bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes
Authors: Nunes-Cabaço Helena , Matoso Paula , Foxall Russell B. , Tendeiro Rita , Pires Ana R. , Carvalho Tânia , Pinheiro Ana I. , Soares Rui S. , Sousa Ana E. 
Published: December 2014

ABSTRACT
A unique HIV-host equilibrium exists in untreated HIV-2-infected individuals. This equilibrium is characterized by low to undetectable levels of viremia throughout the disease course, despite the establishment of disseminated HIV-2 reservoirs at levels comparable to those observed in untreated HIV-1 infection. Although the clinical spectrum is similar in the two infections, HIV-2 infection is associated with a much lower rate of CD4 T-cell decline and has a limited impact on the mortality of infected adults. Here we investigated HIV-2 infection of the human thymus, the primary organ for T-cell production. Human thymic tissue and suspensions of total or purified CD4 single-positive thymocytes were infected with HIV-2 or HIV-1 primary isolates using either CCR5 or CXCR4 coreceptors. We found that HIV-2 infected both thymic organ cultures and thymocyte suspensions, as attested to by the total HIV DNA and cell-associated viral mRNA levels. Nevertheless, thymocytes featured reduced levels of intracellular Gag viral protein, irrespective of HIV-2 coreceptor tropism and cell differentiation stage, in agreement with the low viral load in culture supernatants. Our data show that HIV-2 is able to infect the human thymus, but the HIV-2 replication cycle in thymocytes is impaired, providing a new model to identify therapeutic targets for viral replication control.

IMPORTANCE
HIV-1 infects the thymus, leading to a decrease in CD4 T-cell production that contributes to the characteristic CD4 T-cell loss. HIV-2 infection is associated with a very low rate of progression to AIDS and is therefore considered a unique naturally occurring model of attenuated HIV disease. HIV-2-infected individuals feature low to undetectable plasma viral loads, in spite of the numbers of circulating infected T cells being similar to those found in patients infected with HIV-1. We assessed, for the first time, the direct impact of HIV-2 infection on the human thymus. We show that HIV-2 is able to infect the thymus but that the HIV-2 replication cycle in thymocytes is impaired. We propose that this system will be important to devise immunotherapies that target viral production, aiding the design of future therapeutic strategies for HIV control.
Targeting Cellular Squalene Synthase, an Enzyme Essential for Cholesterol Biosynthesis, Is a Potential Antiviral Strategy against Hepatitis C Virus
Authors: Saito Kyoko , Shirasago Yoshitaka , Suzuki Tetsuro , Aizaki Hideki , Hanada Kentaro , Wakita Takaji , Nishijima Masahiro , Fukasawa Masayoshi 
Published: December 2014

ABSTRACTHepatitis C virus (HCV) exploits host membrane cholesterol and its metabolism for progeny virus production. Here, we examined the impact of targeting cellular squalene synthase (SQS), the first committed enzyme for cholesterol biosynthesis, on HCV production. By using the HCV JFH-1 strain and human hepatoma Huh-7.5.1-derived cells, we found that the SQS inhibitors YM-53601 and zaragozic acid A decreased viral RNA, protein, and progeny production in HCV-infected cells without affecting cell viability. Similarly, small interfering RNA (siRNA)-mediated knockdown of SQS led to significantly reduced HCV production, confirming the enzyme as an antiviral target. A metabolic labeling study demonstrated that YM-53601 suppressed the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations. Unlike YM-53601, the cholesterol esterification inhibitor Sandoz 58-035 did not exhibit an antiviral effect, suggesting that biosynthesis of cholesterol is more important than that of cholesteryl esters for HCV production. YM-53601 inhibited transient replication of a JFH-1 subgenomic replicon and entry of JFH-1 pseudoparticles, suggesting that at least suppression of viral RNA replication and entry contributes to the antiviral effect of the drug. Collectively, our findings highlight the importance of the cholesterol biosynthetic pathway in HCV production and implicate SQS as a potential target for antiviral strategies against HCV.IMPORTANCEHepatitis C virus (HCV) is known to be closely associated with host cholesterol and its metabolism throughout the viral life cycle. However, the impact of targeting cholesterol biosynthetic enzymes on HCV production is not fully understood. We found that squalene synthase, the first committed enzyme for cholesterol biosynthesis, is important for HCV production, and we propose this enzyme as a potential anti-HCV target. We provide evidence that synthesis of free cholesterol is more important than that of esterified cholesterol for HCV production, highlighting a marked free cholesterol dependency of HCV production. Our findings also offer a new insight into a role of the intracellular cholesterol pool that is coupled to its biosynthesis in the HCV life cycle.
Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes
Authors: Tjeerdema Nathanja , Georgiadi Anastasia , Jonker Jacqueline T , van Glabbeek Marjolijn , Dehnavi Reza Alizadeh , Tamsma Jouke T , Smit Johannes W A , Kersten Sander , Rensen Patrick C N 
Published: December 2014

BackgroundAngiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages.ObjectiveTo assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).DesignWe studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS−I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro.ResultsAs compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS−I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS−I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages.ConclusionsPlasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli.
National survey to determine current practices, training and attitudes towards advanced polypectomy in the UK
Authors: Geraghty Joe , O'Toole Paul , Anderson John , Valori Roland , Sarkar Sanchoy 
Published: December 2014

ObjectiveDevelopments in advanced polypectomy technique provide an alternative to surgery in the management of large and complex colorectal polyps. These endoscopic techniques require expertise and can potentially incur high complication rates. This survey evaluates current UK practice, attitudes and training in advanced polypectomy.DesignAnonymous online questionnaire.SettingColonoscopists within the UK were asked about their approach to large polyps (>2 cm).ResultsAmong the 268 respondents (64% of whom were BCSP accredited), 86% were confident in removing lesions >2 cm by endoscopic mucosal resection (EMR). Of these, 27% were classed as low volume operators (<10 lesions resected/annum) and 14% as high volume operators (>50/annum). By comparison, only 3% currently performed endoscopic submucosal dissection (ESD). Referring one or more benign polyps for surgery a year was common among responders of all levels (11–68%). Training deficiencies were common: only 21% of responders had received a period of training dedicated to advanced polypectomy; 58% of responders would welcome a national training scheme and a majority supported the implementation of advanced polypectomy accreditation with national guidelines. However, while 41% wanted nominated regional EMR experts, only 18% would welcome an integrated national referral network for large/complex polyps.ConclusionsEMR is practised widely while ESD service provision is very limited. Most experienced colonoscopists are confident to perform piecemeal EMR, even if their training is suboptimal and annual numbers low. Practices and attitudes were variable, even among self-defined level 4 operators. Improving training and implementation of accreditation were welcomed, but there was little appetite for mandated referral to subspecialist ‘experts' and national networks.
The effect of participatory women's groups on infant feeding and child health knowledge, behaviour and outcomes in rural Bangladesh: a controlled before-and-after study
Authors: Younes Leila , Houweling Tanja A J , Azad Kishwar , Kuddus Abdul , Shaha Sanjit , Haq Bedowra , Nahar Tasmin , Hossen Munir , Beard James , Copas Andrew , Prost Audrey , Costello Anthony , Fottrell Edward 
Published: December 2014

BackgroundDespite efforts to reduce under-5 mortality rates worldwide, an estimated 6.6 million under-5 children die every year. Community mobilisation through participatory women's groups has been shown to improve maternal and newborn health in rural settings, but little is known about the potential of this approach to improve care and health in children after the newborn period.MethodsFollowing on from a cluster-randomised controlled trial to assess the effect of participatory women's groups on maternal and neonatal health outcomes in rural Bangladesh, 162 women's groups continued to meet between April 2010 and December 2011 to identify, prioritise and address issues that affect the health of children under 5 years. A controlled before-and-after study design and difference-in-difference analysis was used to assess morbidity outcomes and changes in knowledge and practices related to child feeding, hygiene and care-seeking behaviour.FindingsSignificant improvements were measured in mothers’ knowledge of disease prevention and management, danger signs and hand washing at critical times. Significant increases were seen in exclusive breast feeding for at least 6 months (15.3% (4.2% to 26.5%)), and mean duration of breast feeding (37.9 days (17.4 to 58.3)). Maternal reports of under-5 morbidities fell in intervention compared with control areas, including reports of fever (−10.5% (−15.1% to −6.0%)) and acute respiratory infections (−12.2% (−15.6% to −8.8%)). No differences were observed in dietary diversity scores or immunisation uptake.ConclusionsCommunity mobilisation through participatory women's groups can be successfully adapted to address health knowledge and practice in relation to child's health, leading to improvements in a number of child health indicators and behaviours.
A Five-Gene Hedgehog Signature Developed as a Patient Preselection Tool for Hedgehog Inhibitor Therapy in Medulloblastoma
Authors: Shou Yaping , Robinson Douglas M. , Amakye Dereck D. , Rose Kristine L. , Cho Yoon-Jae , Ligon Keith L. , Sharp Thad , Haider Asifa S. , Bandaru Raj , Ando Yuichi , Geoerger Birgit , Doz François , Ashley David M. , Hargrave Darren R. , Casanova Michela , Tawbi Hussein A. , Rodon Jordi , Thomas Anne L. , Mita Alain C. , MacDonald Tobey J. , Kieran Mark W. 
Published: December 2014

