bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II‐mediated hypertension
Authors: Porpino Suênia K P , Zollbrecht Christa , Peleli Maria , Montenegro Marcelo F , Brandão Maria C R , Athayde‐Filho Petrônio F , França‐Silva Maria S , Larsson Erik , Lundberg Jon O , Weitzberg Eddie , Persson Erik G , Braga Valdir A , Carlström Mattias 
Published: May 2016

AbstractBackground and PurposeNO deficiency and oxidative stress are crucially involved in the development or progression of cardiovascular disease, including hypertension and stroke. We have previously demonstrated that acute treatment with the newly discovered organic nitrate, 2‐nitrate‐1,3‐dibuthoxypropan (NDBP), is associated with NO‐like effects in the vasculature. This study aimed to further characterize the mechanism(s) and to elucidate the therapeutic potential in a model of hypertension and oxidative stress.Experimental ApproachA combination of ex vivo, in vitro and in vivo approaches was used to assess the effects of NDBP on vascular reactivity, NO release, NADPH oxidase activity and in a model of hypertension.Key ResultsEx vivo vascular studies demonstrated NDBP‐mediated vasorelaxation in mesenteric resistance arteries, which was devoid of tolerance. In vitro studies using liver and kidney homogenates revealed dose‐dependent and sustained NO generation by NDBP, which was attenuated by the xanthine oxidase inhibitor febuxostat. In addition, NDBP reduced NADPH oxidase activity in the liver and prevented angiotensin II‐induced activation of NADPH oxidase in the kidney. In vivo studies showed that NDBP halted the progression of hypertension in mice with chronic angiotensin II infusion. This was associated with attenuated cardiac hypertrophy, and reduced NADPH oxidase‐derived oxidative stress and fibrosis in the kidney and heart.Conclusion and ImplicationsThe novel organic nitrate NDBP halts the progression of angiotensin II‐mediated hypertension. Mechanistically, our findings suggest that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase.
Synthesis and biological evaluation of novel lignan glycosides as anticancer agents
Authors: Wang Ying , Xia Chao , Zhang Wei , Zhao Yu 
Published: May 2016

Novel lignan glycosides 1a–1 h as analogues of cleistanthin A were designed and synthesized. Most of these compounds displayed significant cytotoxicities against four cancer cell lines. Compound 1e displayed better cytotoxicity than cleistanthin A with IC50 values from 1.0 nm to 8.3 nm. Further lysosome acidity assay disclosed that 1e could totally inhibit the activity of V‐ATPase at 60 nm.
Herpes zoster and the search for an effective vaccine
Authors: Arnold N , Messaoudi I 
Published: May 2016

SummaryPrimary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax® is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post-herpetic neuralgia by 66·5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immune-competent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster.
On nonepistemic values in conservation biology
Authors: Baumgaertner Bert , Holthuijzen Wieteke 
Published: May 2016

AbstractConservation biology is a uniquely interdisciplinary science with strong roots in ecology, but it also embraces a value‐laden and mission‐oriented framework. This combination of science and values causes conservation biology to be at the center of critique regarding the discipline's scientific credibility—especially the division between the realms of theory and practice. We identify this dichotomy between seemingly objective (fact‐based) and subjective (value‐laden) practices as the measure‐value dichotomy, whereby measure refers to methods and analyses used in conservation biology (i.e., measuring biodiversity) and value refers to nonepistemic values. We reviewed and evaluated several landmark articles central to the foundation of conservation biology and concepts of biodiversity with respect to their attempts to separate measures and values. We argue that the measure‐value dichotomy is false and that conservation biology can make progress in ways unavailable to other disciplines because its practitioners are tasked with engaging in both the realm of theory and the realm of practice. The entanglement of measures and values is by no means a weakness of conservation biology. Because central concepts such as biodiversity contain both factual and evaluative aspects, conservation biologists can make theoretical progress by examining, reviewing, and forming the values that are an integral part of those concepts. We suggest that values should be included and analyzed with respect to the methods, results, and conclusions of scientific work in conservation biology.
Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study
Authors: Parrinello C. M. , Matsushita K. , Woodward M. , Wagenknecht L. E. , Coresh J. , Selvin E. 
Published: May 2016

