bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost
Authors: Hulot Sandrine L. , Korber Bette , Giorgi Elena E. , Vandergrift Nathan , Saunders Kevin O. , Balachandran Harikrishnan , Mach Linh V. , Lifton Michelle A. , Pantaleo Giuseppe , Tartaglia Jim , Phogat Sanjay , Jacobs Bertram , Kibler Karen , Perdiguero Beatriz , Gomez Carmen E. , Esteban Mariano , Rosati Margherita , Felber Barbara K. , Pavlakis George N. , Parks Robert , Lloyd Krissey , Sutherland Laura , Scearce Richard , Letvin Norman L. , Seaman Michael S. , Alam S. Munir , Montefiori David , Liao Hua-Xin , Haynes Barton F. , Santra Sampa 
Published: April 2015

ABSTRACT

An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4
+
and CD8
+
T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using
in silico
-designed centralized immunogens for global HIV-1 vaccine development strategies.

IMPORTANCE
There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that
in silico
-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.
Investigating Influenza A Virus Infection: Tools To Track Infection and Limit Tropism
Authors: Fiege Jessica K. , Langlois Ryan A. 
Published: April 2015

ABSTRACT
Influenza A viruses display a broad cellular tropism within the respiratory tracts of mammalian hosts. Uncovering the relationship between tropism and virus immunity, pathogenesis, and transmission will be critical for the development of therapeutic interventions. Here we discuss recent developments of several recombinant strains of influenza A virus. These viruses have inserted reporters to track tropism, microRNA target sites to restrict tropism, or barcodes to assess transmission dynamics, expanding our understanding of pathogen-host interactions.
Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort
Authors: Yap K S , Northcott M , Hoi A B-Y , Morand EF , Nikpour M 
Published: April 2015

BackgroundVitamin D status varies with geographic location and no studies of vitamin D in systemic lupus erythematosus (SLE) have been reported in the Southern Hemisphere.ObjectivesTo assess the prevalence of vitamin D deficiency in an Australian SLE cohort, and its relationship with disease activity.MethodsData were collected prospectively on 119 consecutive patients with SLE in the Monash Lupus Clinic in Melbourne, Australia, between January 2007 and January 2013. Patients had simultaneous serum 25-hydroxyvitamin D concentration and disease activity (SLEDAI-2K) recorded. Statistical methods were used to determine the correlation of serum vitamin D level and disease activity both at baseline and at a subsequent time point. Adjustments were made for the use of glucocorticoids, immunosuppressants and vitamin D supplementation.ResultsVitamin D deficiency (<40 nmol/L) was detected in 27.7% of patients at baseline. Multiple regression analysis showed a significant inverse correlation of SLEDAI-2K with baseline vitamin D level and with vitamin D supplementation. Over a 12-month period of observation, among the 119 patients, there were 464 serial vitamin D measurements with corresponding SLEDAI-2K, representing 266 time intervals. The median change in vitamin D level was an increase of 25 nmol/L and this corresponded with a decline in SLEDAI-2K of 2 units. In regression analysis, there was a significant association between low vitamin D at a prior time point and a rise in SLEDAI-2K at the subsequent time point (univariable OR 3.3, 95% CI 1.5 to 7.7, p=0.005) or having a high disease activity (SLEDAI-2k>10) at the subsequent time point (univariable OR 3.1, 95% CI 1.4 to 6.8, p=0.004).ConclusionsIn Australian patients with SLE, low vitamin D was associated with a higher disease activity and an increase in serum vitamin D was associated with reduced disease activity over time. The therapeutic effect of vitamin D in SLE should be further assessed in interventional studies.
PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus–Induced Liver Carcinogenesis
Authors: Zhang Hao , Diab Ahmed , Fan Huitao , Mani Saravana Kumar Kailasam , Hullinger Ronald , Merle Philippe , Andrisani Ourania 
Published: April 2015

