bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Open Chromatin Landscape of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Hilton Isaac B. , Simon Jeremy M. , Lieb Jason D. , Davis Ian J. , Damania Blossom , Dittmer Dirk P. 
Published: August 2013

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus which establishes latent infection in endothelial and B cells, as well as in primary effusion lymphoma (PEL). During latency, the viral genome exists as a circular DNA minichromosome (episome) and is packaged into chromatin analogous to human chromosomes. Only a small subset of promoters, those which drive latent RNAs, are active in latent episomes. In general, nucleosome depletion (“open chromatin”) is a hallmark of eukaryotic regulatory elements such as promoters and transcriptional enhancers or insulators. We applied formaldehyde-assisted isolation of regulatory elements (FAIRE) followed by next-generation sequencing to identify regulatory elements in the KSHV genome and integrated these data with previously identified locations of histone modifications, RNA polymerase II occupancy, and CTCF binding sites. We found that (i) regions of open chromatin were not restricted to the transcriptionally defined latent loci; (ii) open chromatin was adjacent to regions harboring activating histone modifications, even at transcriptionally inactive loci; and (iii) CTCF binding sites fell within regions of open chromatin with few exceptions, including the constitutive LANA promoter and the vIL6 promoter. FAIRE-identified nucleosome depletion was similar among B and endothelial cell lineages, suggesting a common viral genome architecture in all forms of latency.
Promyelocytic Leukemia Protein Modulates Establishment and Maintenance of Latent Gammaherpesvirus Infection in Peritoneal Cells
Authors: Sewatanon Jaturong , Liu Hao , Ling Paul D. 
Published: August 2013

ABSTRACT

Promyelocytic leukemia protein (PML) is an essential organizer of PML nuclear bodies (NBs), which carry out a variety of activities, including antiviral functions. Herpesviruses from all subfamilies encode proteins that counteract PML NB-mediated antiviral defenses by multiple mechanisms. However, because of the species specificity of herpesviruses, only a limited number of
in vivo
studies have been undertaken to investigate the effect of PML or PML NBs on herpesvirus infection. To address this central issue in herpesvirus biology, we studied the course of infection in wild-type and
PML
−/−
mice using murine gammaherpesvirus 68 (MHV68), which encodes a tegument protein that induces PML degradation. While acute infection in
PML
−/−
mice progressed similarly to that in wild-type mice, the lytic reactivation frequency was higher in peritoneal exudate cells, due to both an increase of MHV68 genome-positive cells and greater reactivation efficiency. We also detected a higher frequency of persistent infection in
PML
−/−
peritoneal cells. These findings suggest that the PML protein can repress the establishment or maintenance of gammaherpesvirus latency
in vivo
. Further use of the
PML
−/−
mouse model should aid in dissecting the molecular mechanisms that underlie the role of PML in gammaherpesvirus latency and may yield clues for how PML modulates herpesvirus latency in general.
Kaposi's Sarcoma-Associated Herpesvirus-Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin's Nuclear Translocation
Authors: Bottero Virginie , Sadagopan Sathish , Johnson Karen E. , Dutta Sujoy , Veettil Mohanan Valiya , Chandran Bala 
Published: August 2013

