bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Ethnicity and Genetic Ancestry on Disease Prevalence and Risk in Colombia
Authors: Chande Aroon T. , Nagar Shashwat Deepali , Rishishwar Lavanya , Mariño-Ramírez Leonardo , Medina-Rivas Miguel A. , Valderrama-Aguirre Augusto E. , Jordan I. King , Gallo Juan Esteban
Published: September 2021

Currently, the vast majority of genomic research cohorts are made up of participants with European ancestry. Genomic medicine will only reach its full potential when genomic studies become more broadly representative of global populations. We are working to support the establishment of genomic medicine in developing countries in Latin America via studies of ethnically and ancestrally diverse Colombian populations. The goal of this study was to analyze the effect of ethnicity and genetic ancestry on observed disease prevalence and predicted disease risk in Colombia. Population distributions of Colombia’s three major ethnic groups – Mestizo, Afro-Colombian, and Indigenous – were compared to disease prevalence and socioeconomic indicators. Indigenous and Mestizo ethnicity show the highest correlations with disease prevalence, whereas the effect of Afro-Colombian ethnicity is substantially lower. Mestizo ethnicity is mostly negatively correlated with six high-impact health conditions and positively correlated with seven of eight common cancers; Indigenous ethnicity shows the opposite effect. Malaria prevalence in particular is strongly correlated with ethnicity. Disease prevalence co-varies across geographic regions, consistent with the regional distribution of ethnic groups. Ethnicity is also correlated with regional variation in human development, partially explaining the observed differences in disease prevalence. Patterns of genetic ancestry and admixture for a cohort of 624 individuals from Medellín were compared to disease risk inferred via polygenic risk scores (PRS). African genetic ancestry is most strongly correlated with predicted disease risk, whereas European and Native American ancestry show weaker effects. African ancestry is mostly positively correlated with disease risk, and European ancestry is mostly negatively correlated. The relationships between ethnicity and disease prevalence do not show an overall correspondence with the relationships between ancestry and disease risk. We discuss possible reasons for the divergent health effects of ethnicity and ancestry as well as the implication of our results for the development of precision medicine in Colombia.
Integrative Analyses of Genes Associated With Right Ventricular Cardiomyopathy Induced by Tricuspid Regurgitation
Authors: Tian Chengnan , Yang Yanchen , Ke Yingjie , Yang Liang , Zhong Lishan , Wang Zhenzhong , Huang Huanlei
Published: September 2021

Tricuspid regurgitation (TR) induces right ventricular cardiomyopathy, a common heart disease, and eventually leads to severe heart failure and serious clinical complications. Accumulating evidence shows that long non-coding RNAs (lncRNAs) are involved in the pathological process of a variety of cardiovascular diseases. However, the regulatory mechanisms and functional roles of RNA interactions in TR-induced right ventricular cardiomyopathy are still unclear. Accordingly, we performed integrative analyses of genes associated with right ventricular cardiomyopathy induced by TR to study the roles of lncRNAs in the pathogenesis of this disease. In this study, we used high-throughput sequencing data of tissue samples from nine clinical cases of right ventricular myocardial cardiomyopathy induced by TR and nine controls with normal right ventricular myocardium from the Genotype-Tissue Expression database. We identified differentially expressed lncRNAs and constructed a protein-protein interaction and lncRNA-messenger RNA (mRNA) co-expression network. Furthermore, we determined hub lncRNA-mRNA modules related to right ventricular myocardial disease induced by TR and constructed a competitive endogenous RNA network for TR-induced right ventricular myocardial disease by integrating the interaction of lncRNA-miRNA-mRNA. In addition, we analyzed the immune infiltration using integrated data and the correlation of each immune-related gene with key genes of the integrated expression matrix. The present study identified 648 differentially expressed mRNAs, 201 differentially expressed miRNAs, and 163 differentially expressed lncRNAs. Protein-protein interaction network analysis confirmed that ADRA1A, AVPR1B, OPN4, IL-1B, IL-1A, CXCL4, ADCY2, CXCL12, GNB4, CCL20, CXCL8, and CXCL1 were hub genes. CTD-2314B22.3, hsa-miR-653-5p, and KIF17ceRNA; SRGAP3-AS2, hsa-miR-539-5p, and SHANK1; CERS6-AS1, hsa-miR-497-5p, and OPN4; INTS6-AS1, hsa-miR-4262, and NEURL1B; TTN-AS1, hsa-miR-376b-3p, and TRPM5; and DLX6-AS1, hsa-miR-346, and BIRC7 axes were obtained by constructing the ceRNA networks. Through the immune infiltration analysis, we found that the proportion of CD4 and CD8 T cells was about 20%, and the proportion of fibroblasts and endothelial cells was high. Our findings provide some insights into the mechanisms of RNA interaction in TR-induced right ventricular cardiomyopathy and suggest that lncRNAs are a potential therapeutic target for treating right ventricular myocardial disease induced by TR.
Development and Initial Characterization of Cellular Models for COG Complex-Related CDG-II Diseases
Authors: Sumya Farhana Taher , Pokrovskaya Irina D. , Lupashin Vladimir
Published: September 2021

