bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferior Vena Cava Filters and Prevention of Recurrent Pulmonary Embolism
Authors: Kishore Sirish , Trost David , Madoff David , Winokur Ronald , Malhotra Anuj 
Published: June 2018

AbstractAlthough inferior vena cava (IVC) filters have a clear role in preventing recurrent pulmonary embolism (PE) in patients with venous thromboembolism who cannot be anticoagulated, the role of filters in patients who are candidates for anticoagulation is controversial. With limited and conflicting data, practitioners often have to make an educated patient-specific decision when encountering this scenario. This article reviews the available data on the efficacy and risks associated with adjunctive IVC filter use to prevent recurrent PE.
Intervention in Massive Pulmonary Embolus: Catheter Thrombectomy/Thromboaspiration versus Systemic Lysis versus Surgical Thrombectomy
Authors: Edwards Martin , Plotnik Adam , Moriarty John 
Published: June 2018

AbstractMassive pulmonary embolus (PE), defined as hemodynamic shock from acute PE, is a life-threatening condition. Deaths from massive PE, especially when unsuspected, occur within minutes to hours of onset and as such prompt intervention can be lifesaving. Acute massive PE patients have traditionally been candidates for treatment with intravenous systemic thrombolysis to improve pulmonary artery pressure, arteriovenous oxygenation, and pulmonary perfusion in an effort to reduce mortality. However, patients with contraindications to systemic thrombolysis or those who have failed thrombolysis may benefit from other techniques including endovascular and surgical embolectomy. This article will review the current medical management as well as catheter-directed therapies and surgical embolectomy in the treatment of patients with massive PE.
Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism
Authors: Chiarello Matthew , Sista Akhilesh 
Published: June 2018

AbstractAcute pulmonary embolism (PE) is a leading cause of morbidity and mortality in the United States. PE associated with right ventricular strain, termed submassive or intermediate-risk PE, is associated with an increased rate of clinical deterioration and short-term mortality. Trials have demonstrated systemic thrombolytics may improve patient outcomes, but they carry a risk of major hemorrhage. Catheter-directed thrombolysis (CDT) may offer similar efficacy to and a lower risk of catastrophic hemorrhage than systemic thrombolysis. Three prospective trials have evaluated CDT for submassive PE; ULTIMA, SEATTLE II, and PERFECT. These trials provide evidence that CDT may improve radiographic efficacy endpoints in submassive PE with acceptable rates of major hemorrhage. However, the lack of clinical endpoints, long-term follow-up, and adequate sample size limit their generalizability. Future trials should be adequately powered and controlled so that the short- and long-term effectiveness and safety of CDT can be definitively determined.
The Lectin Pathway in Thrombotic Conditions—A Systematic Review
Authors: Larsen Julie , Hvas Christine , Hvas Anne-Mette 
Published: June 2018

AbstractThe lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) (n = 22), ischaemic stroke (n = 9), CVE and stroke (n = 1) and other conditions (systemic lupus erythematosus [n = 6], sepsis-related coagulopathy [n = 3], pulmonary embolism [n = 1], asparaginase treatment [n = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions.
Inhibition of Protease-Activated Receptor (PAR1) Reduces Activation of the Endothelium, Coagulation, Fibrinolysis and Inflammation during Human Endotoxemia
Authors: Schoergenhofer Christian , Schwameis Michael , Gelbenegger Georg , Buchtele Nina , Thaler Barbara , Mussbacher Marion , Schabbauer Gernot , Wojta Johann , Jilma-Stohlawetz Petra , Jilma Bernd 
Published: June 2018

