bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation
Authors: Sousa A. R. , Marshall R. P. , Warnock L. C. , Bolton S. , Hastie A. , Symon F. , Hargadon B. , Marshall H. , Richardson M. , Brightling C. E. , Haldar P. , Milone R. , Chalk P. , Williamson R. , Panettieri R. , Knowles R. , Bleecker E. R. , Wardlaw A. J. 
Published: May 2017

SummaryBackgroundPatients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear.ObjectiveTo relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation.MethodsPatients with mild/moderate and severe asthma were investigated before and after 2 weeks of oral prednisolone (Clintrials.gov NCT00331058 and NCT00327197). We pooled the results from two studies with common protocols. The US study contained two independent centres and the UK one independent centre. The effect of oral corticosteroids on FEV1, Pc20, airway inflammation and serum cytokines was investigated. Baseline measurements were compared with healthy subjects.ResultsThirty‐two mild/moderate asthmatics, 50 severe asthmatics and 35 healthy subjects took part. At baseline, both groups of asthmatics had a lower FEV1 and Pc20 and increased eosinophilic inflammation compared to healthy subjects. The severe group had a lower FEV1 and more eosinophilic inflammation compared to mild/moderate asthmatics. Oral prednisolone caused a similar degree of suppression of eosinophilic inflammation in all compartments in both groups of asthmatics. There were small improvements in FEV1 and Pc20 for both mild/ moderate and severe asthmatics with a correlation between the baseline eosinophilic inflammation and the change in FEV1. There was a ~50% reduction in the serum concentration of CXCL10 (IP‐10), CCL22 (MDC), CCL17 (TARC), CCL‐2 (MCP‐1) and CCL‐13 (MCP‐4) in both asthma groups after oral corticosteroids.Conclusions and Clinical RelevanceDisease severity does not influence the response to systemic corticosteroids. The study does not therefore support the concept that severe asthma is associated with corticosteroid resistance. Only baseline eosinophilic inflammation was associated with the physiological response to corticosteroids, confirming the importance of measuring eosinophilic inflammation to guide corticosteroid use.
Minor allergen patterns in birch pollen allergen products—A question of pollen?
Authors: Zimmer J. , Döring S. , Strecker D. , Trösemeier J. H. , Hanschmann K. M. , Führer F. , Vieths S. , Kaul S. 
Published: May 2017

AbstractBackgroundContrary to the scientific differentiation between major and minor allergens, the regulatory framework controlling allergen products in the EU distinguishes relevant and non‐relevant allergens. Given the lack of knowledge on their clinical relevance, minor allergens are usually not controlled by allergen product specifications. Especially, in birch pollen (BP) allergen products, minor allergens are commonly disregarded.ObjectivesTo quantify three minor allergens in BP allergen products from different manufacturers and to assess the influence of the utilized BP on minor allergen patterns.MethodsApart from common quality parameters such as Bet v 1 content, Bet v 4, Bet v 6 and Bet v 7 were quantified in 70 BP allergen product batches from six manufacturers, using ELISA systems developed in‐house. Batch‐to‐batch variability was checked for agreement with a variability margin of 50%‐200% from mean of the given batches for individual allergen content. Subsequently, minor allergen patterns were generated via multidimensional scaling and related to information on the pollen lots used in production of the respective product batches.ResultsLike the already established Bet v 4 ELISA, the ELISA systems for quantification of Bet v 6 and Bet v 7 were successfully validated. Differences in minor allergen content between products and batch‐to‐batch consistency were observed. Correlations between minor and major allergen content were low to moderate. About 20% of batches exceeded the variability margin for at least one minor allergen. Interestingly, these fluctuations could not in all cases be linked to the use of certain BP lots.Conclusions and Clinical RelevanceThe impact of the observed minor allergen variability on safety and efficacy of BP allergen products can currently not be estimated. As the described differences could only in few cases be related to the used pollen lots, it is evident that additional factors influence minor allergens in BP allergen products.
Prevalence of primary aldosteronism among patients with type 2 diabetes
Authors: Tancredi Mauro , Johannsson Gudmundur , Eliasson Björn , Eggertsen Robert , Lindblad Ulf , Dahlqvist Sofia , Imberg Henrik , Lind Marcus 
Published: May 2017

