bluuebunny/crossref_metadata_2025_split huggingface dataset:
LC–MS-based multivariate statistical analysis for the screening of potential thrombin/factor Xa inhibitors from Radix Salvia Miltiorrhiza
Authors: Yang Yi-Yao , Wu Zhao-Yu , Zhang Hao , Yin Shi-Jun , Xia Fang-Bo , Zhang Qian , Wan Jian-Bo , Gao Jian-Li , Yang Feng-Qing 
Published: April 2020

Abstract
Background
The dry root and rhizome of Salvia miltiorrhiza Bunge, or Danshen, is a well-known traditional Chinese medicine with anticoagulant activity. Taking into account that thrombin (THR) and factor Xa (FXa) play crucial roles in the coagulation cascade, it is reasonable and meaningful to screening THR and/or FXa inhibitors from Danshen.

Methods
Four extracts [butanol (BA), ethyl acetate (EA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Danshen were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Then, the active EA extract was further separated by silica-gel column chromatography (SC), and its fractions (SC1–SC5) were analyzed by LC–MS. The principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were employed for predicting the specific marker compounds. The chemical structures of targeted compounds were identified by LC–MS/MS and their interactions with THR/FXa were analyzed by the molecular docking analysis.

Results
Danshen EA extract showed strong activity against THR and FXa, and its fractions (SC1–SC5) exhibited obvious difference in inhibitory activity against these two enzymes. Furthermore, four marker compounds with potential THR/FXa inhibitory activity were screened by PCA and OPLS-DA, and were identified as cryptotanshinone, tanshinone I, dihydrotanshinone I and tanshinone IIA. The molecular docking study showed that all these four tanshinones can interact with some key amino acid residues of the THR/FXa active cavities, such as HIS57 and SER195, which were considered to be promising candidates targeting THR and/or FXa with low binding energy (< − 7 kcal mol−1).

Conclusions
LC–MS combined with multivariate statistical analysis can effectively screen potential THR/FXa inhibitory components in Danshen.
miR-615-3p promotes the epithelial-mesenchymal transition and metastasis of breast cancer by targeting PICK1/TGFBRI axis
Authors: Lei Bo , Wang Dandan , Zhang Ming , Deng Yuwei , Jiang Huijie , Li Yiwen 
Published: April 2020

Abstract
Background
Increasing evidence indicates that epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). miR-615-3p was shown to be involved in tumor development. However, the role of miR-615-3p in the metastasis of breast cancer remains largely unknown.

Methods
The expression of miR-615-3p in breast cancer cells and tissues was assessed by qRT-PCR and situ hybridization assays. Effects of miR-615-3p on tumor metastasis were evaluated with experiments in vitro and mouse model. EMT markers were detected by western blot and immunofluorescence assays. Molecular mechanism of miR-615-3p in the regulation of breast cancer cell metastasis was analyzed by Western Blot, Co-immunoprecipitation, and Luciferase assay.

Results
In the present study, we found that miR-615-3p was significantly elevated in breast cancer cells and tissues, especially in those with metastasis. In breast cancer cell lines, stable overexpression of miR-615-3p was sufficient to promote cell motility in vitro, and pulmonary metastasis in vivo, accompanied by the reduced expression of epithelial markers and the increased levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-615-3p increased the downstream signaling of TGF-β, the type I receptor (TGFBRI) by targeting the 3′-untranslated regions (3′-UTR) of PICK1. PICK1 inhibits the binding of DICER1 to Smad2/3 and the processing of pre-miR-615-3p to mature miR-615-3p in breast cancer cells, thus exerting a negative feedback loop.

Conclusions
Our data highlight an important role of miR-615-3p in the molecular etiology of breast cancer, and implicate the potential application of miR-615-3p in cancer therapy.
Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer
Authors: Maeda Kazuya , Sasaki Hiroshi , Ueda Shoko , Miyamoto Shunsuke , Terada Shinichi , Konishi Hiromi , Kogata Yuhei , Ashihara Keisuke , Fujiwara Satoe , Tanaka Yoshimichi , Tanaka Tomohito , Hayashi Masami , Ito Yuko , Kondo Yoichi , Ochiya Takahiro , Ohmichi Masahide 
Published: April 2020

Abstract
Background
Ovarian cancer (OC) is a leading cause of cancer-related death in women, and thus an accurate diagnosis of the predisposition and its early detection is necessary. The aims of this study were to determine whether serum exosomal microRNA-34a (miR-34a) in ovarian cancer could be used as a potential biomarker.

