bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of baseline inflammatory markers in patients with acute coronary syndromes treated with ticagrelor and clopidogrel
Authors: Thomas Mark R , James Stefan K , Becker Richard C , Himmelmann Anders , Katus Hugo A , Cannon Christopher P , Steg Philippe Gabriel , Siegbahn Agneta , Lakic Tatevik , Storey Robert F , Wallentin Lars 
Published: December 2019

Abstract

Background
Inflammation plays a major role in the pathophysiology of coronary artery disease. We aimed to determine whether baseline inflammatory markers were associated with clinical outcomes and the observed superiority of ticagrelor compared to clopidogrel in patients with acute coronary syndromes in the PLATO study.

Methods
Blood samples were collected from 16,400 patients within 24 hours of the onset of acute coronary syndrome, at the time of random assignment to ticagrelor or clopidogrel in the PLATO study and prior to invasive procedures. The differential white blood cell count and plasma levels of C-reactive protein, interleukin-6 and interleukin-10 were determined and their relationships with clinical outcomes were assessed according to quartiles and using continuous models. The substudy primary endpoint was a composite of cardiovascular death and myocardial infarction.

Results
Compared to the lowest quartile, the risk of the primary endpoint was significantly elevated in patients in the highest quartile of white blood cell count (hazard ratio (HR) 1.30; P=0.01), neutrophil count (HR 1.33; P=0.007), monocyte count (HR 1.24; P=0.004), C-reactive protein (HR 1.93; P&lt;0.001) and interleukin-6 (HR 2.29; P&lt;0.001). This was predominantly driven by an association with cardiovascular death. Following adjustment for clinical characteristics, troponin, cystatin C and N-terminal pro-brain-type natriuretic peptide, only white blood cell count and neutrophil count maintained a significant association with the primary endpoint. Ticagrelor had a consistent relative cardiovascular benefit compared to clopidogrel in each quartile of each of the inflammatory markers.

Conclusions
Acute coronary syndrome patients with elevated levels of baseline inflammatory markers are at increased risk of adverse cardiovascular events, particularly cardiovascular death. The consistent cardiovascular benefit of ticagrelor compared to clopidogrel tended to confer a greater absolute risk reduction in patients with the highest levels of inflammatory markers, as they were at highest risk.
Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation
Authors: Zhao Xiang-Yu , Yu Xing-Xing , Xu Zheng-Li , Cao Xun-Hong , Huo Ming-Rui , Zhao Xiao-Su , Chang Ying-Jun , Wang Yu , Zhang Xiao-Hui , Xu Lan-Ping , Liu Kai-Yan , Huang Xiao-Jun 
Published: December 2019

Abstract
The rate and extent of natural killer (NK)–cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.
Allo-HSCT in transplant-naïve patients with Hodgkin lymphoma: a single-arm, multicenter study
Authors: Das-Gupta Emma , Thomson Kirsty J. , Bloor Adrian J. C. , Clark Andrew D. , Mackinnon Stephen , Kayani Irfan , Clifton-Hadley Laura , Patrick Pip , El-Mehidi Nadjet , Lawrie Anthony , Kirkwood Amy A. , Russell Nigel H. , Linch David C. , Peggs Karl S. 
Published: December 2019

Abstract
We evaluated the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in transplant-naïve patients with relapsed/refractory Hodgkin lymphoma (HL) who failed to attain metabolic complete response (mCR) to 1 to 2 lines of salvage chemotherapyThose with residual but nonprogressive disease assessed by positron emission tomography/computed tomography scanning were eligible. An additional 1 to 2 cycles of salvage therapy were permissible in those with progressive disease or when required to bridge to allo-HSCT, with additional imaging at baseline before transplantation. Conditioning consisted of carmustine, etoposide, cytarabine, melphalan, and alemtuzumab. Donor lymphocyte infusions (DLI) were administered for mixed chimerism or residual or relapsed disease. Eleven patients had sibling donors, 13 had HLA-matched unrelated donors, and 7 had HLA-mismatched unrelated donors. There were no graft failures, and no episodes of grade 4 acute graft-versus-host disease (GVHD); only 19.4% of patients had grade 2 to 3 GVHD, and 22.2% had extensive chronic GVHD. The non-relapse mortality rate was 16.1% (95% confidence interval [CI], 7.1%-34.5%). Relapse incidence was 18.7% (95% CI, 8.2%-39.2%). The study met its primary objective, with a 3-year progression-free survival of 67.7% (95% CI, 48.4%-81.2%). Survival outcomes were equivalent in those with residual metabolically active disease immediately before transplantation (n = 24 [70.8%; 95% CI, 17.2%-83.7%]). Two of the 5 patients who relapsed received DLI and remained in mCR at latest follow-up, with a 3-year overall survival of 80.7% (95% CI, 61.9%-90.8%). We demonstrate encouraging results that establish a potential role for allo-HSCT in selected high-risk patients with HL. This trial was registered at www.clinicaltrials.gov as #NCT00908180.
Thoracic ultrasound competence for ultrasound-guided pleural procedures
Authors: McCracken David J. , Laursen Christian B. , Barker Graham , Gleeson Fergus V. , Cullen Kathy M. , Rahman Najib M. 
Published: December 2019