SummaryContextDiabetes and hypertension coexist in 40%‐60% of individuals with type 2 diabetes. The coexistence of these two conditions is associated with increased risk of retinopathy, nephropathy and cardiovascular disease.ObjectiveTo investigate the prevalence of primary aldosteronism (PA) in a general cohort of persons with type 2 diabetes.DesignCross‐sectional study involving six diabetes outpatient clinics in Sweden.Patientswere enrolled individuals with type 2 diabetes between February 2008 and December 2013.MeasurementsPlasma aldosterone concentrations (PAC pmol/L) and direct renin concentrations (DRC mIU/L) were measured. Patients with increased aldosterone renin ratios (ARR) >65 were further evaluated for PA.ResultsOf 578 consecutively screened patients with type 2 diabetes, 27 were treated with mineralocorticoid receptor antagonists (MRA) and potassium‐sparing diuretics not further evaluated. Among the remaining 551 patients, 38 had increased ARR, including 22 who were clinically indicated for PA tests and 16 who were not further evaluated due to severe comorbidities and old age. There were five (0.93%) patients with confirmed PA after computerized tomography and adrenal venous sampling. Patients with PA had higher systolic blood pressure (P=.032) and lower potassium levels (P=.027) than those without PA. No significant association was found between plasma aldosterone and diabetic complications.ConclusionsThe prevalence of PA in an unselected cohort of patients with type 2 diabetes is relatively low, and measures of plasma aldosterone are not strong risk factors for micro‐ and macrovascular diabetic complications.
PAX6 allelic heterogeneity in Mexican congenital aniridia patients: expanding the mutational spectrum with seven novel pathogenic variants
Authors: Pérez‐Solórzano Sofía , Chacón‐Camacho Oscar F , Astiazarán Mirena C , Ledesma‐Gil Gerardo , Zenteno Juan Carlos 
Published: May 2017

AbstractImportanceThe importance of the study was to describe the clinical characteristics and mutational analysis of Mexican patients with aniridia.BackgroundAniridia is a panocular hereditary eye disease caused by mutations in the PAX6 transcription factor. Mutation detection rate is highly variable ranging from 30% to 90% in different populations. Very few studies have been published about the PAX6 mutational analysis in aniridia patients from Mexico. In order to establish a more representative PAX6 mutational frequency in the country, a cohort of 22 Mexican unrelated aniridia probands were analysed in this study.DesignCase series.ParticipantsA total of 22 Mexican probands with bilateral isolated aniridia and their available relatives were included.MethodsSanger sequencing was used for the mutational analysis of all coding exons and flanking intronic regions of PAX6.Main Outcome MeasuresClinical characteristics and results of PAX6 mutational analysis in probands with aniridia and available family members.ResultsMolecular analysis of PAX6 in 22 index cases with aniridia allowed the identification of a total of 16 different mutations. Seven of these pathogenic variants are novel, including c.183C>G, p.(Y61*); c.718delC, p.(R240Efs*3); c.1149_1152delTCAG, p.(P385Wfs*139); c.257_266delAAATAGCCCA, p.(K86Sfs*35); c.836_843dupGCAACACA p.(P282Afs*86); c.1032+2_1032+3insT; and c.141+2T>A. Inter and intrafamilial phenotypic heterogeneity was found.Conclusions and RelevanceThe mutational diagnostic rate in this series was 77%, which is comparable with reports from other populations. Importantly, no founder mutations were identified in this case series. Our results add 7 novel PAX6 pathogenic variants to the aniridia‐related mutational spectrum and reveal considerable PAX6 allelic heterogeneity in this population.
Clinical and virologic outcomes in high‐risk adult Epstein‐Barr virus mismatched organ transplant recipients
Authors: Kumar Deepali , Patil Nikhil , Husain Shahid , Chaparro Cecilia , Bhat Mamatha , Kim S. Joseph , Humar Atul 
Published: May 2017

