bluuebunny/crossref_metadata_2025_split huggingface dataset:
External Validity of the ARISTOTLE Trial in Real‐Life Atrial Fibrillation Patients
Authors: Hägg Lovisa , Johansson Cecilia , Jansson Jan‐Håkan , Johansson Lars 
Published: June 2014

SummaryObjectiveOur primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility.MethodsWe performed a cross‐sectional study of an unselected population including 2274 patients in Skellefteå, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population.ResultsAmong all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria.ConclusionOur study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life.
Treatment of lupus nephritis: practical issues in Asian countries
Authors: Yap Desmond Y. H. , Chan Tak Mao 
Published: June 2014

AbstractLupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus in Asian patients, and is an important cause of renal failure in Asian countries. Immunosuppressive treatments of LN have evolved over the past few decades and resulted in improvements in patient outcomes. Treatment guidelines have been recently published by rheumatology and nephrology communities in the USA and Europe, but the emphasis was more on patients of African or Hispanic descent and Caucasians. There is increasing evidence that racial and ethnic variations are associated with differences in disease manifestations, pharmacogenomics/kinetics, response to therapy and complications of disease or treatment. There is substantial data confirming the efficacy of combined corticosteroids and either cyclophosphamide or mycophenolate mofetil (MMF) as initial treatments for active Class III/IV LN in Asian patients. Azathioprine, MMF or a calcineurin inhibitor, or possibly mizoribine which requires further investigation in non‐Japanese patients, in combination with low‐dose corticosteroids, can be considered as maintenance immunosuppression to prevent disease flares, and the optimal choice needs to take into account tolerability and prior induction therapy. Treatment costs and accessibility to specialist healthcare facilities, compliance which in turn is related to socio‐economic and education status, as well as regional variations in risk of infections, including subacute infection such as tuberculosis or chronic infections such as hepatitis B or C, are issues that are distinctly pertinent in Asia.
Economic burden of inadequate management of allergic diseases in the European Union: a GA2LEN review
Authors: Zuberbier T. , Lötvall J. , Simoens S. , Subramanian S. V. , Church M. K. 
Published: June 2014

AbstractBackgroundIn the European Union (EU), between 44 and 76 million individuals of the 217 million EU employees suffer from allergic disease of the airways or the skin. Up to 90% of these persons are untreated or insufficiently treated. This has major socio‐economic consequences such as absence from work (absenteeism), particularly reduced productivity at work (presenteeism).MethodsWe used published literature and online statistical information from Eurostat and Eurofound to assess the costs of allergic disease to society.ResultsAllergies have an impact on direct, indirect, intangible and opportunity costs. Most importantly, for the EU, avoidable indirect costs per patient insufficiently treated for allergy range between €55 and €151 billion per annum due to absenteeism and presenteeism, that is, €2405 per untreated patient per year. On the other hand, appropriate therapy for allergic diseases is available at comparatively low costs at an average of €125 per patient annually, equalling only 5% of the costs of untreated disease, allowing potential savings of up to €142 billion.ConclusionsA better care for allergies based on guideline‐based treatment would allow Europe's economy substantial savings. In addition, allergies have an impact on learning and performance at school and university, leading to opportunity costs for society. This cannot be calculated moneywise but will have an impact in a modern knowledge‐based society. Still allergies are trivialized in society, noting that the costs of therapy are paid by patients and healthcare services, whereas economic savings are made by employers and society. A change of this mindset is urgently needed.
Comparison of macular GCIPL and peripapillary RNFL deviation maps for detection of glaucomatous eye with localized RNFL defect
Authors: Kim Mi Jeung , Park Ki Ho , Yoo Beong Wook , Jeoung Jin Wook , Kim Hee Chan , Kim Dong Myung 
Published: June 2014