Methods
Exosomes from OC patients’ serum were collected, and exosomal miRNAs were extracted. The relative expression of miR-34a was calculated from 58 OC samples by quantitative real-time polymerase chain reaction.

Results
Serum exosomal miR-34a levels were significantly increased in early-stage OC patients compared with advanced-stage patients. Its levels were significantly lower in patients with lymph node metastasis than in those with no lymph node metastasis. Furthermore, its levels in the recurrence group were significantly lower than those in the recurrence-free group.

Conclusions
Serum exosomal miR-34a could be a potential biomarker for improving the diagnostic efficiency of OC.
Acupressure to improve sleep quality of older people in residential aged care: a randomised controlled trial protocol
Authors: Hmwe Nant Thin Thin , Browne Graeme , Mollart Lyndall , Allanson Viv , Chan Sally Wai-Chi 
Published: April 2020

Abstract
Background
Sleep disturbance in older people is an important health issue that is associated with many other health problems. Effective interventions are required to address sleep problems in this group. Acupressure has been suggested as a potential therapeutic technique to improve sleep. The aim of this study is to evaluate the effects of an acupressure intervention on sleep quality, anxiety, depression, and quality of life among older persons in residential aged care facilities within an Australian context.

Methods/design
This is a randomised controlled trial with two parallel groups in a pre- and post-test study. Study participants will be older people living in residential aged care facilities. They will be assigned to intervention and control groups using computer-generated random numbers. The intervention group will receive 12-min acupressure three times per week for four consecutive weeks, applied on three acupoints: HT7, PC6, and SP6. The control group will receive only routine care. The primary outcome measure is sleep quality, and secondary outcomes include anxiety, depression, and quality of life. Data will be collected before the intervention, immediately after the end of the intervention, and 2 weeks after the intervention.

Discussion
This study targets a poorly met healthcare need of older people who are experiencing sleep disturbance and its negative consequences. To the researchers’ knowledge, this is the first study evaluating acupressure in an Australian aged care context, using specific acupoints and a standardised acupressure protocol. If the results show positive outcomes, acupressure could be used to manage sleep disturbances for older people in the Australian context as well as in the global ageing population. This will contribute to reducing negative consequences of sleep disturbance and use of sleep medications.

Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12619000262101. Registered on 20 February 2019.
Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease
Authors: Giles Andrew C. , Grill Brock 
Published: April 2020

AbstractHuwe1 is a highly conserved member of the HECT E3 ubiquitin ligase family. Here, we explore the growing importance of Huwe1 in nervous system development, function and disease. We discuss extensive progress made in deciphering how Huwe1 regulates neural progenitor proliferation and differentiation, cell migration, and axon development. We highlight recent evidence indicating that Huwe1 regulates inhibitory neurotransmission. In covering these topics, we focus on findings made using both vertebrate and invertebrate in vivo model systems. Finally, we discuss extensive human genetic studies that strongly implicate HUWE1 in intellectual disability, and heighten the importance of continuing to unravel how Huwe1 affects the nervous system.
Habitat suitability modelling to assess the introductions of Aedes albopictus (Diptera: Culicidae) in the Netherlands
Authors: Ibáñez-Justicia Adolfo , Alcaraz-Hernández Juan Diego , van Lammeren Ron , Koenraadt Constantianus J. M. , Bergsma Aldo , Delucchi Luca , Rizzoli Annapaola , Takken Willem 
Published: April 2020

Abstract
Background
In the Netherlands, Aedes albopictus has been found each year since 2010 during routine exotic mosquito species surveillance at companies that import used tires. We developed habitat suitability models to investigate the potential risk of establishment and spread of this invasive species at these locations.

Methods
We used two methodologies: first, a species distribution model based on the maximum entropy modelling approach (MaxEnt) taking into consideration updated occurrence data of the species in Europe, and secondly, a spatial logic conditional model based on the temperature requirements of the species and using land surface temperature data (LST model).

Results
Suitability assessment obtained with the MaxEnt model at European level accurately reflect the current distribution of the species and these results also depict moderately low values in parts of the Netherlands, Belgium, Denmark, the British islands and southern parts of Scandinavia. Winter temperature was the variable that contributed most to the performance of the model (47.3%). The results of the LST model showed that: (i) coastal areas are suitable for overwintering of eggs; (ii) large areas in the northern part of the country have a low suitability for adult survival; and (iii) the entire country is suitable for successful completion of the life-cycle if the species is introduced after the winter months. Results of the LST model revealed that temperatures in 2012 and 2014 did not limit the overwintering of eggs or survival of adults at the locations where the species was found. By contrast, for the years 2010, 2011 and 2013, overwintering of eggs at these locations is considered unlikely.