Conserved Oligomeric Golgi (COG) is an octameric protein complex that orchestrates intra-Golgi trafficking of glycosylation enzymes. Over a hundred individuals with 31 different COG mutations have been identified until now. The cellular phenotypes and clinical presentations of COG-CDGs are heterogeneous, and patients primarily represent neurological, skeletal, and hepatic abnormalities. The establishment of a cellular COG disease model will benefit the molecular study of the disease, explaining the detailed sequence of the interplay between the COG complex and the trafficking machinery. Moreover, patient fibroblasts are not a good representative of all the organ systems and cell types that are affected by COG mutations. We developed and characterized cellular models for human COG4 mutations, specifically in RPE1 and HEK293T cell lines. Using a combination of CRISPR/Cas9 and lentiviral transduction technologies, both myc-tagged wild-type and mutant (G516R and R729W) COG4 proteins were expressed under the endogenous COG4 promoter. Constructed isogenic cell lines were comprehensively characterized using biochemical, microscopy (superresolution and electron), and proteomics approaches. The analysis revealed similar stability and localization of COG complex subunits, wild-type cell growth, and normal Golgi morphology in all three cell lines. Importantly, COG4-G516R cells demonstrated increased HPA-647 binding to the plasma membrane glycoconjugates, while COG4-R729W cells revealed high GNL-647 binding, indicating specific defects in O- and N-glycosylation. Both mutant cell lines express an elevated level of heparin sulfate proteoglycans. Moreover, a quantitative mass-spectrometry analysis of proteins secreted by COG-deficient cell lines revealed abnormal secretion of SIL1 and ERGIC-53 proteins by COG4-G516R cells. Interestingly, the clinical phenotype of patients with congenital mutations in the SIL1 gene (Marinesco-Sjogren syndrome) overlaps with the phenotype of COG4-G516R patients (Saul-Wilson syndrome). Our work is the first compressive study involving the creation of different COG mutations in different cell lines other than the patient’s fibroblast. It may help to address the underlying cause of the phenotypic defects leading to the discovery of a proper treatment guideline for COG-CDGs.
Quantitative Analyses Reveal How Hypoxia Reconfigures the Proteome of Primary Cytotoxic T Lymphocytes
Authors: Ross Sarah H. , Rollings Christina M. , Cantrell Doreen A.
Published: September 2021

Metabolic and nutrient-sensing pathways play an important role in controlling the efficacy of effector T cells. Oxygen is a critical regulator of cellular metabolism. However, during immune responses T cells must function in oxygen-deficient, or hypoxic, environments. Here, we used high resolution mass spectrometry to investigate how the proteome of primary murine CD8+ cytotoxic T lymphocytes (CTLs) is reconfigured in response to hypoxia in vitro. We identified and quantified over 7,600 proteins and discovered that hypoxia increased the abundance of a selected number of proteins in CTLs. This included glucose transporters, metabolic enzymes, transcription factors, cytolytic effector molecules, checkpoint receptors and adhesion molecules. While some of these proteins may augment the effector functions of CTLs, others may limit their cytotoxicity. Moreover, we determined that hypoxia could inhibit IL-2-induced proliferation cues and antigen-induced pro-inflammatory cytokine production in CTLs. These data provide a comprehensive resource for understanding the magnitude of the CTL response to hypoxia and emphasise the importance of oxygen-sensing pathways for controlling CD8+ T cells. Additionally, this study provides new understanding about how hypoxia may promote the effector function of CTLs, while contributing to their dysfunction in some contexts.
Pulmonary-Resident Memory Lymphocytes: Pivotal Orchestrators of Local Immunity Against Respiratory Infections
Authors: Humphries Duncan C. , O’Connor Richard A. , Larocque Daniel , Chabaud-Riou Martine , Dhaliwal Kevin , Pavot Vincent
Published: September 2021

There is increasing evidence that lung-resident memory T and B cells play a critical role in protecting against respiratory reinfection. With a unique transcriptional and phenotypic profile, resident memory lymphocytes are maintained in a quiescent state, constantly surveying the lung for microbial intruders. Upon reactivation with cognate antigen, these cells provide rapid effector function to enhance immunity and prevent infection. Immunization strategies designed to induce their formation, alongside novel techniques enabling their detection, have the potential to accelerate and transform vaccine development. Despite most data originating from murine studies, this review will discuss recent insights into the generation, maintenance and characterisation of pulmonary resident memory lymphocytes in the context of respiratory infection and vaccination using recent findings from human and non-human primate studies.
Novel Roles of the Tim Family in Immune Regulation and Autoimmune Diseases
Authors: Liu Yikai , Chen Hongzhi , Chen Zhiying , Qiu Junlin , Pang Haipeng , Zhou Zhiguang
Published: September 2021

