bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Effects of Supportive Interaction and Facilitator Input Variety on Treatment Adherence of Young People with Chronic Health Conditions: A Dynamic Mechanism in Mutual Aid Groups
Authors: Ngai Steven Sek-Yum , Cheung Chau-Kiu , Ng Yuen-Hang , Shang Liang , Tang Hon-Yin , Ngai Hiu-Lam , Wong Kenix Hok-Ching
Published: March 2021

This study aims to examine the mechanism of how supportive interaction and facilitator input variety in mutual aid groups impact treatment adherence of young people with chronic health conditions, with consideration of time effects, which have been rarely studied in the existing literature. A stratified random sample of 391 individuals aged 12–45 years with chronic health conditions were recruited from mutual aid groups in Hong Kong and completed both the baseline and 12-month follow-up surveys. The results of the structural equation modeling indicated that supportive interaction and facilitator input variety positively predicted treatment adherence in a delayed condition, whereas members’ treatment adherence in the baseline survey had reversed effects on members’ supportive interaction in the follow-up survey. The findings of this study shed light on the dynamic mechanism of the mutual aid groups and provide important implications to promote better rehabilitation outcomes of young people with chronic health conditions.
Effect of COVID-19-Related Home Confinement on Sleep Quality, Screen Time and Physical Activity in Tunisian Boys and Girls: A Survey
Authors: Abid Rihab , Ammar Achraf , Maaloul Rami , Souissi Nizar , Hammouda Omar
Published: March 2021

COVID-19 home confinement has led to a stressful situation for children around the world and affected their lifestyle. The present study aimed to investigate the effect of these restrictions on sleep quality, screen time (ST) and physical activity (PA) in Tunisian children with a special focus on gender differences. An online survey was launched in April 2020. Questions were presented in a differential format, with expected responses related to “before” and “during” confinement. Participants (52 boys and 48 girls, age: 8.66 ± 3.3 years) responded to the Pittsburgh Sleep Quality Index (PSQI), the digital media use, and the Ricci and Gagnon sedentary behavior questionnaires. Findings revealed that COVID19 home confinement had a negative effect on all the considered parameters (p < 0.05). Significant effects of gender were found on sleep disturbances (p = 0.016, np2 = 0.05), subjective sleep quality (p < 0.01, np2 = 0.07), global score of PSQI (p = 0.01, np2 = 0.01) and nocturnal and global screen time (p < 0.001, np2 = 0.09) with poorer sleep and higher screen time in girls compared to boys during home confinement. A significant correlation was shown between Global ST and PSQI score (r = 0.39, p < 0.001). Programs of PA for children and sensitization campaigns against the use of screens have been deemed urgent with special focus oriented to girls.
Surveillance of U.S. Corporate Filings Provides a Proactive Approach to Inform Tobacco Regulatory Research Strategy
Authors: Sarles Samantha Emma , Hensel Edward C. , Robinson Risa J.
Published: March 2021

The popularity of electronic cigarettes in the United States and around the world has led to a startling rise in youth nicotine use. The Juul® e-cigarette was introduced in the U.S. market in 2015 and had captured approximately 13% of the U.S. market by 2017. Unlike many other contemporary electronic cigarette companies, the founders behind the Juul® e-cigarette approached their product launch like a traditional high-tech start-up company, not like a tobacco company. This article presents a case study of Juul’s corporate and product development history in the context of US regulatory actions. The objective of this article is to demonstrate the value of government-curated archives as leading indicators which can (a) provide insight into emergent technologies and (b) inform emergent regulatory science research questions. A variety of sources were used to gather data about the Juul® e-cigarette and the corporations that surround it. Sources included government agencies, published academic literature, non-profit organizations, corporate and retail websites, and the popular press. Data were disambiguated, authenticated, and categorized prior to being placed on a timeline of events. A timeline of four significant milestones, nineteen corporate filings and events, twelve US regulatory actions, sixty-four patent applications, eighty-seven trademark applications, twenty-three design patents and thirty-two utility patents related to Juul Labs and its associates is presented, spanning the years 2004 through 2020. This work demonstrates the probative value of findings from patent, trademark, and SEC filing literature in establishing a premise for emergent regulatory science research questions which may not yet be supported by traditional archival research literature. The methods presented here can be used to identify key aspects of emerging technologies before products actually enter the market; this shifting policy formulation and problem identification from a paradigm of being reactive in favor of becoming proactive. Such a proactive approach may permit anticipatory regulatory science research and ultimately shorten the elapsed time between market technology innovation and regulatory response.
Distance Motor Learning during the COVID-19 Induced Confinement: Video Feedback with a Pedagogical Activity Improves the Snatch Technique in Young Athletes
Authors: Souissi Mohamed Abdelkader , Ammar Achraf , Trabelsi Omar , Glenn Jordan M. , Boukhris Omar , Trabelsi Khaled , Bouaziz Bassem , Zmijewski Piotr , Souissi Hichem , Chikha Anis Ben , Driss Tarak , Chtourou Hamdi , Hoekelmann Anita , Souissi Nizar
Published: March 2021

