bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine Leukemia Virus Uses NXF1 for Nuclear Export of Spliced and Unspliced Viral Transcripts
Authors: Sakuma Toshie , Davila Jaime I. , Malcolm Jessica A. , Kocher Jean-Pierre A. , Tonne Jason M. , Ikeda Yasuhiro 
Published: January 2014

ABSTRACT

Intron-containing mRNAs are subject to restricted nuclear export in higher eukaryotes. Retroviral replication requires the nucleocytoplasmic transport of both spliced and unspliced RNA transcripts, and RNA export mechanisms of gammaretroviruses are poorly characterized. Here, we report the involvement of the nuclear export receptor NXF1/TAP in the nuclear export of gammaretroviral RNA transcripts. We identified a conserved
cis
-acting element in the
pol
gene of gammaretroviruses, including murine leukemia virus (MLV) and xenotropic murine leukemia virus (XMRV), named the CAE (cytoplasmic accumulation element). The CAE enhanced the cytoplasmic accumulation of viral RNA transcripts and the expression of viral proteins without significantly affecting the stability, splicing, or translation efficiency of the transcripts. Insertion of the CAE sequence also facilitated Rev-independent HIV Gag expression. We found that the CAE sequence interacted with NXF1, whereas disruption of NXF1 ablated CAE function. Thus, the CAE sequence mediates the cytoplasmic accumulation of gammaretroviral transcripts in an NXF1-dependent manner. Disruption of NXF1 expression impaired cytoplasmic accumulations of both spliced and unspliced RNA transcripts of XMRV and MLV, resulting in their nuclear retention or degradation. Thus, our results demonstrate that gammaretroviruses use NXF1 for the cytoplasmic accumulation of both spliced and nonspliced viral RNA transcripts.

IMPORTANCE
Murine leukemia virus (MLV) has been studied as one of the classic models of retrovirology. Although unspliced host messenger RNAs are rarely exported from the nucleus, MLV actively exports unspliced viral RNAs to the cytoplasm. Despite extensive studies, how MLV achieves this difficult task has remained a mystery. Here, we have studied the RNA export mechanism of MLV and found that (i) the genome contains a sequence which supports the efficient nuclear export of viral RNAs, (ii) the cellular factor NXF1 is involved in the nuclear export of both spliced and unspliced viral RNAs, and, finally, (iii) depletion of NXF1 results in nuclear retention or degradation of viral RNAs. Our study provides a novel insight into MLV nuclear export.
Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Contributes to Viral Latent Replication by Activating Phosphorylation of Survivin
Authors: Lu Jie , Jha Hem C. , Verma Subhash C. , Sun Zhiguo , Banerjee Shuvomoy , Dzeng Richard , Robertson Erle S. 
Published: January 2014

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus casually linked to Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). Previously, we showed that LANA encoded by KSHV upregulates expression of survivin, a member of the inhibitor of apoptosis (IAP) family. This leads to an increase in the rate of cell proliferation of KSHV-infected B cells. LANA is required for tethering of the KSHV episome to the host chromosomes and efficiently segregates the viral genomes into dividing tumor cells. Here we show that LANA interacts with Aurora kinase B (AK-B) and induces phosphorylation of survivin at residue T34. Phosphorylation of survivin specifically on residue T34 enhances the activity of p300 and inhibits the activity of histone deacetylase 1 (HDAC-1), which then leads to an increase in acetylation of histone H3 on the viral genome. Phosphorylation of survivin specifically on residue T34 upregulates the activities of histone acetyltransferases and deacetylases, which then leads to an increase in viral copy number in KSHV-infected B cells. This results in a boost of KSHV replication in latently infected B-lymphoma cells. The studies showed that LANA can also function to regulate viral replication prior to mitosis of the latently infected cells, suggesting that LANA possesses a novel role in regulating KSHV replication in infected B cells.

IMPORTANCE
This work represents a report of KSHV latent protein LANA and its interactions with AK-B leading to induction of phosphorylation of the oncoprotein survivin at residue T34. Phosphorylation of survivin specifically on residue T34 upregulates the activities of histone acetyltransferases and deacetylases. This leads to an increase in viral copy number in KSHV-infected B cells. These studies support a role for LANA in regulating KSHV replication through posttranslation modification in KSHV-infected B cells.
Northern Territory Heart Failure Initiative–Clinical Audit (NTHFI–CA)–a prospective database on the quality of care and outcomes for acute decompensated heart failure admission in the Northern Territory: study design and rationale
Authors: Iyngkaran Pupalan , Tinsley Jeff , Smith David , Haste Mark , Nadarajan Kangaharan , Ilton Marcus , Battersby Malcolm , Stewart Simon , Brown Alex 
Published: January 2014