Abstract
Elucidating mechanisms of hepatitis B virus (HBV)–mediated hepatocarcinogenesis is needed to gain insights into the etiology and treatment of liver cancer. Cells where HBV is replicating exhibit increased expression of Plk1 kinase and reduced levels of two transcription repression factors, SUZ12 and ZNF198. SUZ12 is an essential subunit of the transcription repressive complex PRC2. ZNF198 stabilizes the transcription repressive complex composed of LSD1, Co-REST, and HDAC1. These two transcription repressive complexes are held together by binding the long noncoding RNA HOTAIR. In this study, we linked these regulatory events mechanistically by showing that Plk1 induces proteasomal degradation of SUZ12 and ZNF198 by site-specific phosphorylation. Plk1-dependent ubiquitination of SUZ12 and ZNF198 was enhanced by expression of HOTAIR, significantly reducing SUZ12 and ZNF198 stability. In cells expressing the HBV X protein (HBx), downregulation of SUZ12 and ZNF198 mediated global changes in histone modifications. In turn, HBx-expressing cells propagated an altered chromatin landscape after cell division, as exemplified by changes in histone modifications of the EpCAM promoter, a target of PRC2 and LSD1/Co-REST/HDAC1 complexes. Notably, liver tumors from X/c-myc bitransgenic mice exhibited downregulation of SUZ12 and ZNF198 along with elevated expression of Plk1, HOTAIR, and EpCAM. Clinically, similar effects were documented in a set of HBV-related liver tumors consistent with the likelihood that downregulation of SUZ12 and ZNF198 leads to epigenetic reprogramming of infected hepatocytes. Because both Plk1 and HOTAIR are elevated in many human cancers, we propose that their combined effects are involved in epigenetic reprogramming associated broadly with oncogenic transformation. Cancer Res; 75(11); 2363–74. ©2015 AACR.
Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort
Authors: Ose Jennifer , Schock Helena , Tjønneland Anne , Hansen Louise , Overvad Kim , Dossus Laure , Clavel-Chapelon Françoise , Baglietto Laura , Boeing Heiner , Trichopolou Antonia , Benetou Vassiliki , Lagiou Pagona , Masala Giovanna , Tagliabue Giovanna , Tumino Rosario , Sacerdote Carlotta , Mattiello Amalia , Bueno-de-Mesquita H. B(as). , Peeters Petra H. M. , Onland-Moret N. Charlotte , Weiderpass Elisabete , Gram Inger T. , Sánchez Soledad , Obon-Santacana Mireia , Sànchez-Pérez Maria-José , Larrañaga Nerea , Castaño José María Huerta , Ardanaz Eva , Brändstedt Jenny , Lundin Eva , Idahl Annika , Travis Ruth C. , Khaw Kay-Tee , Rinaldi Sabina , Romieu Isabelle , Merritt Melissa A. , Gunter Marc J. , Riboli Elio , Kaaks Rudolf , Fortner Renée T. 
Published: April 2015

AbstractBackground: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.Methods: We conducted a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.Results: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP &gt;10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03–2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81–1.16); waist &gt;88: ORlog2, 1.78 (1.28–2.48), Pheterogeneity ≤ 0.01].Conclusions: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity.Impact: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. Cancer Epidemiol Biomarkers Prev; 24(6); 951–61. ©2015 AACR.
T-cell Expression of IL10 Is Essential for Tumor Immune Surveillance in the Small Intestine
Authors: Dennis Kristen L. , Saadalla Abdulrahman , Blatner Nichole R. , Wang Shuya , Venkateswaran Vysak , Gounari Fotini , Cheroutre Hilde , Weaver Casey T. , Roers Axel , Egilmez Nejat K. , Khazaie Khashayarsha 
Published: April 2015

AbstractIL10 is attributed with immune-suppressive and anti-inflammatory properties, which could promote or suppress cancer in the gastrointestinal tract. Loss of IL10 exacerbates colonic inflammation, leading to colitis and cancer. Consistent with this, transfer of IL10-competent regulatory T cells (Treg) into mice with colitis or hereditary polyposis protects against disease, while IL10-deficient mice are predisposed to polyposis with increased colon polyp load. Little is known about the protective or pathogenic function of IL10 in cancers of the small intestine. We found CD4+ T cells and CD4+ Foxp3+ Tregs to be the major sources of IL10 in the small intestine and responsible for the increase in IL10 during polyposis in the APCΔ468 mouse model of hereditary polyposis. Targeted ablation of IL10 in T cells caused severe IL10 deficiency and delayed polyp growth. However, these polyps progressively lost cytotoxic activity and eventually progressed to cancer. Several observations suggested that the effect was due to the loss of IFNγ-dependent immune surveillance. IL10-incompetent CD4+ T cells failed to secrete IFNγ when stimulated with polyp antigens and were inefficient in T-helper-1 (TH1) commitment. By contrast, the TH17 commitment was unaffected. These findings were validated using mice whose T cells overexpress IL10. In these mice, we observed high intra-polyp cytotoxic activity and attenuation of polyposis. Thus, expression of IL10 by T cells is protective and required for immune surveillance in the small intestine. Cancer Immunol Res; 3(7); 806–14. ©2015 AACR.
The physiologic anticoagulant and anti-inflammatory role of heparins and their utility in the prevention of pregnancy complications
Authors: Mastrolia Salvatore Andrea , Mazor Moshe , Holcberg Gershon , Leron Elad , Beharier Ofer , Loverro Giuseppe , Erez Offer 
Published: April 2015

