bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excellent Diagnostic Characteristics for Ultrafast Gene Profiling ofDEFA1-IL1B-LTFin Detection of Prosthetic Joint Infections
Authors: Fillerova Regina , Gallo Jiri , Radvansky Martin , Kraiczova Veronika , Kudelka Milos , Kriegova Eva 
Published: June 2017

ABSTRACTThe timely and exact diagnosis of prosthetic joint infection (PJI) is crucial for surgical decision-making. Intraoperatively, delivery of the result within an hour is required. Alpha-defensin lateral immunoassay of joint fluid (JF) is precise for the intraoperative exclusion of PJI; however, for patients with a limited amount of JF and/or in cases where the JF is bloody, this test is unhelpful. Important information is hidden in periprosthetic tissues that may much better reflect the current status of implant pathology. We therefore investigated the utility of the gene expression patterns of 12 candidate genes (TLR1, -2, -4, -6, and10,DEFA1,LTF,IL1B,BPI,CRP,IFNG, andDEFB4A) previously associated with infection for detection of PJI in periprosthetic tissues of patients with total joint arthroplasty (TJA) (n= 76) reoperated for PJI (n= 38) or aseptic failure (n= 38), using the ultrafast quantitative reverse transcription-PCR (RT-PCR) Xxpress system (BJS Biotechnologies Ltd.). Advanced data-mining algorithms were applied for data analysis. For PJI, we detected elevated mRNA expression levels ofDEFA1(P< 0.0001),IL1B(P< 0.0001),LTF(P< 0.0001),TLR1(P= 0.02), andBPI(P= 0.01) in comparison to those in tissues from aseptic cases. A feature selection algorithm revealed that theDEFA1-IL1B-LTFpattern was the most appropriate for detection/exclusion of PJI, achieving 94.5% sensitivity and 95.7% specificity, with likelihood ratios (LRs) for positive and negative results of 16.3 and 0.06, respectively. Taken together, the results show thatDEFA1-IL1B-LTFgene expression detection by use of ultrafast qRT-PCR linked to an electronic calculator allows detection of patients with a high probability of PJI within 45 min after sampling. Further testing on a larger cohort of patients is needed.
Going against the Tide: Selective Cellular Protein Synthesis during Virally Induced Host Shutoff
Authors: Cao Shuai , Dhungel Pragyesh , Yang Zhilong 
Published: June 2017

ABSTRACTMany viral infections cause host shutoff, a state in which host protein synthesis is globally inhibited. Emerging evidence from vaccinia and influenza A virus infections indicates that subsets of cellular proteins are resistant to host shutoff and continue to be synthesized. Remarkably, the proteins of oxidative phosphorylation, the cellular-energy-generating machinery, are selectively synthesized in both cases. Identifying mechanisms that drive selective protein synthesis should facilitate understanding both viral replication and fundamental cell biology.
Discovery of a Highly Divergent Coronavirus in the Asian House Shrew from China Illuminates the Origin of the Alphacoronaviruses
Authors: Wang Wen , Lin Xian-Dan , Liao Yong , Guan Xiao-Qing , Guo Wen-Ping , Xing Jian-Guang , Holmes Edward C. , Zhang Yong-Zhen 
Published: June 2017

ABSTRACT

Although shrews are one of the largest groups of mammals, little is known about their role in the evolution and transmission of viral pathogens, including coronaviruses (CoVs). We captured 266 Asian house shrews (
Suncus murinus
) in Jiangxi and Zhejiang Provinces, China, during 2013 to 2015. CoV RNA was detected in 24 Asian house shrews, with an overall prevalence of 9.02%. Complete viral genome sequences were successfully recovered from the RNA-positive samples. The newly discovered shrew CoV fell into four lineages reflecting their geographic origins, indicative of largely allopatric evolution. Notably, these viruses were most closely related to alphacoronaviruses but sufficiently divergent that they should be considered a novel member of the genus
Alphacoronavirus
, which we denote Wénchéng shrew virus (WESV). Phylogenetic analysis revealed that WESV was a highly divergent member of the alphacoronaviruses and, more dramatically, that the S gene of WESV fell in a cluster that was genetically distinct from that of known coronaviruses. The divergent position of WESV suggests that coronaviruses have a long association with Asian house shrews. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to genes of any known viruses. Together, these data suggest that shrews are natural reservoirs for coronaviruses and may have played an important and long-term role in CoV evolution.

