bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal PGC1α May Be Associated with Recovery after Delayed Graft Function
Authors: Drury Erika R. , Zsengeller Zsuzsanna K. , Stillman Isaac E. , Khankin Eliyahu V. , Pavlakis Martha , Parikh Samir M. 
Published: December 2017

<b><i>Background:</i></b> Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury. <b><i>Objectives:</i></b> We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function. <b><i>Methods:</i></b> We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis. <b><i>Results:</i></b> Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, <i>p</i> &#x3c; 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, <i>p</i> &#x3c; 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes. <b><i>Conclusions:</i></b> These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings.
Refinement of Mouse Protocols for the Study of Platelet Thromboembolic Responses In Vivo
Authors: Rauzi Francesca , Smyth Erica , Emerson Michael 
Published: December 2017

AbstractMouse models of thromboembolism are frequently used to investigate platelet function in vivo and, according to European Union (EU) legislation, must be conducted in the context of replacement, refinement and reduction. We have previously developed a refined real-time mouse model of thromboembolism as an alternative to models of thromboembolic mortality which inflict considerable pain and suffering. Real-time monitoring involves infusion of radiolabelled platelets into the circulation of anaesthetized mice, and platelet aggregation is measured as increases in platelet-associated counts in the pulmonary vasculature following injection of platelet agonists. This gives a definitive data set on the tissue localization and extent of platelet activation. We developed an additional, more simplistic alternative to mortality models based on blood microsampling which entails the measurement of circulating platelet counts following agonist stimulation. Blood microsamples were collected from the tail vein of anaesthetized mice at three different time points leading to a reduction in animal numbers. Platelet counts significantly dropped 1 minute after stimulation with collagen or thrombin and were restored over 10 minutes. These results correlate with those obtained via real-time monitoring and were confirmed by immunohistochemistry. Pre-treatment of mice with aspirin significantly inhibited the decrease in platelet counts following collagen. These data suggest that blood microsampling may be implemented as a simplistic refined alternative to mortality models of thromboembolism when specialized monitoring equipment, or use of radioactive isotopes for real-time monitoring, which remains the ‘gold standard’, is not feasible. Microsampling refines and reduces animal procedures in compliance with current EU legislation.
Enrichment of Circulating Endothelial Cells by CD34 Microbeads Followed by Enumeration Using Flow Cytometry
Authors: Burylo Artur , de Weger Vincent , Stuurman Frederik , Beijnen Jos , Schellens Jan 
Published: December 2017

Background Circulating endothelial cells (CECs) are a potential biomarker of angiogenesis. CECs increase in numbers after vessel injury. Higher CEC numbers are reported in cancer patients. Most methods for CEC detection and enumeration rely on flow cytometry (FCM); however, there is no agreement on CEC phenotype and the detection method to be used. This leads to uncertainty about the clinical applicability and variation between studies on CEC numbers reported.
Objective To develop a selective and accurate method for CEC enumeration in peripheral blood by enrichment, followed by FCM in healthy volunteers (HV) and cancer patients.
Methods Samples were enriched using CD34 microbeads, stained with nuclear dye and anti-CD14, CD15, CD45, CD34 and CD146 antibodies. Putative CECs were examined for Weibel–Palade bodies (WPBs) using anti–von Willebrand factor (vWF) antibody and fluorescence microscopy. Linear range of detection (R
2), recovery and precision (coefficient of variation percentage [CV%]) were defined in three experiments by spiking a known number (range 12–12,800 CECs/4 mL) of surrogate endothelial cells in peripheral blood. Sample storage was determined at –80°C for up to 2 months.
Results Sorted CECs showed vWF in the WPBs. The relationship between spiked and detected surrogate cells was R
2 = 1.0, recovery of 94.0 to 101.4% and CV% of 1.0 to 18.4%. Recovery ± standard deviation (within-run days 1, 2 and 3) were, respectively, 102.5% ± 8.2, 97.8% ± 4.6, 99.1% ± 7.7, and after 2 months 94.3% ± 15.3. The median CECs/mL in patients was 24.1 versus 14.4 in HVs.
Conclusion This method for selective, sensitive and reliable CEC analysis by FCM allows for investigation of CECs as a biomarker in clinical research.
Myeloperoxidase Is a Negative Regulator of Phospholipid-Dependent Coagulation
Authors: Beckmann Lennart , Dicke Christina , Spath Brigitte , Lehr Carina , Sievers Bianca , Klinke Anna , Baldus Stephan , Rudolph Volker , Langer Florian 
Published: December 2017

