bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations for participation in leisure-time physical activity and competitive sports in patients with arrhythmias and potentially arrhythmogenic conditions: Part 1: Supraventricular arrhythmias. A position statement of the Section of Sports Cardiology and Exercise from the European Association of Preventive Cardiology (EAPC) and the European Heart Rhythm Association (EHRA), both associations of the European Society of Cardiology
Authors: Heidbuchel Hein , Adami Paolo E , Antz Matthias , Braunschweig Frieder , Delise Pietro , Scherr Daniel , Solberg Erik E , Wilhelm Matthias , Pelliccia Antonio ,   EHRA/EAPC Scientific Review Group, Heinzel Frank R , Veltmann Christian , Odening Katja E , Boldt Leif Hendrik , Anne Wim , Napolitano Carlo , Davos Constantinos , Piepoli Massimo , Biffi Alessandro , van Buuren Frank 
Published: June 2020

Abstract
Symptoms attributable to arrhythmias are frequently encountered in clinical practice. Cardiologists and sport physicians are required to identify high-risk individuals harbouring such conditions and provide appropriate advice regarding participation in regular exercise programmes and competitive sport. The three aspects that need to be considered are: (a) the risk of life-threatening arrhythmias by participating in sports; (b) control of symptoms due to arrhythmias that are not life-threatening but may hamper performance and/or reduce the quality of life; and (c) the impact of sports on the natural progression of the underlying arrhythmogenic condition. In many cases, there is no unequivocal answer to each aspect and therefore an open discussion with the athlete is necessary, in order to reach a balanced decision. In 2006 the Sports Cardiology and Exercise Section of the European Association of Preventive Cardiology published recommendations for participation in leisure-time physical activity and competitive sport in individuals with arrhythmias and potentially arrhythmogenic conditions. More than a decade on, these recommendations are partly obsolete given the evolving knowledge of the diagnosis, management and treatment of these conditions. The present document presents a combined effort by the Sports Cardiology and Exercise Section of the European Association of Preventive Cardiology and the European Heart Rhythm Association to offer a comprehensive overview of the most updated recommendations for practising cardiologists and sport physicians managing athletes with supraventricular arrhythmias, and provides pragmatic advice for safe participation in recreational physical activities, as well as competitive sport at amateur and professional level. A companion text on recommendations in athletes with ventricular arrhythmias, inherited arrhythmogenic conditions, pacemakers and implantable defibrillators is published as Part 2 in Europace.
The BET inhibitor CPI203 promotes ex vivo expansion of cord blood long-term repopulating HSCs and megakaryocytes
Authors: Hua Peng , Hester Joanna , Adigbli George , Li Rong , Psaila Bethan , Roy Anindita , Bataille Carole J. R. , Wynne Graham M. , Jackson Thomas , Milne Thomas A. , Russell Angela J. , Davies James , Roberts Irene , Issa Fadi , Watt Suzanne M. 
Published: June 2020

Abstract
Although cytokine-mediated expansion of human hematopoietic stem cells (HSCs) can result in high yields of hematopoietic progenitor cells, this generally occurs at the expense of reduced bone marrow HSC repopulating ability, thereby limiting potential therapeutic applications. Because bromodomain-containing proteins (BCPs) have been demonstrated to regulate mouse HSC self-renewal and stemness, we screened small molecules targeting various BCPs as potential agents for ex vivo expansion of human HSCs. Of 10 compounds tested, only the bromodomain and extra-terminal motif inhibitor CPI203 enhanced the expansion of human cord blood HSCs without losing cell viability in vitro. The expanded cells also demonstrated improved engraftment and repopulation in serial transplantation assays. Transcriptomic and functional studies showed that the expansion of long-term repopulating HSCs was accompanied by synchronized expansion and maturation of megakaryocytes consistent with CPI203-mediated reprogramming of cord blood hematopoietic stem and progenitor cells. This approach may therefore prove beneficial for ex vivo gene editing, for enhanced platelet production, and for the improved usage of cord blood for transplantation research and therapy.
Exosomal miR-200c-3p negatively regulates the migration and invasion of lipopolysaccharide (LPS)-stimulated colorectal cancer (CRC)
Authors: Jiang Yimei , Ji Xiaopin , Liu Kun , Shi Yiqing , Wang Changgang , Li You , Zhang Tao , He Yonggang , Xiang Ming , Zhao Ren 
Published: June 2020