The purpose of the present study was to investigate which of two strategies, Video Feedback with Pedagogical Activity (VF-PA) or Video Feedback (VF), would be more beneficial for the remote error correction of the snatch weightlifting technique during the confinement period. Thirty-five school aged children with at least three months of weightlifting experience were randomized to one of three training conditions: VF-PA, VF or the Control group (CONT). Subjects underwent test sessions one week before (T0) and one day after (T1) a six-session training period and a retention test session a week later (T2). During each test session, the Kinovea version 0.8.15 software measured the kinematic parameters of the snatch performance. Following distance learning sessions (T1), the VF-PA improved various kinematic parameters (i.e., barbell horizontal displacements, maximum height, looping and symmetry) compared with T0 (p < 0.5; Cohen’s d = 0.58–1.1). Most of these improvements were maintained during the retention test (T2) (p<0.01, Cohen’s d = 1.2–1.3) when compared withT0. However, the VF group improved only twoparameters (i.e., barbell symmetry and horizontal displacement) at T1 (p < 0.05; Cohen’s d = 0.9), which were not maintained at T2. Better horizontal displacement and looping values were registered during the retention test in the VF-PA group compared with theCONT group (p < 0.05, Cohen’s d = 1.49–1.52). The present findings suggest combining video feedback with pedagogical activity during the pandemic induced online coaching or physical education to improve movement learning in school aged children.
Synthesizing Vulnerability, Risk, Resilience, and Sustainability into VRRSability for Improving Geoinformation Decision Support Evaluations
Authors: Nyerges Timothy , Gallo John A. , Prager Steven D. , Reynolds Keith M. , Murphy Philip J. , Li WenWen
Published: March 2021

This paper synthesizes vulnerability, risk, resilience, and sustainability (VRRS) in a way that can be used for decision evaluations about sustainable systems, whether such systems are called coupled natural–human systems, social–ecological systems, coupled human–environment systems, and/or hazards influencing global environmental change, all considered geospatial open systems. Evaluations of V-R-R-S as separate concepts for complex decision problems are important, but more insightful when synthesized for improving integrated decision priorities based on trade-offs of V-R-R-S objectives. A synthesis concept, called VRRSability, provides an overarching perspective that elucidates Tier 2 of a previously developed four-tier framework for organizing measurement-informed ontology and epistemology for sustainability information representation (MOESIR). The new synthesis deepens the MOESIR framework to address VRRSability information representation and clarifies the Tier 2 layer of abstraction. This VRRSability synthesis, composed of 13 components (several with sub-components), offers a controlled vocabulary as the basis of a conceptual framework for organizing workflow assessment and intervention strategies as part of geoinformation decision support software. Researchers, practitioners, and machine learning algorithms can use the vocabulary results for characterizing functional performance relationships between elements of geospatial open systems and the computing technology systems used for evaluating them within a context of complex sustainable systems.
Habitat Connectivity for the Conservation of Small Ungulates in A Human-Dominated Landscape
Authors: Niyogi Rajashekhar , Sarkar Mriganka Shekhar , Hazra Poushali , Rahman Masidur , Banerjee Subham , John Robert
Published: March 2021