AbstractPurpose: Distinct molecular subgroups of medulloblastoma, including hedgehog (Hh) pathway–activated disease, have been reported. We identified and clinically validated a five-gene Hh signature assay that can be used to preselect patients with Hh pathway–activated medulloblastoma.Experimental Design: Gene characteristics of the Hh medulloblastoma subgroup were identified through published bioinformatic analyses. Thirty-two genes shown to be differentially expressed in fresh-frozen and formalin-fixed paraffin-embedded tumor samples and reproducibly analyzed by RT-PCR were measured in matched samples. These data formed the basis for building a multi-gene logistic regression model derived through elastic net methods from which the five-gene Hh signature emerged after multiple iterations. On the basis of signature gene expression levels, the model computed a propensity score to determine Hh activation using a threshold set a priori. The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.Results: Five differentially expressed genes in medulloblastoma (GLI1, SPHK1, SHROOM2, PDLIM3, and OTX2) were found to associate with Hh pathway activation status. In an independent validation study, Hh activation status of 25 medulloblastoma samples showed 100% concordance between the five-gene signature and Affymetrix profiling. Further, in medulloblastoma samples from 50 patients treated with sonidegib, all 6 patients who responded were found to have Hh-activated tumors. Three patients with Hh-activated tumors had stable or progressive disease. No patients with Hh-nonactivated tumors responded.Conclusions: This five-gene Hh signature can robustly identify Hh-activated medulloblastoma and may be used to preselect patients who might benefit from sonidegib treatment. Clin Cancer Res; 21(3); 585–93. ©2014 AACR.
Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation
Authors: Riva Nicoletta , Donadini Marco P. , Ageno Walter 
Published: December 2014

SummaryVenous thromboembolism (VTE) is a multifactorial disease. Major provoking factors (e. g. surgery, cancer, major trauma, and immobilisation) are identified in 50–60 % of patients, while the remaining cases are classified as unprovoked. However, minor predisposing conditions may be detectable in these patients, possibly concurring to the pathophysiology of the disease, especially when co-existing. In recent years, the role of chronic inflammatory disorders, infectious diseases and traditional cardiovascular risk factors has been extensively investigated. Inflammation, with its underlying prothrombotic state, could be the potential link between these risk factors, as well as the explanation for the reported association between arterial and venous thromboembolic events.
Von Willebrand factor in relation to coronary plaque characteristics and cardiovascular outcome
Authors: Sonneveld Michelle A. , Cheng Jin , Oemrawsingh Rohit , de Maat Moniek P. M. , Kardys Isabella , Garcia-Garcia Hector , van Geuns Robert-Jan , Regar Evelyn , Serruys Patrick , Boersma Eric , Akkerhuis K. Martijn , Leebeek Frank W. 
Published: December 2014

SummaryHigh von Willebrand factor (VWF) plasma levels are associated with an increased risk of coronary artery disease. It has been suggested that the increase of VWF levels is partly due to endothelial dysfunction and atherosclerosis. Our aim was to investigate the association between coronary plaque burden, the presence of high-risk coronary lesions as measured by intravascular ultrasound virtual histology (IVUS-VH) and VWF levels. In addition, we studied the association between VWF levels and one-year cardiovascular outcome. Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) (n= 318) or stable angina pectoris (SAP) (n= 263). Arterial blood was sampled prior to the coronary angiography. VWF antigen (VWF:Ag) levels were measured using ELISA (n= 577). Patients with ACS had significantly higher VWF:Ag levels than SAP patients (median 1.73 IU/ml [IQR 1.27–2.31] vs 1.26 IU/ml [0.93–1.63], p < 0.001). High coronary plaque burden was associated with higher VWF:Ag levels (β= 0.12, p=0.027) in SAP patients, but not in ACS patients. In ACS patients, VWF:Ag levels were associated with 1-year MACE (HR 4.14 per SD increase of lnVWF:Ag, 95 % CI 1.47–11.6), whereas in SAP patients VWF:Ag levels predicted 1-year all-cause death and hospitalisation for ACS (HR 7.07 95 % CI 1.40–35.6). In conclusion, coronary plaque burden was associated with VWF:Ag levels in SAP patients undergoing coronary angiography. In ACS and SAP patients, high VWF levels are predictive of adverse cardiovascular outcome and death during one-year follow-up.
The Annual Cycle of East African Precipitation
Authors: Yang Wenchang , Seager Richard , Cane Mark A. , Lyon Bradfield 
Published: December 2014

