bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical presentation, treatment and outcome of focal segmental glomerulosclerosis in Far North Queensland Australian adults
Authors: Greenwood Alice M , Gunnarsson Ronny , Neuen Brendon L , Oliver Kimberley , Green Stella J , Baer Richard A 
Published: May 2016

AbstractAimThe aim is to describe the clinical features, treatment and outcomes in Australian adults with focal segmental glomerulosclerosis and identify predictors of disease progression and all‐cause mortality.MethodsThe study included all patients with biopsy confirmed focal segmental glomerulosclerosis between January 1997 and June 2014 at participating hospitals. Clinical factors, histopathological findings, biochemical markers and treatments were analysed and potential predictors of doubling serum creatinine, end stage kidney disease or death identified.ResultsA total of 98 patients were included with a median follow up of 4.3 years. Thirty‐four (35%) patients were Aboriginal or Torres Strait Islander. Focal segmental glomerulosclerosis not‐otherwise‐specified was the most common variant. Seventeen (59%) patients initially treated with immunosuppression experienced an improvement in renal function. At the end of follow up, 43 (44%) patients had progressed to the composite outcome. Baseline tubulointerstitial scarring and lower haemoglobin predicted shorter time to doubling serum creatinine. Dual diagnosis, higher serum creatinine, lower estimated glomerular filtration rate and doubling creatinine were associated with shorter time to end stage kidney disease with remission the only protective factor. Age was the only variable associated with all‐cause mortality.ConclusionFocal segmental glomerulosclerosis holds serious implications for patients. Concomitant diabetic nephropathy, higher serum creatinine and lower estimated glomerular filtration rate at renal biopsy were associated with poorer renal prognosis. Indigenous people had a female predominance and are over‐represented in relation to their population size, however, were not associated with poorer prognosis. Remission was the only modifiable variable and thus should be at the forefront of patient management goals and future studies.
The application of platelet‐rich plasma in the treatment of deep dermal burns: A randomized, double‐blind, intra‐patient controlled study
Authors: Marck Roos E. , Gardien Kim L. M. , Stekelenburg Carlijn M. , Vehmeijer Marielle , Baas D. , Tuinebreijer Wim E. , Breederveld Roelf S. , Middelkoop Esther 
Published: May 2016

AbstractPlatelet‐rich plasma (PRP) is a fraction of blood with a platelet concentration above baseline. When platelets get activated, growth factors involved in wound healing are released. The application of PRP has shown good results in wound care, however, up to date no substantial research has been performed on the effect of PRP in burn treatment. This randomized double blind intra‐patient controlled study investigates the effect of autologous PRP on wound healing in burns that require surgery with a meshed split skin graft (SSG). Fifty‐two patients with various areas of deep dermal to full thickness burns, receiving surgery with a SSG were included after informed consent. Comparable study areas A and B (intra‐patient) were appointed, randomized and either treated with a SSG and PRP or with a SSG alone. At day 5 to 7 postoperative, the epithelialization and graft take rate were assessed. Three, six, and twelve months postoperative, follow‐up measurements were performed in the form of POSAS‐questionnaires, DermoSpectroMeter, and Cutometer measurements. There was no statistically significant difference between the mean take rate nor the mean epithelialization rate at day 5–7 between the PRP‐treated and control areas. However, PRP‐treated wound areas showed more often better or equal epithelialization and take rates at day 5–7 than the standard treated areas. Minor effects were also seen in the reoperated and early operated subgroups. At 3, 6, and 12 months postoperative, POSAS scores from the patients and the observers, Dermaspectro‐, and Cutometer measurements did not depict a significant difference between the PRP and standard treated areas. Concluding, the addition of PRP in the treatment of burn wounds did not result in improved graft take and epithelialization, nor could we demonstrate better scar quality. There was, however, a considerable variation in our clinical population.
Technical Note: High temporal resolution characterization of gating response time
Authors: Wiersma Rodney D. , McCabe Bradley P. , Belcher Andrew H. , Jensen Patrick J. , Smith Brett , Aydogan Bulent 
Published: May 2016

