bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Levels of miR‐133a Predict the Regression Potential of Left Ventricular Hypertrophy After Valve Replacement Surgery in Patients With Aortic Stenosis
Authors: García Raquel , Villar Ana V. , Cobo Manuel , Llano Miguel , Martín‐Durán Rafael , Hurlé María A. , Francisco Nistal J. 
Published: August 2013

Background

Myocardial micro
RNA
‐133a (miR‐133a) is directly related to reverse remodeling after pressure overload release in aortic stenosis patients. Herein, we assessed the significance of plasma miR‐133a as an accessible biomarker with prognostic value in predicting the reversibility potential of
LV
hypertrophy after aortic valve replacement (
AVR
) in these patients.

Methods and Results

The expressions of mi
R
‐133a and its targets were measured in
LV
biopsies from 74 aortic stenosis patients. Circulating miR‐133a was measured in peripheral and coronary sinus blood.
LV
mass reduction was determined echocardiographically. Myocardial and plasma levels of miR‐133a correlated directly (
r
=0.46,
P
<0.001) supporting the myocardium as a relevant source of plasma miR‐133a. Accordingly, a significant gradient of miR‐133a was found between coronary and systemic venous blood. The preoperative plasma level of mi
R
‐133a was higher in the patients who normalized
LV
mass 1 year after
AVR
than in those exhibiting residual hypertrophy. Logistic regression analysis identified plasma miR‐133a as a positive predictor of the hypertrophy reversibility after surgery. The discrimination of the model yielded an area under the receiver operator characteristic curve of 0.89 (
P
<0.001). Multiple linear regression analysis revealed plasma miR‐133a and its myocardial target Wolf‐Hirschhorn syndrome candidate 2/Negative elongation factor A as opposite predictors of the
LV
mass loss (g) after
AVR
.

Conclusions

Preoperative plasma levels of miR‐133a reflect their myocardial expression and predict the regression potential of
LV
hypertrophy after
AVR
. The value of this bedside information for the surgical timing, particularly in asymptomatic aortic stenosis patients, deserves confirmation in further clinical studies.
Does An ENSO-Conditional Skill Mask Improve Seasonal Predictions?
Authors: Pegion Kathy , Kumar Arun 
Published: August 2013

Abstract
The National Centers for Environmental Prediction Climate Prediction Center uses statistical tools together with the Climate Forecast System (CFS) to produce forecasts for seasonal outlooks of U.S. temperature and precipitation. They are combined using an optimal weighting procedure that depends on a skill mask consisting of the average historical forecast skill of each tool. However, it is likely that skill during El Niño–Southern Oscillation events is higher and the use of this information in developing forecasts could lead to improved seasonal predictions. This study explores the potential to improve the skill of seasonal predictions by developing an ENSO-conditional skill mask. The conditional masks are developed in a perfect-model framework using the CFS version 2 hindcasts and two indices of ENSO. The skill of the indices in forecasting variations in conditional skill is evaluated. The ENSO-conditional skill masks provide improvements in correlation skill over the unconditional mask when averaged over the globe. The masks are applied to tercile forecasts of seasonal temperature and precipitation during the spring and forecasts are verified in a perfect-model context. Application of the conditional masks to tercile forecasts results in modified Heidke skill scores of more than 10% less than using the average mask for temperature and little difference in skill for precipitation. This is attributed to the larger number of equal chances forecasts when using the conditional masks, particularly for temperature. For precipitation, the skill predicted by the average and conditional masks is frequently below 0.3, leading to low skill regardless of which mask is used.
A Strategy for Verifying Near-Convection-Resolving Model Forecasts at Observing Sites
Authors: Mittermaier Marion P. 
Published: August 2013