AbstractPurposeTo evaluate the ability of the deviation map of macular ganglion cell–inner plexiform layer (GCIPL) thickness compared with that of peripapillary retinal nerve fibre layer (pRNFL) thickness for detection of localized RNFL defects shown on red‐free RNFL photography.MethodsThis prospective cross‐sectional study included 69 eyes of 69 subjects with preperimetric or perimetric glaucoma (mean deviation (MD) >−12dB) and localized RNFL defects along with 79 eyes of 79 normal control subjects. The number of abnormal superpixels on the both macular GCIPL and pRNFL deviation maps by Cirrus OCT corresponding to localized RNFL defects was calculated using a customized Matlab program and presented as severity indices according to each of the probability levels. The areas under the receiver operating characteristic curves (AUROCs) of the severity indices were compared between the two deviation maps.ResultsAccording to three criteria and corresponding probability levels, the AUROCs of the GCIPL and pRNFL deviation maps ranged from 0.910 to 0.931 and 0.934 to 0.950, respectively. However, the differences were not statistically significant (all p > 0.05). Significant correlations were observed between the severity indices of the GCIPL deviation map and those of the pRNFL deviation map, regardless of the criteria (all p < 0.0001).ConclusionsIn the detection of glaucomatous eyes with localized RNFL defects, the macular GCIPL thickness deviation map showed a level of diagnostic performance comparable to that of the pRNFL thickness deviation map.
Genetic parameters of postnatal mortality and birth weight in Japanese Black calves
Authors: Ibi Takayuki , Kahi Alexander K. , Hirooka Hiroyuki 
Published: June 2014

AbstractPostnatal mortality (PM) of calves is an economically important trait, because a high mortality rate of calves decreases farm income and significantly increases production costs. In spite of the economic importance of PM, genetic studies on PM have been scarce for Japanese Black cattle. The objectives of this study were to estimate the direct and maternal heritability for PM using a Bayesian threshold model with Gibbs sampling in Japanese Black cattle. The original data consisted of 43 723 records of animals born from January 2005 to June 2006. Four binary traits of mortality were considered: D1‐14, D15‐60, D61‐180 and D1‐180 with numbers indicating the period of risk in days after birth. Direct heritabilities for PM ranged from 0.12 to 0.31 and maternal heritabilities for PM were lower than the direct heritabilities and ranged from 0.02 to 0.16. Direct genetic correlations between D1‐14 and D15‐60, between D15‐60 and D61‐180, and between D1‐14 and D61‐180 were 0.501, 0.689 and 0.062, respectively. Direct genetic correlations of birth weight with D1‐14, D15‐60, D61‐180 and D1‐180 were 0.089, 0.482, 0.434 and 0.394, respectively. These results indicated that different genes were responsible for early and late PM and early PM (D1‐14) can be genetically reduced without influencing birth weight.
Milk as a diagnostic sample for a commercially available ELISA to identify bovine viral diarrhoea (BVD) antibodies in dairy herds
Authors: Lanyon SR , McCoy R , Bergman E , Reichel MP 
Published: June 2014

ObjectiveThe aims of this study were to evaluate a commercially available ELISA for the detection of bovine viral diarrhoea virus (BVDV)‐specific antibodies in individual milk compared with individual serum samples, and in bulk milk samples compared with within‐herd antibody prevalence and bulk milk quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results.MethodsPaired individual serum and individual milk samples were collected from 125 lactating cows and tested by ELISA; 96 bulk milk samples were also tested. Within‐herd antibody prevalence was calculated based on milk ELISA results for 25 individual cows in each herd. Additionally, 167 bulk milk samples were tested for BVDV‐specific antibodies by ELISA and for the presence of BVDV by qRT‐PCR to establish the correlation between antibody result and virus presence.ResultsGood agreement was observed between individual milk and serum results (Kappa = 0.865). The ELISA was observed to detect BVDV‐specific antibodies in individual milk samples with a relative sensitivity of 96.6% and specificity of 89.2%. The bulk milk samples revealed a strong (r2 = 0.95) relationship between the ELISA result and the within‐herd antibody prevalence. The proportion of herds that tested positive by bulk milk qRT‐PCR increased as the bulk milk antibody S/P ratio increased.ConclusionCommercially available ELISA testing of individual and bulk milk samples is an appropriate alternative to serum testing with good test performance in these samples. Determining a threshold for the detection of herds containing active BVD infection by testing bulk milk is a novel use for an antibody ELISA kit and provides more practical, relevant test results.
Acquired urethral obstruction in New World camelids: 34 cases (1995–2008)
Authors: Duesterdieck‐Zellmer KF , Van Metre DC , Cardenas A , Cebra CK 
Published: June 2014

