bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of patients with abnormalities on intraoperative cholangiogram: time to abandon endoscopic retrograde cholangiopancreatography as the initial follow-up study
Authors: Bill Jason G , Kushnir Vladimir M , Mullady Daniel K , Murad Faris M , Azar Riad R , Easler Jeffery J , Early Dayna S , Edmundowicz Steven A 
Published: June 2015

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is currently the method of choice for the postoperative evaluation of suspected bile duct stones seen on intraoperative cholangiogram (IOC); however, the sensitivity of IOC for identifying biliary pathology is unclear, with studies reporting false positive rates between 30% and 60%.ObjectiveEvaluate the sensitivity of IOC for biliary pathology, using ERCP with sphincterotomy and balloon sweep as gold standard.DesignRetrospective cohort study.SettingTertiary medical centre.Patients130 consecutive patients (age 51.3±1.7 years, 69.2% women) who underwent ERCP for the evaluation of abnormalities identified on IOC between 2005 and 2013.InterventionsEndoscopic retrograde cholangiopancreatographyMain outcome measurementsSensitivity of IOC, identify predictors of positive postoperative ERCP and ERCP-related complications.ResultsERCP was successful in all 130 subjects. ERCP-related adverse events occurred in six (4.3%) patients, including self-limited post-sphincterotomy bleeding in three (2.3%) and mild post-ERCP pancreatitis in three (2.3%). Overall, 41 (31.5%) patients had normal cholangiogram at time of ERCP. Finding of a filling defect on IOC was the only predictor for the presence of common bile duct stones on postoperative ERCP (OR 3.3, 95% CI 1.0 to 10.8, p=0.05).LimitationsRetrospective study design.ConclusionsNearly one-third of patients with abnormal IOC had a normal postoperative ERCP. Significant pathology could have been missed in 1/130 patients. Based on these findings, we believe the use of less-invasive diagnostic modalities may be used in place of ERCP in patients with suspected choledocholithiasis on IOC.
Social disparities in Disease Management Programmes for coronary heart disease in Germany: a cross-classified multilevel analysis
Authors: Bozorgmehr Kayvan , Maier Werner , Brenner Hermann , Saum Kai-Uwe , Stock Christian , Miksch Antje , Holleczek Bernd , Szecsenyi Joachim , Razum Oliver 
Published: June 2015

BackgroundDisease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels.MethodsCross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models.ResultsAmong N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates.ConclusionsWe found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency.
Childhood and adolescence risk factors and development of depressive symptoms: the 32-year prospective Young Finns follow-up study
Authors: Elovainio Marko , Pulkki-Råback Laura , Hakulinen Christian , Ferrie Jane E , Jokela Markus , Hintsanen Mirka , Raitakari Olli T , Keltikangas-Järvinen Liisa 
Published: June 2015

BackgroundEnvironmental risks in childhood have been shown to predict later depressive symptoms. In this study, we examined whether various environmental risk domains in childhood and adolescence, socioeconomic, psychoemotional, parental lifestyle and life-events, predict depressive symptom trajectories in adulthood individually by domain and as a cumulative risk score across domains.MethodsParticipants were a nationally representative sample of 1289 men and 1585 women from the Young Finns study, aged 3–18 years at study entry in 1980. They responded to questions on depressive symptoms (modified version of the Beck Depression Inventory) at four study phases from 1997 to 2012.ResultsFindings from longitudinal repeated multilevel modelling showed that all clusters of risk within domain and the cumulative risk score were associated with later depressive symptoms (regression coefficient range from 0.07 to 0.34). Socioeconomic risk, psychoemotional risk and the cumulative risk score predicted later depressive symptoms after adjustment for the effects of adulthood risk. No interaction with time was observed.ConclusionsOur findings suggest that environment risks in childhood and adolescence, particularly in the socioeconomic and psychoemotional domains, are associated with a higher risk, but not an increased progression, of depressive symptoms in adulthood.
A novel method of continuous cage‐side monitoring of hyperthyroid cats treated with radio‐iodine
Authors: Roberts E. , Gray J. M. , Gunn E. , Ramsey I. K. 
Published: June 2015

