bluuebunny/crossref_metadata_2025 huggingface dataset:
Well-Being and Fear of Missing Out (FOMO) on Digital Content in the Time of COVID-19: A Correlational Analysis among University Students
Authors: Hayran Ceren , Anik Lalin
Published: February 2021

The majority of research on the fear of missing out (FOMO) has focused on understanding how social media posts about attractive unattended experiences taking place in the physical world (e.g., a friend’s vacation) influence individuals’ affective states. With quarantine measures in place, and in the absence of travel and party photos on social media, do individuals feel they are missing out on enjoyable experiences? The current work shows that FOMO has not disappeared during the pandemic, even when socially distancing at home, but has been replaced by feelings towards new online activities (e.g., online concerts, virtual gatherings). As a consequence, we find that FOMO threatens well-being by causing important psychological and health issues, such as sleep deprivation, loss of focus, declined productivity, and finding relief in knowing that others have difficulty keeping up with abundant digital content. Importantly, we find these consequential effects both during the initial (May 2020) and late stages (December 2020) of the pandemic. With excessive Internet use and virtual FOMO likely to be a continuing reality of life, questions remain as to how one can refrain from its negative effects and stay healthy during the pandemic and in the post-pandemic era. We discuss remedies and suggest new research avenues that may help elevate the negative consequences of FOMO on well-being.
Evaluation of Fetal Exposures to Metals and Metalloids through Meconium Analyses: A Review
Authors: Michelsen-Correa Stephani , Martin Clyde F. , Kirk Andrea B.
Published: February 2021

This paper surveys the existing scientific literature on metals concentrations in meconium. We examine some 32 papers that analyzed meconium for aluminum, arsenic, barium, calcium, chromium, copper, iron, lithium, magnesium, manganese, zinc, lead, mercury, manganese, molybdenum, nickel, phosphorus, lead, antimony, selenium, tin, vanadium, and zinc. Because of the lack of detail in the statistics it is not possible to do a rigorous meta-analysis. What stands out is that almost every study had subjects with seemingly large amounts of at least one of the metals. The significance of metals in meconium is not clear beyond an indication of exposure although some studies have correlated metals in meconium to a number of adverse outcomes. A number of outstanding questions have been identified that, if resolved, would greatly increase the utility of meconium analysis for assessment of long-term gestational metals exposures. Among these are questions of the developmental and long-term significance of metals detected in meconium, the kinetics and interactions among metals in maternal and fetal compartments and questions on best methods for meconium analyses.
Understanding Online Voluntary Self-Exclusion in Gambling: An Empirical Study Using Account-Based Behavioral Tracking Data
Authors: Catania Maris , Griffiths Mark D.
Published: February 2021

Online gambling has continued to grow alongside new ways to analyze data using behavioral tracking as a way to enhance consumer protection. A number of studies have analyzed consumers that have used voluntary self-exclusion (VSE) as a proxy measure for problem gambling. However, some scholars have argued that this is a poor proxy for problem gambling. Therefore, the present study examined this issue by analyzing customers (from the gambling operator Unibet) that have engaged in VSE. The participants comprised of costumers that chose to use the six-month VSE option (n = 7732), and customers that chose to close their Unibet account due to a specific self-reported gambling addiction (n = 141). Almost one-fifth of the customers that used six-month VSE only had gambling activity for less than 24 h (19.15%). Moreover, half of the customers had less than seven days of account registration prior to six-month VSE (50.39%). Customers who use VSE are too different to be treated as a homogenous group and therefore VSE is not a reliable proxy measure for problem gambling. The findings of this research are beneficial for operators, researchers, and policymakers because it provides insight into gambling behavior by analyzing real player behavior using tracking technologies, which is objective and unbiased.
Facilitating Factors and Opportunities for Local Food Purchases in School Meals in Spain
Authors: Soares Panmela , Suárez-Mercader Sandra , Comino Iris , Martínez-Milán María Asunción , Cavalli Suzi Barletto , Davó-Blanes María Carmen
Published: February 2021

The objective of this study is to explore the facilitating factors and opportunities that can promote the implementation of local food purchase (LFP) in Spanish school meals in the opinions of key informants (IK). A qualitative study was carried out based on in-depth interviews with 14 KI capable of influencing Spanish food policy (Representatives of consumers and/or producers, representatives of organizations that promote LFP, and representatives of the government and/or academics). They were asked about opportunities and facilitating factors for implementation of LFP. Interviews were recorded and transcribed. A qualitative content analysis was carried out with Atlas ti. The analysis of the interviews produced two categories that include factors that- in the interviewees’ opinions- can promote LFP (social fabric and policy) and three categories that bring together the factors that represent opportunities for implementation in school meal programs in Spain (the policy agenda, regional characteristics and regional context). The overlap between social and political demands were considered to be facilitating factors for LFP. Furthermore, in the opinions of KI, the presence of health and sustainability issues on the public agenda, the existence of a structured productive system and political changes represent an opportunity to implement LFP.
Influential Factors of Burnout among Village Doctors in China: A Cross-Sectional Study
Authors: Zhao Xinyi , Liu Shu , Chen Yifan , Zhang Quan , Wang Yue
Published: February 2021

