bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-κB signaling pathways
Authors: Zhang Qi , Zhang Jian-hua , He Yu-qiong , Zhang Quan-long , Zhu Bo , Shen Yi , Liu Meng-qin , Zhu Lu-lin , Xin Hai-liang , Qin Lu-ping , Zhang Qiao-yan 
Published: June 2020

Abstract
Background
The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages.

Methods
MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis.

Results
MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages.

Conclusion
MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.
Online yoga to reduce post traumatic stress in women who have experienced stillbirth: a randomized control feasibility trial
Authors: Huberty Jennifer , Sullivan Mariah , Green Jeni , Kurka Jonathan , Leiferman Jenn , Gold Katherine , Cacciatore Joanne 
Published: June 2020

Abstract
Background
About 1 in every 150 pregnancies end in stillbirth. Consequences include symptoms of post traumatic stress disorder (PTSD), depression, and anxiety. Yoga has been used to treat PTSD in other populations and may improve health outcomes for stillbirth mothers. The purpose of this study was to determine: (a) feasibility of a 12-week home-based, online yoga intervention with varying doses; (b) acceptability of a “stretch and tone” control group; and (c) preliminary efficacy of the intervention on reducing symptoms of PTSD, anxiety, depression, perinatal grief, self-compassion, emotional regulation, mindfulness, sleep quality, and subjective health.

Methods
Participants (N = 90) were recruited nationally and randomized into one of three groups for yoga or exercise (low dose (LD), 60 min per week; moderate dose (MD), 150 min per week; and stretch-and-tone control group (STC)). Baseline and post-intervention surveys measured main outcomes (listed above). Frequency analyses were used to determine feasibility. Repeated measures ANCOVA were used to determine preliminary efficacy. Multiple regression analyses were used to determine a dose-response relationship between minutes of yoga and each outcome variable.

Results
Over half of participants completed the intervention (n = 48/90). Benchmarks (≥70% reported > 75% satisfaction) were met in each group for satisfaction and enjoyment. Participants meeting benchmarks (completing > 90% of prescribed minutes 9/12 weeks) for LD and MD groups were 44% (n = 8/18) and 6% (n = 1/16), respectively. LD and MD groups averaged 44.0 and 77.3 min per week of yoga, respectively. The MD group reported that 150 prescribed minutes per week of yoga was too much. There were significant decreases in PTSD and depression, and improvements in self-rated health at post-intervention for both intervention groups. There was a significant difference in depression scores (p = .036) and grief intensity (p = .009) between the MD and STC groups. PTSD showed non-significant decreases of 43% and 56% at post-intervention in LD and MD groups, respectively (22% decrease in control).

Conclusions
This was the first study to determine the feasibility and preliminary efficacy of an online yoga intervention for women after stillbirth. Future research warrants a randomized controlled trial.

Trial registration
ClinicalTrials.gov. NCT02925481. Registered 10–04-16.
Towards a comprehensive and interoperable representation of consent-based data usage permissions in the German medical informatics initiative
Authors: Bild Raffael , Bialke Martin , Buckow Karoline , Ganslandt Thomas , Ihrig Kristina , Jahns Roland , Merzweiler Angela , Roschka Sybille , Schreiweis Björn , Stäubert Sebastian , Zenker Sven , Prasser Fabian 
Published: June 2020

Abstract
Background
The aim of the German Medical Informatics Initiative is to establish a national infrastructure for integrating and sharing health data. To this, Data Integration Centers are set up at university medical centers, which address data harmonization, information security and data protection. To capture patient consent, a common informed consent template has been developed. It consists of different modules addressing permissions for using data and biosamples. On the technical level, a common digital representation of information from signed consent templates is needed. As the partners in the initiative are free to adopt different solutions for managing consent information (e.g. IHE BPPC or HL7 FHIR Consent Resources), we had to develop an interoperability layer.

Methods
First, we compiled an overview of data items required to reflect the information from the MII consent template as well as patient preferences and derived permissions. Next, we created entity-relationship diagrams to formally describe the conceptual data model underlying relevant items. We then compared this data model to conceptual models describing representations of consent information using different interoperability standards. We used the result of this comparison to derive an interoperable representation that can be mapped to common standards.

Results
The digital representation needs to capture the following information: (1) version of the consent, (2) consent status for each module, and (3) period of validity of the status. We found that there is no generally accepted solution to represent status information in a manner interoperable with all relevant standards. Hence, we developed a pragmatic solution, comprising codes which describe combinations of modules with a basic set of status labels. We propose to maintain these codes in a public registry called ART-DECOR. We present concrete technical implementations of our approach using HL7 FHIR and IHE BPPC which are also compatible with the open-source consent management software gICS.

