bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectromelia Virus Encodes a BTB/kelch Protein, EVM150, That Inhibits NF-κB Signaling
Authors: Wang Qian , Burles Kristin , Couturier Brianne , Randall Crystal M. H. , Shisler Joanna , Barry Michele 
Published: February 2014

ABSTRACT
The NF-κB signaling pathway plays a critical role in inflammation and innate immunity. Consequently, many viruses have evolved strategies to inhibit NF-κB in order to facilitate replication and evasion of the host immune response. Recently, we determined that ectromelia virus, the causative agent of mousepox, contains a family of four BTB/kelch proteins that interact with cullin-3-based ubiquitin ligases. We demonstrate here that expression of EVM150, one of the four BTB/kelch proteins, inhibited NF-κB activation induced by tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β). Although EVM150 inhibited NF-κB p65 nuclear translocation, IκBα degradation was observed, indicating that EVM150 functioned downstream of IκBα degradation. Significantly, expression of the BTB-only domain of EVM150 blocked NF-κB activation, demonstrating that EVM150 functioned independently of the kelch domain and its role as an adapter for cullin-3-based ubiquitin ligases. Furthermore, cullin-3 knockdown by small interfering RNA demonstrated that cullin-3-based ubiquitin ligases are dispensable for TNF-α-induced NF-κB activation. Interestingly, nuclear translocation of IRF3 and STAT1 still occurred in the presence of EVM150, indicating that EVM150 prevented NF-κB nuclear translocation specifically. In addition to identifying EVM150 as an inhibitor of the NF-κB pathway, this study provides new insights into the role of BTB/kelch proteins during virus infection.

IMPORTANCE
With the exception of virulence studies, little work has been done to determine the role of poxviral BTB/kelch proteins during infection. This study, for the first time, has identified a mechanism for the ectromelia virus BTB/kelch protein EVM150. Here, we show that EVM150 is a novel inhibitor of the cellular NF-κB pathway, an important component of the antiviral response. This study adds EVM150 to the growing list of NF-κB inhibitors in poxviruses and provides new insights into the role of BTB/kelch proteins during virus infection.
Naturally Occurring Mutations in the PA Gene Are Key Contributors to Increased Virulence of Pandemic H1N1/09 Influenza Virus in Mice
Authors: Sun Yipeng , Xu Qi , Shen Ye , Liu Linqing , Wei Kai , Sun Honglei , Pu Juan , Chang Kin-Chow , Liu Jinhua 
Published: February 2014

ABSTRACT

We examined the molecular basis of virulence of pandemic H1N1/09 influenza viruses by reverse genetics based on two H1N1/09 virus isolates (A/California/04/2009 [CA04] and A/swine/Shandong/731/2009 [SD731]) with contrasting pathogenicities in mice. We found that four amino acid mutations (P224S in the PA protein [PA-P224S], PB2-T588I, NA-V106I, and NS1-I123V) contributed to the lethal phenotype of SD731. In particular, the PA-P224S mutation when combined with PA-A70V in CA04 drastically reduced the virus's 50% mouse lethal dose (LD
50
), by almost 1,000-fold.
Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus
Authors: Whisnant Adam W. , Kehl Timo , Bao Qiuying , Materniak Magdalena , Kuzmak Jacek , Löchelt Martin , Cullen Bryan R. 
Published: February 2014

ABSTRACT
While numerous viral microRNAs (miRNAs) expressed by DNA viruses, especially herpesvirus family members, have been reported, there have been very few reports of miRNAs derived from RNA viruses. Here we describe three miRNAs expressed by bovine foamy virus (BFV), a member of the spumavirus subfamily of retroviruses, in both BFV-infected cultured cells and BFV-infected cattle. All three viral miRNAs are initially expressed in the form of an ∼122-nucleotide (nt) pri-miRNA, encoded within the BFV long terminal repeat U3 region, that is subsequently cleaved to generate two pre-miRNAs that are then processed to yield three distinct, biologically active miRNAs. The BFV pri-miRNA is transcribed by RNA polymerase III, and the three resultant mature miRNAs were found to contribute a remarkable ∼70% of all miRNAs expressed in BFV-infected cells. These data document the second example of a retrovirus that is able to express viral miRNAs by using embedded proviral RNA polymerase III promoters.