(1) Background: The heavy workload and understaffed personnel of village doctors is a challenge to the rural healthcare system in China. Previous studies have documented the predictors of doctors’ burnout; however, little attention has been paid to village doctors. This study aims to investigate the prevalence and influential factors of burnout among village doctors. (2) Methods: Data was collected by a self-administered questionnaire from 1248 village doctors who had worked at rural clinics for more than a year. Burnout was measured using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) with three dimensions—emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). A logistic regression model was applied to estimate the influential factors of burnout. (3) Results: The prevalence of overall burnout was 23.6%. Being male (OR = 0.58, 95%CI: 0.41–0.82), poor health status (OR = 0.80, 95%CI: 0.67–0.94), low income (OR = 0.62, 95%CI: 0.40–0.95), and a poor doctor–patient relationship (OR = 0.57, 95%CI: 0.48–0.67) were significantly related to burnout. Conclusion: Burnout is prevalent among Chinese village doctors. Policies such as increasing village doctors’ income and investing more resources in rural healthcare system should be carried out to mitigate and prevent burnout.
“Everything Is Gonna Be Alright with Me”: The Role of Self-Compassion, Affect, and Coping in Negative Emotional Symptoms during Coronavirus Quarantine
Authors: Beato Ana Filipa , da Costa Leonor Pereira , Nogueira Rita
Published: February 2021

Self-compassion has been associated with less distress, particularly when people face stressful and negative events. This study analyzed the mediation role of coping and affect in the relation between self-compassion and negative emotional symptoms during the quarantine decreed by Portuguese Health Authorities in the first phase of the coronavirus outbreak. A total of 428 Portuguese adults (75% women; Mage = 40.8, SD = 11.6) completed an online survey comprised by the Self-Compassion Scale (predictor); Short Version of Depression, Anxiety and Stress Scale (outcomes); The Positive and Negative Affect Schedule; and Brief-COPE. These instruments were adapted to COVID 19’s epidemic. Parallel mediation analyses demonstrated that self-compassionate participants were at less risk of suffering from symptoms of depression, anxiety, and stress during the quarantine. Plus, the relation between self-compassion and depressive, anxious, and stress symptoms were mediated by negative affect and dysfunctional coping style, but only for symptoms of depression. The findings support coping strategies and affect as links between self-compassion and distress but also the importance of separately analyzing the role of self-compassion, negative affect, and coping on symptoms of anxiety, depression, and stress. Low self-compassion might increase negative affect, maintaining stress responses to face demanding events during the COVID-19 epidemic. Results were discussed in the context of the pandemic outbreak.
Company Representatives’ Experiences of Occupational Health Surveillance for Workers Exposed to Hand-Intensive Work: A Qualitative Study
Authors: Eliasson Kristina , Dahlgren Gunilla , Hellman Therese , Lewis Charlotte , Palm Peter , Svartengren Magnus , Nyman Teresia
Published: February 2021

Exposure assessment seldom precedes the medical health checks in occupational health surveillance. In order to emphasize the interconnection between exposure assessment and medical health checks, a process model was developed. The process model aimed to guide employers and Occupational Health Service providers through the execution of occupational health surveillance. The objective of this qualitative study is to explore company representatives’ experiences of the process model, in terms of feasibility and values, and to identify factors that facilitate or impede the process. Thirty-three company representatives from ten companies were interviewed. Interviews were analyzed using content analysis. The company representatives experienced that the model contributed to increased risk awareness and understanding of the exposure effects on workers’ health. They valued the exposure assessments performed by an ergonomics expert, which led to the discovery of previously unidentified risks. The feasibility was facilitated by: a joint start-up meeting in which the process was planned, clear communication between the involved parties, and clarity regarding the process ownership. The findings reveal that a guiding process model is valuable for the execution of occupational health surveillance. However, the model should not only define the components included; a practical guide concerning how the process can be executed is also needed.
Effect of Ridge Height, Row Grade, and Field Slope on Nutrient Losses in Runoff in Contour Ridge Systems under Seepage with Rainfall Condition
Authors: An Juan , Geng Jibiao , Yang Huiling , Song Hongli , Wang Bin
Published: February 2021