A continuous monitoring system (MGP DM2000X) was assessed for monitoring γ radiation emissions and determining appropriate isolation times for hyperthyroid cats treated with radioactive iodine (I131). Daily radiation emitted by 12 cats who had received a range of doses of I131(80–200 MBq) was measured and average background radiation readings deducted. The effective half‐lives of the I131in the cats were found to have a median of 2.54 days (range 1.40–3.24 days). Cats treated with 200 MBq emitted 5 µGy/day more exposure than cats treated with lower doses throughout the study period (P=0.032). All cats were found to emit a total radiation dose exposure less than 100 µGy (range 0–43 µGy) during days 18–21 of isolation. The potential additional dose exposure to owners was calculated at various days that might be considered for the cats to be returned to their owners. Using this provisional data, maximum isolation periods at this institution could be safely reduced to 17 days as long as certain precautions are followed. This preliminary study demonstrated that this novel cage‐side monitoring system can be used to calculate the effective half‐life of I131and to measure γ radiation exposure from treated cats, which may assist other institutions in determining appropriate isolation times for individual cats.
Interleukin-6 Stimulates Defective Angiogenesis
Authors: Gopinathan Ganga , Milagre Carla , Pearce Oliver M.T. , Reynolds Louise E. , Hodivala-Dilke Kairbaan , Leinster David A. , Zhong Haihong , Hollingsworth Robert E. , Thompson Richard , Whiteford James R. , Balkwill Frances 
Published: June 2015

Abstract
The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here, we show that IL6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies, there was an association between levels of IL6 mRNA, Jagged1, and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease, and stroke. Cancer Res; 75(15); 3098–107. ©2015 AACR.
Systematic Screening of Promoter Regions Pinpoints Functional Cis-Regulatory Mutations in a Cutaneous Melanoma Genome
Authors: Poulos Rebecca C. , Thoms Julie A.I. , Shah Anushi , Beck Dominik , Pimanda John E. , Wong Jason W.H. 
Published: June 2015

Abstract
With the recent discovery of recurrent mutations in the TERT promoter in melanoma, identification of other somatic causal promoter mutations is of considerable interest. Yet, the impact of sequence variation on the regulatory potential of gene promoters has not been systematically evaluated. This study assesses the impact of promoter mutations on promoter activity in the whole-genome sequenced malignant melanoma cell line COLO-829. Combining somatic mutation calls from COLO-829 with genome-wide chromatin accessibility and histone modification data revealed mutations within promoter elements. Interestingly, a high number of potential promoter mutations (n = 23) were found, a result mirrored in subsequent analysis of TCGA whole-melanoma genomes. The impact of wild-type and mutant promoter sequences were evaluated by subcloning into luciferase reporter vectors and testing their transcriptional activity in COLO-829 cells. Of the 23 promoter regions tested, four mutations significantly altered reporter activity relative to wild-type sequences. These data were then subjected to multiple computational algorithms that score the cis-regulatory altering potential of mutations. These analyses identified one mutation, located within the promoter region of NDUFB9, which encodes the mitochondrial NADH dehydrogenase (ubiquinone) 1 beta subcomplex 9, to be recurrent in 4.4% (19 of 432) of TCGA whole-melanoma exomes. The mutation is predicted to disrupt a highly conserved SP1/KLF transcription factor binding motif and its frequent co-occurrence with mutations in the coding sequence of NF1 supports a pathologic role for this mutation in melanoma. Taken together, these data show the relatively high prevalence of promoter mutations in the COLO-829 melanoma genome, and indicate that a proportion of these significantly alter the regulatory potential of gene promoters.
Implications: Genomic-based screening within gene promoter regions suggests that functional cis-regulatory mutations may be common in melanoma genomes, highlighting the need to examine their role in tumorigenesis. Mol Cancer Res; 13(8); 1218–26. ©2015 AACR.
Charting Immune Signaling Proteomes En Route to New Therapeutic Strategies
Authors: Haura Eric B. , Beg Amer A. , Rix Uwe , Antonia Scott 
Published: June 2015

Abstract
The activation state of an antitumor effector T cell in a tumor depends on the sum of all stimulatory signals and inhibitory signals that it receives in the tumor microenvironment. Accumulating data address the increasing complexity of these signals produced by a myriad of immune checkpoint molecules, cytokines, and metabolites. While reductionist experiments have identified key molecules and their importance in signaling, less clear is the integration of all these signals that allows T cells to guide their responses in health and in disease. Mass spectrometry–based proteomics is well poised to offer such insights, including monitoring emergence of resistance mechanisms to immunotherapeutics during treatments. A major application of this technology is in the discovery and characterization of small-molecule agents capable of enhancing the response to immunotherapeutic agents. Such an approach would reinvigorate small-molecule drug development aimed not at tumor cells but rather at tumor-resident T cells capable of producing dramatic and durable antitumor responses. Cancer Immunol Res; 3(7); 714–20. ©2015 AACR.
Is There Still a Role for Complex Fractionated Atrial Electrogram Ablation in Addition to Pulmonary Vein Isolation in Patients With Paroxysmal and Persistent Atrial Fibrillation?
Authors: Providência Rui , Lambiase Pier D. , Srinivasan Neil , Ganesh Babu Girish , Bronis Konstantinos , Ahsan Syed , Khan Fakhar Z. , Chow Anthony W. , Rowland Edward , Lowe Martin , Segal Oliver R. 
Published: June 2015

Background—
Ablation of complex fractionated atrial electrograms (CFAEs) has been proposed as a strategy to improve outcomes in atrial fibrillation (AF) catheter ablation, but the use of this technique remains contentious. We aimed to assess the impact of CFAE ablation in addition to pulmonary vein isolation (PVI) in patients undergoing ablation for AF.