Purpose:Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions.Methods:A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted.Results:For phase based gating, a real‐time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively.Conclusions:Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly.
Proposal for an Enhanced Physical Education Program in the Primary School: Evaluation of Feasibility and Effectiveness in Improving Physical Skills and Fitness
Authors: Dallolio Laura , Ceciliani Andrea , Sanna Tiziana , Garulli Andrea , Leoni Erica 
Published: May 2016

Background:A large proportion of children do not reach the recommended levels of physical activity for health. A quasiexperimental study with nonrandom assignment was performed to evaluate the effectiveness and feasibility of a school-based physical education intervention aimed at increasing the levels of moderate-to-vigorous physical activity (MVPA).Methods:Ten classes from 4 primary schools, including 241 children aged 8 to 10 years, were recruited. The experimental group (n = 97) received 4 additional sessions/week of 60 minutes of MVPA for 8 months. The control group (n = 135) continued their standard program (2 sessions of 50 minutes/week). Motor abilities (standing long jump, handgrip strength, Harre circuit, sit and reach), physical fitness (Yo-Yo Intermittent Recovery Level-1), anthropometric measures (body mass index, waist to height ratio), and self-efficacy (Perceived Physical Ability Scale for Children) were evaluated at baseline and after the intervention.Results:The experimental group significantly improved in the Harre circuit both in males (P < .001) and females (P < .01), whereas physical fitness test improved only in males (P < .001). Males in the experimental group improved the perception of self-efficacy in coordinative abilities (P = .017).Conclusions:The proposed school-based MVPA program showed effectiveness and feasibility. The differences observed by gender highlight the need to use different strategies to increase the involvement of all the participants.
HIV-1 Vpu Antagonizes CD317/Tetherin by Adaptor Protein-1-Mediated Exclusion from Virus Assembly Sites
Authors: Pujol François M. , Laketa Vibor , Schmidt Florian , Mukenhirn Markus , Müller Barbara , Boulant Steeve , Grimm Dirk , Keppler Oliver T. , Fackler Oliver T. 
Published: May 2016

ABSTRACT
The host cell restriction factor CD317/tetherin traps virions at the surface of producer cells to prevent their release. The HIV-1 accessory protein Vpu antagonizes this restriction. Vpu reduces the cell surface density of the restriction factor and targets it for degradation; however, these activities are dispensable for enhancing particle release. Instead, Vpu has been suggested to antagonize CD317/tetherin by preventing recycling of internalized CD317/tetherin to the cell surface, blocking anterograde transport of newly synthesized CD317/tetherin, and/or displacing the restriction factor from virus assembly sites at the plasma membrane. At the molecular level, antagonism relies on the physical interaction of Vpu with CD317/tetherin. Recent findings suggested that phosphorylation of a diserine motif enables Vpu to bind to adaptor protein 1 (AP-1) trafficking complexes via two independent interaction motifs and to couple CD317/tetherin to the endocytic machinery. Here, we used a panel of Vpu proteins with specific mutations in individual interaction motifs to define which interactions are required for antagonism of CD317/tetherin. Impairing recycling or anterograde transport of CD317/tetherin to the plasma membrane was insufficient for antagonism. In contrast, excluding CD317/tetherin from HIV-1 assembly sites depended on Vpu motifs for interaction with AP-1 and CD317/tetherin and correlated with antagonism of the particle release restriction. Consistently, interference with AP-1 function or its expression blocked these Vpu activities. Our results define displacement from HIV-1 assembly sites as active principle of CD317/tetherin antagonism by Vpu and support a role of tripartite complexes between Vpu, AP-1, and CD317/tetherin in this process.