Focused thoracic ultrasound has become essential in the guidance and direction of pleural interventions to reduce unwanted complications and as a result now forms a crucial component of physician training. Current training standards along with assessment methods vary widely, and are often not robust enough to ensure adequate competence.This review assesses the current state of training and assessment of thoracic ultrasound competence in various settings, allowing comparison with alternative competency based programmes. Future directions for training and assessment of thoracic ultrasound competence are discussed.
SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/β-catenin signaling
Authors: Fu Qiang , Sun Zhenye , Yang Fan , Mao Tianci , Gao Yanyao , Wang He 
Published: December 2019

Abstract
Background
Sex-determining region Y-box containing gene 30 (SOX30) is a newly identified tumor-associated gene in several types of cancer. However, whether SOX30 is involved in the development and progression of prostate cancer remains unknown. This study investigated the potential role of SOX30 in prostate cancer.

Methods
Prostate cancer cell lines and a normal prostate epithelial cell line were used for the experiments. The expression of SOX30 was determined using quantitative real-time PCR and western blot analysis. The malignant cellular behaviors of prostate cancer were assessed using the Cell Counting Kit-8, colony formation and Matrigel invasion assays. The miRNA–mRNA interaction was validated using the dual-luciferase reporter assay.

Results
SOX30 expression was lower in cells of prostate cancer lines than in cells of the normal prostate epithelial line. Its overexpression repressed the proliferation and invasion of prostate cancer cells. SOX30 was identified as a target gene of microRNA-653-5p (miR-653-5p), which is upregulated in prostate cancer tissues. MiR-653-5p overexpression decreased SOX30 expression, while its inhibition increased SOX30 expression in prostate cancer cells. MiR-653-5p inhibition also markedly restricted prostate cancer cell proliferation and invasion. SOX30 overexpression or miR-653-5p inhibition significantly reduced β-catenin expression and downregulated the activation of Wnt/β-catenin signaling. SOX30 knockdown significantly reversed the miR-653-5p inhibition-mediated inhibitory effect on the proliferation, invasion and Wnt/β-catenin signaling in prostate cancer cells.

Conclusions
These results reveal a tumor suppressive function for SOX30 in prostate cancer and confirmed the gene as a target of miR-653-5p. SOX30 upregulation due to miR-653-5p inhibition restricted the proliferation and invasion of prostate cancer cells, and this was associated with Wnt/β-catenin signaling suppression. These findings highlight the importance of the miR-653-5p–SOX30–Wnt/β-catenin signaling axis in prostate cancer progression.
Optical coherence tomography angiography in uveitis
Authors: Tranos Paris , Karasavvidou Evdoxia-Maria , Gkorou Olga , Pavesio Carlos 
Published: December 2019

AbstractBefore the introduction of optical coherence tomography angiography (OCTA) in the early 2000s, dye-based angiography was considered the “gold standard” for the diagnosis and monitoring of ocular inflammation. OCTA is a novel technique, which demonstrates capillary networks based on the amount of light returned from moving blood cells, providing further information on pathophysiological changes in uveitis.The aim of this review is to describe the basic principles of OCTA and its application to ocular inflammatory disorders. It particularly emphasizes on its contribution not only in the diagnosis and management of the disease but also in the identification of possible complications, comparing it with fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Although the advent of OCTA has remarkably enhanced the assessment of uveitic entities, we highlight the need for further investigation in order to better understand its application to these conditions.
A 2018 workshop: vaccine and drug ontology studies (VDOS 2018)
Authors: Hur Junguk , Tao Cui , He Yongqun 
Published: December 2019

AbstractThis Editorial first introduces the background of the vaccine and drug relations and how biomedical terminologies and ontologies have been used to support their studies. The history of the seven workshops, initially named VDOSME, and then named VDOS, is also summarized and introduced. Then the 7th International Workshop on Vaccine and Drug Ontology Studies (VDOS 2018), held on August 10th, 2018, Corvallis, Oregon, USA, is introduced in detail. These VDOS workshops have greatly supported the development, applications, and discussion of vaccine- and drug-related terminology and drug studies.
Enhancing the drug ontology with semantically-rich representations of National Drug Codes and RxNorm unique concept identifiers
Authors: Bona Jonathan P. , Brochhausen Mathias , Hogan William R. 
Published: December 2019

Abstract
Background
The Drug Ontology (DrOn) is a modular, extensible ontology of drug products, their ingredients, and their biological activity created to enable comparative effectiveness and health services researchers to query National Drug Codes (NDCs) that represent products by ingredient, by molecular disposition, by therapeutic disposition, and by physiological effect (e.g., diuretic). It is based on the RxNorm drug terminology maintained by the U.S. National Library of Medicine, and on the Chemical Entities of Biological Interest ontology. Both national drug codes (NDCs) and RxNorm unique concept identifiers (RXCUIS) can undergo changes over time that can obfuscate their meaning when these identifiers occur in historic data. We present a new approach to modeling these entities within DrOn that will allow users of DrOn working with historic prescription data to more easily and correctly interpret that data.