ABSTRACT

Angiogenin (ANG) is a 14-kDa multifunctional proangiogenic secreted protein whose expression level correlates with the aggressiveness of several tumors. We observed increased ANG expression and secretion in endothelial cells during
de novo
infection with Kaposi's sarcoma-associated herpesvirus (KSHV), in cells expressing only latency-associated nuclear antigen 1 (LANA-1) protein, and in KSHV latently infected primary effusion lymphoma (PEL) BCBL-1 and BC-3 cells. Inhibition of phospholipase Cγ (PLCγ) mediated ANG's nuclear translocation by neomycin, an aminoglycoside antibiotic (not G418-neomicin), resulted in reduced KSHV latent gene expression, increased lytic gene expression, and increased cell death of KSHV
+
PEL and endothelial cells. ANG detection in significant levels in KS and PEL lesions highlights its importance in KSHV pathogenesis. To assess the
in vivo
antitumor activity of neomycin and neamine (a nontoxic derivative of neomycin), BCBL-1 cells were injected intraperitoneally into NOD/SCID mice. We observed significant extended survival of mice treated with neomycin or neamine. Markers of lymphoma establishment, such as increases in animal body weight, spleen size, tumor cell spleen infiltration, and ascites volume, were observed in nontreated animals and were significantly diminished by neomycin or neamine treatments. A significant decrease in LANA-1 expression, an increase in lytic gene expression, and an increase in cleaved caspase-3 were also observed in neomycin- or neamine-treated animal ascitic cells. These studies demonstrated that ANG played an essential role in KSHV latency maintenance and BCBL-1 cell survival
in vivo
, and targeting ANG function by neomycin/neamine to induce the apoptosis of cells latently infected with KSHV is an attractive therapeutic strategy against KSHV-associated malignancies.
Mitochondrial Nucleases ENDOG and EXOG Participate in Mitochondrial DNA Depletion Initiated by Herpes Simplex Virus 1 UL12.5
Authors: Duguay Brett A. , Smiley James R. 
Published: August 2013

ABSTRACT
Herpes simplex virus 1 (HSV-1) rapidly eliminates mitochondrial DNA (mtDNA) from infected cells, an effect that is mediated by UL12.5, a mitochondrial isoform of the viral alkaline nuclease UL12. Our initial hypothesis was that UL12.5 directly degrades mtDNA via its nuclease activity. However, we show here that the nuclease activities of UL12.5 are not required for mtDNA loss. This observation led us to examine whether cellular nucleases mediate the mtDNA loss provoked by UL12.5. We provide evidence that the mitochondrial nucleases endonuclease G (ENDOG) and endonuclease G-like 1 (EXOG) play key redundant roles in UL12.5-mediated mtDNA depletion. Overall, our data indicate that UL12.5 deploys cellular proteins, including ENDOG and EXOG, to destroy mtDNA and contribute to a growing body of literature highlighting roles for ENDOG and EXOG in mtDNA maintenance.
Cluster-randomised controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale
Authors: Arnold Benjamin F , Null Clair , Luby Stephen P , Unicomb Leanne , Stewart Christine P , Dewey Kathryn G , Ahmed Tahmeed , Ashraf Sania , Christensen Garret , Clasen Thomas , Dentz Holly N , Fernald Lia C H , Haque Rashidul , Hubbard Alan E , Kariger Patricia , Leontsini Elli , Lin Audrie , Njenga Sammy M , Pickering Amy J , Ram Pavani K , Tofail Fahmida , Winch Peter J , Colford John M 
Published: August 2013

IntroductionEnteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development. Water quality, sanitation, handwashing and nutritional interventions can independently reduce enteric infections and growth faltering. There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children. The objective of the WASH Benefits study is to help fill this knowledge gap.Methods and analysisWASH Benefits includes two cluster-randomised trials to assess improvements in water quality, sanitation, handwashing and child nutrition—alone and in combination—to rural households with pregnant women in Kenya and Bangladesh. Geographically matched clusters (groups of household compounds in Bangladesh and villages in Kenya) will be randomised to one of six intervention arms or control. Intervention arms include water quality, sanitation, handwashing, nutrition, combined water+sanitation+handwashing (WSH) and WSH+nutrition. The studies will enrol newborn children (N=5760 in Bangladesh and N=8000 in Kenya) and measure outcomes at 12 and 24 months after intervention delivery. Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea. Secondary outcomes include stunting prevalence, markers of environmental enteropathy and child development scores (verbal, motor and personal/social). We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests.Ethics and disseminationStudy protocols have been reviewed and approved by human subjects review boards at the University of California, Berkeley, Stanford University, the International Centre for Diarrheal Disease Research, Bangladesh, the Kenya Medical Research Institute, and Innovations for Poverty Action. Independent data safety monitoring boards in each country oversee the trials. This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Berkeley.RegistrationTrial registration identifiers (http://www.clinicaltrials.gov):NCT01590095(Bangladesh),NCT01704105(Kenya).
A prospective study comparing contamination rates between a novel mid-stream urine collection device (Peezy) and a standard method in renal patients
Authors: Collier S , Matjiu F , Jones G , Harber M , Hopkins S 
Published: August 2013