AbstractThe protease-activated receptor-1 (PAR-1) is critically involved in the co-activation of coagulation and inflammatory responses. Vorapaxar is a reversible, orally active, low molecular weight, competitive antagonist of PAR-1.We investigated the effects of PAR-1 inhibition by vorapaxar on the inflammatory response, the activation of coagulation, fibrinolysis and endothelium during experimental endotoxemia. In this randomized, double blind, crossover trial, 16 healthy volunteers received a bolus infusion of 2 ng/kg lipopolysaccharide (LPS) ± placebo/vorapaxar with a washout period of 8 weeks. Vorapaxar dosing was guided by thrombin receptor-activating peptide-6-induced whole blood aggregometry. Participants received 10 mg vorapaxar or placebo as an initial dose and, depending on the aggregometry, potentially an additional 10 mg. Goal was > 80% inhibition of aggregation compared with baseline. Vorapaxar significantly reduced the LPS-induced increase in pro-thrombin fragments F1 + 2 by a median of 27% (quartiles: 11–49%), thrombin–anti-thrombin concentrations by 22% (–3 to 46%) and plasmin–anti-plasmin levels by 38% (23–53%). PAR-1 inhibition dampened peak concentrations of tumour necrosis factor -α, interleukin-6 and consequently C-reactive protein by 66% (−11–71%), 50% (15–79%) and 23% (16–38%), respectively. Vorapaxar decreased maximum von Willebrand factor levels by 29% (26–51%) and soluble E-selectin concentrations by 30% (25–38%) after LPS infusion. PAR-1 inhibition did not affect thrombomodulin, soluble P-selectin and platelet factor-4 concentrations.PAR-1 inhibition significantly reduced the activation of coagulation, fibrinolysis, the inflammatory response and endothelial activation during experimental human endotoxemia.
Factor V Has Anticoagulant Activity in Plasma in the Presence of TFPIα: Difference between FV1 and FV2
Authors: van Doorn Peter , Rosing Jan , Duckers Connie , Hackeng Tilman , Simioni Paolo , Castoldi Elisabetta 
Published: June 2018

Background Activated factor V (FVa) is a potent procoagulant cofactor in the prothrombinase complex, whereas its precursor factor V (FV) stimulates the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-α (TFPIα), presumably by promoting TFPIα binding to phospholipids. Plasma FV comprises two glycosylation isoforms (FV1 and FV2) with low and high phospholipid-binding affinity, respectively. The FV1/FV2 ratio is increased in carriers of the FV R2 haplotype.
Objective This article demonstrates the TFPIα-cofactor function of FV in plasma and compares FV1 and FV2.
Materials and Methods Thrombin generation at low TF concentration was measured in FV-depleted plasma reconstituted with 0 to 100% FV, FV1 or FV2, and in 122 individuals genotyped for the R2 haplotype. The TFPIα-cofactor activities of FV1 and FV2 were also investigated in a model system of TFPIα-mediated FXa inhibition.
Results In the FV titration, thrombin generation first increased (up to 5% FV) and then progressively decreased at higher FV concentrations. This anticoagulant effect of FV, which was also observed with FV2 but not with FV1, was largely abolished by anti-TFPIα antibodies, suggesting that it reflects TFPIα-cofactor activity of FV. In the model system of TFPIα-mediated FXa inhibition, FV2 was a more potent TFPIα-cofactor than FV1, in line with their respective phospholipid affinities. Accordingly, FV R2 carriers had higher thrombin generation than non-carriers, even after correction for demographics and plasma levels of coagulation factors and inhibitors.
Conclusion FV (and particularly its FV2 isoform) contributes to the TFPIα-dependent down-regulation of thrombin generation in plasma triggered with low TF.
New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof
Authors: Jiménez-Serranía María-Isabel , Martínez-García Raquel , Corzo-Delibes Francisco , Martín Arias Luis , Treceño-Lobato Carlos 
Published: June 2018

AbstractThe aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed—average international normalized ratio (INR) of 2.6—and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01–4.74) and hematoma (OR, 2.43; 95% CI, 1.39–4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28–0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09–10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs.
Sudden Cardiac and Noncardiac Death in Sports: Epidemiology, Causes, Pathogenesis, and Prevention
Authors: Favaloro Emmanuel , Sanchis-Gomar Fabian , Lippi Giuseppe 
Published: June 2018

AbstractAlthough few doubts remain that physical exercise should be widely promoted for maintenance of health and fitness, the risk of adverse events such as sudden death (especially due to cardiac causes, i.e., sudden cardiac death [SCD]) during exercise remains tangible. The overall risk of sudden death in athletes is relatively low (i.e., usually comprised between 0.1 and 38/100,000 person-years), and globally comparable to that of the general population. However, up to 20% of all sudden death cases are still recorded while exercising. The most frequent underlying disorders encountered in SCD are hypertrophic cardiomyopathy and coronary artery disease (CAD), representing three quarters of all conditions. The risk related to CAD increases with aging (>35 years old), while that attributable to cardiomyopathies or fatal arrhythmias is especially frequent among young people (<35 years old). Taken together, these findings would lead to the conclusion that physical exercise may be seen as an acute trigger of myocardial ischemia or arrhythmias in some predisposed individuals. Nonetheless, the prevalence of coronary atherosclerosis seems to be higher in athletes than in sedentary subjects with comparable risk profile. On the contrary, coronary plaques in physically active subjects appear more stable, thereby attenuating the risk of rupture and subsequent myocardial ischemia. These findings, along with evidence of a considerable increase of peak coronary blood flow during exercise, make it very likely that an imbalance between oxygen demand and supply may be the most frequent cause of myocardial ischemia in athletes suffering SCD and/or cardiac arrest. Therefore, all subjects who wish to practice moderate- to high-intensity exercise are recommended to undergo preparticipation screening and annual follow-up.
Buildup of speaking skills in an online learning community: a network-analytic exploration
Authors: Shafipour Rasoul , Baten Raiyan Abdul , Hasan Md Kamrul , Ghoshal Gourab , Mateos Gonzalo , Hoque Mohammed Ehsan 
Published: June 2018