Abstract
Routine verification of deterministic numerical weather prediction (NWP) forecasts from the convection-permitting 4-km (UK4) and near-convection-resolving 1.5-km (UKV) configurations of the Met Office Unified Model (MetUM) has shown that it is hard to consistently demonstrate an improvement in skill from the higher-resolution model, even though subjective comparison suggests that it performs better. In this paper the use of conventional metrics and precise matching (through extracting the nearest grid point to an observing site) of the forecast to conventional synoptic observations in space and time is replaced with the use of inherently probabilistic metrics such as the Brier score, ranked probability, and continuous ranked probability scores applied to neighborhoods of forecast grid points. Three neighborhood sizes were used: ~4, ~12, and ~25 km, which match the sizes of the grid elements currently used operationally. Six surface variables were considered: 2-m temperature, 10-m wind speed, total cloud amount (TCA), cloud-base height (CBH), visibility, and hourly precipitation. Any neighborhood has a positive impact on skill, either in reducing the skill deficit or enhancing the skillfulness over and above the single grid point. This is true for all variables. An optimal neighborhood appears to depend on the variable and threshold. Adopting this probabilistic approach enables easy comparison to future near-convection-resolving ensemble prediction systems (EPS) and also enables the optimization of postprocessing to maximize the skill of forecast products.
Therapeutic drug monitoring of ciclosporin A and tacrolimus in heart lung transplant patients using dried blood spots
Authors: Hinchliffe Edward , Adaway Joanne , Fildes James , Rowan Anna , Keevil Brian G 
Published: August 2013

Background Therapeutic drug monitoring of ciclosporin A (CsA) and tacrolimus is traditionally performed using venous whole blood sampling. A number of reports have described development of ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for the quantitation of CsA and tacrolimus from dried blood spots (DBS), which may offer a convenient alternative. As yet, no such reports have validated this methodology using fingerprick capillary DBS samples collected from transplant patients. Methods Capillary fingerprick DBS were collected from heart and lung transplant patients in a specialist cardiothoracic transplant centre. We utilized our previously published method for the extraction and simultaneous quantitation of CsA and tacrolimus from DBS using UPLC-MS/MS. Drug concentrations measured from DBS were compared to concentrations measured in venous whole blood by our routine clinical UPLC-MS/MS assay. Results In total, 91 heart or lung transplant patients were enrolled onto the study; 46 patients were on CsA therapy and 45 on tacrolimus therapy. Passing–Bablock analysis demonstrated excellent agreement between capillary fingerprick DBS samples and venous whole blood samples. There was a mean positive bias of 2.6  µg/L (95% confidence interval (CI) −2.2 to 7.5  µg/L) for CsA ( n = 45) and mean negative bias of −0.7  µg/L (95% CI −1.1 to −0.3  µg/L) for tacrolimus ( n = 42). Conclusions We demonstrate utility of DBS for serial monitoring of CsA and tacrolimus using UPLC-MS/MS in heart and lung transplant patients. This may offer significant advantages for these patients including the ability to take capillary DBS samples in the community prior to clinic visits.
Increasing Use of Less-Invasive Hemodynamic Monitoring in 3 Specialty Surgical Intensive Care Units
Authors: Kirton Orlando C. , Calabrese Rebecca C. , Staff Ilene 
Published: August 2013

