bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of loss of function variants in clinical contexts
Authors: Lescai Francesco , Marasco Elena , Bacchelli Chiara , Stanier Philip , Mantovani Vilma , Beales Philip 
Published: October 2013

AbstractThe choice of an appropriate variant calling pipeline for exome sequencing data is becoming increasingly more important in translational medicine projects and clinical contexts. Within GOSgene, which facilitates genetic analysis as part of a joint effort of the University College London and the Great Ormond Street Hospital, we aimed to optimize a variant calling pipeline suitable for our clinical context. We implemented the GATK/Queue framework and evaluated the performance of its two callers: the classical UnifiedGenotyper and the new variant discovery tool HaplotypeCaller. We performed an experimental validation of the loss‐of‐function (LoF) variants called by the two methods using Sequenom technology. UnifiedGenotyper showed a total validation rate of 97.6% for LoF single‐nucleotide polymorphisms (SNPs) and 92.0% for insertions or deletions (INDELs), whereas HaplotypeCaller was 91.7% for SNPs and 55.9% for INDELs. We confirm that GATK/Queue is a reliable pipeline in translational medicine and clinical context. We conclude that in our working environment, UnifiedGenotyper is the caller of choice, being an accurate method, with a high validation rate of error‐prone calls like LoF variants. We finally highlight the importance of experimental validation, especially for INDELs, as part of a standard pipeline in clinical environments.
Postprandial fatty acid specific changes in circulating oxylipins in lean and obese men after high‐fat challenge tests
Authors: Strassburg Katrin , Esser Diederik , Vreeken Rob J. , Hankemeier Thomas , Müller Michael , van Duynhoven John , van Golde Jolanda , van Dijk Susan J. , Afman Lydia A. , Jacobs Doris M. 
Published: October 2013

ScopeCirculating oxylipins may affect peripheral tissues and are assumed to play an important role in endothelial function. They are esterified in triglyceride‐rich lipoproteins that are increased after a high‐fat (HF) meal, depending on BMI and fatty acid (FA) type. Yet, it is unclear which oxylipins appear in circulation after HF meals differing in FA composition.Methods and resultsIn a double‐blind randomized crossover challenge study, we characterized the postprandial oxylipin response after different HF challenges in lean and obese men receiving HF milkshakes, either high in saturated FAs (SFA), monounsaturated FAs (MUFA), or omega 3 (n‐3) polyunsaturated FAs (PUFA). Plasma oxylipin profiles were significantly altered at 2 and 4 h after shake consumption when compared to baseline. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins increased after n‐3 PUFA shake consumption. MUFA shake consumption increased levels of cytochrome P450 mediated oxylipins. SFA shake consumption led to strong increases in linoleic acid (LA) derived HODEs. No differences were observed between lean and obese individuals at baseline and after any shake consumption.ConclusionWe are the first demonstrating acute effects on circulating oxylipins after HF meal challenges. These changes were strongly influenced by different dietary FAs and may affect endothelial function.
Mirabegron in overactive bladder: A review of efficacy, safety, and tolerability
Authors: Chapple Christopher R. , Cardozo Linda , Nitti Victor W. , Siddiqui Emad , Michel Martin C. 
Published: October 2013

