bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous thromboembolism and subsequent risk of cancer in patients with liver disease: a population-based cohort study
Authors: Montomoli Jonathan , Erichsen Rune , Søgaard Kirstine Kobberøe , Körmendiné Farkas Dóra , Bloch Münster Anna-Marie , Sørensen Henrik Toft 
Published: June 2015

ObjectiveVenous thromboembolism (VTE) may be a marker of occult cancer in the general population. While liver disease is known to increase the risk of VTE and cancer, it is unclear whether VTE in patients with liver disease is also a marker of occult cancer.DesignA population-based cohort study.SettingDenmark.ParticipantsWe used population-based health registries to identify all patients with liver disease in Denmark with a first-time diagnosis of VTE (including superficial or deep venous thrombosis and pulmonary embolism) during 1980–2010. Patients with non-cirrhotic liver disease and patients with liver cirrhosis were followed as two separate cohorts from the date of their VTE.MeasuresFor each cohort, we computed the absolute and relative risk (standardised incidence ratio; SIR) of cancer after VTE.ResultsDuring the study period, 1867 patients with non-cirrhotic liver disease and 888 with liver cirrhosis were diagnosed with incident VTE. In the first year following VTE, the absolute risk of cancer was 2.7% among patients with non-cirrhotic liver disease and 4.3% among those with liver cirrhosis. The SIR for the first 90 days of follow-up was 9.96 (95% CI 6.85 to 13.99) among patients with non-cirrhotic liver disease and 13.11 (95% CI 8.31 to 19.67) among patients with liver cirrhosis. After 1 year of follow-up, SIRs declined, but remained elevated in patients with non-cirrhotic liver disease (SIR=1.50, 95% CI 1.23 to 1.81) and patients with liver cirrhosis (SIR=1.95, 95% CI 1.45 to 2.57).ConclusionsVTE may be a marker of occult cancer in patients with liver disease.
Perioperative dexamethasone administration in tonsillectomy patients: A three-cycle audit showing improvement using printed theatre lists
Authors: Bola Summy , Bartlett Annie , Williams Richard 
Published: June 2015

AbstractDexamethasone administration prior to tonsillectomy has been shown to reduce morbidity and is part of SIGN guideline 117. We conducted a three-cycle audit of 149 patients to ascertain how well guidelines were being met and introduce a sustainable method to improve compliance. A 3-month audit was conducted to ascertain how many tonsillectomy patients didn’t receive pre-operative dexamethasone. ENT secretaries were requested to add ‘Dex Please’ to tonsillectomy theatre lists. A 3-month re-audit was conducted; the intervention was only implemented in half of cases and so a reminding tool for the secretarial staff was administered before a third cycle. Initially, there was 73% compliance to SIGN guidelines, this improved to 87% in the second cycle. After the second intervention, all tonsillectomy theatre lists had the ‘Dex Please’ note and compliance to SIGN guidelines was 100%. There were five readmissions in the first cycle, three in the second and two in the third cycle. All readmissions were underdosed according to guidelines. Understanding there are regular staff rotations throughout many U.K. hospitals, we implemented a reliable method to increase compliance to guidelines which helped reduce post-operative readmission after tonsillectomy. This can be easily introduced to other institutions and for other perioperative requirements.
Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration
Authors: Frenel Jean Sebastien , Carreira Suzanne , Goodall Jane , Roda Desam , Perez-Lopez Raquel , Tunariu Nina , Riisnaes Ruth , Miranda Susana , Figueiredo Ines , Nava-Rodrigues Daniel , Smith Alan , Leux Christophe , Garcia-Murillas Isaac , Ferraldeschi Roberta , Lorente David , Mateo Joaquin , Ong Michael , Yap Timothy A. , Banerji Udai , Gasi Tandefelt Delila , Turner Nick , Attard Gerhardt , de Bono Johann S. 
Published: June 2015