Conserving landscape connections among favorable habitats is a widely used strategy to maintain populations in an increasingly fragmented world. A species can then exist as a metapopulation consisting of several subpopulations connected by dispersal. Our study focuses on the importance of human–wildlife coexistence areas in maintaining connectivity among primary habitats of small ungulates within and outside protected areas in a large landscape in central India. We used geospatial information and species presence data to model the suitable habitats, core habitats, and connectivity corridors for four antelope species in an ~89,000 km2 landscape. We found that about 63% of the core habitats, integrated across the four species, lie outside the protected areas. We then measured connectivity in two scenarios: the present setting, and a hypothetical future setting—where habitats outside protected areas are lost. We also modelled the areas with a high risk of human-influenced antelope mortality using eco-geographical variables and wildlife mortality records. Overall, we found that the habitats in multiple-use forests play a central role in maintaining the connectivity network for antelopes. Sizable expanses of privately held farmlands and plantations also contribute to the essential movement corridors. Some perilous patches with greater mortality risk for species require mitigation measures such as underpasses, overpasses, and fences. Greater conservation efforts are needed in the spaces of human–wildlife coexistence to conserve the habitat network of small ungulates.
A Modified Actin (Gly65Val Substitution) Expressed in Cotton Disrupts Polymerization of Actin Filaments Leading to the Phenotype of Ligon Lintless-1 (Li1) Mutant
Authors: Cao Yuefen , Huang Hui , Yu Yanjun , Dai Huaqin , Hao Huanfeng , Zhang Hua , Jiang Yurong , Ding Mingquan , Li Feifei , Tu Lili , Kong Zhaosheng , Rong Junkang
Published: March 2021

Dynamic remodeling of the actin cytoskeleton plays a central role in the elongation of cotton fibers, which are the most important natural fibers in the global textile industry. Here, a high-resolution mapping approach combined with comparative sequencing and a transgenic method revealed that a G65V substitution in the cotton actin Gh_D04G0865 (GhACT17D in the wild-type) is responsible for the Gossypium hirsutum Ligon lintless-1 (Li1) mutant (GhACT17DM). In the mutant GhACT17DM from Li1 plant, Gly65 is substituted with valine on the lip of the nucleotide-binding domain of GhACT17D, which probably affects the polymerization of F-actin. Over-expression of GhACT17DM, but not GhACT17D, driven by either a CaMV35 promoter or a fiber-specific promoter in cotton produced a Li1-like phenotype. Compared with the wild-type control, actin filaments in Li1 fibers showed higher growth and shrinkage rates, decreased filament skewness and parallelness, and increased filament density. Taken together, our results indicate that the incorporation of GhACT17DM during actin polymerization disrupts the establishment and dynamics of the actin cytoskeleton, resulting in defective fiber elongation and the overall dwarf and twisted phenotype of the Li1 mutant.
Comparative Transcriptome and Expression Profiling of Resistant and Susceptible Banana Cultivars during Infection by Fusarium oxysporum
Authors: Kaushal Manoj , Mahuku George , Swennen Rony
Published: March 2021

Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the most destructive diseases of banana. Methods to control the disease are still inadequate. The present investigation targeted expression of defense-related genes in tissue cultured banana plantlets of Fusarium resistant and susceptible cultivars after infection with biological control agents (BCAs) and Fusarium (Foc race 1). In total 3034 differentially expressed genes were identified which annotated to 58 transcriptional families (TF). TF families such as MYB, bHLH and NAC TFs were mostly up-regulated in response to pathogen stress, whereas AP2/EREBP were mostly down-regulated. Most genes were associated with plant–pathogen response, plant hormone signal transduction, starch and sucrose metabolism, cysteine and methionine metabolism, flavonoid biosynthesis, selenocompound metabolism, phenylpropanoid biosynthesis, mRNA surveillance pathway, mannose type O-glycan biosynthesis, amino acid and nucleotide sugar metabolism, cyanoamino acid metabolism, and hormone signal transduction. Our results showed that the defense mechanisms of resistant and susceptible banana cultivars treated with BCAs, were regulated by differentially expressed genes in various categories of defense pathways. Furthermore, the association with different resistant levels might serve as a strong foundation for the control of Fusarium wilt of banana.
Bioengineering Clinically Relevant Cardiomyocytes and Cardiac Tissues from Pluripotent Stem Cells
Authors: James Emma Claire , Tomaskovic-Crook Eva , Crook Jeremy Micah
Published: March 2021

