bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trichoplusia ni Kinesin-1 Associates with Autographa californica Multiple Nucleopolyhedrovirus Nucleocapsid Proteins and Is Required for Production of Budded Virus
Authors: Biswas Siddhartha , Blissard Gary W. , Theilmann David A. 
Published: January 2016

ABSTRACT

The mechanism by which nucleocapsids of
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) egress from the nucleus to the plasma membrane, leading to the formation of budded virus (BV), is not known. AC141 is a nucleocapsid-associated protein required for BV egress and has previously been shown to be associated with β-tubulin. In addition, AC141 and VP39 were previously shown by fluorescence resonance energy transfer by fluorescence lifetime imaging to interact directly with the
Drosophila melanogaster
kinesin-1 light chain (KLC) tetratricopeptide repeat (TPR) domain. These results suggested that microtubule transport systems may be involved in baculovirus nucleocapsid egress and BV formation. In this study, we investigated the role of lepidopteran microtubule transport using coimmunoprecipitation, colocalization, yeast two-hybrid, and small interfering RNA (siRNA) analyses. We show that nucleocapsid AC141 associates with the lepidopteran
Trichoplusia ni
KLC and kinesin-1 heavy chain (KHC) by coimmunoprecipitation and colocalization. Kinesin-1, AC141, and microtubules colocalized predominantly at the plasma membrane. In addition, the nucleocapsid proteins VP39, FP25, and BV/ODV-C42 were also coimmunoprecipitated with
T. ni
KLC. Direct analysis of the role of
T. ni
kinesin-1 by downregulation of KLC by siRNA resulted in a significant decrease in BV production. Nucleocapsids labeled with VP39 fused with three copies of the mCherry fluorescent protein also colocalized with microtubules. Yeast two-hybrid analysis showed no evidence of a direct interaction between kinesin-1 and AC141 or VP39, suggesting that either other nucleocapsid proteins or adaptor proteins may be required. These results further support the conclusion that microtubule transport is required for AcMNPV BV formation.

IMPORTANCE
In two key processes of the replication cycle of the baculovirus
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV), nucleocapsids are transported through the cell. These include (i) entry of budded virus (BV) into the host cell and (ii) egress and budding of nucleocapsids newly produced from the plasma membrane. Prior studies have shown that the entry of nucleocapsids involves the polymerization of actin to propel nucleocapsids to nuclear pores and entry into the nucleus. For the spread of infection, progeny viruses must rapidly exit the infected cells, but the mechanism by which AcMNPV nucleocapsids traverse the cytoplasm is unknown. In this study, we examined whether nucleocapsids interact with lepidopteran kinesin-1 motor molecules and are potentially carried as cargo on microtubules to the plasma membrane in AcMNPV-infected cells. This study indicates that microtubule transport is utilized for the production of budded virus.
Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial
Authors: Erdem-Eraslan Lale , van den Bent Martin J. , Hoogstrate Youri , Naz-Khan Hina , Stubbs Andrew , van der Spek Peter , Böttcher René , Gao Ya , de Wit Maurice , Taal Walter , Oosterkamp Hendrika M. , Walenkamp Annemiek , Beerepoot Laurens V. , Hanse Monique C.J. , Buter Jan , Honkoop Aafke H. , van der Holt Bronno , Vernhout René M. , Smitt Peter A.E. Sillevis , Kros Johan M. , French Pim J. 
Published: January 2016