Conclusions
The proposed digital representation is (1) generic enough to capture relevant information from a wide range of consent documents and data use regulations and (2) interoperable with common technical standards. We plan to extend our model to include more fine-grained status codes and rules for automated access control.
Co-production in health policy and management: a comprehensive bibliometric review
Authors: Fusco Floriana , Marsilio Marta , Guglielmetti Chiara 
Published: June 2020

Abstract
Background
Due to an increasingly elderly population, a higher incidence of chronic diseases and higher expectations regarding public service provision, healthcare services are under increasing strain to cut costs while maintaining quality. The importance of promoting systems of co-produced health between stakeholders has gained considerable traction both in the literature and in public sector policy debates. This study provides a comprehensive map of the extant literature and identifies the main themes and future research needs.

Methods
A quantitative bibliometric analysis was carried out consisting of a performance analysis, science mapping, and a scientific collaboration analysis. Web of Science (WoS) was chosen to extract the dataset; the search was refined by language, i.e. English, and type of publication, i.e. journal academic articles and reviews. No time limitation was selected.

Results
The dataset is made up of 295 papers ranging from 1994 to May 2019. The analysis highlighted an annual percentage growth rate in the topic of co-production of about 25%. The articles retrieved are split between 1225 authors and 148 sources. This fragmentation was confirmed by the collaboration analysis, which revealed very few long-lasting collaborations. The scientific production is geographically polarised within the EU and Anglo-Saxon countries, with the United Kingdom playing a central role. The intellectual structure consists of three main areas: public administration and management, service management and knowledge translation literature. The co-word analysis confirms the relatively low scientific maturity of co-production applied to health services. It shows few well-developed and central terms, which refer to traditional areas of co-production (e.g. public health, social care), and some emerging themes related to social and health phenomena (e.g. the elderly and chronic diseases), the use of technologies, and the recent patient-centred approach to care (patient involvement/engagement).

Conclusions
The field is still far from being mature. Empirical practices, especially regarding co-delivery and co-management as well as the evaluation of their real impacts on providers and on patients are lacking and should be more widely investigated.
Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial
Authors: Day Nicola C. , Kumar Subramanya , Criner Gerard , Dransfield Mark , Halpin David M. G. , Han MeiLan K. , Jones C. Elaine , Kaisermann Morrys C. , Kilbride Sally , Lange Peter , Lomas David A. , Martin Neil , Martinez Fernando J. , Singh Dave , Wise Robert , Lipson David A. 
Published: June 2020

Abstract
Background
This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy.

Methods
IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death.

Results
Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments.

Conclusions
In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI.

Trial registration
NCT02164513 (GSK study number CTT116855).
RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p
Authors: Li Jianfa , Huang Chenchen , Zou Yifan , Ye Jing , Yu Jing , Gui Yaoting 
Published: June 2020

Abstract
Background
Circular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown.

Methods
Through circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1.

Results
circTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells.

Conclusion
Collectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.
Burnout in nursing: a theoretical review
Authors: Dall’Ora Chiara , Ball Jane , Reinius Maria , Griffiths Peter 
Published: June 2020

AbstractBackgroundWorkforce studies often identify burnout as a nursing ‘outcome’. Yet, burnout itself—what constitutes it, what factors contribute to its development, and what the wider consequences are for individuals, organisations, or their patients—is rarely made explicit. We aimed to provide a comprehensive summary of research that examines theorised relationships between burnout and other variables, in order to determine what is known (and not known) about the causes and consequences of burnout in nursing, and how this relates to theories of burnout.MethodsWe searched MEDLINE, CINAHL, and PsycINFO. We included quantitative primary empirical studies (published in English) which examined associations between burnout and work-related factors in the nursing workforce.ResultsNinety-one papers were identified. The majority (n= 87) were cross-sectional studies; 39 studies used all three subscales of the Maslach Burnout Inventory (MBI) Scale to measure burnout. As hypothesised by Maslach, we identified high workload, value incongruence, low control over the job, low decision latitude, poor social climate/social support, and low rewards as predictors of burnout. Maslach suggested that turnover, sickness absence, and general health were effects of burnout; however, we identified relationships only with general health and sickness absence. Other factors that were classified as predictors of burnout in the nursing literature were low/inadequate nurse staffing levels, ≥ 12-h shifts, low schedule flexibility, time pressure, high job and psychological demands, low task variety, role conflict, low autonomy, negative nurse-physician relationship, poor supervisor/leader support, poor leadership, negative team relationship, and job insecurity. Among the outcomes of burnout, we found reduced job performance, poor quality of care, poor patient safety, adverse events, patient negative experience, medication errors, infections, patient falls, and intention to leave.ConclusionsThe patterns identified by these studies consistently show that adverse job characteristics—high workload, low staffing levels, long shifts, and low control—are associated with burnout in nursing. The potential consequences for staff and patients are severe. The literature on burnout in nursing partly supports Maslach’s theory, but some areas are insufficiently tested, in particular, the association between burnout and turnover, and relationships were found for some MBI dimensions only.
Inhibition of lysine acetyltransferases impairs tumor angiogenesis acting on both endothelial and tumor cells
Authors: Di Martile Marta , Gabellini Chiara , Desideri Marianna , Matraxia Marta , Farini Valentina , Valentini Elisabetta , Carradori Simone , Ercolani Cristiana , Buglioni Simonetta , Secci Daniela , Andreazzoli Massimiliano , Del Bufalo Donatella , Trisciuoglio Daniela 
Published: June 2020