AbstractMyeloperoxidase (MPO) is a cationic heme enzyme stored in neutrophilic polymorphonuclear leukocytes (PMNs) that has recently been implicated in inflammatory cell signaling and tissue damage. Although PMNs play a critical role in both innate immunity and vascular thrombosis, no previous study has systematically investigated the effect of MPO on blood coagulation. Here, we show that PMN-derived MPO inhibits the procoagulant activity (PCA) of lipidated recombinant human tissue factor (rhTF) in a time- and concentration-dependent manner that involves, but is not entirely dependent on the enzyme's catalytic activity. Similarly, MPO together with its substrate, H2O2, inhibited the PCA of plasma microvesicles isolated from lipopolysaccharide (LPS)-stimulated whole blood, an effect additive to that of a function blocking TF antibody. Treatment of whole blood with LPS or phorbol-myristate-acetate dramatically increased MPO plasma levels, and co-incubation with 4-ABAH, a specific MPO inhibitor, significantly enhanced the PCA in plasma supernatants. MPO and MPO/H2O2 also inhibited the PCA of activated platelets and purified phospholipids (PLs), suggesting that modulation of negatively charged PLs, i.e., phosphatidylserine, rather than direct interference with the TF/FVIIa initiation complex was involved. Consistently, pretreatment of activated platelets with MPO or MPO/H2O2 attenuated the subsequent binding of lactadherin, which specifically recognizes procoagulant PS on cell membranes. Finally, endogenously released MPO regulated the PCA of THP1 cells in an autocrine manner dependent on the binding to CD11b/CD18 integrins. Collectively, these findings indicate that MPO is a negative regulator of PL-dependent coagulation and suggest a more complex role of activated PMNs in haemostasis and thrombosis.
Diagnostic Accuracy of a Novel Chromogenic Direct Thrombin Inhibitor Assay: Clinical Experiences for Dabigatran Monitoring
Authors: Poli Sven , Härtig Florian , Spencer Charlotte , Ebner Matthias , Birschmann Ingvild , Kuhn Joachim , Faix Susanne , Ziemann Ulf , Häring Hans-Ulrich , Lehmann Rainer , Peter Andreas , Hörber Sebastian 
Published: December 2017

Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists (VKA) for clinical indications requiring long-term oral anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran—the only direct thrombin inhibitor amongst them—does not require therapeutic drug monitoring. However, in case of treatment complications (e.g., major haemorrhage) and conditions requiring urgent surgery or thrombolytic therapy, information about actual DOAC plasma levels is needed to guide treatment decisions. Due to short reagent stability, limited accuracy at low dabigatran levels and high heparin sensitivity, the applicability of the widely used Hemoclot thrombin inhibitor (HTI) coagulation assay is limited in the emergency setting.
Methods Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran-treated patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with HTI using ultra performance liquid chromatography—tandem mass spectrometry as the reference method for measuring dabigatran plasma concentrations.
Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p < 0.0001) as well as a low intra- and inter-assay variation of <5%. Compared with HTI, BDTI provides an improved on-board reagent stability of 72 hours, rapid turnaround times comparable to routine coagulation assays, high accuracy at low drug levels and reduced heparin sensitivity.
Conclusion The BDTI is an ideal coagulation assay for the around-the-clock determination of dabigatran plasma levels in clinical routine including emergency situations.
Outpatient Management in Patients with Venous Thromboembolism with Edoxaban: A Post Hoc Analysis of the Hokusai-VTE Study
Authors: Medina Andria , Raskob Gary , Ageno Walter , Cohen Alexander , Brekelmans Marjolein , Chen Cathy , Grosso Michael , Mercuri Michele , Segers Annelise , Verhamme Peter , Vanassche Thomas , Wells Philip , Lin Min , Winters Shannon , Weitz Jeffrey , Büller Harry 
Published: December 2017

