bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bimodal sequence composition underlies functional duality of transcribed enhancers
Authors: Flores Mario , Ovcharenko Ivan 
Published: August 2020

Abstract
Background:Recent studies have drawn attention to transcribed enhancers (trEs) as important regulatory elements of gene expression; however, their characteristics and mechanisms of action remain poorly understood. Results:We profiled the characteristics of trEs and obtained insights into their mechanisms of action. We found that trEs harbor functional duality related to bimodal sequence composition. TrEs are composed of nonoverlapping cores and flanking regions (flanks): cores function as regular enhancers, while flanks transcribe enhancer RNAs (eRNAs) that can potentially regulate the expression of their target genes in trans. Cores are evolutionarily conserved and compact, while flanks are significantly longer. We observed that approximately 25% of eRNAs transcribed from the flanks likely contribute to trans DNA:RNA triple helix formation, while another 10% likely employ classical mechanisms of RNA-based regulation. We found that the majority of human enhancers are not transcribed, and trEs are strikingly different from regular enhancers in their functional characteristics. In addition, we found evidence for trEs exhibiting functional duality in regulatory locus encapsulation (RLE), effectively providing localized control over the spread of gene expression upregulation by trE cores and other locus enhancers. Conclusions:In summary, our results advocate for enhancer transcription being an uncommon mechanism of gene regulation, and the duality of transcribed enhancer function being a product of additive, not overlapping, DNA sequence encryption.
WITHDRAWN: Transcriptome Sequencing of Trichoderma Koningiopsis Strain Tk1 to Identify and Analyze Differential Gene Expression Patterns
Authors: Luo Mei , Dong Zhangyong , Shu Yongxin , Chen Mobing 
Published: August 2020

Abstract
Background: Trichoderma koningiopsis strain Tk1 shows good biocontrol potential. However, its biocontrol function may differ under different conditions. The objective of this study is to elucidate the biological and transcriptome differences of T. koningiopsis Tk1 under different media. Results: In this study, the mycelium weight and sporulation of T. koningiopsis Tk1 was found to differ in various media. Further, the Tk1 strain inhibited the growth of the pathogen Fusarium oxysporum in the three media tested. Fries3, PD, and PS were collected for RNA sequencing of Tk1 mycelia to identify the genes that are differentially expressed genes (DEGs) between Tk1 grown on different media. De novo transcriptome assembly resulted in identification of 14,208 unigenes. The differential gene expression pattern was more similar between the Fries3 and PS samples, whereas PD samples showed a different expression pattern. The DEGs were enriched in some metabolic and biosynthetic pathways. Additional analysis of the DEGs identified a set of carbohydrate-active enzymes that are upregulated or downregulated under different conditions.Conclusions: These results indicate that the Tk1 strain cultured in Fires3 and PS mediums can produce specific metabolic and carbohydrate-active enzymes to enhance their antimicrobial effect, providing a foundation for the subsequent mining of specific genes.
Acid Sphingomyelinase Deficiency Normalizes Neuronal Function in GCase Deficiency - Unexpected Biological Rescue Effect of Combined Genetic Risk Factors for Parkinson’s Disease
Authors: Keatinge Marcus , Gegg Matthew E , Watson Lisa , Mortiboys Heather , Bui Hai , Lefeber Dirk , Rens Astrid Van , MacDonald Ryan , Schapira Anthony , Bandmann Oliver 
Published: August 2020