T cell Ig and mucin domain (Tim) protein family members were identified to be important regulators of the immune response. As their name indicates, Tim proteins were originally considered a T cell-specific markers, and they mainly regulate the responses of T helper cells. However, accumulating evidence indicates that Tims are also expressed on antigen-presenting cells (APCs), such as monocytes, macrophages, dendritic cells (DCs) and B cells, and even plays various roles in natural killer cells (NKs) and mast cells. In recent years, the expression and function of Tims on different cells and the identification of new ligands for the Tim family have suggested that the Tim family plays a crucial role in immune regulation. In addition, the relationship between Tim family gene polymorphisms and susceptibility to several autoimmune diseases has expanded our knowledge of the role of Tim proteins in immune regulation. In this review, we discuss how the Tim family affects immunomodulatory function and the potential role of the Tim family in typical autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). A deeper understanding of the immunoregulatory mechanism of the Tim family might provide new insights into the clinical diagnosis and treatment of autoimmune diseases.
Case Report: Efficiency of Embolization Microcoils for the Repair of Brachiocephalic Vein Perforation During Hemodialysis Catheter Placement
Authors: Hu Ying , Gu Fujia , Yuan Ping , Shi Min , Ma Liang , Zha Yan , Fu Ping
Published: September 2021

Background: The cuff catheter is one of the most common routes of vascular access in hemodialysis patients, while severe complications can occur during cuff catheter placement, such as bleeding, hematoma, and artery or vein damage. During catheterization, brachiocephalic vein perforation associated with a mediastinal lesion is rare. Open chest repair is effective for brachiocephalic vein perforation during catheter placement, but it entails a risk of potentially lethal trauma. Interventional treatment can be considered to reduce injury in this context, but relevant reports are limited.

Case report: Herein, we describe our experience with a 68-year-old male hemodialyzed patient in whom cuff catheter vascular access was required for regular hemodialysis. He complained of mild pain in the left side of his chest during cuff catheter placement. The surgeon immediately checked the location of the catheter. Digital subtraction angiography revealed that the hemodialysis cuff catheter had punctured the mediastinal area from the left brachiocephalic vein. The patient was diagnosed with left brachiocephalic vein perforation (d ≈ 5 mm). Fortunately, the brachiocephalic vein perforation was successfully repaired with two embolization microcoils after comprehensive assessment and multidisciplinary consultation.

Conclusion: Brachiocephalic vein perforation can be repaired with embolization microcoils during hemodialysis catheter placement, and this method of interventional treatment is safe and effective.
Targeted Screening of Lactic Acid Bacteria With Antibacterial Activity Toward Staphylococcus aureus Clonal Complex Type 1 Associated With Atopic Dermatitis
Authors: Christensen Ida B. , Vedel Charlotte , Clausen Maja-Lisa , Kjærulff Søren , Agner Tove , Nielsen Dennis S.
Published: September 2021

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by an epidermal barrier impairment, as well as a Th2/Th22-skewed immune response, both favoring skin colonization with Staphylococcus aureus. Colonization is strongly related to severity of the disease, and a reduction of S. aureus has been found to alleviate symptoms. Lactic acid bacteria (LAB) produce antimicrobial compounds such as organic acids and bacteriocins and are widely used as probiotics. The aim of this study was to isolate LAB and screen for antibacterial effect specifically toward S. aureus clonal complex type 1. A total of 680 LAB were isolated from fermented vegetables and swab samples from healthy volunteers (vaginal, stool and skin). Screening for antibacterial activity toward S. aureus, narrowed the field of isolates down to four LAB strains with high antibacterial activity. The activity varied according to the specific LAB strain and the origin of the strain. The results suggested different modes of action, including co-aggregation, expression of bacteriocins and production of specific organic acids. However, the ability to acidify the surroundings appeared as the main effect behind inhibition of S. aureus. Broth microdilution assays showed a significant reduction of S. aureus growth when using down to 10% cell free supernatant (CFS). Our results underline the use of specific living LAB or their CFS as potential future treatment strategies to reduce S. aureus colonization of AD skin.
Taxonomic Compositions and Co-occurrence Relationships of Protists in Bulk Soil and Rhizosphere of Soybean Fields in Different Regions of China
Authors: Zhang Jun , Xing Pengcheng , Niu Mengyu , Wei Gehong , Shi Peng
Published: September 2021

As the main consumers of bacteria and fungi in farmed soils, protists remain poorly understood. The aim of this study was to explore protist community assembly and ecological roles in soybean fields. Here, we investigated differences in protist communities using high-throughput sequencing and their inferred potential interactions with bacteria and fungi between the bulk soil and rhizosphere compartments of three soybean cultivars collected from six ecological regions in China. Distinct protist community structures characterized the bulk soil and rhizosphere of soybean plants. A significantly higher relative abundance of phagotrophs was observed in the rhizosphere (25.1%) than in the bulk soil (11.3%). Spatial location (R2 = 0.37–0.51) explained more of the variation in protist community structures of soybean fields than either the compartment (R2 = 0.08–0.09) or cultivar type (R2 = 0.02–0.03). The rhizosphere protist network (76 nodes and 414 edges) was smaller and less complex than the bulk soil network (147 nodes and 880 edges), indicating a smaller potential of niche overlap and interactions in the rhizosphere due to the increased resources in the rhizosphere. Furthermore, more inferred potential predator-prey interactions occur in the rhizosphere. We conclude that protists have a crucial ecological role to play as an integral part of microbial co-occurrence networks in soybean fields.
SeamDock: An Interactive and Collaborative Online Docking Resource to Assist Small Compound Molecular Docking
Authors: Murail Samuel , de Vries Sjoerd J. , Rey Julien , Moroy Gautier , Tufféry Pierre
Published: September 2021