Results
We have implemented a full accounting of national drug codes and RxNorm unique concept identifiers as information content entities, and of the processes involved in managing their creation and changes. This includes an OWL file that implements and defines the classes necessary to model these entities. A separate file contains an instance-level prototype in OWL that demonstrates the feasibility of this approach to representing NDCs and RXCUIs and the processes of managing them by retrieving and representing several individual NDCs, both active and inactive, and the RXCUIs to which they are connected. We also demonstrate how historic information about these identifiers in DrOn can be easily retrieved using a simple SPARQL query.

Conclusions
An accurate model of how these identifiers operate in reality is a valuable addition to DrOn that enhances its usefulness as a knowledge management resource for working with historic data.
Conceiving an application ontology to model patient human papillomavirus vaccine counseling for dialogue management
Authors: Amith Muhammad , Roberts Kirk , Tao Cui 
Published: December 2019

AbstractBackgroundIn the United States and parts of the world, the human papillomavirus vaccine uptake is below the prescribed coverage rate for the population. Some research have noted that dialogue that communicates the risks and benefits, as well as patient concerns, can improve the uptake levels. In this paper, we introduce an application ontology for health information dialogue called Patient Health Information Dialogue Ontology for patient-level human papillomavirus vaccine counseling and potentially for any health-related counseling.ResultsThe ontology’s class level hierarchy is segmented into 4 basic levels -Discussion,Goal,Utterance, andSpeech Task. The ontology also defines core low-level utterance interaction for communicating human papillomavirus health information. We discuss the design of the ontology and the execution of the utterance interaction.ConclusionWith an ontology that represents patient-centric dialogue to communicate health information, we have an application-driven model that formalizes the structure for the communication of health information, and a reusable scaffold that can be integrated for software agents. Our next step will to be develop the software engine that will utilize the ontology and automate the dialogue interaction of a software agent.
VIO: ontology classification and study of vaccine responses given various experimental and analytical conditions
Authors: Ong Edison , Sun Peter , Berke Kimberly , Zheng Jie , Wu Guanming , He Yongqun 
Published: December 2019

Abstract
Background
Different human responses to the same vaccine were frequently observed. For example, independent studies identified overlapping but different transcriptomic gene expression profiles in Yellow Fever vaccine 17D (YF-17D) immunized human subjects. Different experimental and analysis conditions were likely contributed to the observed differences. To investigate this issue, we developed a Vaccine Investigation Ontology (VIO), and applied VIO to classify the different variables and relations among these variables systematically. We then evaluated whether the ontological VIO modeling and VIO-based statistical analysis would contribute to the enhanced vaccine investigation studies and a better understanding of vaccine response mechanisms.

Results
Our VIO modeling identified many variables related to data processing and analysis such as normalization method, cut-off criteria, software settings including software version. The datasets from two previous studies on human responses to YF-17D vaccine, reported by Gaucher et al. (2008) and Querec et al. (2009), were re-analyzed. We first applied the same LIMMA statistical method to re-analyze the Gaucher data set and identified a big difference in terms of significantly differentiated gene lists compared to the original study. The different results were likely due to the LIMMA version and software package differences. Our second study re-analyzed both Gaucher and Querec data sets but with the same data processing and analysis pipeline. Significant differences in differential gene lists were also identified. In both studies, we found that Gene Ontology (GO) enrichment results had more overlapping than the gene lists and enriched pathway lists. The visualization of the identified GO hierarchical structures among the enriched GO terms and their associated ancestor terms using GOfox allowed us to find more associations among enriched but often different GO terms, demonstrating the usage of GO hierarchical relations enhance data analysis.