ObjectiveDocument the clinical features, short‐ and long‐term outcomes and prognostic factors in New World camelids with acquired urethral obstruction.DesignRetrospective case study.MethodsCase data from medical records of 34 New World camelids presenting with acquired urethral obstruction were collected and follow‐up information on discharged patients was obtained. Associations with short‐ and long‐term survival were evaluated using Wilcoxon rank‐sum tests, exact‐logistic regressions and Kaplan‐Meier survival curves.ResultsOf the 34 New World camelids 23 were intact males and 11 were castrated; 4 animals were euthanased upon presentation, 7 were treated medically and 23 surgically, including urethrotomy, bladder marsupialisation, tube cystostomy alone or combined with urethrotomy, urethrostomy or penile reefing. Necrosis of the distal penis was found in 4 animals and all were short‐term non‐survivors. Short‐term survival for surgical cases was 65%, and 57% for medical cases. Incomplete urethral obstruction at admission and surgical treatment were associated with increased odds of short‐term survival. Of 14 records available for long‐term follow‐up, 6 animals were alive and 8 were dead (median follow‐up 4.5 years, median survival time 2.5 years). Recurrence of urethral obstruction was associated with long‐term non‐survival.ConclusionsSurgically treated New World camelids with incomplete urethral obstruction have the best odds of short‐term survival and those with recurrence of urethral obstruction have a poor prognosis for long‐term survival.
Inhibition of UVB‐Induced Skin Damage by Exopolymers from Aureobasidium pullulans SM‐2001 in Hairless Mice
Authors: Kim Kyung Hu , Park Soo Jin , Lee Young Joon , Lee Ji Eun , Song Chang Hyun , Choi Seong Hun , Ku Sae Kwang , Kang Su Jin 
Published: June 2014

AbstractBecause antioxidants from natural sources may be an effective approach to the treatment and prevention of UV radiation‐induced skin damage, the effects of purified exopolymers from Aureobasidium pullulans SM‐2001 (‘E‐AP‐SM2001’) were evaluated in UVB‐induced hairless mice. E‐AP‐SM2001 consists of 1.7% β‐1,3/1,6‐glucan, fibrous polysaccharides and other organic materials, such as amino acids, and mono‐ and di‐unsaturated fatty acids (linoleic and linolenic acids) and shows anti‐osteoporotic and immunomodulatory effects, through antioxidant and anti‐inflammatory mechanisms. Hairless mice were treated topically with vehicle, E‐AP‐SM2001 stock and two and four times diluted solutions once per day for 15 weeks against UVB irradiation (three times per week at 0.18 J/cm2). The following parameters were evaluated in skin samples: myeloperoxidase (MPO) activity, cytokine levels [interleukin (IL)‐1β and IL‐10], endogenous antioxidant content (glutathione, GSH), malondialdehyde (MDA) levels, superoxide anion production; matrix metalloproteases (MMP‐1, ‐9 and ‐13), GSH reductase and Nox2 (gp91phox) mRNA levels, and immunoreactivity for nitrotyrosine (NT), 4‐hydroxynonenal (HNE), caspase‐3, and cleaved poly(ADP‐ribose) polymerase (PARP). Photoageing was induced by UVB irradiation through ROS‐mediated inflammation, which was related to the depletion of endogenous antioxidants, activation of MMPs and keratinocyte apoptosis. Topical treatment with all three doses of E‐AP‐SM2001 and 5 nm myricetin attenuated the UV‐induced depletion of GSH, activation of MMPs, production of IL‐1β, the decrease in IL‐10 and keratinocyte apoptosis. In this study, E‐AP‐SM2001 showed potent inhibitory effects against UVB‐induced skin photoageing. Thus, E‐AP‐SM2001 may be useful as a functional ingredient in cosmetics, especially as a protective agent against UVB‐induced skin photoageing.
Oseltamivir Blocks Human Neuronal Nicotinic Acetylcholine Receptor‐Mediated Currents
Authors: Muraki Katsuhiko , Hatano Noriyuki , Suzuki Hiroka , Muraki Yukiko , Iwajima Yui , Maeda Yasuhiro , Ono Hideki 
Published: June 2014