Abstract
East African precipitation is characterized by a dry annual mean climatology compared to other deep tropical land areas and a bimodal annual cycle with the major rainy season during March–May (MAM; often called the “long rains”) and the second during October–December (OND; often called the “short rains”). To explore these distinctive features, ERA-Interim data are used to analyze the associated annual cycles of atmospheric convective stability, circulation, and moisture budget. The atmosphere over East Africa is found to be convectively stable in general year-round but with an annual cycle dominated by the surface moist static energy (MSE), which is in phase with the precipitation annual cycle. Throughout the year, the atmospheric circulation is dominated by a pattern of convergence near the surface, divergence in the lower troposphere, and convergence again at upper levels. Consistently, the convergence of the vertically integrated moisture flux is mostly negative across the year, but becomes weakly positive in the two rainy seasons. It is suggested that the semiarid/arid climate in East Africa and its bimodal precipitation annual cycle can be explained by the ventilation mechanism, in which the atmospheric convective stability over East Africa is controlled by the import of low MSE air from the relatively cool Indian Ocean off the coast. During the rainy seasons, however, the off-coast sea surface temperature (SST) increases (and is warmest during the long rains season) and consequently the air imported into East Africa becomes less stable. This analysis may be used to aid in understanding overestimates of the East African short rains commonly found in coupled models.
Does Afternoon Precipitation Occur Preferentially over Dry or Wet Soils in Oklahoma?
Authors: Ford Trent W. , Rapp Anita D. , Quiring Steven M. 
Published: December 2014

Abstract
Soil moisture is an integral part of the climate system and can drive land–atmosphere interactions through the partitioning of latent and sensible heat. Soil moisture feedback to precipitation has been documented in several regions of the world, most notably in the southern Great Plains. However, the impact of soil moisture on precipitation, particularly at short (subdaily) time scales, has not been resolved. Here, in situ soil moisture observations and satellite-based precipitation estimates are used to examine if afternoon precipitation falls preferentially over wet or dry soils in Oklahoma. Afternoon precipitation events during the warm season (May–September) in Oklahoma from 2003 and 2012 are categorized by how favorable atmospheric conditions are for convection, as well as the presence or absence of the Great Plains low-level jet. The results show afternoon precipitation falls preferentially over wet soils when the Great Plains low-level jet is absent. In contrast, precipitation falls preferentially over dry soils when the low-level jet is present. Humidity (temperature) is increased (decreased) as soil moisture increases for all conditions, and convective available potential energy prior to convection is strongest when atmospheric humidity is above normal. The results do not demonstrate a causal link between soil moisture and precipitation, but they do suggest that soil moisture feedback to precipitation could potentially manifest itself over wetter- and drier-than-normal soils, depending on the overall synoptic and dynamic conditions.
On the Alternate Transmission Mode for Polarimetric Phased Array Weather Radar
Authors: Melnikov Valery M. , Zrnić Dušan S. 
Published: December 2014

AbstractPulse-to-pulse switching of polarizations (alternate transmission mode) is considered for polarimetric phased array radar (PAR). It is argued that the performance of the radar in terms of data quality should match or exceed the achieved standards of the Weather Surveillance Radar-1988 Doppler (WSR-88D). It turns out that the most stringent demand on the radar concerns the surveillance scan at the lowest elevations wherein the polarimetric variables are free of overlaid echoes, while ground clutter is significantly reduced. The scan uses a long pulse repetition time that has repercussion on the standard errors of the polarimetric variables and hence the choice of polarimetric mode. Herein the dwell time of this scan serves as a benchmark for comparisons of the accuracy of estimates. Because weather PAR should provide useful information at low signal-to-noise ratios (SNR) as low as those measured by the WSR-88D, the statistics of polarimetric variables, known at high SNR, is extended to low SNRs. It follows that the alternate mode would not match the performance of the simultaneous mode in the surveillance scans on the WSR-88D. Quasi-simultaneous transmission and reception of horizontally polarized and vertically polarized waves is discussed as a cost-effective alternative.
The origin of nausea in migraine–A PET study
Authors: Maniyar Farooq H , Sprenger Till , Schankin Christoph , Goadsby Peter J 
Published: December 2014

Abstract

Background
Nausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea.

Methods
We performed positron emission tomography scans with H2
15O PET in premonitory phase of nitroglycerin-induced migraine and compared patients with and without nausea.

Results
The results showed activation in rostral dorsal medulla and periaqueductal grey (PAG) in the nausea group, which was absent in the no nausea group. The rostral dorsal medullary area included the nucleus tractus solitarius, dorsal motor nucleus of the vagus nerve and the nucleus ambiguus, all of which are thought to be involved in brain circuits mediating nausea.

Conclusions
The results demonstrate that nausea can occur as a premonitory symptom in migraine, independent of pain and trigeminal activation. This is associated with activation of brain structures known to be involved in nausea. We conclude that nausea is a centrally driven symptom in migraine.