IMPORTANCE
CD317/tetherin poses an intrinsic barrier to human immunodeficiency virus type 1 (HIV-1) replication in human cells by trapping virus particles at the surface of producer cells and thereby preventing their release. The viral protein Vpu antagonizes this restriction, and molecular interactions with the restriction factor and adaptor protein complex 1 (AP-1) were suggested to mediate this activity. Vpu modulates intracellular trafficking of CD317/tetherin and excludes the restriction factor from HIV-1 assembly sites at the plasma membrane, but the relative contribution of these effects to antagonism remain elusive. Using a panel of Vpu mutants, as well as interference with AP-1 function and expression, we show here that Vpu antagonizes CD317/tetherin by blocking its recruitment to viral assembly sites in an AP-1-dependent manner. These results refine our understanding of the molecular mechanisms of CD317/tetherin antagonism and suggest complexes of Vpu with the restriction factor and AP-1 as targets for potential therapeutic intervention.
Both CD8+and CD4+T Cells Contribute to Corneal Clouding and Viral Clearance following Vaccinia Virus Infection in C57BL/6 Mice
Authors: Larsen I. V. , Clausius H. , Kolb A. W. , Brandt C. R. 
Published: May 2016

ABSTRACTVaccinia virus (VACV) keratitis is a serious complication following smallpox vaccination and can lead to blindness. The pathological mechanisms involved in ocular VACV infection are poorly understood. Previous studies have used rabbits, but the lack of immune reagents and transgenic or knockout animals makes them less suitable for mechanistic studies. We report that infection of C57BL/6 mice with 1 × 107PFU of vaccinia virus strain WR results in blepharitis, corneal neovascularization, and stromal keratitis. The DryVax strain of VACV was completely attenuated. Infection required corneal scarification and replication-competent virus, and the severity of ocular disease was similar in 4- to 6-week-old and 1-year-old mice. Viral titers peaked at approximately 1 × 106PFU on day 5 postinfection, and virus had not cleared by day 13 postinfection. Neutrophils were found in the peripheral cornea on day 1 after infection and then declined, followed by infiltration of both CD4+and CD8+T cells, which remained peripheral throughout the infection. Blood vessel growth extended 2 to 5 mm into the cornea from the limbus. Infection of CD4−/−, CD8−/−, or antibody-depleted mice resulted in similar disease severity and corneal clouding, indicating that both T-cell subsets were involved in the immunopathological response. Depletion of both CD4+and CD8+T cells resulted in significantly more severe disease and failure to clear the virus. On the basis of our results, the pathology of VACV keratitis is significantly different from that of herpes simplex virus keratitis. Further studies are likely to reveal novel information regarding virulence and immune responses to viral ocular infection.IMPORTANCEPotentially blinding eye infections can occur after vaccination for smallpox. Very little is known about the pathological mechanisms that are involved, and the information that is available was generated using rabbit models. The lack of immunological reagents for rabbits makes such studies difficult. We characterized a mouse model of vaccinia virus ocular disease using C57BL/6 mice and strain WR and show that both CD4+and CD8+T-cell subsets play a role in the blinding eye disease and in controlling virus replication. On the basis of these results, vaccinia virus keratitis is significantly different from herpes simplex virus keratitis, and further studies using this model should generate novel insights into immunopathological responses to viral ocular infection.
HIV-1 Gag, Envelope, and Extracellular Determinants Cooperate To Regulate the Stability and Turnover of Virological Synapses
Authors: Gardiner Jaye C. , Mauer Eric J. , Sherer Nathan M. 
Published: May 2016

ABSTRACT
Retroviruses spread more efficiently when infected and uninfected cells form tight, physical interfaces known as virological synapses (VSs). VS formation is initiated by adhesive interactions between viral Envelope (Env) glycoproteins on the infected cell and CD4 receptor molecules on the uninfected cell. How high-avidity Env-CD4 linkages are resolved over time is unknown. We describe here a tractable two-color, long-term (>24 h) live cell imaging strategy to study VS turnover in the context of a large cell population, quantitatively. We show that Env's conserved cytoplasmic tail (CT) can potently signal the recruitment of Gag capsid proteins to the VS, a process also dependent on residues within Gag's N-terminal matrix (MA) domain. Additionally, we demonstrate that Env's CT and Gag's MA domain both regulate the duration of interactions between viral donor and target cells, as well as the stability of this interaction over time (i.e., its capacity to resolve or form a syncytium). Finally, we report the unexpected finding that modulating extracellular fluid viscosity markedly impacts target T cell trafficking and thus affects the duration, stability, and turnover of virus-induced cell-cell contacts. Combined, these results suggest a stepwise model for viral cell-to-cell transmission wherein (i) Env-receptor interactions anchor target cells to infected cells, (ii) Env signals Gag's recruitment to the cell-cell contact dependent on an intact Env CT and Gag MA, and (iii) Env CT and Gag MA, in conjunction with extracellular forces, combine to regulate VS stability and infectious outcomes.