IMPORTANCE
Foamy viruses are a ubiquitous family of nonpathogenic retroviruses that have potential as gene therapy vectors in humans. Here we demonstrate that bovine foamy virus (BFV) expresses high levels of three viral microRNAs (miRNAs) in BFV-infected cells in culture and also in infected cattle. The BFV miRNAs are unusual in that they are initially transcribed by RNA polymerase III as a single, ∼122-nt pri-miRNA that is subsequently processed to release three fully functional miRNAs. The observation that BFV, a foamy virus, is able to express viral miRNAs in infected cells adds to emerging evidence that miRNA expression is a common, albeit clearly not universal, property of retroviruses and suggests that these miRNAs may exert a significant effect on viral replication
in vivo
.
Examination of Surface Conditions and Other Physical Properties of Commonly Used Stainless Steel Acupuncture Needles
Authors: Xie Yi Min , Xu Shanqing , Zhang Claire Shuiqing , Xue Charlie Changli 
Published: February 2014

Objectives The present work examined the surface conditions and various other physical properties of sterilised single-use stainless steel acupuncture needles from two of the most popular brands widely used in many countries. Methods Scanning electron microscope (SEM) images were taken for 10 randomly chosen needles from each brand. Further SEM images were taken after each of these needles underwent a standard manipulation with an acupuncture needling practice gel. A comparison of forces and torques during the needling process was also carried out. Results The SEM images revealed significant surface irregularities and inconsistencies at the needle tips, especially for needles from one of the two brands. Metallic lumps and small, loosely attached pieces of material were observed on the surfaces of some needles. Some of the lumps and pieces of material seen on the needle surfaces disappeared after the acupuncture manipulation. If these needles had been used on patients, the metallic lumps and small pieces of material could have been deposited in human tissues, which could have caused adverse events such as dermatitis. Malformed needle tips might also cause other adverse effects including bleeding, haematoma/bruising, or strong pain during needling. An off-centre needle tip could result in the needle altering its direction during insertion and consequently failing to reach the intended acupuncture point or damaging adjacent tissues. Conclusions These findings highlight the need for improved quality control of acupuncture needles, with a view to further enhancing the safety and comfort of acupuncture users.
Factors associated with the clinical outcomes of paediatric out-of-hospital cardiac arrest in Japan
Authors: Nagata Takashi , Abe Takeru , Noda Eiichiro , Hasegawa Manabu , Hashizume Makoto , Hagihara Akihito 
Published: February 2014

ObjectivesTo better understand and predict clinical outcomes of paediatric out-of-hospital cardiac arrest (OHCA).DesignA population-based, observational study.SettingThe National Japan Utstein Registry.Participants2900 children aged 5–17 years who experienced OHCA and received resuscitation by emergency responders. Signal detection analysis using 17 variables was applied to identify factors associated with OHCA outcomes; the primary endpoint was cerebral performance category (CPC) 1 or 2. A validation study was conducted to verify the model.ResultsOHCA was identified as cardiac origin in 706 participants and non-cardiac origin in 2194 participants. Rates of CPC 1 or 2 for cardiac and non-cardiac causes were 20% and 6.4%, respectively. Cardiac origin arrest was categorised following signal detection into six subgroups defined by public automated external defibrillator use, defibrillation by emergency medical service, age, initial ECG rhythm and eye-witness to arrest; the ranges of CPC 1 or 2 in the six subgroups were between 87.5% and 0.7%. Non-cardiac origin arrest was categorised into four subgroups. Bystander rescue breathing was the most significant factor contributing to outcome; additionally, two other factors—eye-witness to arrest and age—were also significant. CPC 1 or 2 rates ranged between 38.5% and 4% across the four subgroups. Rates of CPC 1 or 2 in the validation study did not differ among any subgroup.ConclusionsFor children who have OHCA from non-cardiac origin, bystander rescue breathing is mandatory to achieve CPC 1 or 2.
A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010
Authors: Liew Gerald , Michaelides Michel , Bunce Catey 
Published: February 2014