Introduction: Less-invasive hemodynamic monitoring (eg, esophageal doppler monitoring [EDM] and arterial pressure contour analysis, FloTrac) is increasingly used as an alternative to pulmonary artery catheters (PACs) in critically ill intensive care unit (ICU). Hypothesis: The decrease in use of PACs is not associated with increased mortality. Methods: Five-year retrospective review of 1894 hemodynamically monitored patients admitted to 3 surgical ICUs in a university-affiliate, tertiary care urban hospital. Data included the number of admissions, diagnosis-related group discharge case mix, length of stay, insertion of monitoring devices (PAC, EDM, and FloTrac probes), administered intravenous vasoactive agents (β-predominant agonists—dobutamine, epinephrine, and dopamine; vasopressors—norepinephrine and phenylephrine), and mortality. Data from hospital administrative databases were compiled to create patient characteristic and monitoring variables across a 5-year time period, 2005 to 2009 inclusive. Chi-square for independent proportions, 1-way analysis of variance, and Kruskal-Wallis tests were used; tests for trend were conducted. An α level of .05 was considered significant. Statistical Package for the Social Sciences v14 was used for all statistical testing. Results: There was a significant change in the type of hemodynamic monitors inserted in 2 of the 3 surgical ICUs (in the general surgery and neurointensive care but not in the cardiac ICU) from PACs to less-invasive devices (FloTrac or EDM) during the 5-year study period ( P < .001). There was no change in mortality rate over the time period ( P = .492). There was an overall increase in the proportion of monitored patients who received intravenous vasoactive agents ( P < .001) with a progressive shift from β-agonists to vasopressors ( P < .002). Multivariate analyses indicated that age, case mix, and use of vasoactive agents were all independent predictors of inhospital mortality ( P = .001) but that type of monitoring was not ( P = .638). Conclusions: In a 5-year period, the decreased insertions of PACs were replaced by increased utilization of less-invasive hemodynamic monitoring devices. This change in practice did not adversely impact mortality.
An ecological approach to seeking and utilising the views of young people with intellectual disabilities in transition planning
Authors: Small Neil , Raghavan Raghu , Pawson Nicole 
Published: August 2013

Transition planning using a person-centred approach has, in the main, failed to shape service provision. We offer an alternative based on an ecological understanding of human development linked to public health approaches that prioritise whole system planning. A total of 43 young people with intellectual disabilities, in Bradford, England, who were approaching transition from school or college were recruited to a qualitative study. Their ethnic breakdown was as follows: 16 white British, 24 Pakistani, 2 Bangladeshi and 1 Black African. Each young person was interviewed twice, at recruitment and a year later, to observe any changes in their social networks during transition. Interviews were undertaken with a semi-structured interview schedule and with the pictorial approach of Talking Mats. Both the networks the young people live within, and their sense of what the future might hold for them, are described and linked to Bronfenbrenner’s ecological model of human development. The importance of the family and school is emphasised, as is the absence of engagement in leisure activities and work. Transition planning needs to start with mapping the systems individuals live within, areas of strength should be supported and parts of the system, which are not fit for purpose for these young people, should be prioritised for interventions.
C-reactive protein to predict the need for surgical intervention in acute renal colic
Authors: McSorley ST , Drury M , Majumdar P , Halsall A , Nalagatla SK 
Published: August 2013

Objectives: C-reactive protein (CRP) is a serum marker of systemic inflammation which has been suggested to predict need for emergent surgical intervention in patients with acute renal colic at a value of > 28 mg/l on admission.1 We aimed to determine if this applied to our patients. Patients and methods: We prospectively collected data from all patients admitted with symptomatic urolithiasis, confirmed by CT-KUB, over three months. Fifty-nine patients were included; however, four were excluded because of co-morbidites which could influence CRP, or recent urological surgery, giving N = 55, age 50.0±14.6 years (mean±SD), M:F 40:15. The decision to proceed to intervention was made by each patient’s clinical team and not by the authors; however, there was no blinding to CRP. Results: A total of 24 of 55 patients required intervention on their index admission (22 retrograde ureteric stent, one nephrostomy, one ureteroscopic stone extraction), and 31 were managed conservatively. Those undergoing intervention had higher CRP on admission (mean 16.3 vs 9.4 mg/l, p = 0.06) and higher maximum CRP (mean 94.7 vs 25.7 mg/l, p < 0.001) than those managed conservatively. Nineteen (79%) of those requiring intervention had CRP < 28 mg/l on admission. There were no deaths, no intensive care admissions and all were discharged to outpatient follow-up. Conclusion: Rising CRP during admission is a strong predictor of the need for emergency surgical intervention in patients with acute renal colic; however, CRP at admission is less useful.
GentrepidV2.0: a web server for candidate disease gene prediction
Authors: Ballouz Sara , Liu Jason Y , George Richard A , Bains Naresh , Liu Arthur , Oti Martin , Gaeta Bruno , Fatkin Diane , Wouters Merridee A 
Published: August 2013

Abstract

Background
Candidate disease gene prediction is a rapidly developing area of bioinformatics research with the potential to deliver great benefits to human health. As experimental studies detecting associations between genetic intervals and disease proliferate, better bioinformatic techniques that can expand and exploit the data are required.