Abstract
BackgroundThe additive mechanistic effect of genetic risk variants for Parkinson’s disease (PD) is a plausible but largely unproven hypothesis. We investigated the mechanistic interaction between the two lysosomal PD risk genes glucocerebrosidase 1 (GBA1) and sphingomyelinase 1 (SMPD1) in complementing model systems.MethodsUsing CRISPR/Cas gene editing, smpd1 mutant (smpd1-/-) zebrafish were generated and crossed to our previously characterised gba1-/- zebrafish line, generating double knockouts (gba1-/-;smpd1-/-). Spontaneous motor behaviour and survival were assessed in WT, single mutants and double mutants. HPLC-based sphingolipid quantification was combined with RNAseq based pathway analysis, assessment of the mitochondrial respiratory chain and quantification of lipid membrane oxidation for in-depth assessment of cellular health across all four genotypes. We also determined the effect of combined glucocerebrosidase (GCase) and acid sphingomyelinase (ASM) inactivation on autophagy and alpha-synuclein homeostasis in the human neuronal cell line SH-SY5Y.ResultsUnexpectedly, ASM deficiency rescued the marked behavioural phenotype and prolonged survival in gba1-/-;smpd1-/- double-mutant zebrafish compared to gba1-/-. RNAseq-based pathway analysis confirmed a profound rescue of neuronal function and intracellular homeostasis. We identified complete reciprocal rescue of mitochondrial respiratory chain function and abolished lipid membrane oxidation in gba1-/-;smpd1-/- compared to gba1-/- or smpd1-/- as the underlying rescue mechanism. The complementing in vitro experiments demonstrated an unexpected reduction of α-synuclein levels in human cell lines with combined GCase and ASM deficiency.ConclusionsOur study highlights the importance of functional validation for any putative mechanistic interactions between genetic risk factors and their overall effect on disease-relevant mechanisms rather than readily assuming an additive effect.
Interaction Between Clopidogrel and Panax Notoginseng Saponins
Authors: Hu Yunzhen , Yang Xi 
Published: August 2020

Abstract
Background: Panax notoginseng saponins (PNS) is commonly used in combination with clopidogrel in clinic. This study was to investigate the effect of PNS on the pharmacokinetics of clopidogrel active metabolite CAMD and the effect on the activities of clopidogrel metabolic enzymes in rats. Methods: In pharmacokinetics studies, the rats were divided into clopidogrel and combination groups, and continuously administered for seven days. The concentration of CAMD was determined by LC-MS/MS. In enzymes studies, the rats were divided into control and PNS groups. After administration for seven days, CYP2C19 and CYP3A4 activities were measured by the metabolic rate of the specific substrate in rat liver microsomes. The activity of CES1 enzyme was determined by double antibody sandwich method.Results: PNS significantly increased AUC0-∞ of CAMD from 43.1±11.6 to 72.0±25.1 h·ng/mL (p<0.05). Combination group had lower CL/F and Vd/F than clopidogrel group (p<0.05). PNS significantly decreased the activity of CYP3A4 and CES1 (p<0.01), but no significant effect on CYP2C19.Conclusions: The combination use of PNS and clopidogrel produced a significant increase in the AUC of clopidogrel active metabolite CAMD. PNS could inhibit the activity of CYP3A4 and CES1 enzyme in rat.
Vascular Access Support Team: A Multi-Disciplinary Response to Optimise Patients’ Care during COVID-19 Pandemic
Authors: Sinha Manish , Saha Prakash , Nabil Melhem , Kessaris Nicos , Biasi Lukla , Booth Caroline , Callaghan Chris J. , Donati Tommaso , Ostermann Marliese , Patel Sanjay , Ware Nick , Zayed Hany , Drage Martin , Sallam Morad 
Published: August 2020

Abstract
Background: Vascular access support teams have been set up to help offload procedural tasks from critical care teams during the coronavirus disease 2019 (COVID-19) global pandemic. However, the impact of VAST on clinical outcomes and on workload has not been shown previously with no reports to date from the UK. Our aim was to evaluate clinical outcomes of a multidisciplinary vascular access support team (VAST) and the value of the service to critical care teams. Methods: Prospectively collected data on all patients requiring vascular access at St Thomas’ Hospital, London over a 5-week period during the first wave of the pandemic in the UK. At the end of study period, online anonymised questionnaire administered to critical care team members, including nursing and medical professionals, to evaluate their experience of the service. We report access-related complication until discharge from centre and description of results of online survey.Results: 122 patients aged 52.1 ± 13 years with high rate of pre-existing co-morbidities, underwent line insertion including 190 catheters (central venous n=182, arterial n=8). Median (range) number of 5 (0-17) lines were placed per day in patients of whom 90% tested positive for Severe Acute Respiratory Syndrome Coronavirus-type 2 pathogen (SARS-CoV-2). A single line (n=146) was inserted in 96 out of 122 patients (78.7%) and n=18 patients (14.7%) ‘double puncture’ technique used. 45 line insertions (24%) had complications with minor [bleeding (n=19), line infection (n=10)] and 2 lines (1%) with major complication. The survey respondents, n=54 professionals, highlighted ease of referral and timely access placement (>90% responses); with agreement that VAST service saved them precious time and allow them to focus on other jobs.Conclusions: We describe the successful deployment of a multidisciplinary vascular access team with low complication rates and high rates of satisfaction. We recommend similar models can be considered by health services to optimise patient care and ICU management.
Expression and clinical significance of SARS-COV-2 receptor ACE2 in colon cancer
Authors: Nie Hui , Wang Yutong , Wu Geting , He Xiaoyun , Liao Zhiming , Ou Chunlin , Zhou Jianhua 
Published: August 2020