ObjectivesTo report on the causes of blindness certifications in England and Wales in working age adults (16–64 years) in 2009–2010; and to compare these with figures from 1999 to 2000.DesignAnalysis of the national database of blindness certificates of vision impairment (CVIs) received by the Certifications Office.Setting and participantsWorking age (16–64 years) population of England and Wales.Main outcome measuresNumber and cause of blindness certifications.ResultsThe Certifications Office received 1756 CVIs for blindness from persons aged between 16 and 64 inclusive between 1 April 2009 and 31 March 2010. The main causes of blindness certifications were hereditary retinal disorders (354 certifications comprising 20.2% of the total), diabetic retinopathy/maculopathy (253 persons, 14.4%) and optic atrophy (248 persons, 14.1%). Together, these three leading causes accounted for almost 50% of all blindness certifications. Between 1 April 1999 and 31 March 2000, the leading causes of blindness certification were diabetic retinopathy/maculopathy (17.7%), hereditary retinal disorders (15.8%) and optic atrophy (10.1%).ConclusionsFor the first time in at least five decades, diabetic retinopathy/maculopathy is no longer the leading cause of certifiable blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders. This change may be related to factors including the introduction of nationwide diabetic retinopathy screening programmes in England and Wales and improved glycaemic control. Inherited retinal disease, now representing the commonest cause of certification in the working age population, has clinical and research implications, including with respect to the provision of care/resources in the NHS and the allocation of research funding.
Behavioural sleep problems in children with attention-deficit/hyperactivity disorder (ADHD): protocol for a prospective cohort study
Authors: Lycett Kate , Sciberras E , Mensah F K , Gulenc A , Hiscock H 
Published: February 2014

IntroductionChildren with attention-deficit/hyperactivity disorder (ADHD) commonly experience behavioural sleep problems, yet these difficulties are not routinely assessed and managed in this group. Presenting with similar symptoms to ADHD itself, sleep problems are complex in children with ADHD and their aetiology is likely to be multifactorial. Common internalising and externalising comorbidities have been associated with sleep problems in children with ADHD; however, this relationship is yet to be fully elucidated. Furthermore, limited longitudinal data exist on sleep problems in children with ADHD, thus their persistence and impact remain unknown. In a diverse sample of children with ADHD, this study aims to: (1) quantify the relationship between sleep problems and internalising and externalising comorbidities; (2) examine sleep problem trajectories and risk factors; and (3) examine the longitudinal associations between sleep problems and child and family functioning over a 12-month period.Methods and analysisA prospective cohort study of 400 children with ADHD (150 with no/mild sleep problems, 250 with moderate/severe sleep problems) recruited from paediatric practices across Victoria, Australia. The children's parents and teacher provide data at baseline and 6-month and 12-month post enrolment.Key measuresParent report of child's sleep problem severity (no, mild, moderate, severe); specific sleep domain scores assessed using the Child Sleep Habits Questionnaire; internalising and externalising comorbidities assessed by the Anxiety Disorders Interview Schedule for Children IV/Parent version.AnalysesMultiple variable logistic and linear regression models examining the associations between key measures, adjusted for confounders identified a priori.Ethics and disseminationEthics approval has been granted. Findings will contribute to our understanding of behavioural sleep problems in children with ADHD. Clinically, they could improve the assessment and management of sleep problems in this group. We will seek to publish in leading paediatric journals, present at conferences and inform Australian paediatricians through theAustralian Paediatric Research Network.
Facility versus unit level reporting of quality indicators in nursing homes when performance monitoring is the goal
Authors: Norton Peter G , Murray Michael , Doupe Malcolm B , Cummings Greta G , Poss Jeff W , Squires Janet E , Teare Gary F , Estabrooks Carole A 
Published: February 2014