Conclusions
Results using two modelling methodologies show differences in predicted habitat suitability values. Based on the results of both models, the climatic conditions could hamper the successful overwintering of eggs of Ae. albopictus and their survival as adults in many areas of the country. However, during warm years with mild winters, many areas of the Netherlands offer climatic conditions suitable for developing populations. Regular updates of the models, using updated occurrence and climatic data, are recommended to study the areas at risk.
Occurrence of anterior uveitis in patients with spondyloarthritis treated with tumor necrosis factor inhibitors: comparing the soluble receptor to monoclonal antibodies in a large observational cohort
Authors: Khoury Gisèle , Morel Jacques , Combe Bernard , Lukas Cédric 
Published: April 2020

Abstract
Background
The objective of this study was to compare in real life the occurrence of anterior uveitis in patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA), treated with the soluble-receptor etanercept (ETA) or monoclonal antibodies (mAbs).

Methods
This was an observational, retrolective study. Patients with SpA who were prescribed anti-TNF agents between 2000 and 2014 were included. The risk of uveitis was interpreted qualitatively (number of subjects with at least one uveitis) and quantitatively (number of uveitis flares for each individual). Models were adjusted for propensity score of receiving preferentially mAbs or ETA.

Results
Four hundred twenty-nine patients were included (302 with SpA and 127 with PsA); 203 received a mAb and 226 ETA as a first TNF-α inhibitor. Probability of uveitis occurring during the first year of treatment was lower with ETA than with mAbs but not significantly (odds ratio 0.94 [95% confidence interval 0.35; 2.54], p = 0.90, on qualitative analysis and relative risk 0.62 [0.26; 1.46], p = 0.27, on quantitative analysis) after adjustment for the propensity score. The over-time risk of uveitis was numerically higher with ETA than with mAbs, but the differences were not statistically significant.

Conclusion
In this observational study, the risk of uveitis in patients with SpA does not appear to be greater with ETA than with mAb treatment. The occurrence of uveitis in patients receiving an anti-TNF-α agent seems linked more to the history of uveitis than the prescribed molecule.
Real-time ultrasound-guided thoracentesis in the intensive care unit: prevalence of mechanical complications
Authors: Rodriguez Lima David Rene , Yepes Andrés Felipe , Birchenall Jiménez Claudia Inés , Mercado Díaz Mario Andrés , Pinilla Rojas Darío Isaías 
Published: April 2020

Abstract
Background
The use of thoracic ultrasound during thoracentesis reduces complications. The aim of this study was to determine the prevalence of complications for real-time ultrasound-guided thoracentesis performed by intensivists. As a secondary objective, the change in oxygenation before and after the procedure was evaluated.

Patients and methods
An observational prospective study was conducted. A total of 81 cases of real-time ultrasound-guided thoracentesis performed by intensivists in the intensive care unit (ICU) of Méderi Major University Hospital, Bogotá, Colombia, between August 2018 and August 2019 were analyzed. Thoracentesis performed by interventional radiologists and using techniques different from the focus of this study were excluded from the analysis.

Results
There was one pneumothorax, for a prevalence rate of mechanical complications in this population of 1.2%. The mean partial oxygen pressure to inspired oxygen fraction ratio (PaO2/FiO2) prior to the procedure was 198.1 (95% CI 184.75–211.45), with a PaO2/FiO2 after the procedure of 224.6 (95% CI 213.08–226.12) (p < 0.05).

Conclusions
Real-time ultrasound-guided thoracentesis performed by intensivists is a safe procedure and leads to a significant improvement in oxygenation rates. Future studies are required to determine the impact of these results on other outcomes, such as mortality, ICU stay, and days of mechanical ventilation.
The influence of contextual factors on healthcare quality improvement initiatives: a realist review
Authors: Coles Emma , Anderson Julie , Maxwell Margaret , Harris Fiona M. , Gray Nicola M. , Milner Gill , MacGillivray Stephen 
Published: April 2020

Abstract
Background
Recognising the influence of context and the context-sensitive nature of quality improvement (QI) interventions is crucial to implementing effective improvements and successfully replicating them in new settings, yet context is still poorly understood. To address this challenge, it is necessary to capture generalisable knowledge, first to understand which aspects of context are most important to QI and why, and secondly, to explore how these factors can be managed to support healthcare improvement, in terms of implementing successful improvement initiatives, achieving sustainability and scaling interventions. The research question was how and why does context influence quality improvement initiatives in healthcare?