Conclusions
The ontology-based analysis framework supports standardized representation, integration, and analysis of heterogeneous data of host responses to vaccines. Our study also showed that differences in specific variables might explain different results drawn from similar studies.
Root system traits impact early fire blight susceptibility in apple (Malus × domestica)
Authors: Singh Jugpreet , Fabrizio Jack , Desnoues Elsa , Silva Julliany Pereira , Busch Wolfgang , Khan Awais 
Published: December 2019

AbstractBackgroundAlthough it is known that resistant rootstocks facilitate management of fire blight disease, incited byErwinia amylovora,the role of rootstock root traits in providing systemic defense againstE. amylovorais unclear. In this study, the hypothesis that rootstocks of higher root vigor provide higher tolerance to fire blight infection in apples is tested. Several apple scion genotypes grafted onto a single rootstock genotype and non-grafted ‘M.7’ rootstocks of varying root vigor are used to assess phenotypic and molecular relationships between root traits of rootstocks and fire blight susceptibility of apple scion cultivars.ResultsIt is observed that different root traits display significant (p < 0.05) negative correlations with fire blight susceptibility. In fact, root surface area partially dictates differential levels of fire blight susceptibility of ‘M.7’ rootstocks. Furthermore, contrasting changes in gene expression patterns of diverse molecular pathways accompany observed differences in levels of root-driven fire blight susceptibility. It is noted that a singular co-expression gene network consisting of genes from defense, carbohydrate metabolism, protein kinase activity, oxidation-reduction, and stress response pathways modulates root-dependent fire blight susceptibility in apple. In particular, WRKY75 and UDP-glycotransferase are singled-out as hub genes deserving of further detailed analysis.ConclusionsIt is proposed that low root mass may incite resource-limiting conditions to activate carbohydrate metabolic pathways, which reciprocally interact with plant immune system genes to elicit differential levels of fire blight susceptibility.
Integrative genomic analysis identified common regulatory networks underlying the correlation between coronary artery disease and plasma lipid levels
Authors: Chen Liuying , Yao Yinghao , Jin Chaolun , Wu Shen , Liu Qiang , Li Jingjing , Ma Yunlong , Xu Yizhou , Zhong Yigang 
Published: December 2019

Abstract
Background
Coronary artery disease (CAD) and plasma lipid levels are highly correlated, indicating the presence of common pathways between them. Nevertheless, the molecular pathways underlying the pathogenic comorbidities for both traits remain poorly studied. We sought to identify common pathways and key driver genes by performing a comprehensive integrative analysis based on multi-omic datasets.

Methods
By performing a pathway-based analysis of GWAS summary data, we identified that lipoprotein metabolism process-related pathways were significantly associated with CAD risk. Based on LD score regression analysis of CAD-related SNPs, significant heritability enrichments were observed in the cardiovascular and digestive system, as well as in liver and gastrointestinal tissues, which are the main regulators for lipid level.

Results
We found there existed significant genetic correlation between CAD and other lipid metabolism related traits (the smallest P value < 1 × 10− 16). A total of 13 genes (e.g., LPA, APOC1, APOE and SLC22A3) was found to be overlapped between CAD and plasma lipid levels. By using the data-driven approach that integrated transcriptome information, we discovered co-expression modules associated prominently with both CAD and plasma lipids. With the detailed topology information on gene-gene regulatory relationship, we illustrated that the identified hub genes played important roles in the pathogenesis of CAD and plasma lipid turbulence.

Conclusion
Together, we identified the shared molecular mechanisms underlying the correlation between CAD and plasma lipid levels.
Clinical outcomes of over-the-scope-clip system for the treatment of acute upper non-variceal gastrointestinal bleeding: a systematic review and meta-analysis
Authors: Zhong Chunyu , Tan Shali , Ren Yutang , Lü Muhan , Peng Yan , Fu Xiangsheng , Tang Xiaowei 
Published: December 2019

Abstract
Background
Conventional endoscopic treatments can’t control bleeding in as many as 20% of patients with non-variceal gastrointestinal (GI) bleeding. Recent studies have shown that over-the-scope-clip (OTSC) system allowed for effective hemostasis for refractory GI bleeding lesions. So we aimed to conduct a systematic review to evaluate the effectiveness and safety of the OTSC system for management of acute non-variceal upper GI bleeding.

Method
A comprehensive literature search was conducted on PubMed, EMBASE, and Cochrane Library covering the period from January 2007 to May 2019. The literature was selected independently by two reviewers according to the inclusion and exclusion criteria. The statistical analysis was carried out using Comprehensive Meta-Analysis software version 3.0.

Results
A total of 16 studies including 769 patients with 778 GI bleeding lesions were identified. Pooled technical success was achieved in 761 lesions [95.7%; 95% confidence interval (CI), 93.5–97.2%], and the pooled clinical success was achieved in 666 lesions (84.2, 95% CI, 77.4–89.2%). The incidence of re-bleeding was reported in 81 patients and the post-procedure mortality was 10.9% (n = 84). Only 2 (0.3%) patients occurred complications after OTSC system procedure.

Conclusions
Our study demonstrated that the OTSC system was a technically feasible modality and highly efficacious in achieving hemostasis in acute non-variceal upper gastrointestinal bleeding.