AbstractDirect oral anticoagulants (DOACs) facilitate the outpatient treatment of venous thromboembolism (VTE). However, the pivotal trials of DOACs have not reported outcomes separately for patients managed either as outpatients or in the hospital. We performed a subgroup analysis of the Hokusai-VTE study comparing efficacy and safety of edoxaban with warfarin in 8,292 patients with acute VTE. Patients received initial therapy with open-label enoxaparin or unfractionated heparin for ≥5 days in the hospital or as an outpatient at the discretion of the treating physician. Edoxaban or warfarin was then given for 3 to 12 months. The primary efficacy outcome was the cumulative incidence of symptomatic recurrent VTE at 12 months. The principal safety outcome was the incidence of clinically relevant bleeding (composite of major or clinically relevant non-major bleeding). Of the 5,223 consecutively enrolled patients with recorded hospital status and length of stay, 1,414 patients (27.1%) were managed as outpatients and 3,809 were managed in hospital. Among the outpatients, initial presentation was symptomatic deep-vein thrombosis (DVT) in 1,183 patients (83.7%) and pulmonary embolism (PE) in 231 patients (16.3%). Among the outpatients with DVT, recurrent VTE occurred in 18 (3.0%) given edoxaban and in 21 (3.6%) given warfarin (risk difference: −0.61, 95% confidence interval [CI]: −2.6 to 1.4). The principal safety outcome in outpatients occurred in 46 edoxaban patients (7.7%) and in 48 warfarin patients (8.3%; risk difference: −0.59, 95% CI: −3.7 to 2.5). Most outpatients had symptomatic DVT at presentation. In these patients, initial heparin followed by edoxaban had similar efficacy and safety to standard therapy with heparin and warfarin.
Age of First Arrhythmic Event in Brugada Syndrome
Authors: Milman Anat , Andorin Antoine , Gourraud Jean-Baptiste , Sacher Frederic , Mabo Philippe , Kim Sung-Hwan , Maeda Shingo , Takahashi Yoshihide , Kamakura Tsukasa , Aiba Takeshi , Conte Giulio , Juang Jimmy J.M. , Leshem Eran , Rahkovich Michael , Hochstadt Aviram , Mizusawa Yuka , Postema Pieter G. , Arbelo Elena , Huang Zhengrong , Denjoy Isabelle , Giustetto Carla , Wijeyeratne Yanushi D. , Napolitano Carlo , Michowitz Yoav , Brugada Ramon , Casado-Arroyo Ruben , Champagne Jean , Calo Leonardo , Sarquella-Brugada Georgia , Tfelt-Hansen Jacob , Priori Silvia G. , Takagi Masahiko , Veltmann Christian , Delise Pietro , Corrado Domenico , Behr Elijah R. , Gaita Fiorenzo , Yan Gan-Xin , Brugada Josep , Leenhardt Antoine , Wilde Arthur A.M. , Brugada Pedro , Kusano Kengo F. , Hirao Kenzo , Nam Gi-Byoung , Probst Vincent , Belhassen Bernard 
Published: December 2017

Background
Data on the age at first arrhythmic event (AE) in Brugada syndrome are from limited patient cohorts. The aim of this study is 2-fold: (1) to define the age at first AE in a large cohort of patients with Brugada syndrome, and (2) to assess the influence of the mode of AE documentation, sex, and ethnicity on the age at first AE.

Methods and Results

A survey of 23 centers from 10 Western and 4 Asian countries gathered data from 678 patients with Brugada syndrome (91.3% men) with first AE documented at time of aborted cardiac arrest (group A, n=426) or after prophylactic implantable cardioverter–defibrillator implantation (group B, n=252). The vast majority (94.2%) of the patients were 16 to 70 years old at the time of AE, whereas pediatric (<16 years) and elderly patients (>70 years) comprised 4.3% and 1.5%, respectively. Peak AE rate occurred between 38 and 48 years (mean, 41.9±14.8; range, 0.27–84 years). Group A patients were younger than in Group B by a mean of 6.7 years (46.1±13.2 versus 39.4±15.0 years;
P
<0.001). In adult patients (≥16 years), women experienced AE 6.5 years later than men (
P
=0.003). Whites and Asians exhibited their AE at the same median age (43 years).

Conclusions
SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) presents the first analysis on the age distribution of AE in Brugada syndrome, suggesting 2 age cutoffs (16 and 70 years) that might be important for decision-making. It also allows gaining insights on the influence of mode of arrhythmia documentation, patient sex, and ethnic origin on the age at AE.
Effect of Plant Protein on Blood Lipids: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Li Siying S. , Blanco Mejia Sonia , Lytvyn Lyubov , Stewart Sarah E. , Viguiliouk Effie , Ha Vanessa , de Souza Russell J. , Leiter Lawrence A. , Kendall Cyril W. C. , Jenkins David J. A. , Sievenpiper John L. 
Published: December 2017

Background
There is a heightened interest in plant‐based diets for cardiovascular disease prevention. Although plant protein is thought to mediate such prevention through modifying blood lipids, the effect of plant protein in specific substitution for animal protein on blood lipids remains unclear. To assess the effect of this substitution on established lipid targets for cardiovascular risk reduction, we conducted a systematic review and meta‐analysis of randomized controlled trials using the Grading of Recommendations Assessment, Development, and Evaluation system.

Methods and Results

MEDLINE
,
EMBASE
, and the Cochrane Registry were searched through September 9, 2017. We included randomized controlled trials of ≥3 weeks comparing the effect of plant protein in substitution for animal protein on low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, and apolipoprotein B. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences with 95% confidence intervals. Heterogeneity was assessed (Cochran Q statistic) and quantified (I
2
statistic). The overall quality (certainty) of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. One‐hundred twelve randomized controlled trials met the eligibility criteria. Plant protein in substitution for animal protein decreased low‐density lipoprotein cholesterol by 0.16 mmol/L (95% confidence interval, −0.20 to −0.12 mmol/L;
P
<0.00001; I
2
=55%; moderate‐quality evidence), non–high‐density lipoprotein cholesterol by 0.18 mmol/L (95% confidence interval, −0.22 to −0.14 mmol/L;
P
<0.00001; I
2
=52%; moderate‐quality evidence), and apolipoprotein B by 0.05 g/L (95% confidence interval, −0.06 to −0.03 g/L;
P
<0.00001; I
2
=30%; moderate‐quality evidence).