In silico assessment of protein receptor interactions with small ligands is now part of the standard pipeline for drug discovery, and numerous tools and protocols have been developed for this purpose. With the SeamDock web server, we propose a new approach to facilitate access to small molecule docking for nonspecialists, including students. The SeamDock online service integrates different docking tools in a common framework that allows ligand global and/or local docking and a hierarchical approach combining the two for easy interaction site identification. This service does not require advanced computer knowledge, and it works without the installation of any programs with the exception of a common web browser. The use of the Seamless framework linking the RPBS calculation server to the user’s browser allows the user to navigate smoothly and interactively on the SeamDock web page. A major effort has been put into the 3D visualization of ligand, receptor, and docking poses and their interactions with the receptor. The advanced visualization features combined with the seamless library allow a user to share with an unlimited number of collaborators, a docking session, and its full visualization states. As a result, SeamDock can be seen as a free, simple, didactic, evolving online docking resource best suited for education and training.
Motor Neuron Diseases and Neuroprotective Peptides: A Closer Look to Neurons
Authors: Zuccaro Emanuela , Piol Diana , Basso Manuela , Pennuto Maria
Published: September 2021

Motor neurons (MNs) are specialized neurons responsible for muscle contraction that specifically degenerate in motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), spinal and bulbar muscular atrophy (SBMA), and spinal muscular atrophy (SMA). Distinct classes of MNs degenerate at different rates in disease, with a particular class named fast-fatigable MNs (FF-MNs) degenerating first. The etiology behind the selective vulnerability of FF-MNs is still largely under investigation. Among the different strategies to target MNs, the administration of protective neuropeptides is one of the potential therapeutic interventions. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with beneficial effects in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and more recently SBMA. Another neuropeptide that has a neurotrophic effect on MNs is insulin-like growth factor 1 (IGF-1), also known as somatomedin C. These two peptides are implicated in the activation of neuroprotective pathways exploitable in the amelioration of pathological outcomes related to MNDs.
Characterization of Age-Related Differences in the Human Choroid Plexus Volume, Microstructural Integrity, and Blood Perfusion Using Multiparameter Magnetic Resonance Imaging
Authors: Alisch Joseph S. R. , Kiely Matthew , Triebswetter Curtis , Alsameen Maryam H. , Gong Zhaoyuan , Khattar Nikkita , Egan Josephine M. , Bouhrara Mustapha
Published: September 2021

The choroid plexus (CP) is an important cerebral structure involved in cerebrospinal fluid production and transport of solutes into the brain. Recent studies have uncovered the involvement of the CP in neurological disorders such as Alzheimer’s disease and multiple sclerosis. However, our understanding of human age-related microstructural and functional changes in the CP with aging and neuropathology is limited. In this cross-sectional study, we investigated age and sex differences in the CP structure and function using advanced quantitative magnetic resonance imaging methodology in a large cohort (n= 155) of cognitively unimpaired individuals over a wide age range between 21 and 94 years. Our analysis included volumetric measurements, relaxometry measures (T1andT2), diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) and mean diffusivity (MD), as well as measures of cerebral blood flow (CBF). Our results revealed that CP volume was increasing with advancing age. We conjecture that this novel observation is likely attributed to alterations in the CP microstructure or function as well as to ventriculomegaly. Indeed, we also found that CBF was lower with advanced age, while, consistent with previous studies,T1,T2and MD were higher, and FA was lower with advanced age. We attribute these functional and microstructural differences to a deteriorated CP structural integrity with aging. Furthermore, our relaxometry and DTI measures were found to be associated with differences in blood perfusion revealing lower microstructural integrity with lower CBF. Finally, in agreement with literature, sex-related differences in MD and CBF were statistically significant. This work lays the foundation for ongoing investigation of the involvement of CP in neurodegeneration.
Fingolimod and Diabetic Retinopathy: A Drug Repurposing Study
Authors: Gesualdo Carlo , Balta Cornel , Platania Chiara Bianca Maria , Trotta Maria Consiglia , Herman Hildegard , Gharbia Sami , Rosu Marcel , Petrillo Francesco , Giunta Salvatore , Della Corte Alberto , Grieco Paolo , Bellavita Rosa , Simonelli Francesca , D’Amico Michele , Hermenean Anca , Rossi Settimio , Bucolo Claudio
Published: September 2021