AbstractStudies in learning communities have consistently found evidence that peer-interactions contribute to students’ performance outcomes. A particularly important competence in the modern context is the ability to communicate ideas effectively. One metric of this is speaking, which is an important skill in professional and casual settings. In this study, we explore peer-interaction effects in online networks on speaking skill development. In particular, we present an evidence for gradual buildup of skills in a small-group setting that has not been reported in the literature. Evaluating the development of such skills requires studying objective evidence, for which purpose, we introduce a novel dataset of six online communities consisting of 158 participants focusing on improving their speaking skills. They video-record speeches for 5 prompts in 10 days and exchange comments and performance-ratings with their peers. We ask (i) whether the participants’ ratings are affected by their interaction patterns with peers, and (ii) whether there is any gradual buildup of speaking skills in the communities towards homogeneity. To analyze the data, we employ tools from the emerging field of Graph Signal Processing (GSP). GSP enjoys a distinction from Social Network Analysis in that the latter is concerned primarily with the connection structures of graphs, while the former studies signals on top of graphs. We study the performance ratings of the participants as graph signals atop underlying interaction topologies. Total variation analysis of the graph signals show that the participants’ rating differences decrease with time (slope = −0.04, p < 0.01), while average ratings increase (slope = 0.07, p < 0.05)—thereby gradually building up the ratings towards community-wide homogeneity. We provide evidence for peer-influence through a prediction formulation. Our consensus-based prediction model outperforms baseline network-agnostic regression models by about 23% in predicting performance ratings. This in turn shows that participants’ ratings are affected by their peers’ ratings and the associated interaction patterns, corroborating previous findings. Then, we formulate a consensus-based diffusion model that captures these observations of peer-influence from our analyses. We anticipate that this study will open up future avenues for a broader exploration of peer-influenced skill development mechanisms, and potentially help design innovative interventions in small-groups to maximize peer-effects.
Proterozoic Milankovitch cycles and the history of the solar system
Authors: Meyers Stephen R. , Malinverno Alberto 
Published: June 2018

Significance
Periodic variations in Earth’s orbit and rotation axis occur over tens of thousands of years, producing rhythmic climate changes known as Milankovitch cycles. The geologic record of these climate cycles is a powerful tool for reconstructing geologic time, for understanding ancient climate change, and for evaluating the history of our solar system, but their reliability dramatically decreases beyond 50 Ma. Here, we extend the analysis of Milankovitch cycles into the deepest stretches of Earth history, billions of years ago, while simultaneously reconstructing the history of solar system characteristics, including the distance between the Earth and Moon. Our results improve the temporal resolution of ancient Earth processes and enhance our knowledge of the solar system in deep time.
Altered p53 functionality in cancer-associated fibroblasts contributes to their cancer-supporting features
Authors: Arandkar Sharathchandra , Furth Noa , Elisha Yair , Nataraj Nishanth Belugali , van der Kuip Heiko , Yarden Yosef , Aulitzky Walter , Ulitsky Igor , Geiger Benjamin , Oren Moshe 
Published: June 2018

Significance
p53 research has primarily addressed its cell-autonomous tumor-suppressive features. Yet, recent evidence suggests that, in normal tissues, p53 can also exert cell nonautonomous tumor suppressor activities. Cancer-associated fibroblasts (CAFs) enhance the malignant features of adjacent cancer cells. Surprisingly, we found that the conversion of normal fibroblasts to CAFs entails nonmutational alteration of their p53, such that it now becomes cancer supportive rather than cancer inhibitory. This is achieved through reprogramming the transcriptional output of the CAF p53, rendering it a positive regulator of cancer-promoting genes and secreted proteins. Overall, our study highlights a function of nonmutated p53 in the tumor microenvironment and suggests that molecules that can “re-educate” the renegade p53 may have therapeutic value.
Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility
Authors: Chen Zhongwen , Oh Dongmyung , Biswas Kabir H. , Yu Cheng-Han , Zaidel-Bar Ronen , Groves Jay T. 
Published: June 2018