Methods
A realist review explored the contextual conditions that influence healthcare improvement. Realist methodology integrates theoretical understanding and stakeholder input with empirical research findings. The review aimed to identify and understand the role of context during the improvement cycle, i.e. planning, implementation, sustainability and transferability; and distil new knowledge to inform the design and development of context-sensitive QI initiatives. We developed a preliminary theory of the influence of context to arrive at a conceptual and theoretical framework.

Results
Thirty-five studies were included in the review, demonstrating the interaction of key contextual factors across healthcare system levels during the improvement cycle. An evidence-based explanatory theoretical model is proposed to illustrate the interaction between contextual factors, system levels (macro, meso, micro) and the stages of the improvement journey. Findings indicate that the consideration of these contextual factors would enhance the design and delivery of improvement initiatives, across a range of improvement settings.

Conclusions
This is the first realist review of context in QI and contributes to a deeper understanding of how context influences quality improvement initiatives. The distillation of key contextual factors offers the potential to inform the design and development of context-sensitive interventions to enhance improvement initiatives and address the challenge of spread and sustainability. Future research should explore the application of our conceptual model to enhance improvement-planning processes.

Systematic review registration
PROSPERO CRD42017062135
Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis
Authors: Ferreyro Bruno L. , Angriman Federico , Munshi Laveena , Del Sorbo Lorenzo , Ferguson Niall D. , Rochwerg Bram , Ryu Michelle J. , Saskin Refik , Wunsch Hannah , da Costa Bruno R. , Scales Damon C. 
Published: April 2020

AbstractBackgroundAcute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure.MethodsWe will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology.DiscussionThis study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure.Systematic review registrationPROSPEROCRD42019121755
Numerical Simulation of Consolidation Behavior of Large Hydrating Fill Mass
Authors: Cui Liang , Fall Mamadou 
Published: April 2020

AbstractUnderground mined-out voids need to be backfilled for the stability of the surrounding rock and also to increase ore extraction from adjacent pillars. One of the relatively newer means is cemented paste backfilling, which has been extensively adopted in underground mining operations around the world. During and after the placement of cemented paste backfill (CPB) into stopes, complex multiphysics (thermal, hydraulic, mechanical and chemical) processes take place in the large mass of CPB and could affect its consolidation behavior. An analysis of the consolidation process in CPB mass is essential for the assessment of CPB behavior and cost-effective designs in practice. In this paper, multiphysics simulation of the consolidation behavior of CPB mass is performed under different conditions, including the mixture recipe, and backfilling, drainage, surrounding rock and curing conditions. It is found that the in situ consolidation behavior of CPB structures is a function of the multiphysics processes that occur in the cementing backfill mass. Moreover, the rock mass conditions, including the geometry and rock wall roughness, influence the consolidation process of CPB structures. Cement content, curing time and backfilling rate play a crucial role in the consolidation process of CPB. The obtained results can facilitate a better understanding of the consolidation behaviour of CPB for backfill designers and engineers, and thus contribute to enhance the engineering of CPB structures.
Metacognitive beliefs mediate the relationship between anxiety sensitivity and traits of obsessive-compulsive symptoms
Authors: Gutierrez Roberto , Hirani Tulsi , Curtis Leo , Ludlow Amanda K. 
Published: April 2020

Abstract
Background
Metacognition has been shown as a key contributor to Obsessive Compulsive Disorder as well as other anxiety-related disorders, yet its role in the development and maintenance of these disorders remains unclear. This study aims to investigate whether anxiety sensitivity traits are related to obsessive-compulsive symptoms in the general population and whether the relationship between anxiety sensitivity and obsessive-compulsive symptoms is mediated by metacognition.

Methods
Non-clinical volunteers (N = 156, mean age: 23.97, 121 females) completed measures related to state/trait anxiety, anxiety sensitivity, obsessive compulsive symptoms and metacognition.

Results
A direct relationship between anxiety sensitivity and obsessive-compulsive symptoms was established. Further analysis revealed that metacognition was the strongest mediator of this relationship, even when accounting for state and trait anxiety.

Conclusions
Results suggest that the relationships between traits of anxiety sensitivity and obsessive-compulsive symptoms are partially attributable to the role of metacognition.