IntroductionIt is imperative that laboratories receive uncontaminated urine samples to avoid giving false-positive results and reduce antimicrobial use.AimThe aim of the study was to investigate a novel urine collection device (Peezy) in a renal outpatient clinic to determine whether it reduced contamination of urine samples.MethodsThe novel device was used in 420 renal transplant recipients and the results were compared with 424 matched historical controls, who used the standard method of urine collection. High epithelial cell counts on microscopy and mixed urine cultures were used to identify contaminated samples.ResultsPeezy increased the rates of both epithelial cells and mixed growths in the urine samples when compared with the historical controls.ConclusionsFurther randomised studies in other more generalisable populations need to be performed.
Expression of cancer stem cell markers is more frequent in anaplastic thyroid carcinoma compared to papillary thyroid carcinoma and is related to adverse clinical outcome
Authors: Yun Ji Yun , Kim Young A , Choe Ji-Young , Min Hyesook , Lee Kyu Sang , Jung Youngho , Oh Sohee , Kim Ji Eun 
Published: August 2013

BackgroundThyroid cancer is one of the most commonly detected cancers worldwide, and papillary thyroidal carcinoma (PTC) accounts for the majority of thyroid cancers. In contrast to the indolent nature of PTC, anaplastic thyroid carcinoma (ATC) shows an extremely poor prognosis and has not responded to any therapeutic modalities. Many researchers postulate that the dedifferentiation of thyroid follicular cells into primitive cells might be related to the pathogenesis of ATC because several cases of ATC have revealed pre-existing PTC lesions. Additionally, the cancer stem cell (CSC) theory has been widely accepted in the pathogenesis of ATC.ObjectiveTo explore the expression of various CSC markers in thyroid carcinoma tissues and analyse their clinical significance.Methods133 patients with PTC and 25 patients with ATC were enrolled. Immunohistochemistry for aldehyde dehydrogenase 1 (ALDH1), CD133, CXCR4, ATP-binding cassette (ABC)G2, multidrug resistance associated protein-1 (MRP1), lung resistance protein-1 (LRP), P-glycoprotein 1 (P-Gp1), SOX2, SOX9 and Oct4 was performed using tissue microarray.ResultsCSC marker expression was significantly high in ATC, particularly chemoresistance markers such as ABCG2, MRP1, LRP and CXCR4. In PTC, ABCG2 was highly positive in more advanced pathological stages and was associated with lymph node involvement, with borderline significance. In ATC, high expression of CXCR4 correlated with distant metastasis, and LRP showed a tendency to correlate with lymph node metastasis. High expression of CSC markers was related to shorter overall survival in patients with ATC.ConclusionsThese results provide strong evidence that CSCs are related to the pathogenesis of ATC and can explain the frequent treatment failure and aggressiveness of ATC.
Fractional Flow Reserve–Guided Versus Angiography-Guided Coronary Artery Bypass Graft Surgery
Authors: Toth Gabor , De Bruyne Bernard , Casselman Filip , De Vroey Frederic , Pyxaras Stylianos , Di Serafino Luigi , Van Praet Frank , Van Mieghem Carlos , Stockman Bernard , Wijns William , Degrieck Ivan , Barbato Emanuele 
Published: August 2013

Background—
Fractional flow reserve (FFR) is well established for patients undergoing percutaneous coronary intervention, yet little is known about candidates for coronary artery bypass graft surgery.