IntroductionCongestive heart failure is a significant cause of morbidity and mortality in Australia. Accurate data for the Northern Territory and Indigenous Australians are not presently available. The economic burden of this chronic cardiovascular disease is felt by all funding bodies and it still remains unclear what impact current measures have on preventing the ongoing disease burden and how much of this filters down to more remote areas. Clear differentials also exist in rural areas including a larger Indigenous community, greater disease burden, differing aetiologies for heart failure as well as service and infrastructure discrepancies. It is becoming increasingly clear that urban solutions will not affect regional outcomes. To understand regional issues relevant to heart failure management, an understanding of the key performance indicators in that setting is critical.Methods and analysisTheNorthernTerritoryHeartFailureInitiative—ClinicalAudit (NTHFI-CA) is a prospective registry of acute heart failure admissions over a 12-month period across the two main Northern Territory tertiary hospitals. The study collects information across six domains and five dimensions of healthcare. The study aims to set in place an evidenced and reproducible audit system for heart failure and inform the developing heart failure disease management programme. The findings, is believed, will assist the development of solutions to narrow the outcomes divide between remote and urban Australia and between Indigenous and Non-Indigenous Australians, in case they exist. A combination of descriptive statistics and mixed effects modelling will be used to analyse the data.Ethics and disseminationThis study has been approved by respective ethics committees of both the admitting institutions. All participants will be provided a written informed consent which will be completed prior to enrolment in the study. The study results will be disseminated through local and international health conferences and peer reviewed manuscripts.
Association among work exposure, alcohol intake, smoking and Dupuytren's disease in a large cohort study (GAZEL)
Authors: Descatha Alexis , Carton Matthieu , Mediouni Zakia , Dumontier Christian , Roquelaure Yves , Goldberg Marcel , Zins Marie , Leclerc Annette 
Published: January 2014

ObjectivesIn view of the debate of factors in Dupuytren’s disease, we aimed to describe its relationship with certain occupational factors, alcohol intake and smoking.SettingThe French GAZEL cohort (employees of Electricité de France and Gaz de France).ParticipantsParticipants of the cohort who answered a questionnaire in 2012, that is, 13 587 participants (73.7% of the questionnaire sent). In 2007, self-assessed lifetime occupational biomechanical exposure was recorded (carrying loads, manipulating a vibrating tool and climbing stairs), as well as alcohol intake, smoking and diabetes mellitus. Analyses were performed on high alcohol intake, smoking and duration of relevant work exposure, stratified by gender.Primary and secondary outcome measuresFrom a specific question on Dupuytren’s disease assessed in 2012, the outcome measures were self-reported Dupuytren’s disease (yes/no) and disabling Dupuytren’s disease (including surgery).ResultsA total of 10 017 men and 3570 women, aged 64–73 years, were included; the mean age for men was 68 years and for women was 65 years. Among men, the following were significantly associated with Dupuytren’s disease: age (OR 1.03 (1.00; 1.06)), diabetes (OR 1.31 (1.07; 1.60)), heavy drinking (OR 1.36 (1.10; 1.69)) and over 15 years of manipulating a vibrating tool at work (OR 1.52 (1.15; 2.02)); except for diabetes, the association with these factors was stronger for disabling Dupuytren’s disease (or surgery), with OR 1.07 (1.03; 1.11), 1.71 (1.25; 2.33) and 1.98(1.34; 2.91), respectively, for age, heavy drinking and over 15 years of manipulating a vibrating tool at work. Among the 3570 women included, 160 reported Dupuytren’s disease (4.5%). The number of cases in the group of women was too low to reach conclusions, although the findings seemed similar for age, diabetes and vibration exposure.ConclusionsIn this large French cohort study, Dupuytren’s disease in men was associated with high levels of alcohol consumption and exposure to hand-transmitted vibration. It is likely that the same applied to women.
A cohort study on mental disorders, stage of cancer at diagnosis and subsequent survival
Authors: Chang Chin-Kuo , Hayes Richard D , Broadbent Matthew T M , Hotopf Matthew , Davies Elizabeth , Møller Henrik , Stewart Robert 
Published: January 2014