IMPORTANCE
The subfamily
Coronavirinae
contains several notorious human and animal pathogens, including severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and porcine epidemic diarrhea virus. Because of their genetic diversity and phylogenetic relationships, it has been proposed that the alphacoronaviruses likely have their ultimate ancestry in the viruses residing in bats. Here, we describe a novel alphacoronavirus (Wénchéng shrew virus [WESV]) that was sampled from Asian house shrews in China. Notably, WESV is a highly divergent member of the alphacoronaviruses and possesses an S gene that is genetically distinct from those of all known coronaviruses. In addition, the genome of WESV contains a distinct NS7 gene that exhibits no sequence similarity to those of any known viruses. Together, these data suggest that shrews are important and longstanding hosts for coronaviruses that merit additional research and surveillance.
The relationship between physician burnout and quality of healthcare in terms of safety and acceptability: a systematic review
Authors: Dewa Carolyn S , Loong Desmond , Bonato Sarah , Trojanowski Lucy 
Published: June 2017

ObjectivesThis study reviews the current state of the published peer-reviewed literature related to physician burnout and two quality of care dimensions. The purpose of this systematic literature review is to address the question, ‘How does physician burnout affect the quality of healthcare related to the dimensions of acceptability and safety?’DesignUsing a multiphase screening process, this systematic literature review is based on publically available peer-reviewed studies published between 2002 and 2017. Six electronic databases were searched: (1)MEDLINE Current, (2)MEDLINE In-process, (3)MEDLINE Epub Ahead of Print, (4)PsycINFO, (5)Embaseand (6)Web of Science.SettingPhysicians practicing in civilian settings.ParticipantsPracticing physicians who have completed training.Primary and secondary outcome measuresQuality of healthcare related to acceptability (ie, patient satisfaction, physician communication and physician attitudes) and safety (ie, minimising risks or harm to patients).Results4114 unique citations were identified. Of these, 12 articles were included in the review. Two studies were rated as having high risk of bias and 10 as having moderate risk. Four studies were conducted in North America, four in Europe, one in the Middle East and three in East Asia. Results of this systematic literature review suggest there is moderate evidence that burnout is associated with safety-related quality of care. Because of the variability in the way patient acceptability-related quality of care was measured and the inconsistency in study findings, the evidence supporting the relationship between burnout and patient acceptability-related quality of care is less strong.ConclusionsThe focus on direct care-related quality highlights additional ways that physician burnout affects the healthcare system. These studies can help to inform decisions about how to improve patient care by addressing physician burnout. Continued work looking at the relationship between dimensions of acceptability-related quality of care measures and burnout is needed to advance the field.
Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire
Authors: Santosh Paramala , Lievesley Kate , Fiori Federico , Singh Jatinder 
Published: June 2017

IntroductionRett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT—methyl-CpG-binding protein 2(MECP2) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT. As part of the HealthTracker-based Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database, the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire will be able to marry with the physiological aspects of the disease obtained using wearable sensor technology, along with genetic and psychosocial data to stratify patients. Taken together, the web-based TRIAL database will empower clinicians and researchers with the confidence to delineate between different aspects of disorder symptomatology to streamline care pathways for individuals or for those patients entering clinical trials. This protocol describes the anticipated development of the REST questionnaire and the TRIAL database which links with the outcomes of the wearable sensor technology, and will serve as a barometer for longitudinal patient monitoring in patients with RTT.Methods and analysisThe US Food and Drug Administration Guidance for Patient-Reported Outcome Measures will be used as a template to inform the methodology of the study. It will follow an iterative framework that will include item/concept identification, item/concept elicitation in parent/carer-mediated focus groups, expert clinician feedback, web-based presentation of questionnaires, initial scale development, instrument refinement and instrument validation.Ethics and disseminationThe study has received favourable opinion from the National Health Service (NHS) Research Ethics Committee (REC): NHS Research Ethics Committee (REC)—London, Bromley Research Ethics Committee (reference: 15/LO/1772).
Transcatheter closure, mini-invasive closure and open-heart surgical repair for treatment of perimembranous ventricular septal defects in children: a protocol for a network meta-analysis
Authors: You Tao , Yi Kang , Ding Zhao-hong , Hou Xiao-dong , Liu Xing-guang , Wang Xin-kuan , Ge Long , Tian Jin-hui 
Published: June 2017