Methods and Results—

We performed a random effects meta-analysis of studies comparing PVI versus PVI+CFAE ablation. The outcomes of freedom from AF/atrial tachycardia after 1 or several ablation procedures and acute procedural–related complications were assessed. Studies were searched on MEDLINE, EMBASE, COCHRANE, and
clinicaltrials.gov
, and sensitivity analyses were performed. Thirteen studies including a total of 1415 patients were considered eligible. Additional ablation of CFAEs resulted in no improvement in mid-term procedural outcome or freedom from AF or atrial tachycardia (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.58–1.10;
P
=0.17). Sensitivity analysis of 398 paroxysmal AF ablation procedures showed no incremental benefit of CFAE ablation (OR, 0.80; 95% CI, 0.46–1.38;
P
=0.42). PVI+CFAE ablation versus PVI alone did not improve the overall rate of freedom from AF or atrial tachycardia in patients with persistent AF (OR, 1.01; 95% CI, 0.63–1.64;
P
=0.96) or longstanding persistent AF (OR, 0.84; 95% CI, 0.24–2.96;
P
=0.79). There was no increase in procedural-related adverse events (OR, 1.06; 95% CI, 0.41–2.75;
P
=0.91).

Conclusions—
Despite the apparent safety of this technique, CFAE ablation did not improve freedom from AF/atrial tachycardia in patients with paroxysmal or persistent AF. The role of CFAE ablation in addition to PVI should be questioned and other alternatives assessed to improve the outcome of AF ablation.
Expansion and Characterization of Neonatal Cardiac Pericytes Provides a Novel Cellular Option for Tissue Engineering in Congenital Heart Disease
Authors: Avolio Elisa , Rodriguez‐Arabaolaza Iker , Spencer Helen L. , Riu Federica , Mangialardi Giuseppe , Slater Sadie C. , Rowlinson Jonathan , Alvino Valeria V. , Idowu Oluwasomidotun O. , Soyombo Stephanie , Oikawa Atsuhiko , Swim Megan M. , Kong Cherrie H. T. , Cheng Hongwei , Jia Huidong , Ghorbel Mohamed T. , Hancox Jules C. , Orchard Clive H. , Angelini Gianni , Emanueli Costanza , Caputo Massimo , Madeddu Paolo 
Published: June 2015

Background
Living grafts produced by combining autologous heart‐resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiation capacity, paracrine activity, and pro‐angiogenic potential of cardiac pericytes and to assess their engrafting capacity in clinically certified prosthetic grafts.

Methods and Results

CD
34
pos
cells, negative for the endothelial markers
CD
31 and
CD
146, were identified by immunohistochemistry in cardiac leftovers from infants and children undergoing palliative repair of congenital cardiac defects. Following isolation by immunomagnetic bead‐sorting and culture on plastic in
EGM
‐2 medium supplemented with growth factors and serum,
CD
34
pos
/
CD
31
neg
cells gave rise to a clonogenic, highly proliferative (>20 million at P5), spindle‐shape cell population. The following populations were shown to expresses pericyte/mesenchymal and stemness markers. After exposure to differentiation media, the expanded cardiac pericytes acquired markers of vascular smooth muscle cells, but failed to differentiate into endothelial cells or cardiomyocytes. However, in Matrigel, cardiac pericytes form networks and enhance the network capacity of endothelial cells. Moreover, they produce collagen‐1 and release chemo‐attractants that stimulate the migration of c‐Kit
pos
cardiac stem cells. Cardiac pericytes were then seeded onto clinically approved xenograft scaffolds and cultured in a bioreactor. After 3 weeks, fluorescent microscopy showed that cardiac pericytes had penetrated into and colonized the graft.

Conclusions
These findings open new avenues for cellular functionalization of prosthetic grafts to be applied in reconstructive surgery of congenital heart disease.
Carotid Plaque Morphological Classification Compared With Biomechanical Cap Stress
Authors: Gijsen Frank J.H. , Nieuwstadt Harm A. , Wentzel Jolanda J. , Verhagen Hence J.M. , van der Lugt Aad , van der Steen Antonius F.W. 
Published: June 2015

Background and Purpose—
Two approaches to target plaque vulnerability—a histopathologic classification scheme and a biomechanical analysis—were compared and the implications for noninvasive risk stratification of carotid plaques using magnetic resonance imaging were assessed.