SummaryAccumulating evidence supports the concept of increased thrombin generation, placental vascular lesions, and inflammation as crucial points in the development of the great obstetrical syndromes [preeclampsia, intrauterine growth restriction (IUGR), preterm labor (PTL), preterm prelabor rupture of membranes (PROM), fetal demise and recurrent abortions]. In light of this, the role of heparins for primary or secondary prevention of these syndromes is becoming more and more apparent, mainly due to the antithrombotic and anti-inflammatory effects of heparins. There is agreement regarding the use of heparin in the prevention of gestational complications in patients with antiphospholipid syndrome, while its use for other obstetrical complications is under debate. In the present review we will describe the physiologic role of heparins on coagulation and inflammation and we will discuss current evidence regarding the use of heparins for the prevention/ treatment of obstetrical syndromes.
Vegetation Dynamics on the Tibetan Plateau (1982–2006): An Attribution by Ecohydrological Diagnostics
Authors: Cai Danlu , Fraedrich Klaus , Sielmann Frank , Zhang Ling , Zhu Xiuhua , Guo Shan , Guan Yanning 
Published: April 2015

Abstract
Vegetation greenness distributions [based on remote sensing normalized difference vegetation index (NDVI)] and their change are analyzed as functional vegetation–climate relations in a two-dimensional ecohydrological state space spanned by surface flux ratios of energy excess (U; loss by sensible heat H over supply by net radiation N) versus water excess (W; loss by discharge Ro over gain by precipitation P). An ecohydrological ansatz attributes state change trajectories in (U, W) space to external (or climate) and internal (or anthropogenic) causes jointly with vegetation greenness interpreted as an active tracer. Selecting the Tibetan Plateau with its complex topographic, climate, and vegetation conditions as target area, ERA-Interim weather data link geographic and (U, W) state space, into which local remote sensing Global Inventory Modeling and Mapping Studies (GIMMS) data (NDVI) are embedded; a first and second period (1982–93 and 1994–2006) are chosen for change attribution analysis. The study revealed the following results: 1) State space statistics are characterized by a bimodal distribution with two distinct geobotanic regimes (semidesert and steppe) of low and moderate vegetation greenness separated by gaps at aridity D ~ 2 (net radiation over precipitation) and greenness NDVI ~ 0.3. 2) Changes between the first and second period are attributed to external (about 70%) and internal (30%) processes. 3) Attribution conditioned joint distributions of NDVI (and its change) show 38.2% decreasing (61.8% increasing) area cover with low (moderate) greenness while high greenness areas are slightly reduced. 4) Water surplus regions benefit most from climate change (showing vegetation greenness growth) while the energy surplus change is ambiguous, because ecohydrological diagnostics attributes high mountainous regions (such as the Himalayas) as internal without considering the heat storage deficit due to increasing vegetation.
Delirium as letting go: An ethnographic analysis of hospice care and family moral experience
Authors: Wright David Kenneth , Brajtman Susan , Cragg Betty , Macdonald Mary Ellen 
Published: April 2015

Background: Delirium is extremely common in dying patients and appears to be a major threat to the family’s moral experience of a good death in end-of-life care. Aim: To illustrate one of the ways in which hospice caregivers conceptualize end-of-life delirium and the significance of this conceptualization for the relationships that they form with patients’ families in the hospice setting. Design: Ethnography. Setting/participants: Ethnographic fieldwork was conducted at a nine-bed, freestanding residential hospice, located in a suburban community of Eastern Canada. Data collection methods included 15 months of participant observation, 28 semi-structured audio-recorded interviews with hospice caregivers, and document analysis. Results: Hospice caregivers draw on a culturally established framework of normal dying to help families come to terms with clinical end-of-life phenomena, including delirium. By offering explanations about delirium as a natural feature of the dying process, hospice caregivers strive to protect for families the integrity of the good death ideal. Conclusion: Within hospice culture, there is usefulness to deemphasizing delirium as a pathological neuropsychiatric complication, in favor of acknowledging delirious changes as signs of normal dying. This has implications for how we understand the role of nurses and other caregivers with respect to delirium assessment and care, which to date has focused largely on practices of screening and management.
A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease
Authors: Idilman Ilkay S , Keskin Onur , Celik Azim , Savas Berna , Halil Elhan Atilla , Idilman Ramazan , Karcaaltincaba Musturay 
Published: April 2015