IntroductionBoth transcatheter device closure and surgical repair are effective treatments with excellent midterm outcomes for perimembranous ventricular septal defects (pmVSDs) in children. The mini-invasive periventricular device occlusion technique has become prevalent in research and application, but evidence is limited for the assessment of transcatheter closure, mini-invasive closure and open-heart surgical repair. This study comprehensively compares the efficacy, safety and costs of transcatheter closure, mini-invasive closure and open-heart surgical repair for treatment of pmVSDs in children using Bayesian network meta-analysis.Methods and analysisA systematic search will be performed using Chinese Biomedical Literature Database, China National Knowledge Infrastructure, PubMed, EMBASE.com and the Cochrane Central Register of Controlled Trials to include random controlled trials, prospective or retrospective cohort studies comparing the efficacy, safety and costs of transcatheter closure, mini-invasive closure and open-heart surgical repair. The risk of bias for the included prospective or retrospective cohort studies will be evaluated according to the risk of bias in non-randomised studies of interventions (ROBINS-I). For random controlled trials, we will use risk of bias tool from Cochrane Handbook version 5.1.0. A Bayesian network meta-analysis will be conducted using R-3.3.2 software.Ethics and disseminationEthical approval and patient consent are not required since this study is a network meta-analysis based on published trials. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication.Protocol registration numberCRD42016053352.
Management of shoulder pain by UK general practitioners (GPs): a national survey
Authors: Artus Majid , van der Windt Danielle A , Afolabi Ebenezer K , Buchbinder Rachelle , Chesterton Linda S , Hall Alison , Roddy Edward , Foster Nadine E 
Published: June 2017

ObjectivesStudies in Canada, the USA and Australia suggested low confidence among general practitioners (GPs) in diagnosing and managing shoulder pain, with frequent use of investigations. There are no comparable studies in the UK; our objective was to describe the diagnosis and management of shoulder pain by GPs in the UK.MethodsA national survey of a random sample of 5000 UK GPs collected data on shoulder pain diagnosis and management using two clinical vignettes that described primary care presentations with rotator cuff tendinopathy (RCT) and adhesive capsulitis (AdhC).ResultsSeven hundred and fourteen (14.7%) responses were received. 56% and 83% of GPs were confident in their diagnosis of RCT and AdhC, respectively, and a wide range of investigations and management options were reported. For the RCT presentation, plain radiographs of the shoulder were most common (60%), followed by blood tests (42%) and ultrasound scans (USS) (38%). 19% of those who recommended a radiograph and 76% of those who recommended a USS did so ‘to confirm the diagnosis’. For the AdhC presentation, the most common investigations were blood tests (60%), plain shoulder radiographs (58%) and USS (31%). More than two-thirds of those recommending a USS did so ‘to confirm the diagnosis’. The most commonly recommended treatment for both presentations was physiotherapy (RCT 77%, AdhC 71%) followed by non-steroidal anti-inflammatory drugs (RCT 58%, AdhC 74%). 17% opted to refer the RCT to secondary care (most often musculoskeletal interface service), compared with 31% for the AdhC.ConclusionsThis survey of GPs in the UK highlights reliance on radiographs and blood tests in the management of common shoulder pain presentations. GPs report referring more than 7 out of 10 patients with RCT and AdhC to physiotherapists. These findings need to be viewed in the context of low response to the survey and, therefore, potential non-response bias.
Development of the Human Factors Skills for Healthcare Instrument: a valid and reliable tool for assessing interprofessional learning across healthcare practice settings
Authors: Reedy Gabriel B , Lavelle Mary , Simpson Thomas , Anderson Janet E 
Published: June 2017

BackgroundA central feature of clinical simulation training is human factors skills, providing staff with the social and cognitive skills to cope with demanding clinical situations. Although these skills are critical to safe patient care, assessing their learning is challenging. This study aimed to develop, pilot and evaluate a valid and reliable structured instrument to assess human factors skills, which can be used pre- and post-simulation training, and is relevant across a range of healthcare professions.MethodThrough consultation with a multi-professional expert group, we developed and piloted a 39-item survey with 272 healthcare professionals attending training courses across two large simulation centres in London, one specialising in acute care and one in mental health, both serving healthcare professionals working across acute and community settings. Following psychometric evaluation, the final 12-item instrument was evaluated with a second sample of 711 trainees.ResultsExploratory factor analysis revealed a 12-item, one-factor solution with good internal consistency (α=0.92). The instrument had discriminant validity, with newly qualified trainees scoring significantly lower than experienced trainees (t(98)=4.88, p<0.001) and was sensitive to change following training in acute and mental health settings, across professional groups (p<0.001). Confirmatory factor analysis revealed an adequate model fit (RMSEA=0.066).ConclusionThe Human Factors Skills for Healthcare Instrument provides a reliable and valid method of assessing trainees’ human factors skills self-efficacy across acute and mental health settings. This instrument has the potential to improve the assessment and evaluation of human factors skills learning in both uniprofessional and interprofessional clinical simulation training.
Genome-Wide Association Studies of Cancer in Diverse Populations
Authors: Park Sungshim L. , Cheng Iona , Haiman Christopher A. 
Published: June 2017

