bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus BZLF1-Mediated Downregulation of Proinflammatory Factors Is Essential for Optimal Lytic Viral Replication
Authors: Li Yuqing , Long Xubing , Huang Lu , Yang Mengtian , Yuan Yan , Wang Yan , Delecluse Henri-Jacques , Kuang Ersheng 
Published: November 2015

ABSTRACT
Elevated secretion of inflammatory factors is associated with latent Epstein-Barr virus (EBV) infection and the pathology of EBV-associated diseases; however, knowledge of the inflammatory response and its biological significance during the lytic EBV cycle remains elusive. Here, we demonstrate that the immediate early transcriptional activator BZLF1 suppresses the proinflammatory factor tumor necrosis factor alpha (TNF-α) by binding to the promoter of TNF-α and preventing NF-κB activation. A BZLF1Δ207-210 mutant with a deletion of 4 amino acids (aa) in the protein-protein binding domain was not able to inhibit the proinflammatory factors TNF-α and gamma interferon (IFN-γ) and reduced viral DNA replication with complete transcriptional activity during EBV lytic gene expression. TNF-α depletion restored the viral replication mediated by BZLF1Δ207-210. Furthermore, a combination of TNF-α- and IFN-γ-neutralizing antibodies recovered BZLF1Δ207-210-mediated viral replication, indicating that BZLF1 attenuates the antiviral response to aid optimal lytic replication primarily through the inhibition of TNF-α and IFN-γ secretion during the lytic cycle. These results suggest that EBV BZLF1 attenuates the proinflammatory responses to facilitate viral replication.

IMPORTANCE
The proinflammatory response is an antiviral and anticancer strategy following the complex inflammatory phenotype. Latent Epstein-Barr virus (EBV) infection strongly correlates with an elevated secretion of inflammatory factors in a variety of severe diseases, while the inflammatory responses during the lytic EBV cycle have not been established. Here, we demonstrate that BZLF1 acts as a transcriptional suppressor of the inflammatory factors TNF-α and IFN-γ and confirm that BZLF1-facilitated escape from the TNF-α and IFN-γ response during the EBV lytic life cycle is required for optimal viral replication. This finding implies that the EBV lytic cycle employs a distinct strategy to evade the antiviral inflammatory response.
Disparities in health and access to healthcare between asylum seekers and residents in Germany: a population-based cross-sectional feasibility study
Authors: Schneider Christine , Joos Stefanie , Bozorgmehr Kayvan 
Published: November 2015

ObjectivesTo assess disparities in health and healthcare between asylum seekers (AS) and residents in Germany as a proof of concept using European Core Health Indicators (ECHI).DesignPopulation-based cross-sectional feasibility study.ParticipantsAll AS (aged 18 years or above) registered in three counties in Germany during a 3-month study period (N=1017). Cross-sectional data on the resident population were taken from the German Health Interview (2008–2011, N=8152), and the European Union Statistics on Income and Living Conditions (2012, N=23 065).Outcome measuresSelf-reported health status and healthcare access (utilisation and unmet medical need) in line with ECHI.MethodInequalities in health and access to healthcare were quantified both by crude and age-stratified/sex-stratified ORs with 95% CI using cross-tabulations.ResultsA total of N=156 AS (15.34%) participated in the study. Compared with residents, AS were significantly more likely to report a bad health status (OR=1.72 (1.23 to 2.41)), activity limitations (OR=1.97 (1.39 to 2.79)) or (only younger age groups) any chronic morbidity (18–24 years: OR=6.23 (2.62 to 14.57); 25–49 years: OR=2.05 (1.23 to 3.37)). AS had significantly lower odds for consulting any physician (OR=0.1 (0.07 to 0.16)) or general practitioners (OR=0.44 (0.31 to 0.62)), but higher odds for hospital admissions (OR=2.29 (1.54 to 3.34)), visits to psychotherapists (OR=4.07 (2.48 to 6.43)) and unmet needs (OR=3.74 (2.62 to 5.21)). The direction of healthcare-related associations was consistent across all strata despite variation in magnitude and statistical significance.ConclusionsQuantifying disparities between AS and the resident population by means of selected ECHI proved to be feasible. The approach yielded first quantitative evidence for disparities in health and access to healthcare in the German context. Further research is needed to generate representative estimates, for example, by including AS in national health monitoring programmes.
Observing temporal trends in cardiac rehabilitation from 1996 to 2010 in Ontario: characteristics of referred patients, programme participation and mortality rates
Authors: Grace Sherry L , Oh Paul I , Marzolini Susan , Colella Tracey , Tan Yongyao , Alter David A 
Published: November 2015