AbstractThe results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva), a humanized monoclonal antibody against circulating VEGF-A, when added to CCNU chemotherapy in patients with recurrent glioblastoma (GBM). In this study, we performed gene expression profiling (DASL and RNA-seq) of formalin-fixed, paraffin-embedded tumor material from participants of the BELOB trial to identify patients with recurrent GBM who benefitted most from beva+CCNU treatment. We demonstrate that tumors assigned to the IGS-18 or “classical” subtype and treated with beva+CCNU showed a significant benefit in progression-free survival and a trend toward benefit in overall survival, whereas other subtypes did not exhibit such benefit. In particular, expression of FMO4 and OSBPL3 was associated with treatment response. Importantly, the improved outcome in the beva+CCNU treatment arm was not explained by an uneven distribution of prognostically favorable subtypes as all molecular glioma subtypes were evenly distributed along the different study arms. The RNA-seq analysis also highlighted genetic alterations, including mutations, gene fusions, and copy number changes, within this well-defined cohort of tumors that may serve as useful predictive or prognostic biomarkers of patient outcome. Further validation of the identified molecular markers may enable the future stratification of recurrent GBM patients into appropriate treatment regimens. Cancer Res; 76(3); 525–34. ©2016 AACR.
Molecular Pathways: AXL, a Membrane Receptor Mediator of Resistance to Therapy
Authors: Scaltriti Maurizio , Elkabets Moshe , Baselga José 
Published: January 2016

Abstract
AXL is a tyrosine kinase membrane receptor that signals via PI3K, MAPK, and protein kinase C (PKC), among other pathways. AXL has oncogenic potential and interacts with other membrane receptors, depending on their relative abundance and availability. The increased expression of AXL in cancer is often the result of pharmacologic selective pressure to a number of chemotherapies and targeted therapies and acts as a mechanism of acquired drug resistance. This resistance phenotype, frequently accompanied by epithelial-to-mesenchymal transition, can be reversed by AXL inhibition. In tumors with high levels of EGFR, including lung, head and neck, and triple-negative breast cancer, AXL dimerizes with this receptor and initiates signaling that circumvents the antitumor effects of anti-EGFR therapies. Likewise, AXL overexpression and dimerization with EGFR can overcome PI3K inhibition by activating the phospholipase C-γ-PKC cascade that, in turn, sustains mTORC1 activity. The causative role of AXL in inducing drug resistance is underscored by the fact that the suppression of AXL restores sensitivity to these agents. Hence, these observations indicate that AXL is selectively expressed in tumor cells refractory to therapy and that cotargeting AXL in this setting would potentially overcome drug resistance. The use of AXL inhibitors should be considered in the clinic. Clin Cancer Res; 22(6); 1313–7. ©2016 AACR.
Atrial fibrillation is associated with high levels of monocyte-platelet-aggregates and increased CD11b expression in patients with aortic stenosis
Authors: Berndt Katharina , Wydra Sandy , Tarnowski Daniel , Barthel Peggy , Quick Silvio , Ulbrich Stefan , Christoph Marian , Waessnig Nadine , Speiser Uwe , Wunderlich Carsten , Poitz David M. , Strasser Ruth H. , Ibrahim Karim , Pfluecke Christian 
Published: January 2016

SummaryA growing body of evidence suggests a pivotal role of inflammatory processes in AF in a bidirectional manner. Infiltrating leukocytes seem to promote both structural and electrical remodelling processes in patients with AF. Monocyte-platelets-aggregates (MPAs) are sensitive markers of both platelets and monocyte activation. So far it is not clear whether the content of MPAs is affected by AF. The present study examined the content of MPAs and the activation of monocytes in elderly patients with an aortic stenosis in dependence of AF. These patients are known to have a high prevalence of AF. Flow-cytometric quantification analysis demonstrated that patients with AF have an increased content of MPAs (207 ± 13 cells/μl vs 307 ± 21 cells/μl, p<0.001), and enhanced expression of CD11b on monocytes (p<0.001), compared to patients in stable sinus rhythm (SR). The number of CD14+/CD16+ monocytes were only slightly elevated in patients with AF. These findings were seen in patients with permanent AF. But also patients with paroxysmal AF, even when presenting in SR, the MPAs were increased by 50 % (p<0.05) as well as the CD11b expression, which was twice as high (p<0.05) compared to stable SR. These results demonstrate for the first time a dependency of MPAs and CD11b expression on monocytes in the presence of AF and support the notion of a close relationship between AF, thrombogenesis and inflammation. The content of MPAs and the extent of activation on monocytes appear promising as biomarkers for paroxysmal AF and as possible future targets for developing novel pharmacological therapeutic strategies.Supplementary Material to this article is available online at www.thrombosis-online.com.
Marked elevation in plasma osteoprotegerin constitutes an early and consistent feature of cerebral malaria
Authors: Gegenbauer Kristina , O’Sullivan Jamie M. , Chion Alain , Smith Owen P. , Preston Roger J. S. , Brophy Teresa M. , Craig Alister G. , O’Regan Niamh , Moxon Chris , O’Donnell James S. 
Published: January 2016