Abstract
Purpose: We evaluated whether next-generation sequencing (NGS) of circulating cell-free DNA (cfDNA) could be used for patient selection and as a tumor clone response biomarker in patients with advanced cancers participating in early-phase clinical trials of targeted drugs.
Experimental Design: Plasma samples from patients with known tumor mutations who completed at least two courses of investigational targeted therapy were collected monthly, until disease progression. NGS was performed sequentially on the Ion Torrent PGM platform.
Results: cfDNA was extracted from 39 patients with various tumor types. Treatments administered targeted mainly the PI3K–AKT–mTOR pathway (n = 28) or MEK (n = 7). Overall, 159 plasma samples were sequenced with a mean sequencing coverage achieved of 1,685X across experiments. At trial initiation (C1D1), 23 of 39 (59%) patients had at least one mutation identified in cfDNA (mean 2, range 1–5). Out of the 44 mutations identified at C1D1, TP53, PIK3CA and KRAS were the top 3 mutated genes identified, with 18 (41%), 9 (20%), 8 (18%) different mutations, respectively. Out of these 23 patients, 13 received a targeted drug matching their tumor profile. For the 23 patients with cfDNA mutation at C1D1, the monitoring of mutation allele frequency (AF) in consecutive plasma samples during treatment with targeted drugs demonstrated potential treatment associated clonal responses. Longitudinal monitoring of cfDNA samples with multiple mutations indicated the presence of separate clones behaving discordantly. Molecular changes at cfDNA mutation level were associated with time to disease progression by RECIST criteria.
Conclusions: Targeted NGS of cfDNA has potential clinical utility to monitor the delivery of targeted therapies. Clin Cancer Res; 21(20); 4586–96. ©2015 AACR.
Antiinflammatory effects of aspirin in ACS: relevant to its cardio coronary actions?
Authors: Schrör Karsten , Hohlfeld Thomas 
Published: June 2015

SummaryVascular injury in acute coronary syndromes (ACS) involves a complex cross-talk between inflammatory mediators, platelets and thrombosis, where the interaction between platelets and coagulation factors (e. g. thrombin) is a central link between thrombosis and inflammation. In ACS, aspirin at antiplatelet doses exhibits anti-inflammatory effects as seen from the decrease in inflammation markers such as CRP, M-CSF, MCP-1 and others. These actions probably occur subsequent to inhibition of platelet COX-1-dependent thromboxane formation and its action as a multipotent autocrine and paracrine agent. This likely involves inhibition of thrombin formation as well as inhibition of secondary pro-inflammatory mediators, such as sphingosine-1-phosphate. Experimental and limited clinical data additionally suggest antiinflammatory effects of aspirin independent of its antiplatelet action. For example, aspirin at antiplatelet doses might acetylate COX-2 in vascular cells, directing the activity of the enzyme into a 15-lipoxygenase which by transcellular metabolism results in the formation of 15-epi-lipoxin (‘aspirin-triggered lipoxin’), an antiinflammatory mediator. Furthermore, aspirin stimulates eNOS via lysine-acetylation, eventually resulting in induction of heme oxygenase (HO-1), which improves the antioxidative potential of vascular cells. All of these effects have been seen at antiplatelet doses of 100–300 mg/day, equivalent to peak plasma levels of 10–30 μM. Many more potentially antiinflammatory mechanisms of aspirin have been described, mostly salicy-late-related, at low to medium millimolar concentrations and, therefore, are of minor clinical interest. Altogether, there is a wealth of data supporting antiiflammatory effects of aspirin in ACS, but studies generating direct evidence for antiinflammatory effects in ACS remain to be done.
Circulating Biomarkers and Abdominal Aortic Aneurysm Incidence
Authors: Folsom Aaron R. , Yao Lu , Alonso Alvaro , Lutsey Pamela L. , Missov Emil , Lederle Frank A. , Ballantyne Christie M. , Tang Weihong 
Published: June 2015

Background—
The pathogenesis of abdominal aortic aneurysm (AAA) is complex. Cross-sectional studies have connected circulating biomarkers with AAA, but prospective evidence is limited.