Abstract
Background
Colorectal cancer (CRC) is a leading cancer and a major cause of death. Lipopolysaccharide (LPS), an abundant component in gut microbiome, is involved in CRC progression and metastasis, potentially through regulating the miRNA composition of CRC-derived exosomes. In this study, we aimed to identify miRNA species in exosome which regulates CRC progression after LPS stimulation.

Results
Firstly, we discovered a shift of miRNA profile in CRC exosome after LPS stimulation. Among the differentially expressed miRNAs, we identified miR-200c-3p as a potential key regulator of CRC progression and metastasis. Retrospective analysis revealed that miR-200c-3p was elevated in CRC tumor tissues, but decreased in the serum exosome in CRC patients. In vitro experiments demonstrated that exosomal miR-200c-3p expression did not influence CRC cell proliferation, but negatively regulated their capacity of migration and invasion in the presence of LPS. miR-200c-3p level in exosome influenced exosomal expression of Zinc finger E-box-binding homeobox-1 (ZEB-1) mRNA, one of the miR-200c targets which affects migration and invasion capacity, and further altered ZEB-1 protein expression in CRC cell. In addition, exosomal miR-200c-3p promotes apoptosis of HCT-116 cells.

Conclusions
Our findings indicate that exosomal miR-200c-3p inhibits CRC migration and invasion, and promotes their apoptosis after LPS stimulation. It is suggested as a potential diagnostic marker and therapeutic target of CRC.
Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis
Authors: Ma Xiao , Cen Shuangshuang , Wang Luming , Zhang Chao , Wu Limin , Tian Xue , Wu Qisheng , Li Xuejun , Wang Xiaoqing 
Published: June 2020

Abstract
Background
The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Pelodiscus sinensis.

Results
We identified 10,446 mature miRNAs, 20,414 mRNAs and 28,500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11,319 mRNAs, and 10,495 lncRNAs showed differential expression. A total of 2814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.

Conclusions
In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.
mitch: multi-contrast pathway enrichment for multi-omics and single-cell profiling data
Authors: Kaspi Antony , Ziemann Mark 
Published: June 2020

Abstract
Background
Inference of biological pathway activity via gene set enrichment analysis is frequently used in the interpretation of clinical and other omics data. With the proliferation of new omics profiling approaches and ever-growing size of data sets generated, there is a lack of tools available to perform and visualise gene set enrichments in analyses involving multiple contrasts.

Results
To address this, we developed mitch, an R package for multi-contrast gene set enrichment analysis. It uses a rank-MANOVA statistical approach to identify sets of genes that exhibit joint enrichment across multiple contrasts. Its unique visualisation features enable the exploration of enrichments in up to 20 contrasts. We demonstrate the utility of mitch with case studies spanning multi-contrast RNA expression profiling, integrative multi-omics, tool benchmarking and single-cell RNA sequencing. Using simulated data we show that mitch has similar accuracy to state of the art tools for single-contrast enrichment analysis, and superior accuracy in identifying multi-contrast enrichments.