ObjectivesWe sought to describe temporal trends in the sociodemographic and clinical characteristics of participants referred to cardiac rehabilitation (CR), and its effect on programme participation and all-cause mortality over 14 years.SettingA large CR centre in Toronto, Canada.ParticipantsConsecutive patients between 1996 and 2010.Primary and secondary outcome measuresReferrals received were deterministically linked to administrative data, to complement referral form abstraction. Out-of-hospital deaths were identified using vital statistics. Patients were tracked until 2012, and mortality was ascertained. Percentage attendance at prescribed sessions was also assessed.ResultsThere were 29 171 referrals received, of which 28 767 (98.6%) were successfully linked, of whom 22 795 (79.2%) attended an intake assessment. The age of the referred population steadily increased, with more females, less affluent and more single patients referred over time (p<0.001). More patients were referred following percutaneous coronary intervention and less following coronary artery bypass graft surgery (p<0.001). The number of comorbidities decreased (p<0.001). Hypertension increased over time (p<0.001), yet the control of cholesterol steadily improved over time. The proportion of smokers decreased over time (p<0.001). Participation in CR significantly declined, and there were no significant changes in mortality. 3-year mortality rates were less than 5%.ConclusionsCharacteristics of referred patients tended to reflect broader trends in risk factors and cardiovascular disease burden. Physicians appear to be referring more sociodemographically diverse patients to CR; however, programmes may need to better adapt to engage these patients to fully participate. More complex patients should be referred, using explicit criteria-based referral processes.
Linking Cancer Metabolism to DNA Repair and Accelerated Senescence
Authors: Efimova Elena V. , Takahashi Satoe , Shamsi Noumaan A. , Wu Ding , Labay Edwardine , Ulanovskaya Olesya A. , Weichselbaum Ralph R. , Kozmin Sergey A. , Kron Stephen J. 
Published: November 2015

AbstractConventional wisdom ascribes metabolic reprogramming in cancer to meeting increased demands for intermediates to support rapid proliferation. Prior models have proposed benefits toward cell survival, immortality, and stress resistance, although the recent discovery of oncometabolites has shifted attention to chromatin targets affecting gene expression. To explore further effects of cancer metabolism and epigenetic deregulation, DNA repair kinetics were examined in cells treated with metabolic intermediates, oncometabolites, and/or metabolic inhibitors by tracking resolution of double-strand breaks (DSB) in irradiated MCF7 breast cancer cells. Disrupting cancer metabolism revealed roles for both glycolysis and glutaminolysis in promoting DSB repair and preventing accelerated senescence after irradiation. Targeting pathways common to glycolysis and glutaminolysis uncovered opposing effects of the hexosamine biosynthetic pathway (HBP) and tricarboxylic acid (TCA) cycle. Treating cells with the HBP metabolite N-acetylglucosamine (GlcNAc) or augmenting protein O-GlcNAcylation with small molecules or RNAi targeting O-GlcNAcase each enhanced DSB repair, while targeting O-GlcNAc transferase reversed GlcNAc's effects. Opposing the HBP, TCA metabolites including α-ketoglutarate blocked DSB resolution. Strikingly, DNA repair could be restored by the oncometabolite 2-hydroxyglutarate (2-HG). Targeting downstream effectors of histone methylation and demethylation implicated the PRC1/2 polycomb complexes as the ultimate targets for metabolic regulation, reflecting known roles for Polycomb group proteins in nonhomologous end-joining DSB repair. Our findings that epigenetic effects of cancer metabolic reprogramming may promote DNA repair provide a molecular mechanism by which deregulation of metabolism may not only support cell growth but also maintain cell immortality, drive therapeutic resistance, and promote genomic instability.Implications: By defining a pathway from deregulated metabolism to enhanced DNA damage response in cancer, these data provide a rationale for targeting downstream epigenetic effects of metabolic reprogramming to block cancer cell immortality and overcome resistance to genotoxic stress. Mol Cancer Res; 14(2); 173–84. ©2015 AACR.
Determining the Volume of Additive Solution and Residual Plasma in Whole Blood Filtered and Buffy Coat Processed Red Cell Concentrates
Authors: Jordan Andrew , Acker Jason P. 
Published: November 2015