The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.
Applications of Metabolomics in Forensic Toxicology and Forensic Medicine
Authors: Szeremeta Michal , Pietrowska Karolina , Niemcunowicz-Janica Anna , Kretowski Adam , Ciborowski Michal
Published: March 2021

Forensic toxicology and forensic medicine are unique among all other medical fields because of their essential legal impact, especially in civil and criminal cases. New high-throughput technologies, borrowed from chemistry and physics, have proven that metabolomics, the youngest of the “omics sciences”, could be one of the most powerful tools for monitoring changes in forensic disciplines. Metabolomics is a particular method that allows for the measurement of metabolic changes in a multicellular system using two different approaches: targeted and untargeted. Targeted studies are focused on a known number of defined metabolites. Untargeted metabolomics aims to capture all metabolites present in a sample. Different statistical approaches (e.g., uni- or multivariate statistics, machine learning) can be applied to extract useful and important information in both cases. This review aims to describe the role of metabolomics in forensic toxicology and in forensic medicine.
Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence
Authors: Mitchell-White James I. , Stockner Thomas , Holliday Nicholas , Briddon Stephen J. , Kerr Ian D.
Published: March 2021

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.
Calmodulin and Its Binding Proteins in Parkinson’s Disease
Authors: Bohush Anastasiia , Leśniak Wiesława , Weis Serge , Filipek Anna
Published: March 2021

Parkinson’s disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca2+ as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca2+ homeostasis and dysfunction of Ca2+ signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca2+ level. The best known and studied Ca2+ sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca2+ with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD.
In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel
Authors: Casagrande Naike , Borghese Cinzia , Agostini Francesco , Durante Cristina , Mazzucato Mario , Colombatti Alfonso , Aldinucci Donatella
Published: March 2021

A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-β, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.
Selecting Subpopulations of High-Quality Protein Conformers among Conformational Mixtures of Recombinant Bovine MMP-9 Solubilized from Inclusion Bodies
Authors: Carratalá Jose Vicente , Gifre-Renom Laia , Roca-Pinilla Ramon , Villaverde Antonio , Arís Anna , Garcia-Fruitós Elena , Sánchez Julieta María , Ferrer-Miralles Neus
Published: March 2021

A detailed workflow to analyze the physicochemical characteristics of mammalian matrix metalloproteinase (MMP-9) protein species obtained from protein aggregates (inclusion bodies—IBs) was followed. MMP-9 was recombinantly produced in the prokaryotic microbial cell factories Clearcoli (an engineered form of Escherichia coli) and Lactococcus lactis, mainly forming part of IBs and partially recovered under non-denaturing conditions. After the purification by affinity chromatography of solubilized MMP-9, four protein peaks were obtained. However, so far, the different conformational protein species forming part of IBs have not been isolated and characterized. Therefore, with the aim to link the physicochemical characteristics of the isolated peaks with their biological activity, we set up a methodological approach that included dynamic light scattering (DLS), circular dichroism (CD), and spectrofluorometric analysis confirming the separation of subpopulations of conformers with specific characteristics. In protein purification procedures, the detailed analysis of the individual physicochemical properties and the biological activity of protein peaks separated by chromatographic techniques is a reliable source of information to select the best-fitted protein populations.
Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure
Authors: Lee Jeong Yong , Ahn Eun Hee , Park Hyeon Woo , Kim Ji Hyang , Kim Young Ran , Lee Woo Sik , Kim Nam Keun
Published: March 2021

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.
Distinct Expression Patterns of Cxcl12 in Mesenchymal Stem Cell Niches of Intact and Injured Rodent Teeth
Authors: Pagella Pierfrancesco , Nombela-Arrieta César , Mitsiadis Thimios A.
Published: March 2021

