bluuebunny/crossref_metadata_2025_split huggingface dataset:
External Validation of Risk Prediction Models Incorporating Common Genetic Variants for Incident Colorectal Cancer Using UK Biobank
Authors: Saunders Catherine L. , Kilian Britt , Thompson Deborah J. , McGeoch Luke J. , Griffin Simon J. , Antoniou Antonis C. , Emery Jon D. , Walter Fiona M. , Dennis Joe , Yang Xin , Usher-Smith Juliet A. 
Published: February 2020

Abstract
The aim of this study was to compare and externally validate risk scores developed to predict incident colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. We externally validated 23 risk models from a previous systematic review in 443,888 participants ages 37 to 73 from the UK Biobank cohort who had 6-year prospective follow-up, no prior history of colorectal cancer, and data for incidence of colorectal cancer through linkage to national cancer registries. There were 2,679 (0.6%) cases of incident colorectal cancer. We assessed model discrimination using the area under the operating characteristic curve (AUC) and relative risk calibration. The AUC of models including only SNPs increased with the number of included SNPs and was similar in men and women: the model by Huyghe with 120 SNPs had the highest AUC of 0.62 [95% confidence interval (CI), 0.59–0.64] in women and 0.64 (95% CI, 0.61–0.66) in men. Adding phenotypic risk factors without age improved discrimination in men but not in women. Adding phenotypic risk factors and age increased discrimination in all cases (P &lt; 0.05), with the best performing models including SNPs, phenotypic risk factors, and age having AUCs between 0.64 and 0.67 in women and 0.67 and 0.71 in men. Relative risk calibration varied substantially across the models. Among middle-aged people in the UK, existing polygenic risk scores discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program.
Identification of Circulating Proteins Associated With Blood Pressure Using Mendelian Randomization
Authors: Thériault Sébastien , Sjaarda Jennifer , Chong Michael , Hess Sibylle , Gerstein Hertzel , Paré Guillaume 
Published: February 2020

Background:
Hypertension is a common modifiable risk factor for cardiovascular disease and mortality. Pathophysiological mechanisms leading to hypertension remain incompletely understood. Mendelian randomization (MR) allows the evaluation of the causal role of markers by minimizing the risk of biases such as reverse causation and confounding. We aimed to identify novel circulating proteins associated with blood pressure through a comprehensive screen of 227 blood biomarkers using MR.

Methods:

Genetic determinants of 227 biomarkers were identified in ORIGIN (Outcome Reduction With Initial Glargine Intervention; URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00069784) participants (N=4147) and combined with genetic effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure from the International Consortium for Blood Pressure (74 064 individuals) using MR. Results were replicated in the UK Biobank (up to 319 103 individuals) and using another biomarker dataset (N=3301). MR analyses with cardiovascular risk factors and outcomes as well as other biomarkers were performed to further evaluate the mechanisms involved.

Results:

Six biomarkers were associated with blood pressure using MR after adjustment for multiple hypothesis testing. Relationships between NT-proBNP (N-terminal Pro-B-type natriuretic peptide), systolic blood pressure, and diastolic blood pressure confirmed previous reports. Novel circulating proteins associated with blood pressure were also identified. uPA (urokinase-type plasminogen activator) was related to systolic blood pressure; ADM (adrenomedullin) was related to systolic blood pressure and pulse pressure; IL (interleukin) 16 was related to diastolic blood pressure; cFn (cellular fibronectin) and IGFBP3 (insulin-like growth factor-binding protein 3) were related to pulse pressure. With the exception of IL16 and diastolic blood pressure (
P
=0.58), these relationships were validated in the UK Biobank (
P
<0.0001). Further MR analyses with cardiovascular risk factors and outcomes showed relationships between NT-proBNP and large-artery atherosclerotic stroke, IGFBP3 and diabetes mellitus as well as cFn and body mass index.

Conclusions:
We identified novel biomarkers associated with blood pressure using MR. These markers could prove useful for risk assessment and as potential therapeutic targets.
Distribution of Iliac Artery Calcification on Unenhanced Computed Tomography Scans Performed on Potential Recipients Prior to Renal Transplantation
Authors: Marcuzzi Adrian , Wang Stella , Tyrrell Pascal N. , Ravichandran Pradeep , Marcuzzi Danny , Prabhudesai Vikramaditya , Stewart Robert 
Published: February 2020