AbstractGenome-wide association studies (GWAS) of cancer have identified more than 700 risk loci, of which approximately 80% were first discovered in European ancestry populations, approximately 15% in East Asians, 3% in multiethnic scans, and less than 1% in African and Latin American populations. These percentages closely mirror the distribution of samples included in the discovery phase of cancer GWAS to date (84% European, 11% East Asian, 4% African, and 1% Latin American ancestry). GWAS in non-European ancestry populations have provided insight into ancestry-specific variation in cancer and have pointed to regions of susceptibility that are of particular importance in certain populations. Uncovering and characterizing cancer risk loci in diverse populations is critical for understanding underlying biological mechanisms and developing future genetic risk prediction models in non-European ancestry populations. New GWAS and continued collaborations will be required to eliminate population inequalities in the number of studies, sample sizes, and variant content on GWAS arrays, and to better align genetic research in cancer to the global distribution of race/ethnicity Cancer Epidemiol Biomarkers Prev; 27(4); 405–17. ©2018 AACR.See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Quantifying the Genetic Correlation between Multiple Cancer Types
Authors: Lindström Sara , Finucane Hilary , Bulik-Sullivan Brendan , Schumacher Fredrick R. , Amos Christopher I. , Hung Rayjean J. , Rand Kristin , Gruber Stephen B. , Conti David , Permuth Jennifer B. , Lin Hui-Yi , Goode Ellen L. , Sellers Thomas A. , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Klein Alison , Petersen Gloria , Risch Harvey , Wolpin Brian , Hsu Li , Huyghe Jeroen R. , Chang-Claude Jenny , Chan Andrew , Berndt Sonja , Eeles Rosalind , Easton Douglas , Haiman Christopher A. , Hunter David J. , Neale Benjamin , Price Alkes L. , Kraft Peter 
Published: June 2017

Abstract
Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.
Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.
Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P &lt; 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10−6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.
Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.
Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427–35. ©2017 AACR.
FUS–DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma
Authors: Trautmann Marcel , Menzel Jasmin , Bertling Christian , Cyra Magdalene , Isfort Ilka , Steinestel Konrad , Elges Sandra , Grünewald Inga , Altvater Bianca , Rossig Claudia , Fröhling Stefan , Hafner Susanne , Simmet Thomas , Åman Pierre , Wardelmann Eva , Huss Sebastian , Hartmann Wolfgang 
Published: June 2017

Abstract
Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS–DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS–DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis.
Experimental Design: Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens. FUS–DDIT3 dependency and biological function of the IGF-IR/PI3K/Akt signaling cascade were analyzed using a HT1080 fibrosarcoma-based myxoid liposarcoma tumor model and multiple tumor–derived myxoid liposarcoma cell lines. An established myxoid liposarcoma avian chorioallantoic membrane model was used for in vivo confirmation of the preclinical in vitro results.
Results: A comprehensive subset of myxoid liposarcoma specimens showed elevated expression and phosphorylation levels of various IGF-IR/PI3K/Akt signaling effectors. In HT1080 fibrosarcoma cells, overexpression of FUS-DDIT3 induced aberrant IGF-IR/PI3K/Akt pathway activity, which was dependent on transcriptional induction of the IGF2 gene. Conversely, RNAi-mediated FUS–DDIT3 knockdown in myxoid liposarcoma cells led to an inactivation of IGF-IR/PI3K/Akt signaling associated with diminished IGF2 mRNA expression. Treatment of myxoid liposarcoma cell lines with several IGF-IR inhibitors resulted in significant growth inhibition in vitro and in vivo.
Conclusions: Our preclinical study substantiates the fundamental role of the IGF-IR/PI3K/Akt signaling pathway in myxoid liposarcoma pathogenesis and provides a mechanism-based rationale for molecular- targeted approaches in myxoid liposarcoma cancer therapy. Clin Cancer Res; 23(20); 6227–38. ©2017 AACR.