Specific stem cell populations within dental mesenchymal tissues guarantee tooth homeostasis and regeneration throughout life. The decision between renewal and differentiation of stem cells is greatly influenced by interactions with stromal cells and extracellular matrix molecules that form the tissue specific stem cell niches. The Cxcl12 chemokine is a general marker of stromal cells and plays fundamental roles in the maintenance, mobilization and migration of stem cells. The aim of this study was to exploit Cxcl12-GFP transgenic mice to study the expression patterns of Cxcl12 in putative dental niches of intact and injured teeth. We showed that endothelial and stromal cells expressed Cxcl12 in the dental pulp tissue of both intact molars and incisors. Isolated non-endothelial Cxcl12+ dental pulp cells cultured in different conditions in vitro exhibited expression of both adipogenic and osteogenic markers, thus suggesting that these cells possess multipotent fates. Taken together, our results show that Cxcl12 is widely expressed in intact and injured teeth and highlight its importance as a key component of the various dental mesenchymal stem cell niches.
If Virchow and Ehrlich Had Dreamt Together: What the Future Holds for KRAS-Mutant Lung Cancer
Authors: Köhler Jens , Jänne Pasi A.
Published: March 2021

Non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma (KRAS) mutations has notoriously challenged oncologists and researchers for three notable reasons: (1) the historical assumption that KRAS is “undruggable”, (2) the disease heterogeneity and (3) the shaping of the tumor microenvironment by KRAS downstream effector functions. Better insights into KRAS structural biochemistry allowed researchers to develop direct KRAS(G12C) inhibitors, which have shown early signs of clinical activity in NSCLC patients and have recently led to an FDA breakthrough designation for AMG-510. Following the approval of immune checkpoint inhibitors for PDL1-positive NSCLC, this could fuel yet another major paradigm shift in the treatment of advanced lung cancer. Here, we review advances in our understanding of the biology of direct KRAS inhibition and project future opportunities and challenges of dual KRAS and immune checkpoint inhibition. This strategy is supported by preclinical models which show that KRAS(G12C) inhibitors can turn some immunologically “cold” tumors into “hot” ones and therefore could benefit patients whose tumors harbor subtype-defining STK11/LKB1 co-mutations. Forty years after the discovery of KRAS as a transforming oncogene, we are on the verge of approval of the first KRAS-targeted drug combinations, thus therapeutically unifying Paul Ehrlich’s century-old “magic bullet” vision with Rudolf Virchow’s cancer inflammation theory.
The MIR-Domain of PbbHLH2 Is Involved in Regulation of the Anthocyanin Biosynthetic Pathway in ”Red Zaosu” (PyrusBretschneideri Rehd.) Pear Fruit
Authors: Li Xieyu , Xiang Fangxin , Han Wei , Qie Bingqing , Zhai Rui , Yang Chengquan , Wang Zhigang , Xu Lingfei
Published: March 2021

The N-terminal of Myc-like basic helix-loop-helix transcription factors (bHLH TFs) contains an interaction domain, namely the MYB-interacting region (MIR), which interacts with the R2R3-MYB proteins to regulate genes involved in the anthocyanin biosynthetic pathway. However, the functions of MIR-domain bHLHs in this pathway are not fully understood. In this study, PbbHLH2 containing the MIR-domain was identified and its function investigated. The overexpression of PbbHLH2 in ”Zaosu” pear peel increased the anthocyanin content and the expression levels of late biosynthetic genes. Bimolecular fluorescence complementation showed that PbbHLH2 interacted with R2R3-MYB TFs PbMYB9, 10, and 10b in onion epidermal cells and confirmed that MIR-domain plays important roles in the interaction between the MIR-domain bHLH and R2R3-MYB TFs. Moreover, PbbHLH2 bound and activated the dihydroflavonol reductase promoter in yeast one-hybrid (Y1H) and dual-luciferase assays. Taken together these results suggested that the MIR domain of PbbHLH2 regulated anthocyanin biosynthesis in pear fruit peel.
Simple Models to Study Spectral Properties of Microbial and Animal Rhodopsins: Evaluation of the Electrostatic Effect of Charged and Polar Residues on the First Absorption Band Maxima
Authors: Shtyrov Andrey A. , Nikolaev Dmitrii M. , Mironov Vladimir N. , Vasin Andrey V. , Panov Maxim S. , Tveryanovich Yuri S. , Ryazantsev Mikhail N.
Published: March 2021