Description

Gentrepid is a web resource which predicts and prioritizes candidate disease genes for both Mendelian and complex diseases. The system can take input from linkage analysis of single genetic intervals or multiple marker loci from genome-wide association studies. The underlying database of the Gentrepid tool sources data from numerous gene and protein resources, taking advantage of the wealth of biological information available. Using known disease gene information from OMIM, the system predicts and prioritizes disease gene candidates that participate in the same protein pathways or share similar protein domains. Alternatively, using an ab initio approach, the system can detect enrichment of these protein annotations without prior knowledge of the phenotype.

Conclusions
The system aims to integrate the wealth of protein information currently available with known and novel phenotype/genotype information to acquire knowledge of biological mechanisms underpinning disease. We have updated the system to facilitate analysis of GWAS data and the study of complex diseases. Application of the system to GWAS data on hypertension using the ICBP data is provided as an example. An interesting prediction is a ZIP transporter additional to the one found by the ICBP analysis. The webserver URL is https://www.gentrepid.org/.
SNP-revealed genetic diversity in wild emmer wheat correlates with ecological factors
Authors: Ren Jing , Chen Liang , Sun Daokun , You Frank M , Wang Jirui , Peng Yunliang , Nevo Eviatar , Beiles Avigdor , Sun Dongfa , Luo Ming-Cheng , Peng Junhua 
Published: August 2013

AbstractBackgroundPatterns of genetic diversity between and within natural plant populations and their driving forces are of great interest in evolutionary biology. However, few studies have been performed on the genetic structure and population divergence in wild emmer wheat using a large number of EST-related single nucleotide polymorphism (SNP) markers.ResultsIn the present study, twenty-five natural wild emmer wheat populations representing a wide range of ecological conditions in Israel and Turkey were used. Genetic diversity and genetic structure were investigated using over 1,000 SNP markers. A moderate level of genetic diversity was detected due to the biallelic property of SNP markers. Clustering based on Bayesian model showed that grouping pattern is related to the geographical distribution of the wild emmer wheat. However, genetic differentiation between populations was not necessarily dependent on the geographical distances. A total of 33 outlier loci under positive selection were identified using aFST-outlier method. Significant correlations between loci and ecogeographical factors were observed.ConclusionsNatural selection appears to play a major role in generating adaptive structures in wild emmer wheat. SNP markers are appropriate for detecting selectively-channeled adaptive genetic diversity in natural populations of wild emmer wheat.This adaptive genetic diversity is significantly associated with ecological factors.
Transcriptional analysis of abdominal fat in genetically fat and lean chickens reveals adipokines, lipogenic genes and a link between hemostasis and leanness
Authors: Resnyk Christopher W , Carré Wilfrid , Wang Xiaofei , Porter Tom E , Simon Jean , Le Bihan-Duval Elisabeth , Duclos Michael J , Aggrey Sam E , Cogburn Larry A 
Published: August 2013