Purpose: To investigate whether a significant difference exists between the calcification of the common iliac arteries (CIAs) and the external iliac arteries (EIAs) and test for associations between clinical factors and the distribution of calcification. Methods: A retrospective review of renal transplant candidates who underwent a routine preoperative unenhanced computed tomography yielded 214 patients. Agatston scores for the patients’ left CIA, left EIA, right CIA, and right EIA were assigned. A retrospective search of patient records screened for 5 clinical factors (diabetes, hypertension, coronary artery disease [CAD], smoking, and dialysis). Data were assessed using a 2-sided t test, odds ratio, and a multivariate linear regression calculated through generalized estimating equation (GEE). Results: The log-transformed Agatston scores in the CIA were found to be significantly greater than that in the EIA ( t = 9.57, P < .0001), with a mean difference of 1.5078 (95% confidence interval: 1.1962-1.8194), indicating relative EIA sparing. There were no significant differences in calcification between the right and left sides. Generalized estimating equation found that CAD and smoking demonstrated independent positive associations with EIA sparing (GEE = 2.6464 [ P = .0197] and 1.9092 [ P = .0470], respectively). Age was also significantly associated and indicated that EIA sparing remained relatively constant throughout patients’ lives (GEE = 1.0711 [ P < .0001]). Conclusion: This study has demonstrated statistically significant EIA sparing in end-stage renal disease patients and identified CAD and smoking as associated factors. This phenomenon warrants further investigation into its biological mechanisms and the impact of EIA sparing on outcomes following transplants.
Minicircle DNA vector expressing interferon-lambda-3 inhibits hepatitis B virus replication and expression in hepatocyte-derived cell line
Authors: Guo Xiaoyan , Chen Dianke , Cai Qingxian , Huang Zhanlian , Xu Wenxiong , Peng Liang , Chen Ping 
Published: February 2020

Abstract
Background
Interferon-alpha (IFNα) is a first-line treatment option for chronic hepatitis B virus (HBV) infection, but the severe systemic side-effects limited its clinical application. Interferon-lambda (IFNλ) with comparable antiviral activity and less toxic side-effects is thought to be a good alternative interferon to IFNα. Additionally, the gene vector mediated sustainably expression of therapeutic product in the target cells/tissue may overcome the shortcomings resulted from the short half-life of IFNs.

Results
We constructed a liver-specific IFNλ3-expressing minicircle (MC) vector under the control of a hepatocyte-specific ApoE promoter (MC.IFNλ3) and investigated its anti-HBV activity in a HBV-expressing hepatocyte-derived cell model (HepG2.2.15). As expected, the MC.IFNλ3 vector capable of expressing IFNλ3 in the recipient hepatocytes has demonstrated robust anti-HBV activity, in terms of suppressing viral antigen expression and viral DNA replication, via activation the interferon-stimulated gene (ISG) expression in HepG2.2.15 cells.

Conclusions
Given the MC vector can be easily delivered into liver, the liver-targeted IFN gene-transfer (MC.IFNλ3), instead of systemic administrating IFN repeatedly, provides a promising concept for the treatment of chronic HBV infection.
Identification of universal and cell-type specific p53 DNA binding
Authors: Hafner Antonina , Kublo Lyubov , Tsabar Michael , Lahav Galit , Stewart-Ornstein Jacob 
Published: February 2020

Abstract
Background
The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53.

Results
To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition.

Conclusions
Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state.
Oxygen therapy in patients with ST elevation myocardial infarction based on the culprit vessel: results from the randomized controlled SOCCER trial
Authors: Mokhtari Arash , Akbarzadeh Mahin , Sparv David , Bhiladvala Pallonji , Arheden Håkan , Erlinge David , Khoshnood Ardavan 
Published: February 2020

AbstractBackgroundOxygen (O2) treatment has been a cornerstone in the treatment of patients with myocardial infarction. Recent studies, however, state that supplemental O2therapy may have no effect or harmful effects in these patients. The aim of this study was thus to evaluate the effect of O2therapy in patients with ST Elevation Myocardial Infarction (STEMI) based on the culprit vessel; Left Anterior Descending Artery (LAD) or Non-LAD.MethodsThis was a two-center, investigator-initiated, single-blind, parallel-group, randomized controlled trial at the Skåne university hospital, Sweden. A simple computer-generated randomization was used. Patients were either randomized to standard care with O2therapy (10 l/min) or air until the end of the primary percutaneous coronary intervention. The patients underwent a Cardiac Magnetic Resonance Imaging (CMRI) days 2–6. The main outcome measures were Myocardium at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI) as measured by CMRI, and median high-sensitive troponin T (hs-cTnT).ResultsA total of 229 patients were assessed for eligibility, and 160 of them were randomized to the oxygen or air arm. Because of primarily technical problems with the CMRI, 95 patients were included in the final analyses; 46 in the oxygen arm and 49 in the air arm. There were no significant differences between patients with LAD and Non-LAD as culprit vessel with regard to their allocation (oxygen or air) with regards to MSI, MaR, IS and hs-cTnT.ConclusionThe results indicate that the location of the culprit vessel has probably no effect on the role of supplemental oxygen therapy in STEMI patients.Trial registrationSwedish Medical Products Agency (EudraCT No. 2011–001452-11) and ClinicalTrials.gov Identifier (NCT01423929).
Uric acid induced hepatocytes lipid accumulation through regulation of miR-149-5p/FGF21 axis
Authors: Chen Shenghui , Chen Dan , Yang Hua , Wang Xinyu , Wang Jinghua , Xu Chengfu 
Published: February 2020

Abstract
Background
Hyperuricemia is a major risk for non-alcoholic fatty liver disease. However, the mechanisms for this phenomenon are not fully understood. This study aimed to investigate whether microRNAs mediated the pathogenic effects of uric acid on non-alcoholic fatty liver disease.