A typical feature of proteins from the rhodopsin family is the sensitivity of their absorption band maximum to protein amino acid composition. For this reason, studies of these proteins often require methodologies that determine spectral shift caused by amino acid substitutions. Generally, quantum mechanics/molecular mechanics models allow for the calculation of a substitution-induced spectral shift with high accuracy, but their application is not always easy and requires special knowledge. In the present study, we propose simple models that allow us to estimate the direct effect of a charged or polar residue substitution without extensive calculations using only rhodopsin three-dimensional structure and plots or tables that are provided in this article. The models are based on absorption maximum values calculated at the SORCI+Q level of theory for cis- and trans-forms of retinal protonated Schiff base in an external electrostatic field of charges and dipoles. Each value corresponds to a certain position of a charged or polar residue relative to the retinal chromophore. The proposed approach was evaluated against an example set consisting of twelve bovine rhodopsin and sodium pumping rhodopsin mutants. The limits of the applicability of the models are also discussed. The results of our study can be useful for the interpretation of experimental data and for the rational design of rhodopsins with required spectral properties.
Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
Authors: Carra Silvia , Gaudenzi Germano , Dicitore Alessandra , Saronni Davide , Cantone Maria Celeste , Plebani Alice , Ghilardi Anna , Borghi Maria Orietta , Hofland Leo J. , Persani Luca , Vitale Giovanni
Published: March 2021

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)y1 transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.
Skin Epidermis and Barrier Function
Authors: Lim Kyung-Min
Published: March 2021

The skin epidermis is the outermost epithelial tissue that protects the body from the external environment [...]
Screening for Gestational Diabetes Mellitus in Early Pregnancy: What Is the Evidence?
Authors: Raets Lore , Beunen Kaat , Benhalima Katrien
Published: March 2021

The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. This has a significant effect on the health of the mother and offspring. There is no doubt that screening for GDM between 24 and 28 weeks is important to reduce the risk of adverse pregnancy outcomes. However, there is no consensus about diagnosis and treatment of GDM in early pregnancy. In this narrative review on the current evidence on screening for GDM in early pregnancy, we included 37 cohort studies and eight randomized controlled trials (RCTs). Observational studies have shown that a high proportion (15–70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. Data from observational studies on the potential benefit of screening and treatment of GDM in early pregnancy show conflicting results. In addition, there is substantial heterogeneity in age and BMI across the different study populations. Smaller RCTs could not show benefit but several large RCTs are ongoing. RCTs are also necessary to determine the appropriate cut-off for HbA1c in pregnancy as there is limited evidence showing that an HbA1c ≥6.5% has a low sensitivity to detect overt diabetes in early pregnancy.
Management Challenges in Chronic Obstructive Pulmonary Disease in the COVID-19 Pandemic: Telehealth and Virtual Reality
Authors: Rutkowski Sebastian
Published: March 2021

For the treatment of chronic obstructive pulmonary disease (COPD), early diagnosis and unconditionally correct management at the initial stage of the disease are very important when the symptoms are not yet too worrying. In this way, the progress of the disease can be slowed down, as can the occurrence of late, life-threatening symptoms. Pulmonary rehabilitation is an essential component of the management of COPD. The selection of appropriate exercises, which are determined during the classification of patients into a suitable improvement program, is of key importance in the process of rehabilitation. The coronavirus disease 2019 (COVID-19) pandemic has resulted in major limitations to public health care. Health systems were largely unprepared for an outbreak of this magnitude. Searching for new, attractive technologies that help patients with chronic diseases seems to be justified. This may be driven by telehealth platforms, likewise with the use of virtual reality (VR). Analysis of the available literature indicates promising effectiveness, high patient acceptance, and high motivations to undertake physical activity with the use of such a solution. Thus, the management of patients with COPD during the COVID-19 pandemic should include options for remote delivery of pulmonary rehabilitation, including home-based, telerehabilitation, and computer-based virtual programs.
Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases
Authors: Magallón María , Pastor Sara , Carrión Ana , Bañuls Lucía , Pellicer Daniel , Castillo Silvia , Bondía Sergio , Navarro-García María , González Cruz , Dasí Francisco
Published: March 2021

Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review.
Does the Construction and Operation of High-Speed Rail Improve Urban Land Use Efficiency? Evidence from China
Authors: Lu Xinhai , Tang Yifeng , Ke Shangan
Published: March 2021

The construction and operation of high-speed rail (HSR) has become an important policy for China to achieve efficiency and fairness and promote high-quality economic growth. HSR promotes the flow of production factors such as labor and capital and affects economic growth, and may further affect urban land use efficiency (ULUE). To explore the impact of HSR on ULUE, this paper uses panel data of 284 cities in China from 2005 to 2018, and constructs Propensity Score Matching-Differences in Differences model to evaluate the effect of HSR on ULUE. The result of entire China demonstrates that the HSR could significantly improves the ULUE. Meanwhile, this paper also considers the heterogeneity of results caused by geographic location, urban levels and scales. It demonstrates that the HSR has a significantly positive effect on ULUE of Eastern, Central China, and large-sized cities. However, in Western China, in medium-sized, and small-sized cities, the impact of HSR on ULUE is not significant. This paper concludes that construction and operation of HSR should be linked to urban development planning and land use planning. Meanwhile, the cities with different geographical locations and scales should take advantage of HSR to improve ULUE and promote urban coordinated development.
Assessment of River-Sea Interaction in the Danube Nearshore Area (Ukraine) by Bioindicators and Statistical Mapping
Authors: Snigirova Anastasiia , Bogatova Yuliya , Barinova Sophia
Published: March 2021

There is a lack of understanding of the main drivers that form the picture of biological communities of transitional waters in deltaic ecosystems under the influence of terrestrial sources. Analysis of hydrochemical parameters in relation to phytoplankton communities in the Ukrainian part of the Danube coastal zone (in August 2018) is the focus of current work. The goal was to identify patterns in the distribution of environmental parameters (salinity and nutrients) in the area of the shipping channel through the Bystry arm, as well as to assess the state of water quality. The ecological bioindicators approach using modern statistical methods, and ecological mapping shows sufficient achievements in interpreting the results. The indicators of salinity (mesohalobes) had better describe the character of the transportation of fresh riverine waters than salinity gradient. The composition of 35 indicator phytoplankton species corresponds to 3 and 4 water quality classes in the coastal zone. High N:P ratios showed an imbalance in the ecosystem as an indicator of production and destruction processes. Statistical maps of the indicator species distribution revealed the river current’s influence on the nearshore water mass. Ecological maps of surface and bottom variables show various environmental impacts resulting from dredging in the shipping channel and excavated soil dumping. Canonical correspondence analysis (CCA) and statistical maps revealed two pools of factors with oppositely directed effects on phytoplankton: salinity, on one hand, and nutrients, on the other. Miozoa and Chlorophyta have an opposite interaction with salinity and oxygen and can be ecosystem change indicators in further analysis
What Drives Landowners to Resist Selling Their Land? Insights from Ethical Capitalism and Landowners’ Perceptions
Authors: Petrescu-Mag Ruxandra Malina , Rastegari Kopaei Hamid , Petrescu Dacinia Crina
Published: March 2021