Methods—

Seventy-five histological plaque cross sections were obtained from carotid endarterectomy specimens from 34 patients (>70% stenosis) and subjected to both a Virmani histopathologic classification (thin fibrous cap atheroma with <0.2-mm cap thickness, presumed vulnerable) and a peak cap stress computation (<140 kPa: presumed stable; >300 kPa: presumed vulnerable). To demonstrate the implications for noninvasive plaque assessment, numeric simulations of a typical carotid magnetic resonance imaging protocol were performed (0.62×0.62 mm
2
in-plane acquired voxel size) and used to obtain the magnetic resonance imaging–based peak cap stress.

Results—
Peak cap stress was generally associated with histological classification. However, only 16 of 25 plaque cross sections could be labeled as high-risk (peak cap stress>300 kPa and classified as a thin fibrous cap atheroma). Twenty-eight of 50 plaque cross sections could be labeled as low-risk (a peak cap stress<140 kPa and not a thin fibrous cap atheroma), leading to a κ=0.39. 31 plaques (41%) had a disagreement between both classifications. Because of the limited magnetic resonance imaging voxel size with regard to cap thickness, a noninvasive identification of only a group of low-risk, thick-cap plaques was reliable.

Conclusions—
Instead of trying to target only vulnerable plaques, a more reliable noninvasive identification of a select group of stable plaques with a thick cap and low stress might be a more fruitful approach to start reducing surgical interventions on carotid plaques.
Incidence of Tube Feeding in 7174 Newly Admitted Nursing Home Residents With and Without Dementia
Authors: Schulze Jana , Mazzola Rosa , Hoffmann Falk 
Published: June 2015

Background: Tube feeding is a common form of long-term nutritional support, especially for nursing home residents, of whom many have dementia. Objective: Estimating the incidence of feeding tube placement in nursing home residents with and without dementia. Methods: Using claims data, we studied a cohort of newly admitted nursing home residents aged 65 years and older between 2004 and 2009. Analyses were stratified by dementia. We estimated incidence rates and performed multivariate Cox regression analyses. Results: The study cohort included 7174 nursing home residents. Over a mean follow-up of 1.3 years, 273 people received a feeding tube. The incidence per 1000 person-years was 28.4, with higher estimates for patients with dementia. When adjusting for age, sex, and level of care as a time-dependent covariate, influence of dementia decreased to a nonsignificant hazard ratio. Conclusion: It seems that not dementia itself but the overall clinical condition might be a predictor of tube feeding placement.
Regulation of AKT signaling by Id1 controls t(8;21) leukemia initiation and progression
Authors: Wang Lan , Man Na , Sun Xiao-Jian , Tan Yurong , García-Cao Marta , Liu Fan , Hatlen Megan , Xu Haiming , Huang Gang , Mattlin Meredith , Mehta Arpit , Rampersaud Evadnie , Benezra Robert , Nimer Stephen D. 
Published: June 2015

Key Points
Using genetically modified mice, we identified the crucial role of Id1 in t(8;21) leukemogenesis through regulating AKT signaling. Id1 inhibitor has a significant therapeutic effect in the mouse model of t(8;21) leukemia.
Evolution of urea transporters in vertebrates: adaptation to urea's multiple roles and metabolic sources
Authors: LeMoine Christophe M. R. , Walsh Patrick J. 
Published: June 2015

ABSTRACTIn the two decades since the first cloning of the mammalian kidney urea transporter (UT-A), UT genes have been identified in a plethora of organisms, ranging from single-celled bacteria to metazoans. In this review, focusing mainly on vertebrates, we first reiterate the multiple catabolic and anabolic pathways that produce urea, then we reconstruct the phylogenetic history of UTs, and finally we examine the tissue distribution of UTs in selected vertebrate species. Our analysis reveals that from an ancestral UT, three homologues evolved in piscine lineages (UT-A, UT-C and UT-D), followed by a subsequent reduction to a single UT-A in lobe-finned fish and amphibians. A later internal tandem duplication of UT-A occurred in the amniote lineage (UT-A1), followed by a second tandem duplication in mammals to give rise to UT-B. While the expected UT expression is evident in excretory and osmoregulatory tissues in ureotelic taxa, UTs are also expressed ubiquitously in non-ureotelic taxa, and in tissues without a complete ornithine–urea cycle (OUC). We posit that non-OUC production of urea from arginine by arginase, an important pathway to generate ornithine for synthesis of molecules such as polyamines for highly proliferative tissues (e.g. testis, embryos), and neurotransmitters such as glutamate for neural tissues, is an important evolutionary driving force for the expression of UTs in these taxa and tissues.