SummaryAdherence of infected erythrocytes to vascular endothelium causes acute endothelial cell (EC) activation during Plasmodium falciparum infection. Consequently, proteins stored in Weibel-Palade (WP) bodies within EC are secreted into the plasma. Osteoprotegerin (OPG) binds to VWF and consequently is stored within WP bodies. Given the critical role of EC activation in the pathogenesis of severe malaria, we investigated plasma OPG levels in children with P. falciparum malaria. At presentation, plasma OPG levels were significantly elevated in children with cerebral malaria (CM) compared to healthy controls (means 16.0 vs 0.8 ng/ml; p<0.01). Importantly, OPG levels were also significantly higher in children with CM who had a fatal outcome, compared to children with CM who survived. Finally, in children with CM, plasma OPG levels correlated with other established prognostic indices (including plasma lactate levels and peripheral parasite density). To further investigate the relationship between severe malaria and OPG, we utilised a murine model of experimental CM in which C57BL/6J mice were infected with P. berghei ANKA. Interestingly, plasma OPG levels were increased 4.6 fold within 24 hours following P. berghei inoculation. This early marked elevation in OPG levels was observed before any objective clinical signs were apparent, and preceded the development of peripheral blood parasitaemia. As the mice became increasingly unwell, plasma OPG levels progressively increased. Collectively, these data suggest that OPG constitutes a novel biomarker with prognostic significance in patients with severe malaria. In addition, further studies are required to determine whether OPG plays a role in modulating malaria pathogenesis.
Administração das Práticas Estudantis de Hotelaria e Turismo nas Principais Universidades do Equador
Authors: Van Hoff Hubert B. , Fan Aileen , Cueva Ana 
Published: January 2016

Este artigo trata sobre um estudo realizado entre os administradores de estágios nos principais programas de hotelaria e turismo do Equador. Em base a estudos prévios sobre os estudantes e os empregadores no setor, o estudo tratou de identificar os melhores estágios e avaliar as opiniões dos coordenadores de estágios que poderiam servir como sugestões para outros programas de hotelaria e turismo. Conjuntamente, trabalha-se em encontrar melhores formas de criar, avaliar e administrar os programas de estágio; e em atender as necessidades dos estudantes e das indústrias de hotelaria e turismo. Sobretudo, o estudo busca melhorar a conexão entre a experiência prática da indústria e a teoria na sala de aula. Finalmente, se oferecem sugestões para futuras pesquisas.
Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients
Authors: Brachmann Johannes , Morillo Carlos A. , Sanna Tommaso , Di Lazzaro Vincenzo , Diener Hans-Christoph , Bernstein Richard A. , Rymer Marylin , Ziegler Paul D. , Liu Shufeng , Passman Rod S. 
Published: January 2016

Background—
Atrial fibrillation (AF) can be a cause of previously diagnosed cryptogenic stroke. However, AF can be paroxysmal and asymptomatic, thereby making detection with routine ECG methods difficult. Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF, but its initiation is dependent on the detection of AF. Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) is the first randomized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors (ICM).

Methods and Results—
Patients with prior cryptogenic stroke were randomized to control (n=220) or ICM (n=221) and followed for ≤36 months. Cumulative AF detection rates in the ICM arm increased progressively during this period (3.7%, 8.9%, 12.4%, and 30.0% at 1, 6, 12, and 36 months, respectively), but remained low in the control arm (3.0% at 36 months). This resulted in oral anticoagulation prescription in 94.7% of ICM patients with AF detected at 6 months, 96.6% at 12 months, and 90.5% at 36 months. Among ICM patients with AF detected, the median time to AF detection was 8.4 months, 81.0% of first AF episodes were asymptomatic, and 94.9% had at least 1 day with >6 minutes of AF.

