , Saitoh Issei
Published: September 2020

Pluripotent stem cells are classified as naïve and primed cells, based on their in vitro growth characteristics and potential to differentiate into various types of cells. Human-induced pluripotent stem cells (iPSCs, also known as epiblast stem cells [EpiSCs]) have limited capacity to differentiate and are slightly more differentiated than naïve stem cells (NSCs). Although there are several in vitro protocols that allow iPSCs to differentiate into pancreatic lineage, data concerning generation of β-cells from these iPSCs are limited. Based on the pluripotentiality of NSCs, it was hypothesized that NSCs can differentiate into pancreatic β-cells when placed under an appropriate differentiation induction condition. We examined whether NSCs can be efficiently induced to form potentially pancreatic β cells after being subjected to an in vitro protocol. Several colonies resembling in vitro-produced β-cell foci, with β-cell-specific marker expression, were observed when NSC-derived embryoid bodies (EBs) were induced to differentiate into β-cell lineage. Conversely, EpiSC-derived EBs failed to form such foci in vitro. Intrapancreatic grafting of the in vitro-formed β-cell foci into nude mice (BALB/c-nu/nu) generated a cell mass containing insulin-producing cells (IPCs), without noticeable tumorigenesis. These NSCs can be used as a promising resource for curing type 1 diabetes.
Analysis of Risk Factors and Long-Term Outcomes in Kidney Transplant Patients with Identified Lymphoceles
Authors: Lehner Lukas J. , Hohberger Arnim , Marschke Lisanne , Lachmann Nils , Peters Robert , Friedersdorff Frank , Khadzhynov Dmytro , Halleck Fabian , Budde Klemens , Staeck Oliver , Duerr Michael
Published: September 2020

The collection of lymphatic fluids (lymphoceles) is a frequent adverse event following renal transplantation. A variety of surgical and medical factors has been linked to this entity, but reliable data on risk factors and long-term outcomes are lacking. This retrospective single-center study included 867 adult transplant recipients who received a kidney transplantation from 2006 to 2015. We evaluated for patient and graft survival, rejection episodes, or detectable donor-specific antibodies (dnDSA) in patients with identified lymphoceles in comparison to controls. We identified 305/867 (35.2%) patients with lymphocele formation, of whom 72/867 (8.3%) needed intervention. Multivariate analysis identified rejection episode as an independent risk factor (OR 1.61, CI 95% 1.17–2.21, p = 0.003) for lymphocele formation, while delayed graft function was independently associated with symptomatic lymphoceles (OR 1.9, CI 95% 1.16–3.12, p = 0.011). Interestingly, there was no difference in detectable dnDSA between groups with a similar graft and patient survival in all groups after 10 years. Lymphoceles frequently occur after transplantation and were found to be independently associated with rejection episodes, while symptomatic lymphoceles were associated with delayed graft function in our cohort. As both are inflammatory processes, they might play a causative role in the formation of lymphoceles. However, development or intervention of lymphoceles did not lead to impaired graft survival in the long-term.
H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
Authors: Saravi Sayeh , Katsuta Eriko , Jeyaneethi Jeyarooban , Amin Hasnat A. , Kaspar Matthias , Takabe Kazuaki , Pados George , Drenos Fotios , Hall Marcia , Karteris Emmanouil
Published: September 2020

Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of H2AX expression to compare OS and perform gene set enrichment. qRT-PCR validated in-silico H2AX findings followed by immunohistochemistry on a tissue microarray. The association between single nucleotide polymorphisms in the area of H2AX; prevalence and five-year OC survival was tested in samples from the UK Biobank. Results: H2AX was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (p = 0.010). Gene Set Enrichment Analysis demonstrated gene sets involved in G2/M checkpoint, DNA repair mTORC1 signalling were enriched in the H2AX highly expressing OCs. Polymorphisms in the area around the gene were associated with both OC prevalence (rs72997349-C, p = 0.005) and worse OS (rs10790282-G, p = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. Conclusions: Our findings suggest that H2AX can be a novel prognostic biomarker for OC.
Impact of Serum Lipid on Breast Cancer Recurrence
Authors: Jung Sung , Kang Danbee , Guallar Eliseo , Yu Jonghan , Lee Jeong , Kim Seok , Nam Seok , Cho Juhee , Lee Se
Published: September 2020

The association between serum lipid level and prognosis of breast cancer is controversial. The purpose of this study was to evaluate the impact of serum lipid level in breast cancer recurrence. We analyzed a total of 4190 patients with operable breast cancer who had baseline serum lipid profiles; total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A-1, and apolipoprotein B. Recurrence-free survival is defined as the elapsed time from the date of curative surgery to the detection of any recurrence, and recurrence includes locoregional recurrence, distant metastasis, or both local and distant metastasis. Cox-proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals (CI) for study outcomes comparing the three lowest quartiles of each lipid parameter to the highest quartile adjusting for age, body mass index (BMI), and pathologic stage, estrogen receptor (ER), progesterone receptor (PR), comorbidities (hypertension, diabetes, or vascular event) at time of breast cancer diagnosis. Patients with dyslipidemia (high bad cholesterol and low good cholesterol level) had worse prognostic factors (i.e., negative hormone receptor status, positive human epidermal growth factor receptor 2 (HER2) expression, higher nuclear grade). After adjusting for these poor prognostic factors, the patients with dyslipidemia showed good prognosis for breast cancer recurrence. Our study showed that baseline high lipid level could be a good prognostic factor of breast cancer. This study indicates that desirable changes in lipid profile for cardiovascular disease risk are not always beneficial for patients with breast cancer. However, as proper control of lipid level has advantages for cardiovascular disease, these findings require careful interpretation.