ObjectivesTo demonstrate the benefit of defining operational management units in nursing homes and computing quality indicators on these units as well as on the whole facility.DesignCalculation of adjusted Resident Assessment Instrument – Minimum Data Set 2.0 (RAI–MDS 2.0) quality indicators for: PRU05 (prevalence of residents with a stage 2–4 pressure ulcer), PAI0X (prevalence of residents with pain) and DRG01 (prevalence of residents receiving an antipsychotic with no diagnosis of psychosis), for quarterly assessments between 2007 and 2011 at unit and facility levels. Comparisons of these risk-adjusted quality indicators using statistical process control (control charts).SettingA representative sample of 30 urban nursing homes in the three Canadian Prairie Provinces.MeasurementsExplicit decision rules were developed and tested to determine whether the control charts demonstrated improving, worsening, unchanging or unclassifiable trends over the time period. Unit and facility performance were compared.ResultsIn 48.9% of the units studied, unit control chart performance indicated different changes in quality over the reporting period than did the facility chart. Examples are provided to illustrate that these differences lead to quite different quality interventions.ConclusionsOur results demonstrate the necessity of considering facility-level and unit-level measurement when calculating quality indicators derived from the RAI–MDS 2.0 data, and quite probably from any RAI measures.
Coastal changes in the Arctic
Authors: Overduin P. P. , Strzelecki M. C. , Grigoriev M. N. , Couture N. , Lantuit H. , St-Hilaire-Gravel D. , Günther F. , Wetterich S. 
Published: February 2014

Abstract
The arctic environment is changing: air temperatures, major river discharges and open water season length have increased, and storm intensities and tracks are changing. Thirteen quantitative studies of the rates of coastline position change throughout the Arctic show that recently observed environmental changes have not led to ubiquitously or continuously increasing coastal erosion rates, which currently range between 0 and 2 m/yr when averaged for the arctic shelf seas. Current data is probably insufficient, both spatially and temporally, however, to capture change at decadal to sub-decadal time scales. In this context, we describe the current understanding of arctic coastal geomorphodynamics with an emphasis on erosional regimes of coasts with ice-rich sedimentary deposits in the Laptev, East Siberian and Beaufort seas, where local coastal erosion can exceed 20 m/yr. We also examine coasts with lithified (rocky) substrates where geomorphodynamics are intensified by rapid glacial retreat. Coastlines of Svalbard, Greenland and the Canadian Archipelago are less frequently studied than ice-rich continental coasts of North America and Siberia, and studies often focus on coastal sections composed of unlithified material. As air temperature and sea ice duration and extent change, longer thaw and wave seasons will intensify coastal dynamics in the Arctic.
Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1αas Adaptive Response to a High Salt Diet
Authors: Della Penna Silvana Lorena , Cao Gabriel , Carranza Andrea , Zotta Elsa , Gorzalczany Susana , Cerrudo Carolina Susana , Rukavina Mikusic Natalia Lucía , Correa Alicia , Trida Verónica , Toblli Jorge Eduardo , Rosón María Inés , Fernández Belisario Enrique 
Published: February 2014

In the kidney, a high salt intake favors oxidative stress and hypoxia and causes the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia inducible factor (HIF-1α) exert cytoprotective effects. We tested the hypothesis that renal expression of ANP and HIF-1αis involved in a mechanism responding to the oxidative stress produced in the kidneys of rats chronically fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4% NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the administration of tempol (T), an inhibitor of oxidative stress, in the drinking water. We measured the mean arterial pressure (MAP), glomerular filtration rate (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP, HIF-1α, and transforming growth factor (TGF-β1) in renal tissues by western blot and immunohistochemistry. The animals fed a high salt diet showed increased MAP andUVNalevels and enhanced renal immunostaining of ANP, HIF-1α, and TGF-β1. The administration of tempol together with the sodium overload increased the natriuresis further and prevented the elevation of blood pressure and the increased expression of ANP, TGF-β1, and HIF-1αcompared to their control. These findings suggest that HIF-1αand ANP, synthesized by the kidney, are involved in an adaptive mechanism in response to a sodium overload to prevent or attenuate the deleterious effects of the oxidative stress and the hypoxia on the development of fibrosis.Erratum to “Renal Overexpression of Atrial Natriuretic Peptide and Hypoxia Inducible Factor-1α as Adaptive Response to a High Salt Diet”
Occurrence of Tertiary Lymphoid Tissue Is Associated with T-Cell Infiltration and Predicts Better Prognosis in Early-Stage Colorectal Cancers
Authors: Di Caro Giuseppe , Bergomas Francesca , Grizzi Fabio , Doni Andrea , Bianchi Paolo , Malesci Alberto , Laghi Luigi , Allavena Paola , Mantovani Alberto , Marchesi Federica 
Published: February 2014