Abstract
Background: Angiotensin-converting enzyme 2 (ACE2), a crucial cell entry receptor for severe acute respiratory syndrome coronavirus 2, has been identified as an oncogene in some tumour types. However, its role in colon cancer is poorly understood.Methods: Integrative bioinformatics analyses were performed to uncover the role of ACE2 in colon cancer-associated immunology. Results: The results showed that ACE2 was overexpressed in colon cancer tissues and correlated with poor survival. Moreover, ACE2 expression was closely associated with the immune-infiltrating levels of CD4+ T, CD8+ T, and neutrophils. Conclusions: ACE2 is closely associated with colon cancer and may be involved in tumourigenesis and cancer–immune interactions, and could be a promising prognostic and therapeutic biomarker in colon cancer.
Barriers and Facilitators Affecting Implementation of a Clinical Decision aid for the Diagnosis of Acute Aortic Syndrome: A Qualitative Study
Authors: Dmitriew Caitlin , Ohle Robert 
Published: August 2020

Abstract
Background: Acute aortic syndrome (AAS) is an uncommon, life-threatening emergency that is frequently misdiagnosed. The Canadian clinical practice guidelines for the diagnosis of AAS were developed to improve patient outcomes and include a clinical decision aid designed to facilitate clinician decision-making. The objective of this study was to prospectively identify barriers and facilitators among physicians prior to implementation of the decision aid.Methods: We conducted semi-structured interviews with emergency room physicians working at five sites distributed between urban academic and rural settings. We used purposive sampling, contacting physicians until data saturation was reached. Interview questions were designed to understand potential barriers and facilitators to decision aid uptake and use. Responses were analysed according to the Theoretical Domains Framework, and overarching themes describing these barriers and facilitators were identified. Results: A majority of interviewees anticipated that the decision aid would support clinical decision making and risk stratification. Potential facilitators identified included guideline validation and publication and endorsement by peers. Barriers to implementation and application of the aid included the fact that the use of D-dimer and knowledge of the rationale for its use in the investigation of AAS were not widespread. The complexity of the decision aid and insufficient specificity of D-dimer were also identified as potential barriers to use. Conclusion: Physicians were amenable to using the AAS decision aid to support clinical decision-making and to reduce resource use. The barriers identified should be addressed prior to implementation in order to support decision aid uptake and use.
Ultrastructure and Functional Morphology of the Appendages in the Reef-Building Sedentary Polychaete Sabellaria Alveolata (Annelida, Sedentaria, Sabellida)
Authors: Meyer Christian , André Thomas , Purschke Günter 
Published: August 2020