AimsTo develop a prediction equation for 10‐year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non‐traditional biomarkers.MethodsWe included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990–1992). Models included self‐reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood‐based biomarkers. We compared models using prediction and discrimination statistics.ResultsSuccessive stages of model development improved risk prediction. The C‐statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non‐traditional biomarkers [β‐2 microglobulin, creatinine‐based estimated glomerular filtration rate (eGFR), and cystatin C‐based eGFR] to Model 3 significantly improved discrimination (C‐statistic = 0.716; p = 0.003) and accuracy of 10‐year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18–68% to 12–87%).ConclusionsThese biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long‐term major complications.
Intraoperative Assessment of Left Atrial Diverticulum and Remnant Stump after Left Atrial Appendage Epicardial Occlusion
Authors: Suwalski Grzegorz , Emery Robert , Gryszko Leszek , Kaczejko Kamil , Mroz Jakub , Skrobowski Andrzej 
Published: May 2016

ObjectivesEpicardial left atrial appendage (LAA) closure with use of occluder is an emerging technique. Absence of remnant LAA stump is major criterion of successful obliteration. The aim of study was to assess early success rate of epicardial LAA closure.MethodsFifteen patients with persistent AF and coronary artery disease underwent off‐pump coronary revascularization with concomitant ablation and LAA epicardial occlusion with use of two types of occluders. Before incision and after appendage closure, TEE was performed to assess the LAA anatomy, diameter of left atrial ridge, and remnant LAA stump after occlusion.ResultsIn 80% (12) of patients, formation of a left atrial diverticulum was observed with the left atrial ridge forming the superior boundary. In 5 patients (33%), a minimal remnant LAA stump was found, none exceeding 1 cm (average length: 1.5 ± 2.3 mm). In all patients, blood flow in LAA cavity distal to the occluder was absent. There was no significant difference in LAA type, average left atrial diameter, LAA orifice, LAA length, left atrial ridge, or size of occluder used between patients with and without a remnant LAA stump. Occurrence of a remnant LAA stump correlated significantly with unfavorable anatomy (LAA orifice < 20 mm and LA ridge > 5 mm; r = 0.5774, P = 0.02).ConclusionThe early success of epicardial LAA occlusion is not dependent on LAA morphologic type or occluder used. A minimal remnant LAA stump not exceeding 1 cm in length without distal blood flow was observed in one‐third of the cases.
The conceptual framework of ontogenetic trajectories: parallel transport allows the recognition and visualization of pure deformation patterns
Authors: Piras P. , Teresi L. , Traversetti L. , Varano V. , Gabriele S. , Kotsakis T. , Raia P. , Puddu P. E. , Scalici M. 
Published: May 2016

SUMMARYOntogeny is usually studied by analyzing a deformation series spanning over juvenile to adult shapes. In geometric morphometrics, this approach implies applying generalized Procrustes analysis coupled with principal component analysis on multiple individuals or multiple species datasets. The trouble with such a procedure is that it mixes intra‐ and inter‐group variation. While MANCOVA models are relevant statistical/mathematical tools to draw inferences about the similarities of trajectories, if one wants to observe and interpret the morphological deformation alone by filtering inter‐group variability, a particular tool, namely parallel transport, is necessary. In the context of ontogenetic trajectories, one should firstly perform separate multivariate regressions between shape and size, using regression predictions to estimate within‐group deformations relative to the smallest individuals. These deformations are then applied to a common reference (the mean of per‐group smallest individuals). The estimation of deformations can be performed on the Riemannian manifold by using sophisticated connection metrics. Nevertheless, parallel transport can be effectively achieved by estimating deformations in the Euclidean space via ordinary Procrustes analysis. This approach proved very useful in comparing ontogenetic trajectories of species presenting large morphological differences at early developmental stages.
Gene networks and developmental context: the importance of understanding complex gene expression patterns in evolution
Authors: Signor Sarah A. , Arbeitman Michelle N. , Nuzhdin Sergey V. 
Published: May 2016

SUMMARYAnimal development is the product of distinct components and interactions—genes, regulatory networks, and cells—and it exhibits emergent properties that cannot be inferred from the components in isolation. Often the focus is on the genotype‐to‐phenotype map, overlooking the process of development that turns one into the other. We propose a move toward micro‐evolutionary analysis of development, incorporating new tools that enable cell type resolution and single‐cell microscopy. Using the sex determination pathway in Drosophila to illustrate potential avenues of research, we highlight some of the questions that these emerging technologies can address. For example, they provide an unprecedented opportunity to study heterogeneity within cell populations, and the potential to add the dimension of time to gene regulatory network analysis. Challenges still remain in developing methods to analyze this data and to increase the throughput. However this line of research has the potential to bridge the gaps between previously more disparate fields, such as population genetics and development, opening up new avenues of research.
High genetic variation in a small population of Cherry leaf roll virus in Betula sp. of montane origin in Corsica
Authors: Langer J. , Rumbou A. , Fauter A. , von Bargen S. , Büttner C. 
Published: May 2016