SignificanceCell receptors are neither uniformly distributed nor uniformly activated across plasma membrane. However, very little is known about how their spatial arrangement affects cellular response to receptor signaling. EphA2 is a receptor tyrosine kinase whose activation depends on binding of EphrinA1 ligands on the opposing cell, and EphA2 signaling plays an important role in cancer metastasis. In adherent cells, integrin adhesions are a key element to regulate cell–matrix interactions and cell migration. However, our understanding of how their activities are spatiotemporally coordinated remains superficial. In this study, we combined microfabrication, live imaging, and single-molecule tracking to directly map the signal transduction from ephrinA1:EphA2 complex to integrin adhesions, and revealed a spatially controlled mechanism for EphA2–integrin signaling cross talk.
Transdifferentiation of human adult peripheral blood T cells into neurons
Authors: Tanabe Koji , Ang Cheen Euong , Chanda Soham , Olmos Victor Hipolito , Haag Daniel , Levinson Douglas F. , Südhof Thomas C. , Wernig Marius 
Published: June 2018

Significance
Recent advances in genomics have revealed that many polygenetic diseases are caused by complex combinations of many common variants with individually small effects. Thus, building informative disease models requires the interrogation of many patient-derived genetic backgrounds in a disease-relevant cell type. Current approaches to obtaining human neurons are not easy to scale to many patients. Here we describe a facile, one-step conversion of human adult peripheral blood T cells directly into functional neurons using episomal vectors without the need for previous in vitro expansion. This approach is more amenable than induced pluripotent stem cell-based approaches for application to larger cohorts of individuals and will enable the development of functional assays to study complex human brain diseases.
Pronounced summer warming in northwest Greenland during the Holocene and Last Interglacial
Authors: McFarlin Jamie M. , Axford Yarrow , Osburn Magdalena R. , Kelly Meredith A. , Osterberg Erich C. , Farnsworth Lauren B. 
Published: June 2018

SignificanceReconstructions of climate over Greenland during past warm periods provide crucial insights into the likely response of the Greenland Ice Sheet to future warming. However, limited preservation of interglacial archives due to extensive glacial scouring has hindered paleoclimate reconstructions along Greenland’s margins. Here, we report a Greenland lake sediment record that preserves both the present and previous interglacial periods. This record, combined with prior studies, demonstrates exceptionally strong warming over the northern Greenland Ice Sheet. Pronounced summer warming in this region helps explain ice sheet changes in the Early Holocene, while highlighting seemingly incongruous evidence for ice sheet extent and temperatures during the Last Interglacial. These findings may portend large future warming in this high-latitude region.
Uncovering pH at both sides of the root plasma membrane interface using noninvasive imaging
Authors: Martinière Alexandre , Gibrat Rémy , Sentenac Hervé , Dumont Xavier , Gaillard Isabelle , Paris Nadine 
Published: June 2018

Significance
The pH on both sides of the plant plasma membrane was accurately measured in vivo using ratiometric fluorescent sensors. This enabled noninvasive access to membrane-associated pH and transmembrane delta pH values from the surface of the root up to the deepest cell layers beyond the Casparian strip barrier. We demonstrate that despite direct contact with the soil, the apoplastic pH close to the plasma membrane was maintained at values ranging from 6.0 to 6.4 in mature root cells, whereas the overall pH in the apoplastic space is far more acidic. Furthermore, we found that the cell wall plays a role in proton homeostasis in mature root.
Trends in health inequalities in 27 European countries
Authors: Mackenbach Johan P. , Valverde José Rubio , Artnik Barbara , Bopp Matthias , Brønnum-Hansen Henrik , Deboosere Patrick , Kalediene Ramune , Kovács Katalin , Leinsalu Mall , Martikainen Pekka , Menvielle Gwenn , Regidor Enrique , Rychtaříková Jitka , Rodriguez-Sanz Maica , Vineis Paolo , White Chris , Wojtyniak Bogdan , Hu Yannan , Nusselder Wilma J. 
Published: June 2018

Significance
Inequalities in mortality and morbidity among socioeconomic groups are a highly persistent phenomenon despite having been the focus of public health policy in many countries. The United States has recently witnessed a widening of health inequalities due to rising mortality and morbidity among the lowly educated. Our study shows that, despite the financial crisis, most European countries have experienced an improvement in the health of the lowly educated in recent years. In Eastern Europe, this even represents a reversal as compared with previous decades. The 2008 financial crisis has had mixed effects without widening health inequalities. Our results suggest that European countries have been successful in avoiding an aggravation of health inequalities.