Conclusions—
Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care. Given the frequency of asymptomatic first episodes and the long median time to detection, these findings highlight the limitations of using traditional AF detection methods. The majority of patients with AF were prescribed oral anticoagulation therapy.

Clinical Trial Registration—

Clinicaltrials.gov
; Unique identifier: NCT00924638.
Myocardial Hemorrhage After Acute Reperfused ST-Segment–Elevation Myocardial Infarction
Authors: Carrick David , Haig Caroline , Ahmed Nadeem , McEntegart Margaret , Petrie Mark C. , Eteiba Hany , Hood Stuart , Watkins Stuart , Lindsay M. Mitchell , Davie Andrew , Mahrous Ahmed , Mordi Ify , Rauhalammi Samuli , Sattar Naveed , Welsh Paul , Radjenovic Aleksandra , Ford Ian , Oldroyd Keith G. , Berry Colin 
Published: January 2016

Background—
The success of coronary reperfusion therapy in ST-segment–elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion.

Methods and Results—

We performed a prospective cohort study in patients with reperfused ST-segment–elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of <20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07–6.49];
P
=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25–27.74;
P
=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9–7.5]; % left ventricular mass) peaked on day 2 (
P
<0.001), whereas microvascular obstruction decreased with time post reperfusion.

Conclusions—
Myocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment–elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02072850.
Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography
Authors: Taniwaki Masanori , Radu Maria D. , Zaugg Serge , Amabile Nicolas , Garcia-Garcia Hector M. , Yamaji Kyohei , Jørgensen Erik , Kelbæk Henning , Pilgrim Thomas , Caussin Christophe , Zanchin Thomas , Veugeois Aurelie , Abildgaard Ulrik , Jüni Peter , Cook Stephane , Koskinas Konstantinos C. , Windecker Stephan , Räber Lorenz 
Published: January 2016

Background—
The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event.

Methods and Results—

Between August 2010 and December 2014, 64 patients were investigated at the time point of VLST as part of an international optical coherence tomography registry. Optical coherence tomography pullbacks were performed after restoration of flow and analyzed at 0.4 mm. A total of 38 early- and 20 newer-generation drug-eluting stents were suitable for analysis. VLST occurred at a median of 4.7 years (interquartile range, 3.1–7.5 years). An underlying putative cause by optical coherence tomography was identified in 98% of cases. The most frequent findings were strut malapposition (34.5%), neoatherosclerosis (27.6%), uncovered struts (12.1%), and stent underexpansion (6.9%). Uncovered and malapposed struts were more frequent in thrombosed compared with nonthrombosed regions (ratio of percentages, 8.26; 95% confidence interval, 6.82–10.04;
P
<0.001 and 13.03; 95% confidence interval, 10.13–16.93;
P
<0.001, respectively). The maximal length of malapposed or uncovered struts (3.40 mm; 95% confidence interval, 2.55–4.25; versus 1.29 mm; 95% confidence interval, 0.81–1.77;
P
<0.001), but not the maximal or average axial malapposition distance, was greater in thrombosed compared with nonthrombosed segments. The associations of both uncovered and malapposed struts with thrombus were consistent among early- and newer-generation drug-eluting stents.

Conclusions—
The leading associated findings in VLST patients in descending order were malapposition, neoatherosclerosis, uncovered struts, and stent underexpansion without differences between patients treated with early- and new-generation drug-eluting stents. The longitudinal extension of malapposed and uncovered stent was the most important correlate of thrombus formation in VLST.
Lifestyle Changes in Young Adulthood and Middle Age and Risk of Cardiovascular Disease and All‐Cause Mortality: The Doetinchem Cohort Study
Authors: Hulsegge Gerben , Looman Moniek , Smit Henriëtte A. , Daviglus Martha L. , van der Schouw Yvonne T. , Verschuren W.M. Monique 
Published: January 2016

Background
The associations between overall lifestyle profile and cardiovascular disease (CVD) and death have been mainly investigated in cross‐sectional studies. The full benefits of a healthy lifestyle may therefore be underestimated, and the magnitude of benefits associated with changes in lifestyle remains unclear. We quantified the association of changes in lifestyle profiles over 5 years with risk of CVD and all‐cause mortality.