Background Many imaging methods have been defined for quantification of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, studies comparing the efficiency of magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and liver histology for quantification of liver fat content are limited. Purpose To compare the efficiency of MRI-PDFF and MRS in the quantification of liver fat content in individuals with NAFLD. Material and Methods A total of 19 NAFLD patients underwent MRI-PDFF, MRS, and liver biopsy for quantification of liver fat content. The MR examinations were performed on a 1.5 HDx MRI system. The MRI protocol included T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling and MRS with STEAM technique. Results A close correlation was observed between liver MRI-PDFF- and histology- determined steatosis (r = 0.743, P < 0.001) and between liver MRS- and histology-determined steatosis (r = 0.712, P < 0.001), with no superiority between them (ƶ = 0.19, P = 0.849). For quantification of hepatic steatosis, a high correlation was observed between the two MRI methods (r = 0.986, P < 0.001). MRI-PDFF and MRS accurately differentiated moderate/severe steatosis from mild/no hepatic steatosis ( P = 0.007 and 0.013, respectively), with no superiority between them (AUCMRI-PDFF = 0.881 ± 0.0856 versus AUCMRS = 0.857 ± 0.0924, P = 0.461). Conclusion Both MRI-PDFF and MRS can be used for accurate quantification of hepatic steatosis.
What are the Benefits of Leisure? An Exploration Using the Leisure Satisfaction Scale
Authors: Di Bona Laura 
Published: April 2015

No occupational therapy study appears to have identified comprehensively the influence of different variables on the leisure experience. This study aimed to establish: (1) if there was a difference in the needs satisfied by leisure between people of different ages, sex, and relationship and parental status (people with or without or cohabiting with a partner or children); (2) whether or not different needs were satisfied by different leisure activities; and (3) whether the adapted form of the Leisure Satisfaction Scale (LSS) (Beard and Ragheb 1980) measured leisure satisfaction. Sixty-five nurses completed an adapted form of the LSS for three leisure activities that they engaged in and rated their overall satisfaction with leisure on a scale of 1 to 10. Relevant demographic details were requested. The data were analysed using non-parametric statistics. The findings lent support to the use of the adapted form of the LSS as a valid measure of leisure satisfaction. The findings suggested that leisure satisfaction was not affected by demographic factors, but they supported previous findings that leisure satisfaction was affected by different leisure activities. This study supported the therapeutic use of carefully selected activities to meet individual needs. It also suggested the potential benefit of using the LSS (Beard and Ragheb 1980) in occupational therapy. However, further research to develop related knowledge is needed.
Compliance with Prescribed Adaptive Equipment: A Literature Review
Authors: Wielandt Trish , Strong Jenny 
Published: April 2015

This article describes a literature review that examined the topic of the postdischarge compliance of individuals with prescribed adaptive equipment. Assisting individuals to accomplish tasks relevant to their activities of daily living and thereby achieve functional independence is central to the role of occupational therapy. The prescription of adaptive equipment is a frequently used intervention. The rationale for prescribing adaptive equipment is that it maximises a client's functional potential, allows for independence in activities of daily living and fosters confidence as a result of being able to accomplish such tasks. All studies that surveyed compliance with prescribed adaptive equipment between 1963 and 1996 were reviewed. The factors that reportedly affect compliance by individuals can be considered under five discrete categories: medical-related, client-related, equipment-related, assessment-related and training-related. On the basis of the findings of this literature review, recommendations are made for further research, specifically investigating methods that therapists could incorporate into current practice to address the problem of non-compliance with prescribed adaptive equipment.
The Empowerment of Clients through Preoperative Education
Authors: Spalding Nicola 
Published: April 2015

The literature suggests that the education of clients is, in theory, an empowering process (Stewart 1994, Opie 1998). The empowerment of clients has been encouraged by the British Government and is seen as central to the occupational therapy process (Stewart 1994). In this initial case study of the empowerment of clients awaiting a total hip replacement, the data were gathered from four occupational therapists working in different preoperative education programmes. The aim of the study was to explore the ways in which these programmes were empowering for the clients. Semi-structured interviews were undertaken with each participant. The occupational therapists' descriptions and discussions of their programmes, and the content of the invitation letters that they sent to clients, were analysed to assess any empowerment strategies. The findings suggest six different strategies that could be used to empower clients awaiting a total hip replacement. The findings will be used to design a preoperative education programme that empowers such clients.