Conclusion
mitch is a versatile tool for rapidly and accurately identifying and visualising gene set enrichments in multi-contrast omics data. Mitch is available from Bioconductor (https://bioconductor.org/packages/mitch).
Comparative genomics and pangenome-oriented studies reveal high homogeneity of the agronomically relevant enterobacterial plant pathogen Dickeya solani
Authors: Motyka-Pomagruk Agata , Zoledowska Sabina , Misztak Agnieszka Emilia , Sledz Wojciech , Mengoni Alessio , Lojkowska Ewa 
Published: June 2020

Abstract
Background
Dickeya solani is an important plant pathogenic bacterium causing severe losses in European potato production. This species draws a lot of attention due to its remarkable virulence, great devastating potential and easier spread in contrast to other Dickeya spp. In view of a high need for extensive studies on economically important soft rot Pectobacteriaceae, we performed a comparative genomics analysis on D. solani strains to search for genetic foundations that would explain the differences in the observed virulence levels within the D. solani population.

Results
High quality assemblies of 8 de novo sequenced D. solani genomes have been obtained. Whole-sequence comparison, ANIb, ANIm, Tetra and pangenome-oriented analyses performed on these genomes and the sequences of 14 additional strains revealed an exceptionally high level of homogeneity among the studied genetic material of D. solani strains. With the use of 22 genomes, the pangenome of D. solani, comprising 84.7% core, 7.2% accessory and 8.1% unique genes, has been almost completely determined, suggesting the presence of a nearly closed pangenome structure. Attribution of the genes included in the D. solani pangenome fractions to functional COG categories showed that higher percentages of accessory and unique pangenome parts in contrast to the core section are encountered in phage/mobile elements- and transcription- associated groups with the genome of RNS 05.1.2A strain having the most significant impact. Also, the first D. solani large-scale genome-wide phylogeny computed on concatenated core gene alignments is herein reported.

Conclusions
The almost closed status of D. solani pangenome achieved in this work points to the fact that the unique gene pool of this species should no longer expand. Such a feature is characteristic of taxa whose representatives either occupy isolated ecological niches or lack efficient mechanisms for gene exchange and recombination, which seems rational concerning a strictly pathogenic species with clonal population structure. Finally, no obvious correlations between the geographical origin of D. solani strains and their phylogeny were found, which might reflect the specificity of the international seed potato market.
Health status and infections in patients with symptomatic primary and secondary immunoglobulin G (IgG) deficiencies receiving intravenous IgG replacement
Authors: Weide Rudolf , Schnell Roland , Schardt Christof , Koenigsmann Michael , Otremba Burkhard , Zahn Mark-Oliver , Wierecky Jan , Braun Ute , Hensel Manfred , Klausmann Martine , Fleckenstein Doris , Ehscheidt Peter , Feiten Stefan 
Published: June 2020

AbstractBackgroundThe effects of intravenous immunoglobulin G replacement on perceived health and infection susceptibility of patients suffering from immunoglobulin G (IgG) deficiencies should be evaluated in a prospective analysis.MethodsPatients with symptomatic primary or secondary IgG deficiencies were interviewed prior to the first IgG infusion (t0) and over the course of their treatment (t1- t6). The respondents rated their current health using a 100 point scale (EQ-5D-5L), ranging from 0 (‘worst imaginable health’) to 100 (‘best imaginable health’). The patients also provided information on the frequency of infections and of infections requiring antibiotics in the past 8 weeks. A healthy control group (CG) without oncologic diseases answered the questions once.ResultsOne hundred six patients with a median age of 65 years (21–85 years) were investigated. The median serum IgG concentration changed from 500 mg/dl (t0) to 772 mg/dl (t6). The mean number of infections and of infections requiring antibiotics decreased during IgG replacement significantly. Current health according to EQ-5D-5L improved from 57 (t0) to 68 (t6), compared to 73 in the CG.ConclusionDuring the course of IgG replacement patients reported fewer and less severe infections. Their health assessment improved but still was inferior to the healthy CG.
Integrated transcriptomics and metabolomics analysis of catechins, caffeine and theanine biosynthesis in tea plant (Camellia sinensis) over the course of seasons
Authors: Gong An-Dong , Lian Shuai-Bin , Wu Nan-Nan , Zhou Yong-Jie , Zhao Shi-Qi , Zhang Li-Min , Cheng Lin , Yuan Hong-Yu 
Published: June 2020

Abstract
Background
Catechins, caffeine, and theanine as three important metabolites in the tea leaves play essential roles in the formation of specific taste and shows potential health benefits to humans. However, the knowledge on the dynamic changes of these metabolites content over seasons, as well as the candidate regulatory factors, remains largely undetermined.