Seepage plays a key role in nutrient loss and easily occurs in widely-used contour ridge systems due to the ponding process. However, the characteristics of nutrient loss and its influential factors under seepage with rainfall condition in contour ridge systems are still unclear. In this study, 23 seepage and rainfall simulation experiments are arranged in an orthogonal rotatable central composite design to investigate the role of ridge height, row grade, and field slope on Nitrate (NO3−–N) and Orthophosphate (PO4+3–P) losses resulting from seepage in contour ridge systems. In total, three types of NO3−–N and PO4+3–P loss were observed according to erosion processes of inter-rill–headward, inter-rill–headward–contour failure, and inter-rill–headward–contour failure–rill. Our results demonstrated that second-order polynomial regression models were obtained to predict NO3−–N and PO4+3–P loss with the independent variables of ridge height, row grade, and field slope. Ridge height was the most important factor for nutrient loss, with a significantly positive effect and the greatest contribution (52.35–53.47%). The secondary factor of row grade exerted a significant and negative effect, and was with a contribution of 19.86–24.11% to nutrient loss. The interaction between ridge height and row grade revealed a significantly negative effect on NO3−–N loss, whereas interactions among the three factors did not significantly affect PO4+3–P loss. Field slope only significantly affected NO3−–N loss. The optimal design of a contour ridge system to control nutrient loss was obtained at ridge height of 8 cm, row grade of 2°, and field slope of 6.5°. This study provides a method to assess and model nutrient loss, and improves guidance to implement contour ridge systems in terms of nutrient loss control.
Prevalence and Determinants of Fatigue after COVID-19 in Non-Hospitalized Subjects: A Population-Based Study
Authors: Stavem Knut , Ghanima Waleed , Olsen Magnus K. , Gilboe Hanne M. , Einvik Gunnar
Published: February 2021

This study assessed the prevalence and determinants of fatigue in a population-based cohort of non-hospitalized subjects 1.5–6 months after COVID-19. It was a mixed postal/web survey of all non-hospitalized patients ≥18 years with a positive PCR for SARS-CoV-2 until 1 June 2020 in a geographically defined area. In total, 938 subjects received a questionnaire including the Chalder fatigue scale (CFQ-11) and the energy/fatigue scale of the RAND-36 questionnaire. We estimated z scores for comparison with general population norms. Determinants were analyzed using multivariable logistic and linear regression analysis. In total, 458 subjects (49%) responded to the survey at median 117.5 days after COVID-19 onset, and 46% reported fatigue. The mean z scores of the CFQ-11 total was 0.70 (95% CI 0.58 to 0.82), CFQ-11 physical 0.66 (0.55 to 0.78), CFQ-11 mental 0.47 (0.35 to 0.59) and RAND-36 energy/fatigue −0.20 (−0.31 to −0.1); all CFQ-11 scores differed from those of the norm population (p < 0.001). Female sex, single/divorced/widowed, short time since symptom debut, high symptom load, and confusion during acute COVID-19 were associated with higher multivariable odds of fatigue. In conclusion, the burden of post-viral fatigue following COVID-19 was high, and higher than in a general norm population. Symptoms of fatigue were most prevalent among women, those having a high symptom load, or confusion during the acute phase.
Spatial Variability of Rainfall Trends in Sri Lanka from 1989 to 2019 as an Indication of Climate Change
Authors: Alahacoon Niranga , Edirisinghe Mahesh
Published: February 2021

Analysis of long-term rainfall trends provides a wealth of information on effective crop planning and water resource management, and a better understanding of climate variability over time. This study reveals the spatial variability of rainfall trends in Sri Lanka from 1989 to 2019 as an indication of climate change. The exclusivity of the study is the use of rainfall data that provide spatial variability instead of the traditional location-based approach. Henceforth, daily rainfall data available at Climate Hazards Group InfraRed Precipitation corrected with stations (CHIRPS) data were used for this study. The geographic information system (GIS) is used to perform spatial data analysis on both vector and raster data. Sen’s slope estimator and the Mann–Kendall (M–K) test are used to investigate the trends in annual and seasonal rainfall throughout all districts and climatic zones of Sri Lanka. The most important thing reflected in this study is that there has been a significant increase in annual rainfall from 1989 to 2019 in all climatic zones (wet, dry, intermediate, and Semi-arid) of Sri Lanka. The maximum increase is recorded in the wet zone and the minimum increase is in the semi-arid zone. There could be an increased risk of floods in the southern and western provinces in the future, whereas areas in the eastern and southeastern districts may face severe droughts during the northeastern monsoon. It is advisable to introduce effective drought and flood management and preparedness measures to reduce the respective hazard risk levels.
Yes-Associated Protein 1 Is a Novel Calcium Sensing Receptor Target in Human Parathyroid Tumors
Authors: Tavanti Giulia Stefania , Verdelli Chiara , Morotti Annamaria , Maroni Paola , Guarnieri Vito , Scillitani Alfredo , Silipigni Rosamaria , Guerneri Silvana , Maggiore Riccardo , Mari Gilberto , Vicentini Leonardo , Dalino Ciaramella Paolo , Vaira Valentina , Corbetta Sabrina
Published: February 2021