ObjectivesTo assess the stage at cancer diagnosis and survival after cancer diagnosis among people served by secondary mental health services, compared with other local people.SettingUsing the anonymised linkage between a regional monopoly secondary mental health service provider in southeast London of four London boroughs, Croydon, Lambeth, Lewisham and Southwark, and a population-based cancer register, a historical cohort study was constructed.ParticipantsA total of 28 477 cancer cases aged 15+ years with stage of cancer recorded at diagnosis were identified. Among these, 2206 participants had been previously assessed or treated in secondary mental healthcare before their cancer diagnosis and 125 for severe mental illness (schizophrenia, schizoaffective or bipolar disorders).Primary and secondary outcome measuresStage when cancer was diagnosed and all-cause mortality after cancer diagnosis among cancer cases registered in the geographical area of southeast London.ResultsComparisons between people with and without specific psychiatric diagnosis in the same residence area for risks of advanced stage of cancer at diagnosis and general survival after cancer diagnosed were analysed using logistic and Cox models. No associations were found between specific mental disorder diagnoses and beyond local spread of cancer at presentation. However, people with severe mental disorders, depression, dementia and substance use disorders had significantly worse survival after cancer diagnosis, independent of cancer stage at diagnosis and other potential confounders.ConclusionsPrevious findings of associations between mental disorders and cancer mortality are more likely to be accounted for by differences in survival after cancer diagnosis rather than by delayed diagnosis.
The accuracy of caries risk assessment in children attending South Australian School Dental Service: a longitudinal study
Authors: Ha Diep H , Spencer A John , Slade Gary D , Chartier Andrew D 
Published: January 2014

ObjectivesTo determine the accuracy of the caries risk assessment system and performance of clinicians in their attempts to predict caries for children during routine practice.DesignLongitudinal study.Setting and participantsData on caries risk assessment conducted by clinicians during routine practice while providing care for children in the South Australian School Dental Service (SA SDS) were collected from electronic patient records. Baseline data on caries experience, clinicians’ ratings of caries risk status and child demographics were obtained for all SA SDS patients aged 5–15 years examined during 2002–2005.Outcome measureChildren’s caries incidence rate, calculated using examination data after a follow-up period of 6–48 months from baseline, was used as the gold standard to compute the sensitivity (Se) and specificity (Sp) of clinicians’ baseline ratings of caries risk. Multivariate binomial regression models were used to evaluate effects of children's baseline characteristics on Se and Sp.ResultsA total of 133 clinicians rated caries risk status of 71 430 children during 2002–2005. The observed Se and Sp were 0.48 and 0.86, respectively (Se+Sp=1.34). Caries experience at baseline was the strongest factor influencing accuracy in multivariable regression model. Among children with no caries experience at baseline, overall accuracy (Se+Sp) was only 1.05, whereas it was 1.28 among children with at least one tooth surfaces with caries experience at baseline.ConclusionsClinicians’ accuracy in predicting caries risk during routine practice was similar to levels reported in research settings that simulated patient care. Accuracy was acceptable in children who had prior caries experience at the baseline examination, while it was poor among children with no caries experience.
The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT)
Authors: Chesser Tim , Fox Rebecca , Harding Karen , Greenwood Rosemary , Javaid Kassim , Barnfield Steven , Halliday Ruth , Willett Keith , Lamb Sallie 
Published: January 2014

IntroductionPertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH.Methods and analysisThe study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6 weeks and 12 weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed.ResultsResults will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size.Ethics and disseminationThe study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and osteoporosis societies, and their relevant specialist journals.Trial RegistrationISRCTN Register reference number:ISRCTN03362357.Eudract Number: 2010-020081-22
Work-related road traffic injury: a multilevel systems protocol
Authors: Newnam Sharon , Sheppard Dianne M , Griffin Mark A , McClure Roderick J , Heller Gillian , Sim Malcolm R , Stevenson Mark R 
Published: January 2014

BackgroundAlthough road traffic injury is reported as the leading cause of work-related death in Australia, it is not clear, due to limitations in previous methods used, just how large a burden it is. Many organisations are unaware of the extent of work-related road traffic injury and, importantly, what can be done to reduce the burden. The proposed research will (i) estimate the prevalence of work-related road traffic injury and (ii) identify the organisational determinants associated with work-related road traffic injury.Methods and designThe current study is designed to enumerate the problem and identify the individual driver-level, the supervisor-level and organisational-level factors associated with work-related road traffic injury. The multilevel systems protocol will involve a series of cross-sectional surveys administered to drivers of fleet vehicles (n=1200), supervisors of the drivers (n=1200) and senior managers (n=300) within the same organisation.DiscussionThe novel use of the multilevel systems protocol is critical to be able to accurately assess the specific determinants of driving safety within each context of an organisation.ResultsThe results are expected to highlight that reducing injury in the workplace requires more than just individual compliance with safety procedures. It will also establish, for the first time, an occupational translation taskforce to ensure that the research findings are adopted into work-place practice and thereby directly contribute to reductions in work-related road traffic injury.
Hospital-based financial analysis of endovascular therapy and intravenous thrombolysis for large vessel acute ischemic strokes: the ‘bottom line’
Authors: Rai Ansaar T , Evans Kim 
Published: January 2014