Results
An integrated transcriptomic and metabolomic approach was used to analyze the dynamic changes of three mainly metabolites including catechins, caffeine, and theanine, and to explore the potential influencing factors associated with these dynamic changes over the course of seasons. We found that the catechins abundance was higher in Summer than that in Spring and Autumn, and the theanine abundance was significantly higher in Spring than that in Summer and Autumn, whereas caffeine exhibited no significant changes over three seasons. Transcriptomics analysis suggested that genes in photosynthesis pathway were significantly down-regulated which might in linkage to the formation of different phenotypes and metabolites content in the tea leaves of varied seasons. Fifty-six copies of nine genes in catechins biosynthesis, 30 copies of 10 genes in caffeine biosynthesis, and 12 copies of six genes in theanine biosynthesis were detected. The correlative analysis further presented that eight genes can be regulated by transcription factors, and highly correlated with the changes of metabolites abundance in tea-leaves.

Conclusion
Sunshine intensity as a key factor can affect photosynthesis of tea plants, further affect the expression of major Transcription factors (TFs) and structural genes in, and finally resulted in the various amounts of catechins, caffeine and theaine in tea-leaves over three seasons. These findings provide new insights into abundance and influencing factors of metabolites of tea in different seasons, and further our understanding in the formation of flavor, nutrition and medicinal function.
Characterisation of early responses in lead accumulation and localization of Salix babylonica L. roots
Authors: Xue Wenxiu , Jiang Yi , Shang Xiaoshuo , Zou Jinhua 
Published: June 2020

Abstract
Background
Lead (Pb) is a harmful pollutant that disrupts normal functions from the cell to organ levels. Salix babylonica is characterized by high biomass productivity, high transpiration rates, and species specific Pb. Better understanding the accumulating and transporting Pb capability in shoots and roots of S. babylonica, the toxic effects of Pb and the subcellular distribution of Pb is very important.

Results
Pb exerted inhibitory effects on the roots and shoots growth at all Pb concentrations. According to the results utilizing inductively coupled plasma atomic emission spectrometry (ICP-AES), S. babylonica can be considered as a plant with great phytoextraction potentials as translocation factor (TF) value > 1 is observed in all treatment groups throughout the experiment. The Leadmium™ Green AM dye test results indicated that Pb ions initially entered elongation zone cells and accumulated in this area. Then, ions were gradually accumulated in the meristem zone. After 24 h of Pb exposure, Pb accumulated in the meristem zone. The scanning electron microscopy (SEM) and energy-dispersive X-ray analyses (EDXA) results confirmed the fluorescent probe observations and indicated that Pb was localized to the cell wall and cytoplasm. In transverse sections of the mature zone, Pb levels in the cell wall and cytoplasm of epidermal cells was the lowest compared to cortical and vessel cells, and an increasing trend in Pb content was detected in cortical cells from the epidermis to vascular cylinder. Similar results were shown in the Pb content in the cell wall and cytoplasm of the transverse sections of the meristem. Cell damage in the roots exposed to Pb was detected by propidium iodide (PI) staining, which was in agreement with the findings of Pb absorption in different zones of S. babylonica roots under Pb stress.