The Hippo pathway is involved in human tumorigenesis and tissue repair. Here, we investigated the Hippo coactivator Yes-associated protein 1 (YAP1) and the kinase large tumor suppressor 1/2 (LATS1/2) in tumors of the parathyroid glands, which are almost invariably associated with primary hyperparathyroidism. Compared with normal parathyroid glands, parathyroid adenomas (PAds) and carcinomas show variably but reduced nuclear YAP1 expression. The kinase LATS1/2, which phosphorylates YAP1 thus promoting its degradation, was also variably reduced in PAds. Further, YAP1 silencing reduces the expression of the key parathyroid oncosuppressor multiple endocrine neoplasia type 1(MEN1), while MEN1 silencing increases YAP1 expression. Treatment of patient-derived PAds-primary cell cultures and Human embryonic kidney 293A (HEK293A) cells expressing the calcium-sensing receptor (CASR) with the CASR agonist R568 induces YAP1 nuclear accumulation. This effect was prevented by the incubation of the cells with RhoA/Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitors Y27632 and H1152. Lastly, CASR activation increased the expression of the YAP1 gene targets CYR61, CTGF, and WNT5A, and this effect was blunted by YAP1 silencing. Concluding, here we provide preliminary evidence of the involvement of the Hippo pathway in human tumor parathyroid cells and of the existence of a CASR-ROCK-YAP1 axis. We propose a tumor suppressor role for YAP1 and LATS1/2 in parathyroid tumors.
Inspiratory Off-Switch Mediated by Optogenetic Activation of Inhibitory Neurons in the preBötzinger Complex In Vivo
Authors: Hülsmann Swen , Hagos Liya , Eulenburg Volker , Hirrlinger Johannes
Published: February 2021

The role of inhibitory neurons in the respiratory network is a matter of ongoing debate. Conflicting and contradicting results are manifold and the question whether inhibitory neurons are essential for the generation of the respiratory rhythm as such is controversial. Inhibitory neurons are required in pulmonary reflexes for adapting the activity of the central respiratory network to the status of the lung and it is hypothesized that glycinergic neurons mediate the inspiratory off-switch. Over the years, optogenetic tools have been developed that allow for cell-specific activation of subsets of neurons in vitro and in vivo. In this study, we aimed to identify the effect of activation of inhibitory neurons in vivo. Here, we used a conditional transgenic mouse line that expresses Channelrhodopsin 2 in inhibitory neurons. A 200 µm multimode optical fiber ferrule was implanted in adult mice using stereotaxic surgery, allowing us to stimulate inhibitory, respiratory neurons within the core excitatory network in the preBötzinger complex of the ventrolateral medulla. We show that, in anesthetized mice, activation of inhibitory neurons by blue light (470 nm) continuously or with stimulation frequencies above 10 Hz results in a significant reduction of the respiratory rate, in some cases leading to complete cessation of breathing. However, a lower stimulation frequency (4–5 Hz) could induce a significant increase in the respiratory rate. This phenomenon can be explained by the resetting of the respiratory cycle, since stimulation during inspiration shortened the associated breath and thereby increased the respiratory rate, while stimulation during the expiratory interval reduced the respiratory rate. Taken together, these results support the concept that activation of inhibitory neurons mediates phase-switching by inhibiting excitatory rhythmogenic neurons in the preBötzinger complex.
A Cumulative Effect of Food and Viruses to Trigger Celiac Disease (CD): A Commentary on the Recent Literature
Authors: Barone Maria Vittoria , Auricchio Salvatore
Published: February 2021

Celiac disease (CD) is a type of inflammatory chronic disease caused by nutrients such as gliadin that induce a TC (T cell)-mediated response in a partially known genetical background in an environment predisposed to inflammation, including viruses and food. Various experimental and clinical observations suggest that multiple agents such as viruses and bacteria have some common, inflammatory pathways predisposing individuals to chronic inflammatory diseases including celiac disease (CD). More recently, a Western diet and lifestyle have been linked to tissue inflammation and increase in chronic inflammatory diseases. In CD, the gliadin protein itself has been shown to be able to induce inflammation. A cooperation between viruses and gliadin is present in vitro and in vivo with common mechanisms to induce inflammation. Nutrients could have also a protective effect on CD, and in fact the anti-inflammatory Mediterranean diet has a protective effect on the development of CD in children. The possible impact of these observations on clinical practice is discussed.
Synergic Effect of Selected Ingredients and Calcium Chloride on the Technological, Molecular and Microbial Usefulness of Eggshells and Their Impact on Sensory Properties in a Food Model System
Authors: Szymandera-Buszka Krystyna , Kobus-Cisowska Joanna , Szymanowska-Powałowska Daria , Rezler Ryszard , Szczepaniak Oskar , Marciniak Grzegorz , Piechocka Justyna , Jarzębski Maciej
Published: February 2021