ABSTRACTAimsMirabegron, the first β3‐adrenoceptor agonist to enter clinical practice, has a different mechanism of action from antimuscarinic agents. This review presents data on the efficacy, safety, and tolerability of mirabegron in studies conducted to date.MethodsAll clinical data on mirabegron that are currently in the public domain are included, including some in‐press manuscripts.ResultsIn Phase III clinical trials in patients with overactive bladder (OAB), mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating the symptoms of OAB, including micturition frequency, urgency incontinence, and urgency. Significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition were seen as early as the first assessment (week 4) for mirabegron 50 and 100 mg, and were maintained throughout treatment. Responder analyses showed a significant improvement with mirabegron 50 and 100 mg in terms of dry rates, ≥50% reduction in mean number of incontinence episodes/24 hr, and the proportion of patients with ≤8 micturitions/24 hr at final visit. The benefit of mirabegron 50 and 100 mg was also evident in patients ≥65 years of age, and in both treatment‐naïve patients and those who previously discontinued antimuscarinic therapy. These data therefore demonstrate a clinically meaningful benefit with mirabegron in the objective endpoints of OAB. Assessment of measures of health‐related quality of life and treatment satisfaction showed that patients perceived treatment with mirabegron as meaningful. In OAB clinical trials of up to 12 months mirabegron appeared to be well tolerated. The most common adverse events (AEs) observed with mirabegron in clinical trials of up to 12 months were hypertension, nasopharyngitis, and urinary tract infection. The incidence of dry mouth was similar to placebo, and was between three and fivefold less than for tolterodine extended release 4 mg. Since dry mouth is the most bothersome AE associated with antimuscarinic drugs and often a reason for treatment discontinuation, mirabegron may be a valuable treatment option for these patients.ConclusionsIn Phase III clinical trials, mirabegron at daily doses of 25, 50, and 100 mg demonstrated significant efficacy in treating symptoms of OAB and, at doses of 50 and 100 mg, demonstrated significant improvements versus placebo on key secondary endpoints, as early as the first assessment (week 4), and these were maintained throughout treatment. In OAB clinical trials of up to 12 months, mirabegron appeared to be well tolerated. Neurourol. Urodynam. 33:17–30, 2014. © 2013 Wiley Periodicals, Inc.
Fully Eulerian finite element approximation of a fluid‐structure interaction problem in cardiac cells
Authors: Laadhari A. , Ruiz‐Baier R. , Quarteroni A. 
Published: October 2013

SUMMARYWe propose in this paper an Eulerian finite element approximation of a coupled chemical fluid‐structure interaction problem arising in the study of mesoscopic cardiac biomechanics. We simulate the active response of a myocardial cell (here considered as an anisotropic, hyperelastic, and incompressible material), the propagation of calcium concentrations inside it, and the presence of a surrounding Newtonian fluid. An active strain approach is employed to account for the mechanical activation, and the deformation of the cell membrane is captured using a level set strategy. We address in detail the main features of the proposed method, and we report several numerical experiments aimed at model validation. Copyright © 2013 John Wiley & Sons, Ltd.
A comparison of techniques for overcoming non‐uniqueness of boundary integral equations for the collocation partition of unity method in two‐dimensional acoustic scattering
Authors: Diwan G.C. , Trevelyan J. , Coates G. 
Published: October 2013

SUMMARYThe Partition of Unity Method has become an attractive approach for extending the allowable frequency range for wave simulations beyond that available using piecewise polynomial elements. The non‐uniqueness of solution obtained from the conventional boundary integral equation (CBIE) is well known. The CBIE derived through Green's identities suffers from a problem of non‐uniqueness at certain characteristic frequencies. Two of the standard methods of overcoming this problem are the so‐called Combined Helmholtz Integral Equation Formulation (CHIEF) method and that of Burton and Miller. The latter method introduces a hypersingular integral, which may be treated in various ways. In this paper, we present the collocation partition of unity boundary element method (PUBEM) for the Helmholtz problem and compare the performance of CHIEF against a Burton–Miller formulation regularised using the approach of Li and Huang. Copyright © 2013 John Wiley & Sons, Ltd.
Sexual dysfunction and sexual health concerns in women with diabetes
Authors: Meeking DR , Fosbury JA , Cummings MH 
Published: October 2013