Methods and Results—

From 2006 to 2010, we retrospectively included in this registry 627 consecutive patients treated by coronary artery bypass graft surgery having at least 1 angiographically intermediate stenosis. In 429 patients, coronary artery bypass graft surgery was based solely on angiography (angiography-guided group). In 198 patients, at least 1 intermediate stenosis was grafted with an FFR ≤0.80 or deferred with an FFR >0.80 (FFR-guided group). The end point was major adverse cardiovascular events at 3 years, defined as the composite of overall death, myocardial infarction, and target vessel revascularization. The rate of angiographic multivessel disease was similar in the angiography-guided and FFR-guided groups (404 [94.2%] versus 186 [93.9%];
P
=0.722). In the FFR-guided group, this was significantly downgraded after FFR measurements to 86.4% (
P
<0.001 versus before FFR) and was associated with a smaller number of anastomoses (3 [2–3] versus 3 [2–4];
P
<0.001) and rate of on-pump surgery (49% versus 69%;
P
<0.001). At 3 years, major adverse cardiovascular events were not different between the angiography-guided and FFR-guided groups (12% versus 11%; hazard ratio, 1.030; 95% confidence interval, 0.627–1.692;
P
=0.908). However, the FFR-guided group compared with the angiography-guided group presented a significantly lower rate of angina (Canadian Cardiovascular Society class II–IV, 31% versus 47%;
P
<0.001).

Conclusions—
FFR-guided coronary artery bypass graft surgery was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided coronary artery bypass graft surgery. This did not result in a higher event rate during up to 36 months of follow-up and was associated with a lower rate of angina.
A Secular Bible?
Authors: Mack Burton L. 
Published: August 2013

AbstractWhat has been called secular criticism among some scholars in the Society of Biblical Literature has been pursued as a critique and alternative to traditional theological studies. The question is whether the term secular is being used to describe a method, characterize the biblical literature, or propose a postmodern hermeneutic for a secular age. The article explores these issues to find that secular criticism has not been able to escape the assumption of biblical authority by criticizing theological interpretations. The alternative would be to study the Christian myth embedded in the Bible and render a cultural critique.
Efficacy and safety of strategies to preserve stable extracorporeal life support flow during simulated hypovolemia
Authors: Simons AP , Lindelauf AAMA , Ganushchak YM , Maessen JG , Weerwind PW 
Published: August 2013

Aim: Without volume-buffering capacity in extracorporeal life support (ELS) systems, hypovolemia can acutely reduce support flow. This study aims at evaluating efficacy and safety of strategies for preserving stable ELS during hypovolemia. Material & Methods: Flow and/or pressure-guided servo pump control, a reserve-driven control strategy and a volume buffer capacity (VBC) device were evaluated with respect to pump flow, venous line pressure and arterial gaseous microemboli (GME) during simulated normovolemia and hypovolemia. Results: Normovolemia resulted in a GME-free pump flow of 3.1±0.0 L/min and a venous line pressure of −10±1 mmHg. Hypovolemia without servo pump control resulted in a GME-loaded flow of 2.3±0.4 L/min with a venous line pressure of −114±52 mmHg. Servo control resulted in an unstable and GME-loaded flow of 1.5±1.2 L/min. With and without servo pump control, the VBC device stabilised flow (SD = 0.2 and 0.0 L/min, respectively) and venous line pressure (SD=51 and 4 mmHg, respectively) with near-absent GME activity. Reserve-driven pump control combined with a VBC device restored a near GME-free flow of 2.7±0.0 L/min with a venous line pressure of −9±0 mmHg. Conclusion: In contrast to a reserve-driven pump control strategy combined with a VBC device, flow and pressure servo control for ELS show evident deficits in preserving stable and safe ELS flow during hypovolemia.
Combination of positioning therapy and venovenous extracorporeal membrane oxygenation in ARDS patients
Authors: Kredel M , Bischof L , Wurmb TE , Roewer N , Muellenbach RM 
Published: August 2013