<b>Background:</b> Residual plasma in transfused red cell concentrates (RCCs) has been associated with adverse transfusion outcomes. Despite this, there is no consensus on the standard procedure for measuring residual plasma volume. <b>Methods: </b>The volumes of residual plasma and additive solution were measured in RCCs processed using two separation methods: whole blood filtration (WBF) and buffy coat (BC)/RCC filtration. The concentration of mannitol and albumin in RCC components was measured using colorimetric assays. Mannitol concentration was used to calculate additive solution volume. Residual plasma volume was calculated using two methods. <b>Results:</b> Calculated RCC supernatant volumes were much lower in BC-processed components compared to WBF-processed components (BC = 97 ± 6 ml, WBF = 109 ± 4 ml; p < 0.05). Calculated additive solution volumes were greater in WBF- than in BC-processed components (BC = 81 ± 4 ml, WBF = 105 ± 2 ml; p < 0.05). Absolute residual plasma volume varied significantly based on the calculation method used. <b>Conclusion:</b> Disparity between plasma volume calculation methods was observed. Efforts should be made to standardize residual plasma volume measurement methods in order to accurately assess the impact of residual plasma on transfusion outcomes.
Operational energy use and power demands in European HVAC components
Authors: Knight IP 
Published: November 2015

This paper is presented in the context of a gradual move from energy management at a Building level to energy management at Component level. This move requires specific energy consumption and power demand benchmarks to allow measured component energy use and power demands to be put into context. The paper presents a methodology for collecting and collating the data needed for producing these benchmarks from measured operational data. This methodology was tested in the European iSERVcmb project. Example benchmarks from iSERVcmb are provided along with links to the full published data. The paper concludes that large scale measurement and comparison of detailed operational data are possible and useful in support of achieving operationally low energy buildings. Practical application: The explosion of low-cost operational data availability at the level of individual components can be used to improve understanding of their operational energy efficiency in the context of the overall efficiency of a building. The paper shows this data can: Be collected from all types of buildings across all EU Member States Produce benchmark ranges of operational energy consumption and power demands at the level of individual components serving given activities Applying this benchmarked data in the design and operation of buildings will: Improve their operational energy efficiency, Enable legislation using this data to show compliance
Quantifying the burden of opioid medication errors in adult oncology and palliative care settings: A systematic review
Authors: Heneka Nicole , Shaw Tim , Rowett Debra , Phillips Jane L 
Published: November 2015