Abstract
Background
Understanding the signalling pathways involved in angiogenesis, and developing anti-angiogenic drugs are one of the major focuses on cancer research. Herein, we assessed the effect of CPTH6, a lysine acetyltransferase inhibitor and anti-tumoral compound, on angiogenesis-related properties of both endothelial and cancer cells.

Methods
The in vitro effect of CPTH6 on protein acetylation and anti-angiogenic properties on endothelial and lung cancer cells was evaluated via wound healing, trans-well invasion and migration, tube formation, immunoblotting and immunofluorescence. Matrigel plug assay, zebrafish embryo and mouse xenograft models were used to evaluate in vivo anti-angiogenic effect of CPTH6.

Results
CPTH6 impaired in vitro endothelial angiogenesis-related functions, and decreased the in vivo vascularization both in mice xenografts and zebrafish embryos. Mechanistically, CPTH6 reduced α-tubulin acetylation and induced accumulation of acetylated microtubules in the perinuclear region of endothelial cells. Interestingly, CPTH6 also affected the angiogenesis-related properties of lung cancer cells, and conditioned media derived from CPTH6-treated lung cancer cells impaired endothelial cells morphogenesis. CPTH6 also modulated the VEGF/VEGFR2 pathway, and reshaped cytoskeletal organization of lung cancer cells. Finally, anti-migratory effect of CPTH6, dependent on α-tubulin acetylation, was also demonstrated by genetic approaches in lung cancer cells.

Conclusion
Overall, this study indicates that α-tubulin acetylation could play a role in the anti-angiogenic effect of CPTH6 and, more in general, it adds information to the role of histone acetyltransferases in tumor angiogenesis, and proposes the inhibition of these enzymes as an antiangiogenic therapy of cancer.
Biomarkers of sepsis: time for a reappraisal
Authors: Pierrakos Charalampos , Velissaris Dimitrios , Bisdorff Max , Marshall John C. , Vincent Jean-Louis 
Published: June 2020

Abstract
Introduction
Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.

Methods
Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included.

Results
We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.

Conclusions
The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
CTCF loss mediates unique DNA hypermethylation landscapes in human cancers
Authors: Damaschke Nathan A. , Gawdzik Joseph , Avilla Mele , Yang Bing , Svaren John , Roopra Avtar , Luo Jian-Hua , Yu Yan P. , Keles Sunduz , Jarrard David F. 
Published: June 2020

Abstract
Background
The chromatin insulator CCCTC-binding factor (CTCF) displays tissue-specific DNA binding sites that regulate transcription and chromatin organization. Despite evidence linking CTCF to the protection of epigenetic states through barrier insulation, the impact of CTCF loss on genome-wide DNA methylation sites in human cancer remains undefined.

Results
Here, we demonstrate that prostate and breast cancers within The Cancer Genome Atlas (TCGA) exhibit frequent copy number loss of CTCF and that this loss is associated with increased DNA methylation events that occur preferentially at CTCF binding sites. CTCF sites differ among tumor types and result in tissue-specific methylation patterns with little overlap between breast and prostate cancers. DNA methylation and transcriptome profiling in vitro establish that forced downregulation of CTCF leads to spatially distinct DNA hypermethylation surrounding CTCF binding sites, loss of CTCF binding, and decreased gene expression that is also seen in human tumors. DNA methylation inhibition reverses loss of expression at these CTCF-regulated genes.

Conclusion
These findings establish CTCF loss as a major mediator in directing localized DNA hypermethylation events in a tissue-specific fashion and further support its role as a driver of the cancer phenotype.