Methods
Microarray was used to determine the hepatic miRNA expression profiles of male C57BL/6 mice fed on standard chow diet, high fat diet (HFD), and HFD combined with uric acid-lowering therapy by allopurinol. We validated the expression of the most significant differentially expressed microRNAs and explored its role and downstream target in uric acid-induced hepatocytes lipid accumulation.

Results
Microarray analysis and subsequent validation showed that miR-149-5p was significantly up-regulated in the livers of HFD-fed mice, while the expression was down-regulated by allopurinol therapy. MiR-149-5p expression was also significantly up-regulated in uric acid-stimulated hepatocytes. Over-expression of miR-149-5p significantly aggregated uric acid-induced triglyceride accumulation in hepatocytes, while inhibiting miR-149-5p ameliorated the triglyceride accumulation. Luciferase report assay confirmed that FGF21 is a target gene of miR-149-5p. Silencing FGF21 abolished the ameliorative effects of miR-149-5p inhibitor on uric acid-induced hepatocytes lipid accumulation, while overexpression of FGF21 prevented the lipid accumulation induced by miR-149-5p mimics.

Conclusions
Uric acid significantly up-regulated the expression of miR-149-5p in hepatocytes and induced hepatocytes lipid accumulation via regulation of miR-149-5p/FGF21 axis.
Impact of urine and mixed incontinence on long-term care preference: a vignette-survey study of community-dwelling older adults
Authors: Carvalho Nicolas , Fustinoni Sarah , Abolhassani Nazanin , Blanco Juan Manuel , Meylan Lionel , Santos-Eggimann Brigitte 
Published: February 2020

Abstract
Background
In view of population aging, a better knowledge of factors influencing the type of long-term care (LTC) among older adults is necessary. Previous studies reported a close relationship between incontinence and institutionalization, but little is known on opinions of older citizens regarding the most appropriate place of care. This study aimed at evaluating the impact of urine and/or fecal incontinence on preferences of community–dwelling older citizens.

Methods
We derived data from the Lausanne cohort 65+, a population-based study of individuals aged from 68 to 82 years. A total of 2974 community-dwelling persons were interviewed in 2017 on the most appropriate place of LTC delivery for three vignettes displaying a fixed level of disability with varying degrees of incontinence (none, urinary, urinary and fecal). Multinomial logistic regression analyses explored the effect of respondents’ characteristics on their opinion according to Andersen’s model.

Results
The level of incontinence described in vignettes strongly determined the likelihood of considering institutional care as most appropriate. Respondents’ characteristics such as age, gender, educational level, being a caregiver, knowledge of shelter housing or feeling supported by family influenced LTC choices. Self-reported incontinence and other indicators of respondents’ need, however, had no significant independent effect.

Conclusion
Among older community-dwelling citizens, urinary and fecal incontinence play a decisive role in the perception of a need for institutionalization. Prevention and early initiation of support for sufferers may be a key to prevent this need and ensure familiar surrounding as long as possible.
Spatial clustering of suicide mortality and associated community characteristics in Kanagawa prefecture, Japan, 2011–2017
Authors: Yamaoka Kazue , Suzuki Masako , Inoue Mariko , Ishikawa Hirono , Tango Toshiro 
Published: February 2020

Abstract
Background
Suicide mortality is high in Japan and early interventional strategies to solve that problem are needed. An accurate evaluation of the regional status of current suicide mortality would be useful for community interventions. A few studies in Kanagawa prefecture, located next to Tokyo and with the second largest population in Japan, have identified spatial clusters of suicide mortality at regional levels. This study examined spatial clustering and clustering over time of such events using spatial data from regional statistics on suicide deaths.

Methods
Data were obtained from regional statistics (58 regions in Kanagawa prefecture) of the National Vital Statistics of Japan from 2011 to 2017. The standardized mortality ratio (SMR) and Empirical Bayes estimator for the SMR (EBSMR) were used as measures. Spatial clusters were examined by Kulldorff’s circular spatial scan statistic, Tango-Takahashi’s flexible spatial scan statistic and Tango’s test. Linear regression and conditional autoregressive (CAR) models were used not only to adjust for covariates but also to estimate regional effects. The analyses were conducted for each year, inclusive.