IMPORTANCE
HIV-1 spreads efficiently at physical, cell-cell interfaces known as virological synapses (VSs). The VS provides for spatiotemporal coupling of virus assembly and entry into new host cells and may transmit signals relevant to pathogenesis. Disrupting this mode of transmission may be critical to the goal of abolishing viral persistence in infected individuals. We describe here a long-term live cell imaging strategy for studying virus-induced effects on cell behavior in the context of a large cell population. We demonstrate cooperative roles for viral Gag capsid proteins and Envelope glycoproteins in regulating VS formation and turnover. We also show that modulating fluid viscosity markedly affects T cell trafficking and VS stability. Thus, extracellular factors also play an important role in modulating the nature of infectious cell-cell interactions. In sum, our study provides new tools and insights relevant to exposing vulnerabilities in how HIV-1 and other viruses spread infection among cells, tissues, and people.
Identification and Characterization of a Ribose 2′-
O
-Methyltransferase Encoded by the Ronivirus Branch of Nidovirales
Authors: Zeng Cong , Wu Andong , Wang Yi , Xu Shan , Tang Yingke , Jin Xu , Wang Shilei , Qin Lei , Sun Ying , Fan Chengpeng , Snijder Eric J. , Neuman Benjamin W. , Chen Yu , Ahola Tero , Guo Deyin 
Published: May 2016

ABSTRACT

The order
Nidovirales
currently comprises four virus families:
Arteriviridae
,
Coronaviridae
(divided into the subfamilies
Coronavirinae
and
Torovirinae
),
Roniviridae
, and the recently recognized
Mesoniviridae
. RNA cap formation and methylation have been best studied for coronaviruses, with emphasis on the identification and characterization of two virus-encoded methyltransferases (MTases) involved in RNA capping, a guanine-N7-MTase and a ribose-2′-
O
-MTase. Although bioinformatics analyses suggest that these MTases may also be encoded by other nidoviruses with large genomes, such as toroviruses and roniviruses, no experimental evidence has been reported thus far. In this study, we show that a ronivirus, gill-associated virus (GAV), encodes the 2′-
O
-MTase activity, although we could not detect 2′-
O
-MTase activity for the homologous protein of a torovirus, equine torovirus, which is more closely related to coronaviruses. Like the coronavirus 2′-
O
-MTase, the roniviral 2′-
O
-MTase harbors a catalytic K-D-K-E tetrad that is conserved among 2′-
O
-MTases and can target only the N7-methylated cap structure of adenylate-primed RNA substrates. However, in contrast with the coronavirus protein, roniviral 2′-
O
-MTase does not require a protein cofactor for stimulation of its activity and differs in its preference for several biochemical parameters, such as reaction temperature and pH. Furthermore, the ronivirus 2′-
O
-MTase can be targeted by MTase inhibitors. These results extend our current understanding of nidovirus RNA cap formation and methylation beyond the coronavirus family.