AbstractThis article aims to investigate the prevalence of female sexual dysfunction and sexual health problems in women with diabetes. We explore the causes, natural history and available treatments.We have examined evidence from clinical and non‐clinical studies for sexual dysfunction in women with diabetes and report this information alongside our own large, self‐reported study of sexual health problems.Sexual dysfunction is more prevalent in diabetic women compared to controls. Problems identified include reduced vaginal lubrication, inability to achieve orgasm, dyspareunia and reduction in libido. Other sexual health concerns include genito‐urinary infection, problems of self‐image, depression and mood‐related issues, plus a range of reproductive and contraceptive worries.In conclusion, sexual health problems are common in women with diabetes. Women should be encouraged to talk about sexual health issues, and specialist advice and therapies should be made available to those who need it. Psychological factors have a more profound effect on sexual functioning in women with diabetes compared to men where physical sexual dysfunction (erectile dysfunction) is the dominant problem. Copyright © 2013 John Wiley & Sons.
Hypoglycaemia in hospital: a re‐audit and root cause analysis using a hypoglycaemic events reporting system
Authors: Rajkanna J , Martin D , Whittle L , Oyibo SO 
Published: October 2013

AbstractHypoglycaemia frequently affects hospitalised patients with diabetes mellitus and most events are both predictable and preventable. A previous audit demonstrated that the documentation of hypoglycaemic events in hospitalised patients was not only incomplete but sometimes non‐existent. We therefore devised a Hypoglycaemic Events Reporting System (HERS) to enable us to re‐audit the management of hypoglycaemic events and to perform root cause analyses.Any member of staff providing treatment for hypoglycaemia documented each event on the paper format of HERS. This was used to enable retrieval of clinical notes for a retrospective audit and root cause analyses.Seventy‐nine patient events were reported on HERS over a one‐year period. This occurred in 56 patients aged 21–92 years. The majority of events were mild, asymptomatic and single events that occurred at night in patients on insulin. Based on documented evidence, all patient events received initial treatment according to guidelines, 90% had a 15‐minute capillary blood glucose (CBG) check, 48% had a 20–40g carbohydrate snack, 54% had a repeat 45–60 minute CBG check, 17% had evidence of a doctor being informed and 49% had the event documented in the notes. Root cause analyses demonstrated common identifiable risk factors/causes and that 46% of patient events were deemed preventable.This audit has demonstrated good compliance with the guidelines for the treatment of hypoglycaemia in hospital with room for improvement, especially around documentation. The HERS improved data quality and quantity for audit purposes. All hypoglycaemic events should be evaluated in terms of risk management and preventative strategies. Copyright © 2013 John Wiley & Sons.
Refill adherence and self‐reported adverse drug reactions and sub‐therapeutic effects: a population‐based study
Authors: Hedna Khedidja , Hägg Staffan , Andersson Sundell Karolina , Petzold Max , Hakkarainen Katja M. 
Published: October 2013

ABSTRACTPurposeTo assess refill adherence to dispensed oral long‐term medications among the adult population and to investigate whether the percentages of self‐reported adverse drug reactions (ADRs) and sub‐therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply.MethodSurvey responses on self‐reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross‐sectional population‐based study. Refill adherence to antihypertensive, lipid‐lowering, and oral anti‐diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self‐reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8–1.2), oversupply (CMA > 1.2), and undersupply (CMA < 0.8).ResultsThe study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti‐diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self‐reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs.ConclusionsAdequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd.
Versatile functional poly(3‐hexylthiophene) for hybrid particles synthesis by the grafting onto technique: Core@shell ZnO nanorods
Authors: Awada Hussein , Medlej Hussein , Blanc Sylvie , Delville Marie‐Hélène , Hiorns Roger C. , Bousquet Antoine , Dagron‐Lartigau Christine , Billon Laurent 
Published: October 2013