This study aimed to investigate the interactions between fingolimod, a sphingosine 1-phosphate receptor (S1PR) agonist, and melanocortin receptors 1 and 5 (MCR1, MCR5). In particular, we investigated the effects of fingolimod, a drug approved to treat relapsing-remitting multiple sclerosis, on retinal angiogenesis in a mouse model of diabetic retinopathy (DR). We showed, by a molecular modeling approach, that fingolimod can bind with good-predicted affinity to MC1R and MC5R. Thereafter, we investigated the fingolimod actions on retinal MC1Rs/MC5Rs in C57BL/6J mice. Diabetes was induced in C57BL/6J mice through streptozotocin injection. Diabetic and control C57BL/6J mice received fingolimod, by oral route, for 12 weeks and a monthly intravitreally injection of MC1R antagonist (AGRP), MC5R antagonist (PG20N), and the selective S1PR1 antagonist (Ex 26). Diabetic animals treated with fingolimod showed a decrease of retinal vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2), compared to diabetic control group. Fingolimod co-treatment with MC1R and MC5R selective antagonists significantly (p < 0.05) increased retinal VEGFR1, VEGFR2, and VEGFA levels compared to mice treated with fingolimod alone. Diabetic animals treated with fingolimod plus Ex 26 (S1PR1 selective blocker) had VEGFR1, VEGFR2, and VEGFA levels between diabetic mice group and the group of diabetic mice treated with fingolimod alone. This vascular protective effect of fingolimod, through activation of MC1R and MC5R, was evidenced also by fluorescein angiography in mice. Finally, molecular dynamic simulations showed a strong similarity between fingolimod and the MC1R agonist BMS-470539. In conclusion, the anti-angiogenic activity exerted by fingolimod in DR seems to be mediated not only through S1P1R, but also by melanocortin receptors.
Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach
Authors: Rattanacheeworn Punyabhorn , Kerr Stephen J , Kittanamongkolchai Wonngarm , Townamchai Natavudh , Udomkarnjananun Suwasin , Praditpornsilpa Kearkiat , Thanusuwannasak Thanundorn , Udomnilobol Udomsak , Jianmongkol Suree , Ongpipattanakul Boonsri , Prueksaritanont Thomayant , Avihingsanon Yingyos , Chariyavilaskul Pajaree
Published: September 2021

Background: Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail.

Methods: Healthy young participants (n = 20), healthy elderly participants (n = 16) and elderly patients with CKD (n = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin. After a 14-day wash-out period, healthy young participants continued to study period 2 with the microdose cocktail plus rifampicin. PK parameters including area under the plasma concentration-time curve (AUC), maximum plasma drug concentration (Cmax), and half-life were estimated before making pairwise comparisons of geometric mean ratios (GMR) between groups.

Results: AUC and Cmax GMR (95% confidence interval; CI) of midazolam, a CYP3A probe substrate, were increased 2.30 (1.70–3.09) and 2.90 (2.16–3.88) fold in healthy elderly and elderly patients with CKD, respectively, together with a prolonged half-life. AUC and Cmax GMR (95%CI) of atorvastatin, another CYP3A substrate, was increased 2.14 (1.52–3.02) fold in healthy elderly and 4.15 (2.98–5.79) fold in elderly patients with CKD, indicating decreased CYP3A activity related to ageing. Associated AUC changes in the probe drug whose activity could be modified by intestinal P-glycoprotein (P-gp) activity, dabigatran etexilate, were observed in patients with CKD. However, whether the activity of pitavastatin and rosuvastatin is modified by organic anion transporting polypeptide 1B (OATP1B) and of breast cancer resistance protein (BCRP), respectively, in elderly participants with or without CKD was inconclusive.

Conclusions: CYP3A activity is reduced in ageing. Intestinal P-gp function might be affected by CKD, but further confirmation appears warranted.

Clinical Trial Registration:http://www.thaiclinicaltrials.org/ (TCTR 20180312002 registered on March 07, 2018)
Berberine Alleviates Non-alcoholic Steatohepatitis Through Modulating Gut Microbiota Mediated Intestinal FXR Activation
Authors: Shu Xiangbing , Li Meng , Cao Ying , Li Chunlin , Zhou Wenjun , Ji Guang , Zhang Li
Published: September 2021

Berberine is a natural plant alkaloid isolated from a diverse range of genera, it obtains anti-inflammatory, anti-obesity, and hepatoprotective properties, and is a promising agent for non-alcoholic steatohepatitis (NASH). Farnesoid X receptor (FXR) is a bile acid receptor and a drug target for NASH, however, the underlying mechanisms of berberine on regulating FXR are still unknown. In the present study, we feed mice with a 12-week high-fat diet with interval dextran sulfate sodium (0.5% in drinking water) diet to induce NASH, and treat the mice with berberine (100 mg/kg per day) via oral gavage for additional 4 weeks. We demonstrate that administration of berberine alleviates steatosis and infiltration of inflammatory cells in the liver of NASH mice. We apply 16S ribosomal DNA sequencing to screen the structure of gut microbiota, and ultra-performance liquid chromatography-tandem mass spectrometry analysis to determine the bile acid profiles. The results show that berberine modulates gut dysbiosis, and specifically increases the relative abundance of Clostridiales, Lactobacillaceae, and Bacteroidale. Berberine modulated microbiomes are associated with bile acid de-conjugation and transformation, which are consistent with the altered bile acid species (e.g., deoxycholic acid, ursodeoxycholic acid) upon berberine treatment. BA species that respond to berberine treatment are known FXR agonists, thus we performed quantitative Real Time-PCR and western blot to examine the FXR pathway, and find that berberine up-regulates intestinal FXR and fibroblast growth factor 15 (FGF15) expression, and the secretion of FGF15 further inhibits lipogenesis and nuclear factor-κB activation in the liver. Whereas the beneficial effects of berberine are blunted in FXR knockout mice. Our results reveal that berberine alleviates NASH by modulating the interplay of gut microbiota and bile acid metabolism, as well as the subsequent intestinal FXR activation.
Differentiating Interpreting Types: Connecting Complex Networks to Cognitive Complexity
Authors: Lin Yumeng , Xu Duo , Liang Junying
Published: September 2021