Results
Among male suicide deaths, being unemployed (50%) was most frequently related to suicide while among female health problem (50%) were frequent. Spatial clusters with significance detected by FlexScan, SatScan and Tango’s test were few and varied somewhat according to the method used. Spatial clusters were detected in some regions including Kawasaki ward after adjustment by covariates. By the linear regression models, selected variables with significance were different between the sexes. For males, unemployment, family size, and proportion of higher education were detected for several of the years studied while for females, family size and divorce rate were detected over this period. These variables were also observed by the CAR model with 5 covariates. Regional effects were much clearer by considering the spatial parameter for both males and females and especially, Kawasaki ward was detected as a high risk region in many years.

Conclusion
The present results detected some spatial clustering of suicide deaths within certain regions. Factors related to suicide deaths were also indicated. These results would provide important information in policy making for suicide prevention.
Overview of international naturopathic practice and patient characteristics: results from a cross-sectional study in 14 countries
Authors: Steel Amie , Foley Hope , Bradley Ryan , Van De Venter Claudine , Lloyd Iva , Schloss Janet , Wardle Jon , Reid Rebecca 
Published: February 2020

Abstract
Background
Naturopathy is a distinct system of traditional and complementary medicine recognized by the World Health Organization and defined by its philosophic approach to patient care, rather than the treatments used by practitioners. Worldwide, over 98 countries have practicing naturopaths, representing 36% of all countries and every world region. The contributions of naturopaths to healthcare delivery services internationally has not been previously examined. Thus, the primary intention of this research was to conduct an international survey of naturopathic practice and patient characteristics in order to gain insight to the breadth of their practices and the type of clinical conditions routinely encountered.

Methods
The cross-sectional study was conducted in naturopathic clinics in 14 countries within 4 world regions including the European (Portugal, United Kingdom, Switzerland, Spain), Americas (Canada, United States, Chile, Brazil), Western Pacific (Hong Kong, Australia, New Zealand) and African (South Africa). Naturopathic practitioners in each country were invited to prospectively complete an online survey for 20 consecutive cases. The survey was administered in four languages.

Results
A total of 56 naturopaths from 14 countries participated in the study, providing a mean of 15.1 cases each (SD 7.6) and 851 cases in total. Most patients were female (72.6%) and all age categories were represented with a similar proportion for 36–45 years (20.2%), 46–55 years (19.5%), and 56–65 years (19.3%). A substantial majority (75%) of patients were considered by the participant to be presenting with chronic health conditions. The most prevalent category of health conditions were musculoskeletal (18.5%), gastrointestinal (12.2%), and mental illness (11.0%). The most common treatment categories prescribed or recommended to patients by the participants were dietary changes (60.5%), lifestyle and behaviour changes (56.9%), herbal medicines (54.2%) and nutritional supplements (52.1%). Many patients were known by participants to be receiving care from a general practitioner (43.2%) or a specialist medical practitioner (27.8%).

Conclusions
Naturopathic practitioners provide health care for diverse health conditions in patients in different age groups. The global population would benefit from researchers and policy makers paying closer attention to the potential risks, benefits, challenges and opportunities of the provision of naturopathic care within the community.
Monitoring stance towards vaccination in twitter messages
Authors: Kunneman Florian , Lambooij Mattijs , Wong Albert , Bosch Antal van den , Mollema Liesbeth 
Published: February 2020

AbstractBackgroundWe developed a system to automatically classify stance towards vaccination in Twitter messages, with a focus on messages with a negative stance. Such a system makes it possible to monitor the ongoing stream of messages on social media, offering actionable insights into public hesitance with respect to vaccination. At the moment, such monitoring is done by means of regular sentiment analysis with a poor performance on detecting negative stance towards vaccination. For Dutch Twitter messages that mention vaccination-related key terms, we annotated their stance and feeling in relation to vaccination (provided that they referred to this topic). Subsequently, we used these coded data to train and test different machine learning set-ups. With the aim to best identify messages with a negative stance towards vaccination, we compared set-ups at an increasing dataset size and decreasing reliability, at an increasing number of categories to distinguish, and with different classification algorithms.ResultsWe found that Support Vector Machines trained on a combination of strictly and laxly labeled data with a more fine-grained labeling yielded the best result, at an F1-score of 0.36 and an Area under the ROC curve of 0.66, considerably outperforming the currently used sentiment analysis that yielded an F1-score of 0.25 and an Area under the ROC curve of 0.57. We also show that the recall of our system could be optimized to 0.60 at little loss of precision.ConclusionThe outcomes of our study indicate that stance prediction by a computerized system only is a challenging task. Nonetheless, the model showed sufficient recall on identifying negative tweets so as to reduce the manual effort of reviewing messages. Our analysis of the data and behavior of our system suggests that an approach is needed in which the use of a larger training dataset is combined with a setting in which a human-in-the-loop provides the system with feedback on its predictions.