Conclusions
Substitution of plant protein for animal protein decreases the established lipid targets low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, and apolipoprotein B. More high‐quality randomized trials are needed to improve our estimates.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02037321.
Variability and Clustering of Midlatitude Summertime Convection: Testing the Craig and Cohen Theory in a Convection-Permitting Ensemble with Stochastic Boundary Layer Perturbations
Authors: Rasp Stephan , Selz Tobias , Craig George C. 
Published: December 2017

Abstract
The statistical theory of convective variability developed by Craig and Cohen in 2006 has provided a promising foundation for the design of stochastic parameterizations. The simplifying assumptions of this theory, however, were made with tropical equilibrium convection in mind. This study investigates the predictions of the statistical theory in real-weather case studies of nonequilibrium summertime convection over land. For this purpose, a convection-permitting ensemble is used in which all members share the same large-scale weather conditions but the convection is displaced using stochastic boundary layer perturbations. The results show that the standard deviation of the domain-integrated mass flux is proportional to the square root of its mean over a wide range of scales. This confirms the general applicability and scale adaptivity of the Craig and Cohen theory for complex weather. However, clouds tend to cluster on scales of around 100 km, particularly in the morning and evening. This strongly impacts the theoretical predictions of the variability, which does not include clustering. Furthermore, the mass flux per cloud closely follows an exponential distribution if all clouds are considered together and if overlapping cloud objects are separated. The nonseparated cloud mass flux distribution resembles a power law. These findings support the use of the theory for stochastic parameterizations but also highlight areas for improvement.
Response of the Internal Wave Field to Remote Wind Forcing by Tropical Cyclones
Authors: Köhler Janna , Völker Georg S. , Walter Maren 
Published: December 2017

AbstractIn the tropical North Atlantic, mean winds introduce relatively little energy into the internal wave field, but hurricanes act as very energetic sources for near-inertial waves. In addition to the eventlike passage of such tropical cyclones, changes in the wind speed north of the trade wind system induce a seasonal cycle in surface swell, with potential implications for the high-frequency part of the internal wave field. Using a 5-yr mooring time series in the interior of the tropical North Atlantic at 16°N, the temporal variability of internal wave energy south of the main hurricane track in different frequency bands is studied, and the magnitude of its variability, along with possible energy transfer mechanisms, is analyzed. The results show that changes in near-inertial energy are dominated by the passage of internal waves generated by hurricanes centered several hundred kilometers north of the mooring. The major role of hurricanes in the generation of near-inertial waves is also seen in an extended slab model that takes the horizontal divergence of the near-inertial current field at the mixed layer base into account. A seasonal cycle is observed in the energy at the high-frequency end (frequencies above 6 cpd) of the internal wave spectrum. It is not in phase with the near-inertial energy variability but covaries with changes in the local surface waves. These high-frequency internal waves are most energetic at times when large-amplitude surface swell with long periods and correspondingly long wavelengths is observed.
A stakeholder perspective on public sector innovation: why position matters
Authors: de Vries Hanna , Tummers Lars , Bekkers Victor 
Published: December 2017

Studies on the adoption of innovations often treat an organization as a uniform entity. Such studies implicitly assume that perceptions regarding the adoption of an innovation are identical across the organization. However, organizational theory and change management literature argue that organizations are composed of distinct groups that have different values and goals. It is therefore important to dissect the organization and to look at the various internal stakeholders involved. In this study, we follow this advice and study how two key organizational groups (city managers and Works Council members) perceive their organization’s members’ views regarding the specific innovation of teleworking. We use unique data collected through two nationwide surveys of city managers and Works Council members. The results show that there are crucial differences in the perceptions of the two groups, with city managers generally being more positive about the innovation. Based on our analysis, we conclude that it is important to distinguish between different organizational stakeholders in the innovation adoption process and that managers should be aware of a bias in their perceptions. Points for practitioners It is important to distinguish between the various organizational stakeholders in the innovation adoption process because they probably have different attitudes regarding an innovation. Managers should look beyond their own perceptions regarding an innovation and be aware that they are probably more positive in their perceptions than are others in their organization. More specifically, we found that Works Council members attach more importance to the ability to try out innovations before their full introduction than city managers. It is also more important for them that an innovation seems easy to implement and use.