ABSTRACTWe demonstrate an efficient strategy to anchor poly(3‐hexylthiophene) (P3HT) onto zinc oxide (ZnO) surfaces. Synthesis of a novel triethoxysilane‐terminated regioregular P3HT is herein reported and supported by thorough characterization. Three triethoxysilane‐terminated P3HTs of different molar masses were prepared via a hydrosilylation reaction from allyl‐terminated P3HT. MALDI‐TOF and 1H NMR were performed to characterize the polymer and show that around 80% of the chains are end‐functionalized. These polymers were then grafted onto the ZnO nanorods to create a macromolecular self‐assembled monolayer. This versatile technique could be subsequently applied to different metal oxide surfaces, such as silicon, titanium, or indium‐tin oxide, and represents a new one‐pot strategy based on triethoxysilane coupling reaction. Importantly, the influence of the molar mass on the grafting density and the polymer shell thickness was studied via thermo gravimetric analysis and transmission electron microscopy. The optical properties of the hybrid materials were determined by UV–visible absorption and photoluminescence to show a quenching effect of P3HT fluorescence by ZnO when grafted. This electronic transfer associated with an improved miscibility of the ZnO@P3HT, makes these hybrid materials suitable candidates for photovoltaic applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 30–38
Symptom burden, loss of dignity, and demoralization in patients with cancer: a mediation model
Authors: Vehling Sigrun , Mehnert Anja 
Published: October 2013

AbstractBackgroundDemoralization is a syndrome of existential distress that occurs in a substantial minority of cancer patients and is associated with a higher number of physical problems. Loss of dignity refers to a range of specific existential concerns. This study examines whether the association between number of physical problems and demoralization is mediated by loss of dignity.MethodsThis cross‐sectional study examined N = 112 inpatients with mixed tumor sites at early and advanced disease stages using the following standardized self‐report questionnaires: Physical problems list of the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT), Patient Dignity Inventory (PDI), Demoralization Scale (DS), Patient Health Questionnaire‐9 (PHQ‐9) and Illness‐Specific Social Support Scale Short Version‐8 (ISSS‐8). The mediation hypothesis was tested by multiple regression analyses controlling for age, gender, curative versus palliative treatment phase, and social support.ResultsPatients reported M = 4.7 (SD = 6.0) dignity‐related problems; 20% showed moderate to severe demoralization. Loss of dignity significantly mediated 81% of the effect of the number of physical problems on demoralization (Sobel zs = 4.4, p < .001). Testing the reverse direction, we found that demoralization mediated only 53% of the association between physical problems and loss of dignity (zs = 3.7, p < .001).ConclusionsBy supporting the mediation hypothesis, our results indicate that loss of dignity partially explains the association between physical problems and demoralization. Early recognition of dignity‐related existential concerns and interventions to enhance the sense of dignity may prevent demoralization in patients with cancer. Results provide a conceptual link between existential concerns (loss of dignity) and existential distress (demoralization) as two approaches to existential suffering in patients with cancer. Copyright © 2013 John Wiley & Sons, Ltd.
Mediators of physical exercise for improvement in cancer survivors' quality of life
Authors: Buffart L. M. , Ros W. J. G. , Chinapaw M. J. M. , Brug J. , Knol D. L. , Korstjens I. , van Weert E. , Mesters I. , van den Borne B. , Hoekstra‐Weebers J. E. H. M. , May A. M. 
Published: October 2013

AbstractObjectiveMediating mechanisms of a 12‐week group‐based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development.MethodsTwo hundred nine cancer survivors ≥3 months posttreatment (57% breast cancer) aged 49.5 (±10.4) years were assigned to physical exercise (n = 147) or wait‐list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self‐efficacy and mastery were assessed at baseline and post‐intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self‐efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL.ResultsThe intervention was associated with increased physical activity (β = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self‐efficacy (β = 2.41, 95%CI = 0.35;4.73), and mastery (β = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (β = −1.09, 95%CI = −2.12;0.01), and an indirect effect (β = −0.54, 95%CI = −1.00;−0.21) via physical activity (β = −0.29, 95%CI = −0.64;−0.07) and general self‐efficacy (β = −0.25, 95%CI = −0.61;−0.05). The intervention had a borderline significant direct effect on reduced distress (β =−1.32, 95%CI =−2.68;0.11), and a significant indirect effect via increased general self‐efficacy and mastery (β =−1.06, 95%CI =−1.89;−0.38). Reductions in fatigue (β =−1.33, 95%CI =−1.85;−0.83) and distress (β =−0.86, 95%CI =−1.25;−0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (β = 3.37, 95%CI = 1.01;5.54).ConclusionThe beneficial effect of group‐based physical exercise on QoL was mediated by increased physical activity, general self‐efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self‐efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors. Copyright © 2013 John Wiley & Sons, Ltd.
Emotions and social relationships for breast and gynecologic patients: a qualitative study of coping with recurrence
Authors: Thornton Lisa M. , Levin Anna O. , Dorfman Caroline S. , Godiwala Neha , Heitzmann Carolyn , Andersen Barbara L. 
Published: October 2013