Abstract
Purpose: Tumor-infiltrating T lymphocytes (TIL) play a key role in the clinical outcome of human colorectal cancer; however, the dynamics of their recruitment along colorectal cancer clinical progression have not been fully elucidated. Tertiary lymphoid tissue (TLT) is an ectopic organized lymph node–like structure that typically forms at sites of chronic inflammation and is involved in adaptive immune responses. Its occurrence in cancer is sporadically documented and its role and clinical relevance is largely unknown.
Experimental Design: The occurrence of TLT, the correlation with TILs, and the clinical relevance were evaluated retrospectively, in a cohort study involving a consecutive series of 351 patients with stage II and III colorectal cancer. The role of TLT in lymphocyte recruitment was assessed in a preclinical model of colorectal cancer.
Results: In both human colorectal cancer and in a murine model of colorectal cancer, we identified organized TLT, highly vascularized (including high endothelial venules), and correlated with the density of CD3+ TILs. Intravenous injection in mice of GFP splenocytes resulted in homing of lymphocytes to TLT, suggesting an active role of TLT in the recruitment of lymphocytes to tumor areas. Accordingly, TLT density and TIL infiltration correlated and were coordinated in predicting better patient's outcome among patients with stage II colorectal cancer.
Conclusions: We provide evidence that TLT is associated with lymphocyte infiltration in colorectal cancer, providing a pathway of recruitment for TILs. TLT cooperates with TILs in a coordinated antitumor immune response, when identifying patients with low-risk early-stage colorectal cancer, thus, representing a novel prognostic biomarker for colorectal cancer. Clin Cancer Res; 20(8); 2147–58. ©2014 AACR.
Myeloid Suppressors Decrease Melanoma Survival by Abating Tumor-Fighting T Cells
Authors: Kiessling Rolf , Mao Yumeng , de Coaña Yago Pico 
Published: February 2014

Abstract
Disseminated malignant melanoma has a poor prognosis. Immunotherapy based on cytokines or checkpoint inhibitors has a protracted beneficial effect in a select group of patients. Understanding the mechanisms that inhibit tumor-specific T cells will help the development of biomarkers to formulate therapy for this disease. Clin Cancer Res; 20(6); 1401–3. ©2014 AACR.
Epidemiology of venous thrombosis in children with cancer
Authors: Piovesan Dana , Attard Chantal , Monagle Paul , Ignjatovic Vera 
Published: February 2014

SummaryThere has been an extensive body of research focusing on the epidemiology of thrombosis in adult cancer populations; however, there is significantly less knowledge about thrombosis in paediatric cancer populations. Thrombosis is diagnosed with increasing frequency in children being treated for cancer, and there is an urgent need to increase our understanding of the epidemiology of thrombosis in this population. Currently, there are no guidelines for identification of high-risk groups, prophylaxis or management of thrombotic complications in paediatric cancer patients. We reviewed the available literature regarding the epidemiology, mechanisms, risk factors, prophylaxis and outcomes of thrombosis in children with cancer and identified areas that require further research. The reported incidence of symptomatic venous thromboembolism (VTE) in children with cancer ranges between 2.1% and 16%, while the incidence of asymptomatic events is approximately 40%. Approximately 30% of VTE in this population is associated with central venous lines (CVL). The most common location of VTE is upper and lower extremity deep venous thrombosis (43 to 50% of events, respectively), while 50% of events in ALL patients occur in the central nervous system. Key characteristics that increase the risk of thrombosis include the type of cancer, age of the patient, the presence of a CVL, presence of pulmonary/intra thoracic disease, as well as the type of chemotherapy. Outcomes for paediatric cancer patients with VTE include post-thrombotic syndrome, pulmonary embolism, recurrent thromboembolism, destruction of upper venous system and death. Prospective studies aimed at enabling risk stratification of patients are required to facilitate development of paediatric specific recommendations related to thromboprophylaxis in this population.