AbstractThe effects of oseltamivir, a neuraminidase inhibitor, were tested on the function of neuronal nicotinic acetylcholine receptors (nAChRs) in a neuroblastoma cell line IMR32 derived from human peripheral neurons and on recombinant human α3β4 nAChRs expressed in HEK cells. IMR32 cells predominately express α3β4 nAChRs. Nicotine (nic, 30 μm)‐evoked currents recorded at −90 mV in IMR32 cells using the whole‐cell patch clamp technique were reversibly blocked by oseltamivir in a concentration‐dependent manner. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) at 30 μm had little effect on the nic‐evoked currents. Oseltamivir also blocked nic‐evoked currents derived from HEK cells with recombinant α3β4 nAChRs. This blockade was voltage‐dependent with 10, 30 and 100 μm oseltamivir inhibiting ~50% at −100, −60 and −40 mV, respectively. Non‐inactivating currents in IMR32 cells and in HEK cells with α3β4 nAChRs, which were evoked by an endogenous nicotinic agonist, ACh (5 μm), were reversibly blocked by oseltamivir. These data demonstrate that oseltamivir blocks nAChRs, presumably via binding to a site in the channel pore.
Unimodal regression using Bernstein–Schoenberg splines and penalties
Authors: Köllmann Claudia , Bornkamp Björn , Ickstadt Katja 
Published: June 2014

SummaryResearch in the field of nonparametric shape constrained regression has been intensive. However, only few publications explicitly deal with unimodality although there is need for such methods in applications, for example, in dose–response analysis. In this article, we propose unimodal spline regression methods that make use of Bernstein–Schoenberg splines and their shape preservation property. To achieve unimodal and smooth solutions we use penalized splines, and extend the penalized spline approach toward penalizing against general parametric functions, instead of using just difference penalties. For tuning parameter selection under a unimodality constraint a restricted maximum likelihood and an alternative Bayesian approach for unimodal regression are developed. We compare the proposed methodologies to other common approaches in a simulation study and apply it to a dose–response data set. All results suggest that the unimodality constraint or the combination of unimodality and a penalty can substantially improve estimation of the functional relationship.
Histopathological features and their prognostic impact in nodular lymphocyte‐predominant Hodgkin lymphoma – a matched pair analysis from the German Hodgkin Study Group (GHSG)
Authors: Hartmann Sylvia , Eichenauer Dennis A. , Plütschow Annette , Mottok Anja , Bob Roshanak , Koch Karoline , Bernd Heinz‐Wolfram , Cogliatti Sergio , Hummel Michael , Feller Alfred C. , Ott German , Möller Peter , Rosenwald Andreas , Stein Harald , Hansmann Martin‐Leo , Engert Andreas , Klapper Wolfram 
Published: June 2014

SummaryNodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched‐pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein–Barr virus status of the malignant lymphocyte‐predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment. None of these features was associated with a particular clinical outcome. However, patients presenting with epithelioid cell clusters showed a non‐significant trend towards a lower relapse rate, justifying further evaluation of this marker.
Engagement of Toll-like receptor 2 enhances interleukin (IL)-17+ autoreactive T cell responses via p38 mitogen-activated protein kinase signalling in dendritic cells
Authors: Wei R , Dong L , Xiao Q , Sun D , Li X , Nian H 
Published: June 2014

Summary
Functional analysis of single Toll-like receptors (TLRs) in vivo is necessary to understand how they shape the ocular inflammation involved in uveitis. In this study we explored the role and mechanisms of TLR-2 agonists on the autoreactive T helper type 17 (Th17) response in experimental autoimmune uveitis (EAU). Treatment by peptidoglycan (PGN), a specific TLR-2 agonist, remarkably increased mRNA levels of Th17-lineage genes interleukin (IL)-17A, IL-21 and RAR-related orphan receptor (ROR)γt and promoted antigen-specific Th17 response in EAU mice. A mixture of PGN and interphotoreceptor retinoid-binding protein peptide (IRBP161–180) could effectively induce EAU in the absence of complete Freund's adjuvant (CFA). PGN treatment also enhanced the pathogenic activities of activated antigen-specific Th17 cells in vivo. PGN significantly increased the production of IL-1β, IL-6 and IL-23 of dendritic cells (DCs) and enhanced their ability to promote IL-17+ uveitogenic T cells. Enhanced immunostimulatory activities of PGN-DCs depend upon p38 activation. Inhibition of p38 mitogen-activated protein kinase (MAPK) activity dramatically decreased IL-17 gene expression and antigen-specific Th17 responses stimulated by PGN-DCs. Our findings suggest that PGN treatment dramatically promotes the IL-17+ uveitogenic T cell responses via enhancing the immunostimulatory activities of DCs. This effect may be mediated, at least in part, by activation of the p38 signalling pathway in DCs.
MEFV gene polymorphisms and TNFRSF1A mutation in patients with inflammatory myopathy with abundant macrophages
Authors: Fujikawa K , Migita K , Shigemitsu Y , Umeda M , Nonaka F , Tamai M , Nakamura H , Mizokami A , Tsukada T , Origuchi T , Yonemitsu N , Yasunami M , Kawakami A , Eguchi K 
Published: June 2014