IMPORTANCE
Methylation of the 5′-cap structure of viral RNAs plays important roles in genome replication and evasion of innate recognition of viral RNAs by cellular sensors. It is known that coronavirus nsp14 acts as an N7-(guanine)-methyltransferase (MTase) and nsp16 as a 2′-
O
-MTase, which are involved in the modification of RNA cap structure. However, these enzymatic activities have not been shown for any other nidoviruses beyond coronaviruses in the order
Nidovirales
. In this study, we identified a 2′-
O
-methyltransferase encoded by ronivirus that shows common and unique features in comparison with that of coronaviruses. Ronivirus 2′-
O
-MTase does not need a protein cofactor for MTase activity, whereas coronavirus nsp16 needs the stimulating factor nsp10 for its full activity. The conserved K-D-K-E catalytic tetrad is identified in ronivirus 2′-
O
-MTase. These results extend our understanding of nidovirus RNA capping and methylation beyond coronaviruses and also strengthen the evolutionary and functional links between roniviruses and coronaviruses.
Impact of integrated health system changes, accelerated due to an earthquake, on emergency department attendances and acute admissions: a Bayesian change-point analysis
Authors: Schluter Philip J , Hamilton Greg J , Deely Joanne M , Ardagh Michael W 
Published: May 2016

ObjectiveTo chart emergency department (ED) attendance and acute admission following a devastating earthquake in 2011 which lead to Canterbury's rapidly accelerated integrated health system transformations.DesignInterrupted time series analysis, modelling using Bayesian change-point methods, of ED attendance and acute admission rates over the 2008–2014 period.SettingED department within the Canterbury District Health Board; with comparison to two other district health boards unaffected by the earthquake within New Zealand.ParticipantsCanterbury's health system services ∼500 000 people, with around 85 000 ED attendances and 37 000 acute admissions per annum.Main outcome measuresDe-seasoned standardised population ED attendance and acute admission rates overall, and stratified by age and sex, compared before and after the earthquake.ResultsAnalyses revealed five global patterns: (1) postearthquake, there was a sudden and persisting decrease in the proportion of the population attending the ED; (2) the growth rate of ED attendances per head of population did not change between the pre-earthquake and postearthquake periods; (3) postearthquake, there was a sudden and persisting decrease in the proportion of the population admitted to hospital; (4) the growth rate of hospital admissions per head of the population declined between pre-earthquake and postearthquake periods and (5) the most dramatic reduction in hospital admissions growth after the earthquake occurred among those aged 65+ years. Extrapolating from the projected and fitted deseasoned rates for December 2014, ∼676 (16.8%) of 4035 projected hospital admissions were avoided.ConclusionsWhile both necessarily and opportunistically accelerated, Canterbury's integrated health systems transformations have resulted in a dramatic and sustained reduction in ED attendances and acute hospital admissions. This natural intervention experiment, triggered by an earthquake, demonstrated that integrated health systems with high quality out-of-hospital care models are likely to successfully curb growth in acute hospital demand, nationally and internationally.
Value of SATB2 immunostaining in the distinction between small intestinal and colorectal adenocarcinomas
Authors: Kim Christopher J , Baruch-Oren Tamar , Lin Fan , Fan Xuemo (Sean) , Yang Ximing J , Wang Hanlin L 
Published: May 2016

AimsSpecial AT-rich sequence-binding protein 2 (SATB2) is a novel immunomarker that is expressed in glandular cells of the lower gastrointestinal tract with retained expression in the majority of primary and metastatic colorectal adenocarcinomas (CRCs). Because of its tissue specificity, SATB2 has been shown to be a clinically useful marker to distinguish CRC from non-CRC. In this study, we investigated whether or not SATB2 can help differentiate CRC from small intestinal adenocarcinoma (SIA), a practical diagnostic challenge due to their morphological and immunophenotypic similarities.MethodsFifty surgically resected primary SIAs and 50 CRCs were immunohistochemically examined for the expression of SATB2. Positive staining was graded as 1+ (5–25% of the tumour cells stained), 2+ (26–50%), 3+ (51–75%) or 4+ (>75%), as well as weak, intermediate or strong for staining intensity.ResultsPositive SATB2 immunoreactivity was observed in 23 (46%) SIAs in contrast to 48 (96%) CRCs (p<0.0001). Among these, only 4 (8%) SIAs showed strong and diffuse (4+) SATB2 staining compared with 38 (76%) of CRCs (p<0.0001).ConclusionsSATB2 is not entirely CRC-specific and is expressed in a subset of SIAs. Unlike CRC, however, SIA infrequently shows a strong and diffuse staining pattern, which still makes SATB2 a useful immunomarker to distinguish SIA from CRC.