Methods and Results—

In the Atherosclerosis Risk in Communities Study cohort, we measured multiple blood biomarkers of inflammation, hemostasis, thrombin generation, cardiac dysfunction, and vascular stiffness and identified incident AAAs during follow-up using hospital discharge codes. Six biomarkers (white blood cell count, fibrinogen, D-dimer, troponin T, N-terminal pro-brain natriuretic peptide, and high-sensitivity C-reactive protein) were strongly associated positively with AAA incidence. Compared with having none of these 6 biomarkers in the highest quartile, the hazard ratios of AAA for those with 1, 2, 3, or 4 to 6 biomarkers in the highest quartile were 2.2, 3.3, 4.0, and 9.9, respectively (
P
for trend < 0.0001) after adjustment for other risk factors.

Conclusions—
This prospective study found that higher concentrations of 6 biomarkers were associated with increased risk of AAA. The more markers that fell into the highest quartile, the higher the AAA risk was. Multiple positive biomarkers identify a subgroup of patients at high risk of AAA.
Long-term results of transjugular coil embolisation for pelvic vein reflux – Results of the abolition of venous reflux at 6–8 years
Authors: Dos Santos Scott J , Holdstock Judy M , Harrison Charmaine C , Whiteley Mark S 
Published: June 2015

Background Pelvic venous reflux is known to be associated with lower limb varicose veins in 20% of women with a history of at least one previous vaginal delivery. Pelvic vein embolisation with coils has been shown to be a successful treatment in the short term. The objective of this study was to ascertain the long-term outcomes of pelvic vein embolisation for pelvic venous reflux. Methods Patients who had undergone pelvic vein embolisation in 2005–2007 were invited back to a specialist vein unit for transvaginal duplex ultrasonography in the summer of 2013. A total of 110 women were contacted. Pre-embolisation transvaginal duplex ultrasonography results were compared to those obtained six weeks post-procedure and at long-term follow-up. Results Twenty-eight female patients aged 40 to 75 years (mean 53.5) attended (response rate 25.5%), with parity prior to embolisation ranging from 1–5 children (mean 2.8). Mean follow-up time was 7.5 years. Six weeks post-procedure, 25 women had complete or virtual elimination of all reflux, and three had persistent reflux in at least one vein. At long-term follow-up, 11 women had complete elimination of all reflux, seven had elimination of all truncal reflux but minor reflux in vulval veins, six had minor reflux in one truncal vein, and four had significant reflux in one or more truncal veins (one of these gave birth one-year post-pelvic vein embolisation and another had coils removed during gynaecological surgery). Conclusions Transjugular pelvic vein embolisation is a durable technique for the abolition of reflux in the pelvic veins and is particularly adept at treating reflux in the ovarian veins.
Surgical management of venous malformation in soft tissue with the guidance of magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging
Authors: Yuan Si-Ming , Zhou Chang-Sheng , Cui Lei , Guo Yao , Hong Zhi-Jian , Jiang Hui-Qing 
Published: June 2015

Background Venous malformation (VM) is a common vascular malformation in soft tissue. Surgical management plays an important role in its treatment. The location, extent, and adjacent anatomy of the lesion are crucial information for the safety of operation. This study introduces the application of magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging in gathering above information. Methods A retrospective analysis was made in the patients with venous malformation from January 2012 to June 2014 in our clinic. All patients underwent magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging. The location, extent of the lesion, its draining veins, and the relationship with around tissues were showed. Surgical management was carried out in the lesions which were well defined, located in the superficial fascia without important vessels and nerves across it. The wound was repaired by skin flap or skin graft. Results A total of 13 patients underwent complete surgical removal of the lesions, including five type I venous malformations and eight type II venous malformations. Ten lesions were removed by undermining dissection, and the wound was repaired by the undermined flap. Three superficial lesions were removed together with the skin over it, and the wound was repaired by the skin graft. In the six months to two years of follow-up period, none of the recurrence of the lesion was observed. Conclusion Magnetic resonance imaging and percutaneous sinus angiography/three-dimensional computed tomography imaging can display abundant morphological details of venous malformation, which are helpful for the surgical management.
Active disease is independently associated with more severe anxiety rather than depressive symptoms in patients with systemic lupus erythematosus
Authors: Tay S H , Cheung P P M , Mak A 
Published: June 2015