Abstract
Background: The sedentary polychaete Sabellaria alveolata, the sandcastle or honeycomb worm, possesses four different kinds of appendages besides the parapodia: opercular papillae, tentacular filaments, palps, and branchiae. It exhibits a highly specialized anterior end, the operculum, formed by the prostomium, peristomium, and two anterior segments. Besides the median organ, the operculum comprises opercular papillae, tentacular filaments, and palps. Paired branchiae are present from the second thoracic chaetiger onwards on the posteriorly following segments except for the last ones. Only the palps have been studied thus far by transmission electron microscopy in late larvae of a different species. In order to bridge the data gap, we investigated the appendages of S. alveolata by applying light microscopy, confocal laser scanning microscopy, scanning, and transmission electron microscopy. Results: In S. alveolata the entire body is covered by a thin cuticle characterized by the absence of layers of parallel collagen fibers with no differentiation between the various body regions including the branchiae. The opercular papillae bear numerous tufts of receptor cells and lack motile cilia. The tentacular filaments show a distinctive ciliation pattern; their most conspicuous morphological feature is their cell-free cartilaginous endoskeletal structure enclosed by ECM. Besides musculature the filaments include a single coelomic cavity but blood vessels are absent. The palps are ciliated with two coelomic cavities and a single blind-ending blood vessel. Besides external ciliation and receptor cells, the coelomate branchiae are highly vascularized and equipped with numerous blood spaces extending deep into the basal regions of the epidermal cells (diffusion distances: 150–400nm). Conclusions: All appendages, including the branchiae, bear receptor cells and, as such, are sensory. The opercular papillae resemble typical parapodial cirri. In contrast, the tentacular filaments have a double function: sensing, collecting and transporting particles. A similarity to branchiae can be excluded. The palps are typical grooved palps similar to another sabellariid studied. A revised classification of polychaete branchiae is suggested; thereby, the branchiae of S. alveolata belong to the most common type comprising coelom, musculature, and blood vessels. The results indicate that diffusion distances between blood and environment have been underestimated in many cases.
The Discovery of a Recombinant SARS2-like CoV Strain Provides Insight Into SARS and COVID-19&nbsp;Pandemics
Authors: Li Xin , Jin Xiufeng , Chen Shunmei , Wang Liangge , Yau Tung On , Yang Jianyi , Hong Zhangyong , Ruan Jishou , Duan Guangyou , Gao Shan 
Published: August 2020

Abstract
Background: In December 2019, the world awoke to a new zoonotic strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Results: In the present study, we classified betacoronavirus subgroup B into the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters, and the ORF8 genes of these three clusters into types 1, 2 and 3, respectively. One important result of our study is that we reported—for the first time—a recombination event of ORF8 at the whole-gene level in a bat, which had been co-infected by two betacoronavirus strains. This result provides substantial proof for long-existing hypotheses regarding the recombination and biological functions of ORF8. Based on the analysis of recombination events in the Spike gene, we propose that the Spike protein of SARS-CoV-2 may have more than one specific receptor for its function as gp120 of HIV has CD4 and CCR5. In the present study, we also found that the ancestor of betacoronavirus had a strong first Internal Ribosome Entry Site (IRES) and at least one furin cleavage site (FCS) in the junction region between S1 and S2 subunits.Conclusions: We concluded that the junction FCS in SARS-CoV-2 may increase the efficiency of its entry into cells, while the type 2 ORF8 acquired by SARS-CoV may increase its replication efficiency. These two most critical events provide the most likely explanation for SARS and COVID-19 pandemics.
Virtual Reality Hypnosis for Anxiety and Pain Management in Intensive Care Units. A Prospective Randomized Trial Among Cardiac Surgery Patients.
Authors: Rousseaux Floriane Marie , Dardenne Nadia , Massion Paul B , Ledoux Didier , Faymonville Marie-Elisabeth , Nyssen Anne-Sophie , Vanhaudenhuyse Audrey 
Published: August 2020

Abstract
Background: Although non-pharmacological tools are nowadays commonly used in medical settings, virtual reality and hypnosis are little studied in complex contexts such as intensive care, where patients need significant physical and psychological assistance. The aim of the project is to evaluate the benefits of hypnosis, virtual reality (VR) and the combination of hypnosis and virtual reality (VRH) on anxiety and pain on patients before and after a cardiac surgery.Methods: This prospective randomized and controlled clinical trial was conducted in the University Hospital of Liege (Belgium). Participants are adults undergoing cardiac surgery, French speaking. Exclusion criteria are patients with psychiatric diseases, claustrophobia, acrophobia, heavy hearing impairment, visual impairment, extreme fatigue, verbal incoherence, surgery cancelled or postponed. The day before the surgery, patients were randomly assigned to four arms (control, hypnosis, VR and VRH) and had 20 minutes of one of the technique. They received the same intervention one day after surgery, in intensive care units. Anxiety, pain, fatigue, relaxation and physiological parameters were evaluated before and after each session.Results: 100 patients (66.38 ± 11.48 years; 76 men, 24 women) were included. Results showed that anxiety decreased from baseline to postoperative day in all groups. Relaxation increased in all groups in preoperative (p = .000) and postoperative period (p = 0.03). There were no significant results for pain and fatigue (p > 0.05). There was no significant difference between control group and hypnosis, VR or VRH.Conclusion: Anxiety decreased and relaxation increased in all groups, including control group. We cannot affirm that one technique is better than another is. Nevertheless, this study helps to expand the knowledge regarding application of virtual reality, hypnosis and virtual reality hypnosis in the specific contexts of cardiac surgery and intensive care units. Additional studies are required to compare and evaluate the costs-effectiveness of these techniques for critical care patients and caregivers (see Figure 1).Trial registration: ClinicalTrials.gov: NCT03820700. https://clinicaltrials.gov/ct2/show/NCT03820700. Registered on January 29 2019. Retrospectively registered.
Stress-related Growth and Perceived Health in Japanese People Living With HIV: Web-based Nationwide Participatory Research.
Authors: Togari Taisuke , Inoue Yoji , Oshima Gaku , Abe Sakurako , Hosokawa Rikuya , Takaku Yosuke 
Published: August 2020