Foreign land grabbing is acknowledged as a phenomenon that generates disempowerment and dispossession of local farmers, human rights violations. Previous studies have revealed the lack of ethical benchmarks in foreign large-scale land transactions that raise moral concerns. It is evident that when resources are scarce and people depend on them, the balance between values and interests transforms itself into a dilemma. Within this context, the aims of the paper were to bring to the fore critical reflection on a more ethical perspective of large-scale land acquisitions and to extend the scant information on what factors determine landowners not to sell their land to foreigners to limit land grabbing. This context justifies the need for a critical reflection on a more ethical perspective of large-scale land acquisitions. Therefore, two objectives were set. The first one is to document the role of ethics in large-scale land transactions. Based on the land grabbing literature, authors selected a set of eight land grabbing narratives, most often interrelated and overlapping, that pose ethical considerations. The second objective is to reveal how well a set of variables can predict the “Resistance to sell” the land to foreigners even when an attractive price is offered. As ethics is a social construct, the analysis captured the stakeholders’ perspective on land grabbing. Therefore, a questionnaire was applied to a sample of 332 Romanian landowners from twelve randomly selected counties to reveal their perceptions. Partial least squares structural equation modeling (PLS-SEM) was used to observe how well a set of seven variables could predict landowners’ “Resistance to sell” their land to foreign buyers. The use of PLS-SEM was justified by the existence of single items and the need to examine many structural model relations. Results showed that the variables with the strongest contribution to the prediction of the dependent variable are the “Probability to join an association for farmers rights defense”, the “Importance of the land price offered by the potential foreign buyer”, and the “Perceived effect of agricultural land conversion to urban land”. Raising awareness on the importance of buyer attributes, increasing people’s perception of the negative effect of agricultural land conversion to urban land, or strengthening the state’s image as a necessary actor to limit land grabbing will increase landowners’ resistance to sell their land to foreigners. Finally, it can be inferred that, within this frame of discussion, ethics should be valued as a means to create economically viable and morally justifiable solutions for foreign large-scale land transactions.
Self-Reported Real-World Safety and Reactogenicity of COVID-19 Vaccines: A Vaccine Recipient Survey
Authors: Mathioudakis Alexander G. , Ghrew Murad , Ustianowski Andrew , Ahmad Shazaad , Borrow Ray , Papavasileiou Lida Pieretta , Petrakis Dimitrios , Bakerly Nawar Diar
Published: March 2021

An online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups. This survey was launched in February 2021 and ran for 11 days. Recipients of a first COVID-19 vaccine dose ≥7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed. The survey was completed by 2002 respondents of whom 26.6% had a prior COVID-19 infection. A prior COVID-19 infection was associated with an increased risk of any side effect (risk ratio 1.08, 95% confidence intervals (1.05–1.11)), fever (2.24 (1.86–2.70)), breathlessness (2.05 (1.28–3.29)), flu-like illness (1.78 (1.51–2.10)), fatigue (1.34 (1.20–1.49)) and local reactions (1.10 (1.06–1.15)). It was also associated with an increased risk of severe side effects leading to hospital care (1.56 (1.14–2.12)). While mRNA vaccines were associated with a higher incidence of any side effect (1.06 (1.01–1.11)) compared with viral vector-based vaccines, these were generally milder (p < 0.001), mostly local reactions. Importantly, mRNA vaccine recipients reported a considerably lower incidence of systemic reactions (RR < 0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue and of side effects requiring hospital care (0.42 (0.31–0.58)). Our study confirms the findings of recent randomised controlled trials (RCTs) demonstrating that COVID-19 vaccines are generally safe with limited severe side effects. For the first time, our study links prior COVID-19 illness with an increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects but more local reactions.
Emerging Treatment Options for Sarcopenia in Chronic Liver Disease
Authors: Kim Yun
Published: March 2021

Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.
Impact of E-Procurement Adoption on Company Performance: Evidence from Indonesian Manufacturing Industry
Authors: Masudin Ilyas , Aprilia Ganis Dwi , Nugraha Adhi , Restuputri Dian Palupi
Published: March 2021

This study was conducted to determine the performance impact of e-procurement adoption in Indonesian manufacturing companies. This study consists of four variables: top management support, information quality, implementation of e-procurement, and company performance. Pilot testing questionnaires were used to test whether the respondents understood the questions given by the researcher. After conducting the pilot test, the final questionnaire was distributed to respondents. The pilot test results and the final questionnaire were analyzed using Statistical Package for Social Science (SPSS) version 21 and SmartPLS v3.0 software to determine the relationship between variables. The results of this study support the acceptance of three hypotheses. The results indicate that top management support has a significant effect on e-procurement implementation. Other results show that information quality has a significant effect on e-procurement implementation, while e-procurement implementation has a significant effect on company performance. From the findings of this article, recommendations from a management perspective are discussed to increase management awareness in adopting electronic procurement.