Objective The inter-correlation between and co-existence of depression and anxiety may engender inconsistency in addressing the relationship between the severity of depression and disease activity of systemic lupus erythematosus (SLE). We aimed at identifying whether lupus disease activity is independently associated with depression and anxiety in lupus patients. Methods Adult lupus patients were assessed for the severity of depressive and anxiety symptoms and lupus disease activity by using the Hospital Anxiety and Depression Scale (HADS) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), respectively. Age- and gender-matched healthy controls (HCs) were recruited for comparison. Prevalence and severity of depressive and anxiety symptoms were compared between lupus patients and HCs. Independent relationships between the severity of anxiety (HADS-Anxiety) and depressive (HADS-Depression) symptoms, and SLEDAI were studied with regression models. Results In total, 110 lupus patients and 110 HCs were studied. Lupus patients had significantly higher HADS scores than HCs (10.82 ± 6.5 vs 7.34 ± 4.9, p < 0.001). Significantly more lupus patients had anxiety (40.9 vs 21.8%, p = 0.002) and depressive symptoms (15.5 vs 6.4%, p = 0.025) than HCs. Multiple linear regression analyses revealed that SLEDAI (β = 0.160, p = 0.016), calcineurin inhibitor non-use (β = –1.929, p = 0.041) and past cyclophosphamide non-use (β = –1.603, p = 0.039) independently predicted HADS-Anxiety amongst lupus patients even after adjusting for HADS-Depression. Conversely, SLEDAI (β = 0.014, p = 0.834) lost its significant univariate correlation with HADS-Depression after controlling for HADS-Anxiety and other covariates. Conclusion Anxiety is more common in lupus patients than in HCs, and its severity is independently associated with more active SLE regardless of the presence or absence of concomitant depression.
Voice onset time and global foreign accent in German–French simultaneous bilinguals during adulthood
Authors: Lein Tatjana , Kupisch Tanja , van de Weijer Joost 
Published: June 2015

Aims and objectives: In this study, we investigated crosslinguistic influence in the phonetic systems of simultaneous bilinguals (2L1s) during adulthood. Methodology: Specifically, we analyzed the voice onset time (VOT) of the voiceless stop /k/ in the spontaneous speech of 14 German–French bilinguals who grew up in France or Germany. We looked at both languages, first comparing the groups, second comparing their VOT to their global accent. Data and analysis: The material consisted of interviews, lasting for about half an hour. Findings/conclusions: Most 2L1s showed distinct VOT-ranges in their two languages, even if they were perceived to have a foreign accent in the minority language of their childhood environment. We conclude that the phonetic systems of 2L1s remain separate and stable throughout the lifespan. However, the 2L1s from France had significantly shorter VOTs in German than the 2L1s from Germany, and their speech was overall more accented. These findings are discussed with respect to the role of intra- and extra-linguistic factors. Originality: Our study adds a new perspective to existing VOT studies of bilinguals by using naturalistic speech data and by comparing two groups of 2L1s who have the same language combination but grew up in different countries, which allows us to evaluate the impact of their childhood environment on VOT development. Significance/implications: Language exposure during childhood seems to be beneficial for pronunciation during adulthood.
Trial Steering Committees in randomised controlled trials: A survey of registered clinical trials units to establish current practice and experiences
Authors: Conroy Elizabeth J , Harman Nicola L , Lane J Athene , Lewis Steff C , Murray Gordon , Norrie John , Sydes Matt R , Gamble Carrol 
Published: June 2015