Background: Opioids are the primary pharmacological treatment for cancer pain and, in the palliative care setting, are routinely used to manage symptoms at the end of life. Opioids are one of the most frequently reported drug classes in medication errors causing patient harm. Despite their widespread use, little is known about the incidence and impact of opioid medication errors in oncology and palliative care settings. Aim: To determine the incidence, types and impact of reported opioid medication errors in adult oncology and palliative care patient settings. Design: A systematic review. Data sources: Five electronic databases and the grey literature were searched from 1980 to August 2014. Empirical studies published in English, reporting data on opioid medication error incidence, types or patient impact, within adult oncology and/or palliative care services, were included. Popay’s narrative synthesis approach was used to analyse data. Results: Five empirical studies were included in this review. Opioid error incidence rate was difficult to ascertain as each study focussed on a single narrow area of error. The predominant error type related to deviation from opioid prescribing guidelines, such as incorrect dosing intervals. None of the included studies reported the degree of patient harm resulting from opioid errors. Conclusion: This review has highlighted the paucity of the literature examining opioid error incidence, types and patient impact in adult oncology and palliative care settings. Defining, identifying and quantifying error reporting practices for these populations should be an essential component of future oncology and palliative care quality and safety initiatives.
Potential Impacts of an Exclusionary Trans-Pacific Partnership Agreement on Agriculture in the US and Japan
Authors: Thompson Jada M. , Leister Amanda M. 
Published: November 2015

The Trans-Pacific Partnership (TPP) is a free trade agreement that hopes to eliminate all tariff and non-tariff trade barriers between 12 participating countries. Japan, the fourth-largest trading partner for the United States, is a significant player in the negotiations. Due to cultural and historical significance it is expected that Japan will ask for exclusions on agricultural products, limiting the overall effectiveness of a fully liberalised agreement. Using a computable general equilibrium modelling framework across varying scenarios, we show the difference between the full liberalisation and potential exclusionary scenarios. Estimates show that a 25 per cent reduction in import tariffs on agricultural commodities in Japan results in a difference of net welfare benefits equal to –USD 7 billion, emphasising the importance of these concessions. JEL Classification: F14, F15, Q17
Fiscal Multipliers for India
Authors: Bose Sukanya , Bhanumurthy N.R. 
Published: November 2015

This article attempts to present a framework for the estimation of fiscal multipliers for the Indian economy in the structural macroeconomic modelling tradition. Empirical estimates of short-run multipliers are obtained by giving shocks to a range of fiscal instruments—expenditures and taxes. As per our estimates, the values of the capital expenditure multiplier, transfer payments multiplier and other revenue expenditure multiplier are 2.45, 0.98 and 0.99, respectively, while the tax multipliers are around −1. Expenditure multipliers were also obtained in the presence of fiscal consolidation targets. These estimates again point to the strong multiplier effect of capital expenditure on output, and underscore the need to prioritise capital expenditure. JEL Classification: H50, C54
Way Forward: an Indigenous approach to well-being
Authors: Andersen Kimina , Henderson Julie , Howarth Emma , Williamson Daniel , Crompton David , Emmerson Brett 
Published: November 2015

Objective: Aboriginal and Torres Strait Islander individuals are overrepresented in mental health services in the state of Queensland (QLD), Australia; indicating greater prevalence and less preventative management of mental illness. This paper describes a project to enhance the model of care to improve mental health, alcohol and other drug outcomes for Aboriginal and Torres Strait Islander Community members in two metropolitan Hospital and Health Services, in Brisbane, Australia. Methods: Individual and focus group consultations were conducted with stakeholders, to determine key themes. Results: The consultative phase of the project revealed three priority areas for action: governance and supervision arrangements for the workforce in the area of Indigenous mental health, alcohol and other drugs; the cultural capability of non-Indigenous clinicians; and consumer access to services. Conclusions: The Way Forward project is a broad workforce redesign approach to address these three key areas. This approach is designed to acknowledge the strengths among the Indigenous Aboriginal and Torres Strait Islander workforce and to utilise their specialised cultural knowledge. This strategy will also include working in relationships with key Community-controlled health and other organisations. The approach will be reviewed and evaluated.
Balint groups: an Australasian perspective for psychiatrists
Authors: Lustig Marion 
Published: November 2015