AbstractEpstein‐Barr virus (EBV) D+/R− organ transplant recipients are a high‐risk group for developing post‐transplant lymphoproliferative disease (PTLD). Little data are available for prevention in the adult EBV mismatched population. We conducted a retrospective study of EBV D+/R− organ transplants performed during 2002‐2014. Of the 153 patients identified, 82.4% patients received antiviral prophylaxis with valganciclovir for a median of 4.5 months (range: 0.8‐22 months) and 36.6% underwent viral load monitoring in the first post‐transplant year. EBV viremia developed in 67.2% monitored patients. In viremic patients, immunosuppression was reduced in 20/37(54.1%) in response to viremia and 17/37 (45.9%) received therapeutic dose valganciclovir. In patients with EBV viremia who received valganciclovir and/or had a reduction in immunosuppression and had sufficient viral load time points (n=31), 28 (90.3%) had a significant decline in viral load at day 14 (median log decline 0.49 (0.24‐0.64), P<.001) and at day 30 (0.87 (0.52‐1.21), P<.001). PTLD developed in 27 (15%) patients (biopsy proven=25, possible=2) at median 8 months (range: 2.4‐130) post‐transplant with the majority (81.5%) within the first year. In multivariate analysis, viral load monitoring and use of mycophenolate were associated with a lower incidence of PTLD. Antiviral prophylaxis was not associated with a lower risk of PTLD, but viral load monitoring and use of mycophenolate mofetil were protective.
Increased risk of portal vein thrombosis in patients with autoimmune hepatitis on the liver transplantation waiting list
Authors: Ruiz Pablo , Sastre Lydia , Crespo Gonzalo , Blasi Annabel , Colmenero Jordi , García‐Valdecasas Juan Carlos , Navasa Miquel 
Published: May 2017

AbstractLiver transplantation (LT) is indicated in autoimmune hepatitis (AIH) for both acute presentation with liver failure and end‐stage chronic liver disease. Few studies have suggested an association between AIH and coagulation disorders and a higher incidence of portal vein thrombosis (PVT) in patients with AIH listed for LT. The aim of this study was to determine the incidence of thrombotic complications, particularly PVT, in a cohort of 37 patients undergoing LT because of AIH. PVT was present before transplantation in 30% (n=11) of these patients compared to 11% in the whole population transplanted in our center (P=.002). On comparing only patients with cirrhosis, PVT was present in 55% of the AIH group, being 12% in the whole cohort (P<.001). Among patients with PVT before LT, no patient receiving anticoagulation therapy early after LT developed recurrence of PVT, whereas two patients (33%) without anticoagulation therapy did. The increased incidence of PVT in the pretransplant period and the possibility of thrombosis recurrence after LT suggest that patients with AIH and PVT could benefit from anticoagulation therapy after transplantation. However, further studies are needed to recommend anticoagulation in these patients in clinical practice.
Long‐term outcomes of early compared to late onset choledochocholedochal anastomotic strictures after orthotopic liver transplantation
Authors: Satapathy Sanjaya K. , Sheikh Imran , Ali Bilal , Yahya Fazal , Kocak Mehmet , Parsa Laxmi Babu , Eason James D. , Vanatta Jason M. , Nair Satheesh P. 
Published: May 2017

AbstractBackgroundEndoscopic treatment of anastomotic biliary stricture (ABS) after liver transplantation (LT) has been proven to be effective and safe, but long‐term outcomes of early compared to late onset ABS have not been studied. The aim of this study is to compare the long‐term outcome of early ABS to late ABS.MethodsOf the 806 adult LT recipients (04/2006‐12/2012), 93 patients met the criteria for inclusion, and were grouped into non‐ABS (no stenosis on ERCP, n=41), early ABS (stenosis <90 days after LT, 18 [19.3%]), and late ABS (stenosis ≥90 days after LT, 34 [36.5%]). A propensity matched control group for the ABS group (n=42) was obtained matched for outcome variables for age, gender, and calculated MELD score at listing.ResultsMean number of ERCPs (2.33±1.3 vs 2.56±1.5, P=.69) were comparable between the groups; however, significantly better long‐term resolution of the stricture was noted in the early ABS group (94.44% vs 67.65%, P=.04). Kaplan‐Meier analysis revealed worst survival in the early ABS group compared to the non‐ABS, late ABS, and control groups (P=.0001).ConclusionLT recipients with early ABS have inferior graft survival despite better response to endoscopic intervention.
Infection of the fittest: devil facial tumour disease has greatest effect on individuals with highest reproductive output
Authors: Wells Konstans , Hamede Rodrigo K. , Kerlin Douglas H. , Storfer Andrew , Hohenlohe Paul A. , Jones Menna E. , McCallum Hamish I. 
Published: May 2017