Conclusion
S. babylonica L. is observed as a plant with great potential of Pb-accumulation and Pb-tolerance. The information obtained here of Pb accumulation and localization in S. babylonica roots can furthers our understanding of Pb-induced toxicity and its tolerance mechanisms, which will provide valuable and scientific information to phytoremediation investigations of other woody plants under Pb stress.
Effect of phyB and phyC loss-of-function mutations on the wheat transcriptome under short and long day photoperiods
Authors: Kippes Nestor , VanGessel Carl , Hamilton James , Akpinar Ani , Budak Hikmet , Dubcovsky Jorge , Pearce Stephen 
Published: June 2020

AbstractBackgroundPhotoperiod signals provide important cues by which plants regulate their growth and development in response to predictable seasonal changes. Phytochromes, a family of red and far-red light receptors, play critical roles in regulating flowering time in response to changing photoperiods. A previous study showed that loss-of-function mutations in eitherPHYBorPHYCresult in large delays in heading time and in the differential regulation of a large number of genes in wheat plants grown in an inductive long day (LD) photoperiod.ResultsWe found that under non-inductive short-day (SD) photoperiods,phyB-null andphyC-null mutants were taller, had a reduced number of tillers, longer and wider leaves, and headed later than wild-type (WT) plants. The delay in heading between WT andphymutants was greater in LD than in SD, confirming the importance ofPHYBandPHYCin accelerating heading date in LDs. Both mutants flowered earlier in SD than LD, the inverse response to that of WT plants. In both SD and LD photoperiods,PHYBregulated more genes thanPHYC. We identified subsets of differentially expressed and alternatively spliced genes that were specifically regulated byPHYBandPHYCin either SD or LD photoperiods, and a smaller set of genes that were regulated in both photoperiods. We found that photoperiod had a contrasting effect on transcript levels of the flowering promoting genesVRN-A1andPPD-B1inphyBandphyCmutants compared to the WT.ConclusionsOur study confirms the major role of bothPHYBandPHYCin flowering promotion in LD conditions. Transcriptome characterization revealed an unexpected reversion of the wheat LD plants into SD plants in thephyB-null andphyC-null mutants and identified flowering genes showing significant interactions between phytochromes and photoperiod that may be involved in this phenomenon. Our RNA-seq data provides insight into light signaling pathways in inductive and non-inductive photoperiods and a set of candidate genes to dissect the underlying developmental regulatory networks in wheat.
Identification of small RNAs during cold acclimation in Arabidopsis thaliana
Authors: Tiwari Bhavika , Habermann Kristin , Arif M. Asif , Weil Heinrich Lukas , Garcia-Molina Antoni , Kleine Tatjana , Mühlhaus Timo , Frank Wolfgang 
Published: June 2020

Abstract
Background
Cold stress causes dynamic changes in gene expression that are partially caused by small non-coding RNAs since they regulate protein coding transcripts and act in epigenetic gene silencing pathways. Thus, a detailed analysis of transcriptional changes of small RNAs (sRNAs) belonging to all known sRNA classes such as microRNAs (miRNA) and small interfering RNA (siRNAs) in response to cold contributes to an understanding of cold-related transcriptome changes.

Result
We subjected A. thaliana plants to cold acclimation conditions (4 °C) and analyzed the sRNA transcriptomes after 3 h, 6 h and 2 d. We found 93 cold responsive differentially expressed miRNAs and only 14 of these were previously shown to be cold responsive. We performed miRNA target prediction for all differentially expressed miRNAs and a GO analysis revealed the overrepresentation of miRNA-targeted transcripts that code for proteins acting in transcriptional regulation. We also identified a large number of differentially expressed cis- and trans-nat-siRNAs, as well as sRNAs that are derived from long non-coding RNAs. By combining the results of sRNA and mRNA profiling with miRNA target predictions and publicly available information on transcription factors, we reconstructed a cold-specific, miRNA and transcription factor dependent gene regulatory network. We verified the validity of links in the network by testing its ability to predict target gene expression under cold acclimation.

Conclusion
In A. thaliana, miRNAs and sRNAs derived from cis- and trans-NAT gene pairs and sRNAs derived from lncRNAs play an important role in regulating gene expression in cold acclimation conditions. This study provides a fundamental database to deepen our knowledge and understanding of regulatory networks in cold acclimation.