Objective: This paper aims to provide a brief overview of the history and scope of the Balint movement; to outline how Balint groups work; to describe what is entailed in leading a Balint group; and to give a brief overview of the current state of Balint work in Australia and New Zealand. Conclusions: Balint groups provide a unique setting in which clinicians can learn how to deal well with challenging doctor–patient relationships and the feelings evoked in clinical practice. Balint work is relatively undeveloped in Australasia. There is scope for involvement by psychiatrists and trainees as both participants and facilitators.
Safe Zone for the Plantar Portal
Authors: Maeda Shingo , Niki Hisateru , Hirano Takaaki , Akiyama Yui 
Published: November 2015

Background: Understanding the plantar nerve anatomy is crucial for safe endoscopic surgery of the sole. We aimed to anatomically dissect the lateral aspect and soles of cadaveric feet to investigate the safety of peroneus longus tendoscopy with a plantar lateral portal and the safe zones for plantar portals. Methods: We studied 36 feet of 24 cadavers (mean age, 86.5 years). A cannula for 2.7-mm scope was inserted from the plantar lateral portal to the peroneus longus tendon, and the positional relationship between the cannula and sural nerve was observed. Then, the soft tissue of the sole was dissected, and the relationships between the plantar nerve and flexor digitorum longus tendon and flexor hallucis longus tendon was observed. The plantar nerve course was digitally imaged and uploaded into Image J software to determine nerve position. We further observed the positional relationship between the cannula and plantar nerve. Result: The mean minimum distance between the cannula and sural nerve was 13.8 mm, and the closest distance was 4.2 mm, allowing for the relatively safe creation of a plantar lateral portal. The use of the plantar lateral portal and evaluation of the peroneal tendon was safe with respect to the lateral plantar nerve as the nerve was in a different tissue layer of the foot. Dissection of the plantar foot demonstrated a relatively safe zone, 36.4% to 56% along a line between the medial aspect of the base of the first metatarsal bone to the proximal tip of the fifth metatarsal. This region may allow for a plantar endoscopic portal; however an anatomic variation may result in the plantar nerve being within this zone. The flexor digitorum longus tendon and peroneus longus tendon passed through the deep layer of the relatively safe zone. Conclusion: Peroneus longus tendoscopy was relatively safe to perform from a plantar lateral portal. No neurovascular structure exists on the slightly medial aspect of the central region of the sole, potentially allowing for a relatively safe creation of plantar central portal. An approach from the plantar central portal to the flexor digitorum longus tendon, flexor hallucis longus tendon, and peroneus longus tendon allows for a greater range of vision and treatment options as compared with conventional approaches. The combination of the plantar central portal with portals such as the plantar lateral portal may further the development of endoscopic surgery of the sole. Clinical Relevance: We found the anatomic characteristics of a relatively safe zone for the plantar portal for plantar lateral portal.
Anatomy of the red cell membrane skeleton: unanswered questions
Authors: Lux Samuel E. 
Published: November 2015

AbstractThe red cell membrane skeleton is a pseudohexagonal meshwork of spectrin, actin, protein 4.1R, ankyrin, and actin-associated proteins that laminates the inner membrane surface and attaches to the overlying lipid bilayer via band 3–containing multiprotein complexes at the ankyrin- and actin-binding ends of spectrin. The membrane skeleton strengthens the lipid bilayer and endows the membrane with the durability and flexibility to survive in the circulation. In the 36 years since the first primitive model of the red cell skeleton was proposed, many additional proteins have been discovered, and their structures and interactions have been defined. However, almost nothing is known of the skeleton’s physiology, and myriad questions about its structure remain, including questions concerning the structure of spectrin in situ, the way spectrin and other proteins bind to actin, how the membrane is assembled, the dynamics of the skeleton when the membrane is deformed or perturbed by parasites, the role lipids play, and variations in membrane structure in unique regions like lipid rafts. This knowledge is important because the red cell membrane skeleton is the model for spectrin-based membrane skeletons in all cells, and because defects in the red cell membrane skeleton underlie multiple hemolytic anemias.