AbstractBackgroundThis descriptive study of the abdominal fat transcriptome takes advantage of two experimental lines of meat-type chickens (Gallus domesticus), which were selected over seven generations for a large difference in abdominal (visceral) fatness. At the age of selection (9 wk), the fat line (FL) and lean line (LL) chickens exhibit a 2.5-fold difference in abdominal fat weight, while their feed intake and body weight are similar. These unique avian models were originally created to unravel genetic and endocrine regulation of adiposity and lipogenesis in meat-type chickens. The Del-Mar 14K Chicken Integrated Systems microarray was used for a time-course analysis of gene expression in abdominal fat of FL and LL chickens during juvenile development (1–11 weeks of age).ResultsMicroarray analysis of abdominal fat in FL and LL chickens revealed 131 differentially expressed (DE) genes (FDR≤0.05) as the main effect of genotype, 254 DE genes as an interaction of age and genotype and 3,195 DE genes (FDR≤0.01) as the main effect of age. The most notable discoveries in the abdominal fat transcriptome were higher expression of many genes involved in blood coagulation in the LL and up-regulation of numerous adipogenic and lipogenic genes in FL chickens. Many of these DE genes belong to pathways controlling the synthesis, metabolism and transport of lipids or endocrine signaling pathways activated by adipokines, retinoid and thyroid hormones.ConclusionsThe present study provides a dynamic view of differential gene transcription in abdominal fat of chickens genetically selected for fatness (FL) or leanness (LL). Remarkably, the LL chickens over-express a large number of hemostatic genes that could be involved in proteolytic processing of adipokines and endocrine factors, which contribute to their higher lipolysis and export of stored lipids. Some of these changes are already present at 1 week of age before the divergence in fatness. In contrast, the FL chickens have enhanced expression of numerous lipogenic genes mainly after onset of divergence, presumably directed by multiple transcription factors. This transcriptional analysis shows that abdominal fat of the chicken serves a dual function as both an endocrine organ and an active metabolic tissue, which could play a more significant role in lipogenesis than previously thought.
Evaluation of the need for routine clinical testing of PALB2 c.1592delT mutation in BRCA negative Northern Finnish breast cancer families
Authors: Haanpää Maria , Pylkäs Katri , Moilanen Jukka S , Winqvist Robert 
Published: August 2013

Abstract

Background
Testing for mutations in the BRCA1 and BRCA2 genes among high-risk breast cancer patients has become a routine practice among clinical geneticists. Unfortunately, however, the genetic background of a majority of the cases coming to the clinics remains currently unexplained, making genetic counseling rather challenging. In recent years it has become evident world-wide that also women carrying a heterozygous germline mutation in PALB2 are at significantly increased risk of getting breast cancer. We have previously studied the clinical as well as biological impact of the PALB2 c.1592delT founder mutation occurring in about 1% of Finnish breast cancer patients unselected for their family history of disease, and our results demonstrated a 40% increased breast cancer risk by age 70 for female mutation carriers. Thus, this relatively common mutation in PALB2 is associated with a high risk of developing breast cancer. The aim of the current study was to analyze whether female index individuals of breast cancer families who had tested negative for germline mutations in BRCA1/BRCA2 as part of genetic counseling services should be offered mutation testing for PALB2 c.1592delT.

Methods
The study cohort consisted of altogether 223 individuals who had contacted the Department of Clinical Genetics at the Oulu University Hospital in Finland between the years 1997 and 2011 for counseling on hereditary breast and/or ovarian cancer risk. 101 of them met our inclusion criteria. Of these, 10 persons were now deceased, but 6 of them had participated in one of our previous studies on PALB2. Seventy (77%) of the remaining 91 persons responded positively to our study invitation. Chart review of updated pedigree data led to the exclusion of 14 further individuals not meeting the selection criteria.

Result
Of the 56 alive affected female individuals screened for PALB2 c.1592delT, altogether two (3.6%) tested positive for this mutation. In addition, of the previously tested but now deceased 6 persons eligible for the current study, one more mutation carrier was observed. Therefore, overall 4.8% (3/62) of the tested individuals belonging to the Northern Finnish 1997–2011 study cohort turned out to be carriers of the PALB2 c.1592delT allele.

Conclusions
Given the potential benefits versus harms of this testing, the result of our study suggest that PALB2 c.1592delT should be a routine part of the genetic counseling protocol for Finnish high-risk breast cancer cases tested negative for mutations in BRCA1/BRCA2.