Positioning therapy may improve lung recruitment and oxygenation and is part of the standard care in severe acute respiratory distress syndrome (ARDS). Venovenous extracorporeal membrane oxygenation (vvECMO) is a rescue strategy that may ensure sufficient gas exchange in ARDS patients failing conventional therapy. The aim of this case series was to describe the feasibility and pitfalls of combining positioning therapy and vvECMO in patients with severe ARDS. A retrospective cohort of nine patients is described. The patients received 20 (15–86) hours (median, 25th and 75th percentile) of positioning therapy while being treated with vvECMO. The initial PaO2/FiO2 index was 64 (51–67) mmHg and the arterial carbon dioxide tension was 60 (50–71) mmHg. Positioning therapy included 135 degrees prone, prone positioning and continuous lateral rotational therapy. During the first three days, the oxygenation index improved from 47 (41–47) to 12 (11–14) cmH2O/mmHg. The lung compliance improved from 20 (17–28) to 42 (27–43) ml/cmH2O. Complications related to positioning therapy were facial oedema (n=9); complications related to vvECMO were entrance of air (n=1) and pump failure (n=1). However, investigation of root causes revealed no association with the positioning therapy and had no documented effect on the outcome. The reported cases suggest that positioning therapy can be performed safely in ARDS patients treated with vvECMO, providing appropriate precautions are in place and a very experienced team is present.
Beasts of burden or organised cooperation: the story of a mental health team in remote, Indigenous Australia
Authors: Hunter Ernest , Onnis Leigh-Ann , Santhanam-Martin Radhika , Skalicky Judy , Gynther Bruce , Dyer Geraldine 
Published: August 2013

Objective: This paper aims to describe the growth of a regionally-based mental health team providing services to remote Indigenous communities in far north Queensland. Conclusions: By drawing on their experience, the authors are able to identify factors supporting the development and sustained capacity of integrated mental health teams, working in challenging remote settings.
Recruitment to clinical trials: a meta-ethnographic synthesis of studies of reasons for participation
Authors: McCann Sharon , Campbell Marion , Entwistle Vikki 
Published: August 2013

Objectives Randomized controlled trials are important for evaluating health care interventions, but recruitment can be difficult. Studies of potential participants’ perspectives on trial participation are accumulating, but their collective contribution is not obvious. In 2007, we conducted a meta-ethnographic synthesis of people’s reasons for accepting or declining participation. This paper reports a second synthesis, conducted separately on the same topic, using studies published subsequently. It discusses both the substantive findings and the methodological implications for updating meta-ethnographies. Methods Systematic searches identified relevant papers published between 1996 and 2005 (first synthesis), then 2005 and 2010 (second synthesis). We used a meta-ethnographic interpretive process of translation to examine the relationships between study findings. Findings The two syntheses were broadly compatible, but the line of argument developed in the second more clearly highlighted how potential participants’ health states and health care situations at the time of recruitment could interact with other considerations. In particular, they could influence the nature and significance for trial entry decisions of people’s judgements about: their communication and relationship with trial recruiters; the personal implications of trial interventions and processes; and the ‘common good’ (helping others) and what their non/participation might say about their identity. Conclusions Our work highlights the need for trialists to consider potential participants’ health and health care situations when designing recruitment approaches. It also provides the first empirical insights on the process of updating meta-ethnographies that we are currently aware of. Approaches to updating meta-ethnographies need further investigation.
Significance of connective tissue diseases features in pulmonary fibrosis
Authors: Cottin Vincent 
Published: August 2013

Interstitial lung disease (ILD) can occur in any of the connective tissue diseases (CTD) with varying frequency and severity, and an overall long-term prognosis that is less severe than that of idiopathic pulmonary fibrosis (IPF). Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD.Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered “highly specific” of an autoimmune condition), but who do not fit with established international CTD criteria may be called undifferentiated CTD or “lung-dominant CTD”. Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.