BackgroundEconomic viability is important to any hospital striving to be a comprehensive stroke center. An inability to recover cost can strain sustained delivery of advanced stroke care.ObjectiveTo carry out a comparative financial analysis of intravenous (IV) recombinant tissue plasminogen activator and endovascular (EV) therapy in treating large vessel strokes from a hospital's perspective.MethodologyActual hospital's charges, costs, and payments were analyzed for 265 patients who received treatment for large vessel strokes. The patients were divided into an EV (n=141) and an IV group (n=124). The net gain/loss was calculated as the difference between payments received and the total cost.ResultsThe charges, costs, and payments were significantly higher for the EV than the IV group (p<0.0001 for all). Medicare A was the main payer. Length of stay was inversely related to net gain/loss (p<0.0001). Favorable outcome was associated with a net gain of $3853 (±$21 155) and poor outcome with a net deficit of $2906 (±$15 088) (p=0.003). The hospital showed a net gain for the EV group versus a net deficit for the IV group in patients who survived the admission (p=0.04), had a favorable outcome (p=0.1), or were discharged to home (p=0.03). There was no difference in the time in hospital based on in-hospital mortality for the EV group but patients who died in the IV group had a significantly shorter length of stay than those who survived (p=0.04). The favorable outcome of 42.3% in the EV group was significantly higher than the 29.4% in the IV group (p=0.03).ConclusionsEndovascular therapy was associated with better outcomes and higher cost–recovery than IV thrombolysis in patients with large vessel strokes.
Prognostic Role of 14F7 Mab Immunoreactivity against N-Glycolyl GM3 Ganglioside in Colon Cancer
Authors: Lahera Tania , Calvo Adanays , Torres Griselda , Rengifo Charles E. , Quintero Santiago , Arango María del Carmen , Danta Debora , Vázquez José M. , Escobar Xiomara , Carr Adriana 
Published: January 2014

Purpose. To assess the prognostic role of 14F7 Mab immunoreactivity, against N-Glycolyl GM3 ganglioside, in patients with colon cancer (CC) and to evaluate the relationship between its expression and clinicopathological features.Methods. Paraffin-embedded specimens were retrospectively collected from 50 patients with CC operated between 2004 and 2008. 14F7 Mab staining was determined by immunohistochemistry technique and its relation with survival and clinicopathologic features was evaluated.Results. The reactivity of 14F7 Mab was detected in all cases. Most cases had high level of immunostaining (70%) that showed statistical correlation with TNM stage(P=0.025). In univariate survival analysis, level of 14F7 Mab immunoreactivity(P=0.0078), TNM Stage(P=0.0007)and lymphovascular invasion(0.027)were significant prognostic factors for overall survival. Among these variables, level of 14F7 Mab immunoreactivity (HR=0.268; 95% CI  0.078–0.920; P=0.036)and TNM stage(HR=0.249; 95% CI   0.066–0.932; P=0.039)were independent prognostic factors on multivariate analysis.Conclusions. This study is the first approach on the prognostic significance of 14F7 Mab immunoreactivity in patients with colon adenocarcinoma and this assessment might be used in the prognostic estimate of CC, although further studies will be required to validate these findings.
Kinetics of Thermal Degradation of Recycled Polyvinyl Chloride Resin
Authors: Alwaan I. M. 
Published: January 2014

The goal of this study is to find the effect of time and temperature on the thermal degradation of recycled polyvinyl chloride (PVC) resin. The isothermal rate of reaction(r)of recycled PVC resin was investigated at the following temperatures to: 100, 110, 120, 130, and 140°C at period of times ranging from 10 to 50 min. The result shows that the rate of reaction(r)of recycled PVC increases with increasing temperatures. The reaction rate constant(K)for temperatures ranging from 100 to 140°C was doubled from 0.028–0.056 mol·L−1·S−1. The process was found to be zero order reaction at all range of temperatures 100–140°C. The activation energy of the thermal weight loss was calculated at different temperatures(E/R = 2739.5°K). The average enthalpy and entropy of reaction at temperature of 298°K were determined.