AbstractEmerging infectious diseases rarely affect all members of a population equally and determining how individuals’ susceptibility to infection is related to other components of their fitness is critical to understanding disease impacts at a population level and for predicting evolutionary trajectories. We introduce a novel state‐space model framework to investigate survival and fecundity of Tasmanian devils (Sarcophilus harrisii) affected by a transmissible cancer, devil facial tumour disease. We show that those devils that become host to tumours have otherwise greater fitness, with higher survival and fecundity rates prior to disease‐induced death than non‐host individuals that do not become infected, although high tumour loads lead to high mortality. Our finding that individuals with the greatest reproductive value are those most affected by the cancer demonstrates the need to quantify both survival and fecundity in context of disease progression for understanding the impact of disease on wildlife populations.
Do sociodemographic, behavioral or health status variables affect longitudinal anthropometric changes in older adults? Population‐based cohort study in Southern Brazil
Authors: Goes Vanessa Fernanda , Wazlawik Elisabeth , d'Orsi Eleonora , Navarro Albert , González‐Chica David Alejandro 
Published: May 2017

AimTo assess the influence of sociodemographic, behavioral and health status variables on longitudinal changes in height, weight, and waist circumference in older adults.MethodsThis is a population‐based cohort study in Southern Brazil (EpiFloripa Study) investigating 1702 individuals aged 70.6 ± 8.0 years (62.5% women). Height, weight and waist circumference were measured in 2009/10 and 2013/14 (n = 1197). Linear mixed regression models were used to estimate age‐related changes in anthropometric measurements according to the explanatory variables.ResultsUnmarried individuals, with higher education level or household income, with excessive alcohol consumption, former smokers and positives for some chronic disease were heavier than their counterparts. Similar associations were observed for waist circumference in terms of marital status, smoking and the presence of chronic diseases. Height was higher among the wealthiest, in former smokers and those physically active. Only in men were a lower education level and being unmarried associated with higher weight loss after the age of 75 years, but not with waist circumference reduction.ConclusionsDespite their association with current height, weight and waist circumference, neither behavioral variables nor the presence of chronic diseases influenced the anthropometric changes. Less educated and unmarried men lose weight at a higher rate, showing a higher risk of sarcopenia. Geriatr Gerontol Int 2017; 17: 2074–2082.
An Elitist Multiobjective Tabu Search for Optimal Design of Groundwater Remediation Systems
Authors: Yang Yun , Wu Jianfeng , Wang Jinguo , Zhou Zhifang 
Published: May 2017

AbstractThis study presents a new multiobjective evolutionary algorithm (MOEA), the elitist multiobjective tabu search (EMOTS), and incorporates it with MODFLOW/MT3DMS to develop a groundwater simulation‐optimization (SO) framework based on modular design for optimal design of groundwater remediation systems using pump‐and‐treat (PAT) technique. The most notable improvement of EMOTS over the original multiple objective tabu search (MOTS) lies in the elitist strategy, selection strategy, and neighborhood move rule. The elitist strategy is to maintain all nondominated solutions within later search process for better converging to the true Pareto front. The elitism‐based selection operator is modified to choose two most remote solutions from current candidate list as seed solutions to increase the diversity of searching space. Moreover, neighborhood solutions are uniformly generated using the Latin hypercube sampling (LHS) in the bounded neighborhood space around each seed solution. To demonstrate the performance of the EMOTS, we consider a synthetic groundwater remediation example. Problem formulations consist of two objective functions with continuous decision variables of pumping rates while meeting water quality requirements. Especially, sensitivity analysis is evaluated through the synthetic case for determination of optimal combination of the heuristic parameters. Furthermore, the EMOTS is successfully applied to evaluate remediation options at the field site of the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts. With both the hypothetical and the large‐scale field remediation sites, the EMOTS‐based SO framework is demonstrated to outperform the original MOTS in achieving the performance metrics of optimality and diversity of nondominated frontiers with desirable stability and robustness.
Cracking induction in health libraries: is there a right way?
Authors: Forgham‐Healey Nicola 
Published: May 2017