Abstract
Background: For Japanese people living with HIV, this study aimed at the following: verifying the three-factor model of stress-related growth scales; confirming the impact of stress-related growth on mental health and physical symptoms; and determining differences in the effects of stress-related growth on health by time since HIV diagnosis.　Methods: A cross-sectional anonymous self-administered online survey which was prepared on the basis of the participatory research method was conducted from July 2013 to February 2014 and from December 2016 to July 2017 for all Japanese web users living with HIV. We analyzed the data of 1,422 participants who responded regarding the number of years since diagnosis and where transmission was sexual. The mean age (standard deviation) was 38.6 (8.3) years.　Results: Stress-related growth comprises three factors: self-perception, interpersonal relationships, and philosophy of life. In the group over 4 years since diagnosis, logistic and Poisson regression analysis simultaneously including all the scales showed a positive effect; in the group with less than 4 years since diagnosis, such an association was found only for self-perception. In the group with over 4 years since diagnosis, positive growth in interpersonal relationships and self-perception led to reduced somatic symptoms; however, philosophy of life was linked to increased physical symptoms. When the group with less than 4 years since diagnosis was included, no correlation was evident with philosophy of life; positive growth in self-perception led to reduced physical symptoms; positive changes in interpersonal relationships produced increased physical symptoms.　Conclusions: Toward assisting people living with HIV/AIDS, we found that personal and group relationships played an important role in creating positive changes regarding respondents’ perceptions of life and other people.
RNF114 suppresses tumour metastasis through the regulation of PARP10
Authors: Zhao Yahui , Liang Xiao , Wei Li , Liu Yao , Liu Juan , Feng Huan , Zheng Fen , Wang Ying , Ma Haijie , Wu Jiaxue 
Published: August 2020

Abstract
Background

ADP-ribosylation is a multifunctional post-translational modification catalysed by intracellular ADP-ribosyltransferases. Previously, we demonstrated that the mono-ADP-ribosyltransferase PARP10 suppresses tumour metastasis through the negative regulation of Aurora A kinase activity. However, the mechanisms of PARP10 regulation and modification were unclear.
Methods

Interaction of RNF114 and PARP10 was identified by exogenous and endogenous reciprocal immunoprecipitation (IP) assays and pull-down assays. Ubiquitination of PARP10 by RNF114 was analysed by in vivo ubiquitination assays. Potential effects of ubiquitination on PARP10’s activity was detected by western blots and pull-down assays. Potential role of RNF114 in tumour metastasis were determined by migration and invasion assays and in vivo metastasis assay.
Results

That E3 ubiquitin ligase RNF114 is a partner of PARP10 was identified by IP assays. The auto-mono-ADP-ribosylation of PARP10 is required for the interaction of RNF114 and PARP10. RNF114 ubiquitinates PARP10 through K27-linked polyubiquitination, which enhances PARP10 enzymatic activity. Moreover, RNF114 deficiency promotes tumour cell migration and tumour metastasis through the regulation of PARP10 and its downstream signalling pathway.
Conclusions

Our findings identify RNF114 as a novel functional regulator of PARP10 and provide evidence of crosstalk between the components of K27-linked polyubiquitination and mono-ADP ribosylation.