Lower levels of calcium in adults increase the risk for osteoporosis, and in children, low calcium levels can impact their potential adult height. The study objective was to analyze the bioavailability and physicochemical properties of a calcium preparation based on chicken eggs. The base calcium preparation was enriched with one of a variety of biologically active substances, inter alia, vitamin D3, vitamin K, lysine, lactose, magnesium chloride and inulin. The newly developed calcium preparations were subjected to structural analysis using X-ray diffraction and scanning electron microscopy, and the hydrodynamic diameter for the molecules was determined using the dynamic light scattering method and their zeta potential. To determine the optimum storage conditions of calcium preparations, their hygroscopicity and bulk density were determined. The calcium preparations were also added to selected food products, such as apple juice with mango, fruit dessert (jelly) and beef meatballs. The enriched food products were subjected to sensory analysis. The study demonstrated the significant influence of additives to calcium preparation in terms of its hygroscopicity and morphology. It was found that all products with the addition of analyzed preparations were characterized by high sensory desirability. The results presented in the study comprise the basis for the development of new food products, enriched with calcium.
One-Dimensional Organic–Inorganic Material (C6H9N2)2BiCl5: From Synthesis to Structural, Spectroscopic, and Electronic Characterizations
Authors: Ferjani Hela , Chebbi Hammouda , Fettouhi Mohammed
Published: February 2021

The new organic–inorganic compound (C6H9N2)2BiCl5 (I) has been grown by the solvent evaporation method. The one-dimensional (1D) structure of the allylimidazolium chlorobismuthate (I) has been determined by single crystal X-ray diffraction. It crystallizes in the centrosymmetric space group C2/c and consists of 1-allylimidazolium cations and (1D) chains of the anion BiCl52−, built up of corner-sharing [BiCl63−] octahedra which are interconnected by means of hydrogen bonding contacts N/C–H⋯Cl. The intermolecular interactions were quantified using Hirshfeld surface analysis and the enrichment ratio established that the most important role in the stability of the crystal structure was provided by hydrogen bonding and H···H interactions. The highest value of E was calculated for the contact N⋯C (6.87) followed by C⋯C (2.85) and Bi⋯Cl (2.43). These contacts were favored and made the main contribution to the crystal packing. The vibrational modes were identified and assigned by infrared and Raman spectroscopy. The optical band gap (Eg = 3.26 eV) was calculated from the diffuse reflectance spectrum and showed that we can consider the material as a semiconductor. The density functional theory (DFT) has been used to determine the calculated gap, which was about 3.73 eV, and to explain the electronic structure of the title compound, its optical properties, and the stability of the organic part by the calculation of HOMO and LUMO energy and the Fukui indices.
Leber Congenital Amaurosis Due to GUCY2D Mutations: Longitudinal Analysis of Retinal Structure and Visual Function
Authors: Jacobson Samuel G. , Cideciyan Artur V. , Sumaroka Alexander , Roman Alejandro J. , Wu Vivian , Swider Malgorzata , Sheplock Rebecca , Krishnan Arun K. , Garafalo Alexandra V.
Published: February 2021

Gene augmentation therapy is being planned for GUCY2D-associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of GUCY2D-LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and efficacy outcome measures previously determined to be useful for monitoring this disorder. In this group of molecularly-identified LCA patients (n = 10; ages 7–37 years at first visit), optical coherence tomography (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus. Full-field stimulus testing (FST) with chromatic stimuli in dark- and light-adapted states was used to assay rod and cone vision. Changes in OCT and FST over the interval were mostly attributable to inter-visit variability. There were no major negative changes in structure or function across the cohort and over the intervals studied. Variation in severity of disease expression between patients occurs; however, despite difficulties in quantifying structure and function in such seriously visually impaired individuals with nystagmus, the present work supports the use of OCT as a safety outcome and FST as an efficacy outcome in a clinical trial of GUCY2D-LCA. A wide age spectrum for therapy was confirmed, and there was relative stability of structure and function during a typical time interval for clinical trials.
Special Issue “Centenarians—A Model to Study the Molecular Basis of Lifespan and Healthspan”
Authors: Caruso Calogero , Puca Annibale Alessandro
Published: February 2021

People are living longer, not, as was previously the case, due to reduced child mortality, but because we are postponing the ill-health of old age [...]
Extracellular Vesicle-Derived microRNAs of Human Wharton’s Jelly Mesenchymal Stromal Cells May Activate Endogenous VEGF-A to Promote Angiogenesis
Authors: Chinnici Cinzia Maria , Iannolo Gioacchin , Cittadini Ettore , Carreca Anna Paola , Nascari David , Timoneri Francesca , Bella Mariangela Di , Cuscino Nicola , Amico Giandomenico , Carcione Claudia , Conaldi Pier Giulio
Published: February 2021