Summary
Inflammatory myopathy with abundant macrophages (IMAM) has recently been proposed as a new clinical condition. Although IMAM shares certain similarities with other inflammatory myopathies, the mechanisms responsible for this condition remain unknown. Patients with familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS) also often develop myalgia. We therefore investigated the polymorphisms or mutations of MEFV and TNFRSF1A genes in patients with IMAM to identify their potential role in this condition. We analysed the clinical features of nine patients with IMAM and sequenced exons of the MEFV and TNFRSF1A genes. The patients with IMAM had clinical symptoms such as myalgia, muscle weakness, erythema, fever and arthralgia. Although none of the patients were diagnosed with FMF or TRAPS, seven demonstrated MEFV polymorphisms (G304R, R202R, E148Q, E148Q-L110P and P369S-R408Q), and one demonstrated a TNFRSF1A mutation (C43R). These results suggest that MEFV gene polymorphisms and TNFRSF1A mutation are susceptibility and modifier genes in IMAM.
Fingolimod ameliorates axonal damage in experimental autoimmune encephalomyelitis
Authors: Jin Shijie , Takeuchi Hideyuki , Horiuchi Hiroshi , Wang Yue , Kawanokuchi Jun , Mizuno Tetsuya , Suzumura Akio 
Published: June 2014

AbstractObjectivesFingolimod (FTY) is a new oral drug for multiple sclerosis. It acts as a functional antagonist for sphingosine 1‐phosphate receptor (S1PR). After phosphorylateion by sphingosine kinase in vivo, FTY binds to S1PR on lymphocytes to downregulate S1PR, thereby preventing lymphocyte egress from lymphoid tissues to reduce infiltration of autoreactive lymphocytes into the central nervous system. FTY easily passes through the blood–brain barrier and directly affects cells in the central nervous system. Recently, we have shown that FTY exerts neuroprotective effects by suppressing pro‐inflammatory functions of glial cells and by upregulating neuroprotective functions of neuronal and glial cells in vitro. In the present study, we examined whether FTY exerts neuroprotective effects in vivo in the chronic phase of experimental autoimmune encephalomyelitis (EAE).MethodsMyelin oligodendrocyte glycoprotein‐induced EAE mice were orally treated with FTY (1 mg/kg/day) or vehicle (water) once a day starting at the disease peak (15 days after immunization). To evaluate gliosis and axonal damage, the lumbar spinal cords were examined immunohistochemically at 28 days after immunization.ResultsFTY treatment starting at disease peak improved the severity of symptoms, and reduced gliosis and axonal damage in the spinal cord, as assessed by glial staining and formation of neuritic bead/spheroid.ConclusionsFTY exerts protective effects on axonal impairments during the chronic phase of EAE. The neuroprotective effect of FTY could synergistically suppress pathology of multiple sclerosis with its immunosuppressive effect.
Variational Tree Synthesis
Authors: Wang Rui , Yang Yinhui , Zhang Hongxin , Bao Hujun 
Published: June 2014

AbstractModelling trees according to desired shapes is important for many applications. Despite numerous methods having been proposed in tree modelling, it is still a non‐trivial task and challenging. In this paper, we present a new variational computing approach for generating realistic trees in specific shapes. Instead of directly modelling trees from symbolic rules, we formulate the tree modelling as an optimization process, in which a variational cost function is iteratively minimized. This cost function measures the difference between the guidance shape and the target tree crown. In addition, to faithfully capture the branch structure of trees, several botanical factors, including the minimum total branches volume and spatial branches patterns, are considered in the optimization to guide the tree modelling process. We demonstrate that our approach is applicable to generate trees with different shapes, from interactive design and complex polygonal meshes.