Background: The Medical Research Council Guidelines for Good Clinical Practice outlines a three-committee trial oversight structure – the day-to-day Trial Management Group, the Data Monitoring Committee and the Trial Steering Committee. In this model, the Trial Steering Committee is the executive committee that oversees the trial and considers the recommendations from the Data Monitoring Committee. There is yet to be in-depth consideration establishing the Trial Steering Committee’s role and functionality. Methods: A survey to establish Trial Steering Committee’s current practices, role and the use and opinion on the Medical Research Council guidelines was undertaken within UK Clinical Research Collaborative registered Clinical Trials Units. Results: Completed surveys were obtained from 38 of 47 fully and partially registered Units. Individual items in the survey were analysed and reported spanning current Trial Steering Committee practices including its role, requirement and experience required for membership; methods to identify members; and meeting frequency. Terms (a document describing the committee’s remit, objectives and functionality) were obtained and analysed from 21 of 33 Units with documents in place at their Unit. A total of 20 responders suggested aspects of the current Medical Research Council Guidelines that need improvement. Conclusion: We present the first survey reporting on practices within UK Clinical Research Collaborative registered Clinical Trials Units on the experience and remits of Trial Steering Committees. We have identified a widespread adoption of Medical Research Council Guidelines for Trial Steering Committees in the United Kingdom, but limitations in this existing provision have been identified that need to be addressed.
The impact of an educational program on HCV patient outcomes using boceprevir in community practices (OPTIMAL trial)
Authors: Poordad Fred , Rustgi Vinod , Brown Robert S. , Patel Vishal , Kugelmas Marcelo , Regenstein Fredric , Balart Luis , LaBrecque Douglas , Brown Kimberly , Avila Mark , Biederman Michael , Freed Glenn , Smith Richard , Bernstein Marc , Arnold Hays , Cahan Joel , Fink Scott , Katkov William , Massoumi Hatef , Harrison Stephen 
Published: June 2015

Objectives: Although effective, direct acting antiviral (DAA) therapies for genotype 1 (GT 1) hepatitis C virus (HCV) have been associated with compliance challenges. Additionally, treatment at predominantly community-based centers has been associated with low retention of patients on treatment and higher dropout rates. The OPTIMAL Phase IV interventional trial ( ClinicalTrials.gov Identifier: NCT01405027) was designed to evaluate the impact of an education program for community investigator (CI) sites participating in a Chronic Liver Disease Foundation study treating chronic GT 1 HCV patients. Methods: This physician educational program was administered by 22 Hepatology Centers of Educational Expertise (HCEE) academic sites to 33 CI sites asked to participate from December 2011 to July 2012. The HCEE mentors from DAA-experienced academic sites educated those at CI sites on therapeutic management, practice, and patient outcomes through a series of four standardized educational sequence visits regarding the use of first generation HCV protease inhibitors and the overall treatment of HCV. Results: Treatment duration compliance rates for patients treated at CI sites versus those treated at HCEE academic sites were evaluable in 77 of 84 HCEE academic site patients, 102 of 113 patients treated at CI sites, and 179 of 197 overall patients. The treatment duration compliance rates for patients treated at HCEE academic sites, CI sites and overall were 85.4 ± 25.39%, 83.8 ± 27.37%, and 84.5 ± 26.48%, respectively, and did not differ statistically between the groups ( p = 0.49). Almost half (47%) of the patients in the study achieved a sustained virological response for 24 weeks (SVR24) regardless of the type of site ( p = 0.64). Safety profiles were similar at both HCEE and CI sites. Conclusions: These results demonstrated that education of CI sites unfamiliar with DAAs resulted in patient outcomes consistent with those observed at DAA-experienced academic sites.
Activated protein C β-glycoform promotes enhanced noncanonical PAR1 proteolysis and superior resistance to ischemic injury
Authors: Gleeson Eimear M. , Dichiara María G. , Salicio Agustina , Quinn Louise M. , Drakeford Clive , Russell Shane E. , Walsh Patrick T. , Orbe Josune , Hermida José , Smith Owen P. , O’Donnell James S. , Montes Ramón , Preston Roger J. S. 
Published: June 2015

Key PointsThis study demonstrates a novel mechanistic role for a specific N-linked glycan in regulating PAR1 proteolysis. We provide the first description of an APC variant with enhanced therapeutic cytoprotective activity in vivo.
Properties of convergence of a class of iterative processes generated by sequences of self-mappings with applications to switched dynamic systems
Authors: De la Sen Manuel , Ibeas Asier 
Published: June 2015

Abstract
This article investigates the convergence properties of iterative processes involving sequences of self-mappings of metric or Banach spaces. Such sequences are built from a set of primary self-mappings which are either expansive or non-expansive self-mappings and some of the non-expansive ones can be contractive including the case of strict contractions. The sequences are built subject to switching laws which select each active self-mapping on a certain activation interval in such a way that essential properties of boundedness and convergence of distances and iterated sequences are guaranteed. Applications to the important problem of stability of dynamic switched systems are also given.