AbstractIn most instances, inductions are the first time that users will be introduced to health library services. The time available in which to deliver library orientation sessions within a broader, Trust induction programme is often limited, and this can present challenges for health librarians. Inductions are a great marketing tool, and it is important that induction sessions make the right impact. Within a brief window of opportunity, the health librarian must impart key information to the inductees whilst ensuring the session is relevant and memorable. In this article, guest writer Nicola Healey, Library Manager of North Somerset Healthcare Library, discusses the range of approaches she and her colleagues have explored in delivering library inductions, explaining what worked, what did not and what areas still remain for development.H. S.
Predictive formula of coma onset and prothrombin time to distinguish patients who recover from acute liver injury
Authors: Kakisaka Keisuke , Suzuki Yuji , Kataoka Kojiro , Okada Yohei , Miyamoto Yasuhiro , Kuroda Hidekatsu , Takikawa Yasuhiro 
Published: May 2017

AbstractBackground and AimAcute liver failure (ALF) is defined as acute liver injury (ALI) associated with coagulopathy. A follow‐up strategy for ALI and characterization of ALI patients with a risk of progressing to ALF have never been established. To establish predictive markers for progression from ALI to ALF, this study compared the clinical characteristics and laboratory data on the day of registration to data from a regional referral system of patients with ALI.MethodsThis prospective, observational study enrolled 365 consecutive patients with ALI/ALF between 2007 and 2016. We evaluated 109 ALI patients, 27 of whom satisfied the ALF criteria during observation and another 82 patients who recovered without progression to ALF.ResultsFour patients died; all were in the ALF group. The variables of age, incidence of autoimmune hepatitis, model of end‐stage liver disease score, values for total bilirubin and prothrombin time (PT)‐international ratio, and Japan Hepatic Encephalopathy Prediction Model (JHEPM) probability at registration were significantly higher in ALF patients than in ALI patients. In multivariate analysis, PT and JHEPM were identified as risk factors for progression to ALF. The cut‐off values of 13%, 4.9%, 65%, and 1.32% for the model of end‐stage liver disease score, JHEPM probability, PT, and PT‐international ratio values, respectively, had high negative predictive values. Furthermore, among patients whose JHEPM was underestimated, none died due to ALF.ConclusionThe JHEPM probability is a predictive parameter that can be used to decide a follow‐up treatment strategy for ALI patients.
Astrocytes contribute to Aβ‐induced blood–brain barrier damage through activation of endothelial MMP9
Authors: Spampinato Simona Federica , Merlo Sara , Sano Yasuteru , Kanda Takashi , Sortino Maria Angela 
Published: May 2017

AbstractThe blood–brain barrier (BBB) plays an important role in the maintenance of the brain homeostasis, and its proper functions are warranted by the interplay between different cellular components (endothelial cells, astrocytes and pericytes). BBB dysfunctions in pathological conditions, and particularly in Alzheimer's disease, have been documented. Here, using an in vitroBBB model, the interaction between endothelial cells and astrocytes exposed to Aβ1‐42 was investigated. Human endothelial cells, cultured in monolayer or co‐cultured with astrocytes, were exposed to Aβ1‐42 (2 μM for 18 h). Aβ induced dysfunction of endothelial barrier, as assessed by enhanced permeability to FITC‐conjugated dextran and reduced expression of claudin‐5; these modifications were observed in the co‐culture model, but not in endothelial cells cultured in monolayer. Similarly, Aβ‐induced damage at the barrier was observed when endothelial cells were challenged in the presence of conditioned medium generated by astrocytes previously exposed to Aβ (ACM Aβ). Endothelial barrier damages were associated with enhanced matrix metalloprotease 9 (MMP9) activity, known to mediate claudin‐5 disruption. These events were not related to the direct effects played by Aβ on endothelial cells, but they were rather the consequence of Aβ‐induced vascular endothelial growth factor (VEGF) expression in astrocytes. Indeed, when vascular endothelial growth factor expression was down‐regulated in astrocytes, neither barrier properties or MMP9 expression in endothelial cells were affected after Aβ exposure both in the co‐culture model or in the presence of ACM Aβ. These data point out the importance of astrocytes’ mediation in inducing endothelial sensitivity to Aβ1‐42.
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