Methods and Results

Lifestyle factors (ie, diet, physical activity, smoking, alcohol consumption) and body mass index were assessed and dichotomized as healthy/unhealthy among 5263 adults ages 26 to 66 in 1993–1997 and 5 years later (1998–2002). Multivariable‐adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were estimated to quantify associations of change in lifestyle with fatal/nonfatal CVD and all‐cause mortality that occurred 8 to 15 years after 1998–2002. Independent of baseline lifestyles, each decrement in number of healthy lifestyle factors was, on average, associated with 35% higher risk of CVD (HR, 1.35; 95% CI, 1.12–1.63) and 37% higher risk of all‐cause mortality (HR, 1.37; 95% CI, 1.10–1.70); no association was noted with increase in the number of healthy lifestyle factors (
P
>0.5). Individuals who maintained 4 to 5 healthy lifestyle factors had 2.5 times lower risk of CVD (HR, 0.43; 95% CI, 0.25–0.63) and all‐cause mortality (HR, 0.40; 95% CI, 0.22–0.73) than those who maintained only 0 to 1 healthy lifestyle factor.

Conclusions
Our findings suggest that the benefits of healthy lifestyles may be easier lost than gained over a 5‐year period. This underscores the need for efforts to promote maintenance of healthy lifestyles throughout the life course.
Quad-Ratures: Visions graphiques dans la poésie de Gabriele Frasca
Authors: Labbate Ettore 
Published: January 2016

Graphic visions in the poetry of Gabriele Frasca.
The writing of Gabriele Frasca, critic and translator of Samuel Beckett in Italy, can be considered Beckettian in its approach, for it is a plastic approach where page and image, canvas and model try to coincide, or, at least, to reach one another ceaselessly. Following a literary and pictorial tradition dear to Beckett, Frasca indeed tries to create 'squared circles' where combinatory logic, language exhaustion or bilingualism (in the Mallarmean sense of this word, as 'défaut des languages') prevail. In such an approach, the necessity of a graphic form wins over any nominalism.
Extracorporeal shock wave therapy versus corticosteroid injection in the treatment of trigger finger: a randomized controlled study
Authors: Yildirim P. , Gultekin A. , Yildirim A. , Karahan A. Y. , Tok F. 
Published: January 2016

The purpose of this study was to compare the efﬁcacies of extracorporeal shock wave therapy and corticosteroid injection for the management of trigger finger. In this prospective randomized clinical trial, 40 patients with actively correctable trigger fingers were randomly assigned to extracorporeal shock wave therapy (1000 impulses and 2.1 bar) or injection groups. The effectiveness of the treatment was assessed using cure rates, a visual analogue scale, the frequency of triggering, the severity of triggering, the functional impact of triggering, and the Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire at 1, 3, and 6 months after treatment. An intention-to- treat analysis was used in this study. Both groups demonstrated statistically significant improvements in all outcome measures after treatment. The intention-to-treat analyses showed no between-group differences for cure rates, pain, and functional status at follow-up. We conclude that extracorporeal shock wave therapy could be a non-invasive option for treating trigger finger, especially for those patients who wish to avoid steroid injections. Level of evidence: Level II.
Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation
Authors: Mielcarek Marco , Furlong Terry , O’Donnell Paul V. , Storer Barry E. , McCune Jeannine S. , Storb Rainer , Carpenter Paul A. , Flowers Mary E. D. , Appelbaum Frederick R. , Martin Paul J. 
Published: January 2016

Key Points
With conventional immunosuppression, the incidence of chronic GVHD is higher after transplantation of mobilized blood compared with marrow. Administration of cyclophosphamide after mobilized blood cell transplantation is associated with a low incidence of chronic GVHD.