Prominent interpreting models have illustrated different processing mechanisms of simultaneous interpreting and consecutive interpreting. Although great efforts have been made, a macroscopic examination into interpreting outputs is sparse. Since complex network is a powerful and feasible tool to capture the holistic features of language, the present study adopts this novel approach to investigate different properties of syntactic dependency networks based on simultaneous interpreting and consecutive interpreting outputs. Our results show that consecutive interpreting networks demonstrate higher degrees, higher clustering coefficients, and a more important role of function words among the central vertices than simultaneous interpreting networks. These findings suggest a better connectivity, better transitivity, and a lower degree of vocabulary richness in consecutive interpreting outputs. Our research provides an integrative framework for the understanding of underlying mechanisms in diverse interpreting types.
Towards Better Understanding of the Harmful Impact of Hindrance and Challenge Stressors on Job Burnout of Nurses. A One-Year Cross-Lagged Study on Mediation Role of Work-Family Conflict
Authors: Baka Łukasz , Prusik Monika
Published: September 2021

The mediation role of work–family conflict (WFC) in job demands – job burnout link is well documented, also in group of nurses. It is still unclear, however, which job demands are particularly conducive to WFC and job burnout. Moreover the mediational effect of WFC was tested mainly in cross-sectional studies that were conducted in countries of North America and Western Europe. Drawing on the Job Demands-Resources and the Effort-Recovery models, this one-year cross-lagged study investigates the effects of five types of job demands related to challenge and hindrance stressors on job burnout (measured with exhaustion and disengagement from work) as well as the mediational role of WFC in Polish nurses. Job demands included emotional, cognitive demands, and demands for hiding emotions (as challenge stressors) as well as quantitative demands and work pace (as hindrance stressors). Data were collected among 516 nurses. Structural equation modelling (SEM) showed that hindrance stressors (T1) are predictor of higher job burnout (T2). The positive role of challenge stressors (T1) were not supported. Only emotional demands were associated with exhaustion but the direction of the relation was opposite than expected. WFC (T1) mediated the harmful effect of the two hindrance stressors and emotional demands on disengagement from work (but not on exhaustion). Cognitive demands and demands for hiding emotions were not related to negative outcomes. The obtained results shed light on the role of the challenge-hindrance stressors and WFI in development of job burnout. The implications for theory and research on the mental health of nurses are discussed.
Age Differences in Leadership Positions Across Cultures
Authors: Vaughan-Johnston Thomas , Imtiaz Faizan , Lee Albert , Ji Li-Jun
Published: September 2021

In most countries around the world, the population is rapidly aging. A by-product of these demographic shifts is that older adults will likely occupy more positions of power and influence in our societies than ever before. Further, cultural differences might shape how these transitions unfold around the globe. Across two studies, we investigated whether business and political leaders differed in age across various cultures. Study 1 (N = 1,034) showed that business leaders were significantly older in Eastern (e.g., China, India, and Japan) cultures than Western (e.g., United States, Sweden, and United Kingdom) cultures, even while controlling for population structure (e.g., percentage of elderly in the society), gross domestic product (GDP), and wealth distribution across the population (GINI). Study 2 (N = 1,268) conceptually replicated these findings by showing that political leaders were once again older in Eastern vs. Western cultures. Furthermore, cultural tightness mediated the relationship between culture and older leadership. These findings highlight how cultural differences impact not only our preferences, but also important outcomes in consequential domains such as business and politics. Potential explanations for why cultural tightness may be related to differences in leader age across cultures are discussed. To build on these findings, future research should assess the potential causal mechanisms underlying the cultural effect on leader age, and explore the various practical implications of this effect.
Fogging With Peracetic Acid in Schools and Kindergartens
Authors: Kruszewska Ewelina , Grześ Henryk , Czupryna Piotr , Pancewicz Sławomir , Groth Monika , Wondim Mulugeta , Moniuszko-Malinowska Anna
Published: September 2021

Disinfection is a key element in controlling infections. Fogging, also known as fumigation, is one of the most effective chemical disinfection methods. Peracetic acid (PAA) is a powerful oxidant with bactericidal and fungicidal properties. The aim of this study is to determine the type of bacteria and fungi present in educational institutions and whether disinfection by PAA fumigation in these institutions is also effective and useful, as demonstrated previously in healthcare centers. This study was carried out in five kindergartens and five primary schools in Bialystok, Poland. Three rooms have been selected in each of these educational institutions, and the disinfection was carried out in 30 rooms in total. Fogging with PAA was performed in selected rooms. Before and after disinfection, samples were collected from four surfaces: walls, tables, doors, and chair backs. Most frequently detected microorganisms in schools and kindergartens were Micrococcus luteus (M. luteus), Staphylococcus warneri (S. warneri), Paracoccus yeei (P. yeei), Staphylococcus hominis ssp. hominis (S. hominis), Kocuria rhizophila (K. rhizophila), Kocuria rosea (K. rosea). In addition, Staphylococcus haemolyticus (S. haemolyticus), Acinetobacter lwoffii (A. lwoffii), Kocuria kristinae (K. kristinae), Lactococcus lactis ssp. lactis (L. lactis) were the most prevalent in kindergartens, whereas Kytococcus sedentarius (K. sedentarius) was the most prevalent in schools. Comparison of the bacterial flora of schools and kindergartens showed statistically significant differences in the prevalence of bacteria on different surfaces. A significant decrease in the number of colonies after disinfection was observed on all surfaces (p < 0.05). In addition, the calculated effectiveness of disinfection was 99.7% in kindergartens and 99.3% in schools. The results indicate that fogging of PAA is a highly effective method of surface disinfection in kindergartens and schools.
COVID-19 Outbreak and Financial Performance of Chinese Listed Firms: Evidence From Corporate Culture and Corporate Social Responsibility
Authors: Sun Yunpeng , Li Ying
Published: September 2021