Despite low levels of vascular endothelial growth factor (VEGF)-A, the secretome of human Wharton’s jelly (WJ) mesenchymal stromal cells (MSCs) effectively promoted proangiogenic responses in vitro, which were impaired upon the depletion of small (~140 nm) extracellular vesicles (EVs). The isolated EVs shared the low VEGF-A profile of the secretome and expressed five microRNAs, which were upregulated compared to fetal dermal MSC-derived EVs. These upregulated microRNAs exclusively targeted the VEGF-A gene within 54 Gene Ontology (GO) biological processes, 18 of which are associated with angiogenesis. Moreover, 15 microRNAs of WJ-MSC-derived EVs were highly expressed (Ct value ≤ 26) and exclusively targeted the thrombospondin 1 (THBS1) gene within 75 GO biological processes, 30 of which are associated with the regulation of tissue repair. The relationship between predicted microRNA target genes and WJ-MSC-derived EVs was shown by treating human umbilical-vein endothelial cells (HUVECs) with appropriate doses of EVs. The exposure of HUVECs to EVs for 72 h significantly enhanced the release of VEGF-A and THBS1 protein expression compared to untreated control cells. Finally, WJ-MSC-derived EVs stimulated in vitro tube formation along with the migration and proliferation of HUVECs. Our findings can contribute to a better understanding of the molecular mechanisms underlying the proangiogenic responses induced by human umbilical cord-derived MSCs, suggesting a key regulatory role for microRNAs delivered by EVs.
Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives
Authors: Cocetta Veronica , Quagliariello Vincenzo , Fiorica Francesco , Berretta Massimiliano , Montopoli Monica
Published: February 2021

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.
Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease
Authors: Moretti Rita , Giuffré Mauro , Caruso Paola , Gazzin Silvia , Tiribelli Claudio
Published: February 2021

Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine metabolism, accumulation of which may be caused by genetic defects or the deficit of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined as hyperhomocysteinemia (HHcy). Hcy has many roles, the most important being the active participation in the transmethylation reactions, fundamental for the brain. Many studies focused on the role of homocysteine accumulation in vascular or degenerative neurological diseases, but the results are still undefined. More is known in cardiovascular disease. HHcy is a determinant for the development and progression of inflammation, atherosclerotic plaque formation, endothelium, arteriolar damage, smooth muscle cell proliferation, and altered-oxidative stress response. Conversely, few studies focused on the relationship between HHcy and small vessel disease (SVD), despite the evidence that mice with HHcy showed a significant end-feet disruption of astrocytes with a diffuse SVD. A severe reduction of vascular aquaporin-4-water channels, lower levels of high-functioning potassium channels, and higher metalloproteinases are also observed. HHcy modulates the N-homocysteinylation process, promoting a pro-coagulative state and damage of the cellular protein integrity. This altered process could be directly involved in the altered endothelium activation, typical of SVD and protein quality, inhibiting the ubiquitin-proteasome system control. HHcy also promotes a constant enhancement of microglia activation, inducing the sustained pro-inflammatory status observed in SVD. This review article addresses the possible role of HHcy in small-vessel disease and understands its pathogenic impact.
Editorial for the Special Issue “Molecular Biomarkers in Colorectal Adenocarcinoma”
Authors: Artemaki Pinelopi I. , Kontos Christos K.
Published: February 2021

Colorectal cancer (CRC) is one of the most common malignancies, with an elevated mortality rate [...]
Abiotic Stress Response of Near-Isogenic Spring Durum Wheat Lines under Different Sowing Densities
Authors: Bányai Judit , Maccaferri Marco , Láng László , Mayer Marianna , Tóth Viola , Cséplő Mónika , Pál Magda , Mészáros Klára , Vida Gyula
Published: February 2021

A detailed study was made of changes in the plant development, morphology, physiology and yield biology of near-isogenic lines of spring durum wheat sown in the field with different plant densities in two consecutive years (2013–2014). An analysis was made of the drought tolerance of isogenic lines selected for yield QTLs (QYld.idw-2B and QYld.idw-3B), and the presence of QTL effects was examined in spring sowings. Comparisons were made of the traits of the isogenic pairs QYld.idw-3B++ and QYld.idw-3B−− both within and between the pairs. Changes in the polyamine content, antioxidant enzyme activity, chlorophyll content of the flag leaf and the normalized difference vegetation index (NDVI) of the plot were monitored in response to drought stress, and the relationship between these components and the yield was analyzed. In the case of moderate stress, differences between the NIL++ and NIL−− pairs appeared in the early dough stage, indicating that the QYld.idw-3B++ QTL region was able to maintain photosynthetic activity for a longer period, resulting in greater grain number and grain weight at the end of the growing period. The chlorophyll content of the flag leaf in phenophases Z77 and Z83 was significantly correlated with the grain number and grain weight of the main spike. The grain yield was greatly influenced by the treatment, while the genotype had a significant effect on the thousand-kernel weight and on the grain number and grain weight of the main spike. When the lines were compared in the non-irrigated treatment, significantly more grains and significantly higher grain weight were observed in the main spike in NIL++ lines, confirming the theory that the higher yields of the QYld.idw-3B++ lines when sown in spring and exposed to drought stress could be attributed to the positive effect of the “Kofa” QTL on chromosome 3B.
The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades
Authors: Terazawa Shuko , Takada Mariko , Sato Yoriko , Nakajima Hiroaki , Imokawa Genji
Published: February 2021

Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. A signal inhibition study demonstrated that the inhibition of p38 significantly abrogates the UVA-accentuated mRNA level of HYBID. Furthermore, the inhibition of STAT3 significantly downregulates the level of HAS2 mRNA in non-UVA exposed HDFs. Analysis using siRNAs demonstrated that transfection of ATF-2 siRNA but not c-Fos siRNA abrogates the increased protein level of HYBID in UVA-exposed HDFs. An inhibitor of protein tyrosine phosphatase but not of protein serine/threonine phosphatase restored the diminished phosphorylation level of STAT3 at Tyr 705, accompanied by a significant abolishing effect on the decreased mRNA expression level of HAS2. Silencing with a protein tyrosine phosphatase PTP-Meg2 siRNA revealed that it abrogates the decreased phosphorylation of STAT3 at Tyr 705 in UVA-exposed HDFs. These findings suggest that the UVA-induced decrease in HA secretion by HDFs is attributable to the down- and upregulation of HAS2 and HYBID expression, respectively, changes that are mainly ascribed to the inactivated signaling of the STAT3 axis due to the activated tyrosine protein phosphatase PTP-Meg2 and the activated signaling of the p38/ATF2 axis, respectively.
Optimisation of AGR-Like FHR Fuel Assembly Using Multi-Objective Particle Swarm Algorithm
Authors: Margulis Marat , Shwageraus Eugene
Published: February 2021

Utilising molten salt as coolant instead of carbon dioxide in traditional advanced gas-cooled reactors (AGRs) can potentially increase their core power density, simplify the safety case and shorten the time needed for the development of the fluoride-salt-cooled high-temperature reactor (FHR). However, the change of coolant has a strong impact on the system behaviour. Therefore, a new type of fuel assembly is required. However, the design of a new assembly is affected by a wide range of parameters. Systematic search through all the potential configurations is prohibitively computationally expensive. In this work, a multi objective particle swarm optimisation (MOPSO) algorithm is utilised to identify the most attractive candidate configurations for the hybrid AGR-like FHR assembly. The first optimisation step targets basic design parameters such as radius and enrichment of the fuel pins, their number and arrangement. MOPSO is based on the concept of Pareto dominance, which is used to determine the flight direction of the simulated particles. The outcome of the optimisation process provides insight on families of possible solutions, which described by the Pareto front.
Versatile CRISPR/Cas9 Systems for Genome Editing in Ustilago maydis
Authors: Wege Sarah-Maria , Gejer Katharina , Becker Fabienne , Bölker Michael , Freitag Johannes , Sandrock Björn
Published: February 2021

The phytopathogenic smut fungus Ustilago maydis is a versatile model organism to study plant pathology, fungal genetics, and molecular cell biology. Here, we report several strategies to manipulate the genome of U. maydis by the CRISPR/Cas9 technology. These include targeted gene deletion via homologous recombination of short double-stranded oligonucleotides, introduction of point mutations, heterologous complementation at the genomic locus, and endogenous N-terminal tagging with the fluorescent protein mCherry. All applications are independent of a permanent selectable marker and only require transient expression of the endonuclease Cas9hf and sgRNA. The techniques presented here are likely to accelerate research in the U. maydis community but can also act as a template for genome editing in other important fungi.
The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol
Authors: Obi Patience O. , Kent Jennifer E. , Jeyaraman Maya M. , Askin Nicole , Pierdoná Taiana M. , Halayko Andrew J. , Saleem Ayesha
Published: February 2021

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.
What Has Driven the U.S. Monthly Oil Production Since 2009? Empirical Results from Two Modeling Approaches
Authors: Bhar Ramaprasad , Malliaris Anastasios G. , Malliaris Mary
Published: February 2021

From the early 1970s to the Global Financial Crisis of 2007–09, U.S. crude oil production followed a declining trend. After the Global Financial Crisis, U.S. crude oil production increased rapidly. This paper addresses the important question “what economic factors have driven U.S. crude oil production since the Global Financial Crisis?”. We propose that factors such as: the price of oil, the one period lagged price of oil, the price of copper, the crude oil price volatility, the Trade Weighted U.S. Dollar Index, and the high yield index spread, are important explanatory variables. Using two modeling approaches, namely, multiple regression, and the random tree methodology, we conclude that the one month lagged price of oil is the most significant explanatory variable, among all considered, for the upward trend of U.S. oil production from 2009 to early 2020.
Understanding High Performance in Late Second Language (L2) Acquisition—What Is the Secret? A Contrasting Case Study in L2 French
Authors: Forsberg Lundell Fanny , Arvidsson Klara
Published: February 2021