SummaryCherry leaf roll virus (CLRV) infection is common in Betula pendula and B. pubescens in Middle and North Europe, easily observable by chlorotic leaf vein banding, mottling and leaf roll, partially adherent with progressive loss of vitality or death of twigs and branches. In Fennoscandia, a severe viral epidemic in various birch species in forest stands, public greens and roadsides is associated with CLRV. In Corsica, CLRV‐typical symptoms were observed on birch trees (Betula sp.) in a montane stand (1470 m) at Col de Vergio. CLRV was detected by RT‐nested PCR in all leaf samples from 11 randomly selected birch trees exhibiting characteristic symptoms. Along with the fact that this is the first report of CLRV in Betula sp. of both montane and Mediterranean origins, remarkably high genetic variation and a new distinct phylogenetic cluster are comprised by a small randomly sampled CLRV population that has evolved in one of the few scattered birch stands in Corsica.
Urgent hemodialysis with the use of peripheral veins to avoid catheter insertion
Authors: Gołębiowski Tomasz , Letachowicz Krzysztof , Letachowicz Waldemar , Kusztal Mariusz , Kanafa Maciej , Weyde Wacław , Klinger Marian 
Published: May 2016

AbstractUrgent hemodialysis (HD) in patients with uremia is usually performed using a central vein catheter unless an arteriovenous fistula (AVF) was created in the predialysis period. We present a unique approach, in a patient in whom the first two HD sessions were conducted without implantation of a catheter or AVF. The perfectly developed peripheral veins of a professional bodybuilder served as vascular access allowing catheter insertion to be avoided. The aim of this short case report is to recall a forgotten method for performing urgent HD in patients without a fistula, but with suitably enlarged superficial veins.
Short‐term in vivo modifications of platelet NADPH oxidase 2 (NOX2) and prostaglandin F2α in HIV‐1 patients on abacavir‐based therapies
Authors: Pastori D , Esposito A , Carnevale R , Bartimoccia S , Nocella C , Fantauzzi A , Pignatelli P , Violi F , Mezzaroma I 
Published: May 2016

ObjectivesThe aim of the study was to investigate the in vivo effect of abacavir (ABC) on platelet oxidative stress.MethodsWe performed a randomized pilot study including 39 HIV‐1‐infected patients, 17 on zidovudine/lamivudine (ZDV/3TC) and 22 on tenofovir/emtricitabine (TDF/FTC). Ten patients on ZDV/3TC and eight patients on TDF/FTC were randomly allocated to switching the nucleoside backbone to ABC/3TC. At baseline and after 6 months, platelet oxidative stress was assessed by platelet NADPH oxidase 2 (NOX2)‐derived peptide (sNOX2‐dp), a marker of NOX2 activation, and platelet prostaglandin F2α (8‐iso‐PGF2α). Platelet activation was measured by soluble CD40L (sCD40L).ResultsAt baseline, no differences between ZDV/3TC or TDF/FTC recipients were found. After 6 months, patients switching from ZDV/3TC showed a decrease of sNOX2‐dp (from 20.9±5.7 to 12.5±3.8 pg/ml, p=0.002) and 8‐iso‐PGF2α (from 154.3±41.9 to 122.9±28.0 pmol/l, p=0.025). No effects on platelet oxidative stress biomarkers were observed in subjects from TDF/FTC, who showed a significant increase in blood glucose (p=0.043) and total cholesterol (p=0.027). ABC showed no effect on sCD40L levels in both groups.ConclusionsABC reduced platelet sNOX2‐dp and 8‐iso‐PGF2α in HIV‐1 subjects switching from ZDV/3TC but not in those from TDF/FTC after 6 months. No changes in platelet activation were found in both groups.
Apoptosis in follicles of individuals with female pattern hair loss is associated with perifollicular microinflammation
Authors: Ramos P. M. , Brianezi G. , Martins A. C. P. , da Silva M. G. , Marques M. E. A. , Miot H. A. 
Published: May 2016