This research described Chinese listed firms' COVID-19 Outbreak and financial performance using corporate culture (CC) and corporate social responsibility (CSR) evidence. The epidemic's impact on Chinese companies' profits was much less than the impact on their sales growth rates. Although the COVID-19 has had a more significant negative impact on the financial performance of Chinese listed companies in sectors that are more severely impacted, such as travel and entertainment, we believe that the financial performance of the medical industry has improved as a result of the outbreak. Meanwhile, Chinese listed companies in high-risk areas experience more significant financial losses during the epidemic, and the Hubei impact is hefty weight. Corporate social responsibility moderated the inverse relationship between this epidemic and Chinese firms' economic success. This research enhances the current literature on the effects of the COVID-19 on financial success and practical, realistic, and theoretical consequences in companies worldwide.
Patterns of Exposure and Infection with Microparasites in Iberian Wild Carnivores: A Review and Meta-Analysis
Authors: Millán Javier , Becker Daniel J.
Published: September 2021

We use a suite of meta-analytic and comparative methods to derive fundamental insights into how sampling effort, pathogen richness, infection prevalence, and seroprevalence vary across Carnivora taxa and Iberian geography. The red fox was the most studied species, the wolf and Iberian lynx were disproportionally studied, and the Arctoidea were understudied. Sampling effort was higher in Mediterranean areas, but central Spain showed the higher pathogen richness. Excluding studies analyzing fecal samples, 53 different pathogens have been detected in Iberian carnivores, including 16 viruses, 27 bacteria, and 10 protozoa but no fungi. Sampling effort and pathogen diversity were generally more similar among closely related carnivore species. Seropositivity to viruses was lower and higher in the Mustelinae and the Canidae, respectively, and seropositivity to protozoa was higher in both taxa. Canine distemper virus exposure was greatest in canids and mustelids. Carnivore protoparvovirus-1 exposure was greatest in the Atlantic regions, and the Felidae and the Musteloidea had lower infection prevalence. A subclade of the Mustelidae had a greater prevalence of Leishmania infection. We observed no relationships between host phylogenetic distance and pathogen sharing among species. Lastly, we identify important research pitfalls and future directions to improve the study of infectious disease in Iberian wild carnivore communities.
Battery Crush Test Procedures in Standards and Regulation: Need for Augmentation and Harmonisation
Authors: Kotak Bhavya , Kotak Yash , Brade Katja , Kubjatko Tibor , Schweiger Hans-Georg
Published: September 2021

Battery safety is a prominent concern for the deployment of electric vehicles (EVs). The battery powering an EV contains highly energetic active materials and flammable organic electrolytes. Usually, an EV battery catches fire due to its thermal runaway, either immediately at the time of the accident or can take a while to gain enough heat to ignite the battery chemicals. There are numerous battery abuse testing standards and regulations available globally. Therefore, battery manufacturers are always in dilemma to choose the safest one. Henceforth, to find the optimal outcome of these two major issues, six standards (SAE J2464:2009, GB/T 31485-2015:2015, FreedomCAR:2006, ISO 12405-3:2014, IEC 62660-2:2010, and SAND2017-6295:2017) and two regulations (UN/ECE-R100.02:2013 and GTR 20:2018), that are followed by more than fifty countries in the world, are investigated in terms of their abuse battery testing conditions (crush test). This research proves that there is a need for (a) augmenting these standards and regulations as they do not consider real-life vehicle crash scenarios, and (b) one harmonised framework should be developed, which can be adopted worldwide. These outcomes will solve the battery manufacturers dilemma and will also increase the safety of EV consumers.
CrowDSL: Platform for Incidents Management in a Smart City Context
Authors: Rodríguez-García Darío , García-Díaz Vicente , González García Cristian
Published: September 2021

The final objective of smart cities is to optimize services and improve the quality of life of their citizens, who can play important roles due to the information they can provide. This information can be used in order to enhance many sectors involved in city activity such as transport, energy or health. Crowd-sourcing initiatives focus their efforts on making cities safer places that are adapted to the population size they host. In this way, citizens are able to report the issues they identify to the relevant body so that they can be fixed and, at the same time, they can provide useful information to other citizens. There are several projects aimed at reporting incidents in a smart city context. In this paper, we propose the use of model-driven engineering by designing a graphical domain-specific language to abstract and improve the incident-reporting process. With the use of a domain-specific language, we can obtain several benefits in our research for users and cities. For instance, we can shorten the time for reporting the events by users and, at the same time, we gain an expressive power compared to other methodologies for incident reporting. In addition, it can be reused and is centered in this specific domain after being studied. Furthermore, we have evaluated the DSL with different users, obtaining a high satisfaction percentage.
Microbiota and Myopericarditis: The New Frontier in the Car-Diological Field to Prevent or Treat Inflammatory Cardiomyo-Pathies in COVID-19 Outbreak
Authors: Piccioni Andrea , Saviano Angela , Cicchinelli Sara , Franza Laura , Rosa Federico , Zanza Christian , Santoro Michele Cosimo , Candelli Marcello , Covino Marcello , Nannini Giulia , Amedei Amedeo , Franceschi Francesco
Published: September 2021