Adult L2 acquisition has often been framed within research on the Critical Period Hypothesis, and the age factor is one of the most researched topics of SLA. However, several researchers suggest that while age is the most important factor for differences between child and adult SLA, variation in adult SLA is more dependent on social and psychological factors than on age of onset. The present qualitative study investigates the role of migratory experience, language use/social networks, language learning experience, identity and attitudes for high performance among Swedish L1 French L2 users in France. The study constitutes an in-depth thematic analysis of interviews with six high-performing individuals and four low-performing individuals. The main results show that the high performers differ from the low performers on all dimensions, except for attitudes towards the host community. High performers are above all characterized by self-reported language aptitude and an early interest in languages, which appears to have led to rich exposure to French. Also, they exhibit self-regulatory behaviors and attribute importance to being perceived as a native speaker of French—both for instrumental and existential reasons.
Exercise Biomechanics and Physiology
Authors: Priego-Quesada Jose I.
Published: February 2021

Biomechanics was defined by Hatze in 1974 as the study of the movement of living things using the science of mechanics [...]
Influence of Hydrofluoric and Nitric Acid Pre-Treatment and Type of Adhesive Cement on Retention of Zirconia Crowns
Authors: Harb Osama , Al-Zordk Walid , Özcan Mutlu , Sakrana Amal Abdelsamad
Published: February 2021

Background: The aim of this study was to test the impact of hot acids etching and two types of adhesive cement on the retention of zirconia crowns. Methods: Forty maxillary premolars were prepared, and zirconia crowns were designed and fabricated with proximal extensions, then divided into 4 groups (n = 10). Group AP; the crowns were air-abraded and cemented using Panavia SA Cement. Group AL; the crowns were air- abraded and cemented using GC LinkForce. Group AHP; the crowns were air-abraded, etched with the hot acids (48% hydrofluoric acid and 69% nitric acid), and cemented using Panavia SA Cement. Group AHL; the crowns were air-abraded, etched with the hot acids, and cemented using GC LinkForce. Each zirconia crown was pre-treated and bonded to its corresponding tooth. After thermocycling (5–55 °C/10,000), the retention test was performed and the load required to dislodge the crown was reported in Newton (N), and mode of failure was recorded. The retention strength (MPa) was calculated for each tested variable and statistically analyzed. Results: Group AHP showed the highest mean value of the retention strength, followed by group AP then group AHL. Group AL showed the lowest value. A statistically significant effect (p = 0.001) of the hot acids etching on the retention of zirconia crown was found. Also, there was a significant effect (p = 0.000) of the cement type. The interaction between surface treatment and the cement type has no significant impact (p = 0.882). The main mode of failure for Panavia SA Cement is mixed mode of failure, while for G-CEM LinkForce is adhesive failure. Conclusions: Hot acid etching pre-treatment improved the retention of zirconia crown. Usage of Panavia SA Cement with hot acids etching is effective can be used for adhesive cementation of zirconia crown.
Development of Novel Oral Formulations of Disulfide Antioxidants Based on Porous Silica for Controlled Release of the Drugs
Authors: Dolinina Ekaterina S. , Parfenyuk Elena V.
Published: February 2021

Powerful antioxidant α-lipoic acid (LA) exhibits limited therapeutic efficiency due to its pharmacokinetic properties. Therefore, the purpose of this work was to evaluate the ability of silica-based composites of LA as well as its amide (lipoamide, LM), as new oral drug formulations, to control their release and maintain their therapeutic concentration and antioxidant activity in the body over a long time. The composites synthesized at different sol–gel synthesis pH and based on silica matrixes with various surface chemistry were investigated. The release behavior of the composites in media mimicking pH of digestive fluids (pH 1.6, 6.8, and 7.4) was revealed. The effects of chemical structure of the antioxidants, synthesis pH, surface chemistry of the silica matrixes in the composites as well as the pH of release medium on kinetic parameters of the drug release and mechanisms of the process were discussed. The comparative analysis of the obtained data allowed the determination of the most promising composites. Using these composites, modeling of the release process of the antioxidants in accordance with transit conditions of the drugs in stomach, proximal, and distal parts of small intestine and colon was carried out. The composites exhibited the release close to the zero order kinetics and maintained the therapeutic concentration of the drugs and antioxidant effect in all parts of the intestine for up to 24 h. The obtained results showed that encapsulation of LA and LM in the silica matrixes is a promising way to improve their bioavailability and antioxidant activity.