AbstractObjectiveThe objective of this study is to evaluate apoptosis in hair follicles of patients with female pattern hair loss (FPHL) and its association with follicular microinflammation.MethodCross‐sectional study involving 17 women with FPHL and five controls. Scalp skin samples were processed for HE and TUNEL assays. The variables were compared according to the categories of follicles (terminal versus miniaturized) and groups of patients (FPHL vs. controls).ResultsThere was a higher apoptosis index among miniaturized follicles and among the test cases (P < 0.01). Microinflammation was prominent among miniaturized follicles, especially from FPHL (P = 0.02). In addition, a positive correlation between inflammatory infiltrate and apoptosis in miniaturized follicles (rS = 0.68; P < 0.01) was found.ConclusionsApoptosis was prominent in hair follicles from the FPHL group, as well as in miniaturized ones. Moreover, it was also correlated with the inflammatory infiltrate, which suggests that inflammation can lead to apoptosis and play a role in the pathogenesis of follicle miniaturization.
Verification and quality control of routine hematology analyzers
Authors: Vis J. Y. , Huisman A. 
Published: May 2016

SummaryVerification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and linearity throughout the expected range of results. Yet, which standard should be met or which verification limit be used is at the discretion of the laboratory specialist. This paper offers practical guidance on verification and quality control of automated hematology analyzers and provides an expert opinion on the performance standard that should be met by the contemporary generation of hematology analyzers. Therefore (i) the state‐of‐the‐art performance of hematology analyzers for complete blood count parameters is summarized, (ii) considerations, challenges, and pitfalls concerning the development of a verification plan are discussed, (iii) guidance is given regarding the establishment of reference intervals, and (iv) different methods on quality control of hematology analyzers are reviewed.
Diagnosis, risk stratification and management of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma
Authors: van de Donk N. W. C. J. , Mutis T. , Poddighe P. J. , Lokhorst H. M. , Zweegman S. 
Published: May 2016

SummaryMonoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders. IgG and IgA MGUS are precursor conditions of multiple myeloma (MM), whereas light‐chain MGUS is a precursor condition of light‐chain MM. Smoldering MM (SMM) is a precursor condition with higher tumor burden and higher risk of progression to symptomatic MM compared to MGUS. Assessment of the risk of progression of patients with asymptomatic monoclonal gammopathies is based on various factors including clonal burden, as well as biological characteristics, such as cytogenetic abnormalities and light‐chain production. Several models have been constructed that are useful in daily practice for predicting risk of progression of MGUS or SMM. Importantly, the plasma cell clone may occasionally be responsible for severe organ damage through the production of a M‐protein which deposits in tissues or has autoantibody activity. These disorders are rare and often require therapy directed at eradication of the underlying clone. Importantly, recent studies have shown that asymptomatic patients with a bone marrow plasma cell percentage ≥60%, free light‐chain ratio ≥100, or >1 focal lesion on MRI (myeloma‐defining events) have a 80% risk of developing symptomatic MM within 2 years. These patients are now considered to have MM requiring therapy, similar to patients with symptomatic disease. In this review, we provide an overview of the new diagnostic criteria of the monoclonal gammopathies and discuss risk of progression to active MM. We also provide recommendations for the management of patients with MGUS and SMM including risk‐adapted follow‐up.
Laboratory testing for antiphospholipid syndrome
Authors: Pengo V. , Banzato A. , Bison E. , Denas G. , Zoppellaro G. , Bracco A. , Padayattil Jose S. , Hoxha A. , Ruffatti A. 
Published: May 2016

SummaryThis is a practical report on laboratory tests for the diagnosis of antiphospholipid syndrome (APS). After a general definition of APS, this study deals with appropriateness and timing in requesting the determination of antiphospholipid (aPL) antibodies. Lupus anticoagulant (LAC), anticardiolipin (aCL), and anti β2‐glycoprotein I (aβGPI) are the mandatory tests to be performed, while other tests are not yet validated for clinical use. Interpretation of results is an important discussed issue that implies a close liaison between clinical pathologists and clinicians. Finally, a personal definition of APS according to aPL antibody profile closes the manuscript.
Weight change in the management of youth‐onset type 2 diabetes: the TODAY clinical trial experience
Authors: Marcus M. D. , Wilfley D. E. , El ghormli L. , Zeitler P. , Linder B. , Hirst K. , Ievers‐Landis C. E. , van Buren D. J. , Walders‐Abramson N. ,   For the TODAY Study Group
Published: May 2016

SummaryBackgroundThe Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy.ObjectivesWe examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms.MethodsThe 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11–17 years) completed assessments of weight‐related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time.ResultsLifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months.ConclusionsAlthough adjunctive intensive lifestyle intervention did not improve weight‐related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.