Myopericarditis is an inflammatory heart condition involving the pericardium and myocardium. It can lead to heart failure, dilated cardiomyopathy, arrhythmia and sudden death. Its pathogenesis is mainly mediated by viral infections but also can be induced by bacterial infections, toxic substances and immune mediated disorders. All these conditions can produce severe inflammation and myocardial injury, often associated with a poor prognosis. The specific roles of these different pathogens (in particular viruses), the interaction with the host, the interplay with gut microbiota, and the immune system responses to them are still not completely clear and under investigation. Interestingly, some research has demonstrated the contribution of the gut microbiota, and its related metabolites (some of which can mimic the cardiac myosin), in cardiac inflammation and in the progression of this disease. They can stimulate a continuous and inadequate immune response, with a subsequent myocardial inflammatory damage. The aim of our review is to investigate the role of gut microbiota in myopericarditis, especially for the cardiovascular implications of COVID-19 viral infection, based on the idea that the modulation of gut microbiota can be a new frontier in the cardiological field to prevent or treat inflammatory cardiomyopathies.
Progressive Fibrosing Interstitial Lung Diseases: A Current Perspective
Authors: Albera Carlo , Verri Giulia , Sciarrone Federico , Sitia Elena , Mangiapia Mauro , Solidoro Paolo
Published: September 2021

Interstitial lung diseases (ILDs) are a large and diverse group of rare and chronic respiratory disorders, with idiopathic pulmonary fibrosis (IPF) being the most common and best-studied member. Increasing interest in fibrosis as a therapeutic target and the appreciation that fibrotic mechanisms may be a treatable target of IPF prompted the development and subsequent approval of the antifibrotics, pirfenidone and nintedanib. The management of ILDs has changed considerably following an understanding that IPF and some ILDs share similar disease behavior of progressive fibrosis, termed “progressive fibrosing phenotype”. Indeed, antifibrotic treatment has shown to be beneficial in ILDs characterized by the progressive fibrosing phenotype. This narrative review summarizes current knowledge in the field of progressive fibrosing ILDs. Here, we discuss the clinical characteristics and pathogenesis of lung fibrosis and highlight relevant literature concerning the mechanisms underlying progressive fibrosing ILDs. We also summarize current diagnostic approaches and the available treatments of progressive fibrosing ILDs and address the optimization of treating progressive fibrosing ILDs with antifibrotics in clinical practice.
DNArepairK: An Interactive Database for Exploring the Impact of Anticancer Drugs onto the Dynamics of DNA Repair Proteins
Authors: Babukov Yordan , Aleksandrov Radoslav , Ivanova Aneliya , Atemin Aleksandar , Stoynov Stoyno
Published: September 2021

Cells are constantly exposed to numerous mutagens that produce diverse types of DNA lesions. Eukaryotic cells have evolved an impressive array of DNA repair mechanisms that are able to detect and repair these lesions, thus preventing genomic instability. The DNA repair process is subjected to precise spatiotemporal coordination, and repair proteins are recruited to lesions in an orderly fashion, depending on their function. Here, we present DNArepairK, a unique open-access database that contains the kinetics of recruitment and removal of 70 fluorescently tagged DNA repair proteins to complex DNA damage sites in living HeLa Kyoto cells. An interactive graphical representation of the data complemented with live cell imaging movies facilitates straightforward comparisons between the dynamics of proteins contributing to different DNA repair pathways. Notably, most of the proteins included in DNArepairK are represented by their kinetics in both nontreated and PARP1/2 inhibitor-treated (talazoparib) cells, thereby providing an unprecedented overview of the effects of anticancer drugs on the regular dynamics of the DNA damage response. We believe that the exclusive dataset available in DNArepairK will be of value to scientists exploring the DNA damage response but, also, to inform and guide the development and evaluation of novel DNA repair-targeting anticancer drugs.
Neuronal Dynamics of Pain in Parkinson’s Disease
Authors: Kinugawa Kaoru , Mano Tomoo , Sugie Kazuma
Published: September 2021

Pain is an important non-motor symptom of Parkinson’s disease (PD). It negatively impacts the quality of life. However, the pathophysiological mechanisms underlying pain in PD remain to be elucidated. This study sought to use electroencephalographic (EEG) coherence analysis to compare neuronal synchronization in neuronal networks between patients with PD, with and without pain. Twenty-four patients with sporadic PD were evaluated for the presence of pain. Time-frequency and coherence analyses were performed on their EEG data. Whole-brain and regional coherence were calculated and compared between pain-positive and pain-negative patients. There was no significant difference in the whole-brain coherence between the pain-positive and pain-negative groups. However, temporal–temporal coherence differed significantly between the two groups (p = 0.031). Our findings indicate that aberrant synchronization of inter-temporal regions is involved in PD-related pain. This will further our understanding of the mechanisms underlying pain in PD.