AbstractBackgroundIn contrast to the large literature on patients' coping with an initial diagnosis of cancer, there have been few quantitative or qualitative studies of patients coping with recurrence. A qualitative study was undertaken to aid in the development of a tailored intervention for these patients.MethodsIndividuals (N=35) receiving follow‐up care for recurrent breast or gynecologic cancer at a university‐affiliated cancer center participated in an individual or a group interview. Transcripts of interviews were analyzed using a coding format with two areas of emphasis. First, we focused on patients' emotions, as there is specificity between emotions and the corresponding ways in which individuals choose to manage them. Secondly, we considered the patients' social environments and relationships, as they too appear key in the adjustment to, and survival from, cancer.ResultsPatients identified notable differences in their responses to an initial diagnosis of cancer and their current ones to recurrence, including the following: (i) depressive symptoms being problematic; (ii) with the passing years and the women's own aging, there is shrinkage in the size of social networks; and (iii) additional losses come from social support erosion, arising from a) intentional distancing by social contacts, b) friends and family not understanding that cancer recurrence is a chronic illness, and/or c) patients stemming their support requests across time.ConclusionThe contribution of these findings to the selection of intervention strategies is discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Which factors predict proposal and uptake of psychological counselling after BRCA1/2 test result disclosure?
Authors: Maheu Christine , Bouhnik Anne‐Deborah , Nogues Catherine , Mouret‐Fourme Emmanuelle , Stoppa‐Lyonnet Dominique , Lasset Christine , Berthet Pascaline , Fricker Jean‐Pierre , Caron Olivier , Luporsi Elizabeth , Gladieff Laurence , Julian‐Reynier Claire 
Published: October 2013

AbstractObjectiveThe aim of this study is to prospectively determine the factors contributing to whether unaffected women from BRCA1/2 families reported that clinicians proposed psychological consultations and that they had attended these consultations during the genetic testing process.MethodsA prospective study was performed on a national cohort, using self‐administered questionnaires to determine the rates of proposal and use of psychological services at the time of BRCA1/2 test result disclosure (N = 533) and during the first year after disclosure (N = 478) among unaffected French women from BRCA1/2 families who had undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out using logistic regression models fitted using generalized estimation equations, with the genetic testing centre as the clustering variable.ResultsAt the time of BRCA1/2 test result disclosure, a psychological consultation was proposed by cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N = 301), respectively (p < 0.001). One year after disclosure, 21% of the carriers had consulted a psychologist, versus 9% of the noncarriers (p < 0.001). Both the proposal and the uptake depended on the women's BRCA1/2 mutation carrier status (proposal adjusted odds ratio (AOR): 4.9; 95% confidence interval (CI) 3.4–7.2; uptake AOR: 2.2; 95% CI 1.2–4.0), their level of education (proposal AOR: 1.7; 95% CI 1.1–2.7; uptake AOR: 4.5; 95% CI 1.7–12.1) and the distress they experienced about their genetic test results (proposal AOR: 1.02; 95% CI 1.01–1.03; uptake AOR: 1.04; 95% CI 1.02–1.06)ConclusionsDeterminants of the proposal/uptake of psychological consultations in the BRCA1/2 testing process highlight the need for inventive strategies to reach the different types of women's profiles. Copyright © 2013 John Wiley & Sons, Ltd.