bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kaposi Sarcoma Herpesvirus Induces HO-1 during
De Novo
Infection of Endothelial Cells via Viral miRNA-Dependent and -Independent Mechanisms
Authors: Botto Sara , Totonchy Jennifer E. , Gustin Jean K. , Moses Ashlee V. 
Published: June 2015

ABSTRACT

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of
heme oxygenase-1
(HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, anti-inflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC
in vitro
proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated the molecular mechanisms underlying KSHV induction of HO-1 in lymphatic EC (LEC), which are the likely spindle cell precursors. In a time course analysis of KSHV-infected cells, HO-1 expression displays biphasic kinetics characterized by an early transient induction that is followed by a more sustained upregulation coincident with the establishment of viral latency. A viral microRNA miR-K12-11 deletion mutant of KSHV was found to be defective for induction of HO-1 during latency. A potential mechanism for this phenotype was provided by BACH1, a cellular
HO-1
transcriptional repressor targeted by miR-K12-11. In fact, in KSHV-infected LEC, the
BACH1
message level is reduced, BACH1 subcellular localization is altered, and miR-K12-11 mediates the inverse regulation of
HO-1
and
BACH1
during viral latency. Interestingly, the data indicate that neither miR-K12-11 nor
de novo
KSHV gene expression is required for the burst of HO-1 expression observed at early times postinfection, which suggests that additional virion components promote this phenotype.

IMPORTANCE
While the mechanisms underlying KSHV induction of HO-1 remain unknown, the cellular mechanisms that regulate HO-1 expression have been extensively investigated in the context of basal and pathophysiological states. The detoxifying action of HO-1 is critical for the protection of cells exposed to high heme levels. KS spindle cells are erythrophagocytic and contain erythrocyte ghosts. Erythrocyte degeneration leads to the localized release of heme, creating oxidative stress that may be further exacerbated by environmental or other cofactors. Our previous work showed that KSHV-infected cells proliferate in response to heme and that this occurs in a HO-1-dependent manner. We therefore hypothesize that KSHV induction of HO-1 contributes to KS tumor development via heme metabolism and propose that HO-1 be evaluated as a therapeutic target for KS. Our present work, which aimed to understand the mechanisms whereby KSHV induces HO-1, will be important for the design and implementation of such a strategy.
Discrimination Accuracy between Real and Sham Press Needles in the Hands
Authors: Kim Sungha , Lee Sanghun , Choi Sunmi , Park Jeonghwan , Kim Sungchul 
Published: June 2015

Objectives To evaluate the blinding effectiveness of a modified blunt sham press needle on the basis of the ability of subjects to discriminate between real and sham acupuncture needles compared with their discrimination ability based on pure guessing, and to define differences between senses (touch and vision) in the rates of correctly identified needles. Methods Sixty-three healthy students and staff members were recruited through convenience sampling. First, real or sham acupuncture was randomly administered to the left LI4 point while subjects could not observe the needle tip. A real or sham needle tip was then shown to the subjects. Finally, a random combination of real or sham acupuncture needles were randomly administered to the left and right LI4 points, this time with the subjects observing the procedure. In all conditions the subjects gave their judgement as Yes or No in response to questions asking them to identify the needle type. The proportion of correct judgements (P(C)) was computed for the last part of the trial in left and right LI4 points, and the rates of correctly identified needles for each trial were obtained. Results The subjects’ accuracy of discrimination between the real and sham acupuncture needles in left and right LI4 points was not significantly different from that based on pure guess (P(C)=0.50 (chance level)), which indicates complete inability to discriminate between needles. The rates of correctly identified needles using touch, vision and a combination of both senses were not significantly different (p=0.807). Conclusions The findings from this study show that this sham acupuncture device successfully blinded subjects to real and sham press needles, suggesting that it is effective for subject blinding in studies on acupuncture using press needles, and facilitating evaluation of the effects of acupuncture in placebo-controlled trials using a rigorous scientific research methodology.
Pattern of symptoms and signs of primary intracranial tumours in children and young adults: a record linkage study
Authors: Chu Thomas P C , Shah Anjali , Walker David , Coleman Michel P 
Published: June 2015

ObjectiveTo describe the age pattern and temporal evolution of symptoms and signs of intracranial tumours in children and young adults before diagnosis.Design and settingA record linkage study using population-based data from the National Cancer Registry, linked to Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES).Patient cohortPatients aged 0–24 years when diagnosed with a primary intracranial tumour between 1989 and 2006 in England.MethodsLinked records of relevant symptoms and signs in primary care and hospitals were extracted from CPRD (1989–2006, 181 patients) and HES (1997–2006, 3959 patients). Temporal and age-specific changes in presentation rates before diagnosis of an intracranial tumour, for each of eight symptom groups, were estimated in generalised additive models.ResultsAll symptoms presented with increasing frequency until eventual diagnosis. The frequency of presentation of raised intracranial pressure (ICP) to hospitals rose rapidly to 36.4 per 100 person-months (95% CI 34.6 to 38.4) in the final month before diagnosis in the entire cohort. Clinical features in primary care were less specific: the main features were visual disturbance (rate: 0.49 per 100 person-months; 95% CI 0.33 to 0.72) in newborns to 4-year-olds, headache in 5-year-olds to 11-year-olds (0.64; 0.47 to 0.88), 12-year-olds to 18-year-olds (1.59; 1.21 to 2.08) and 19-year-olds to 24-year-olds (2.44; 1.71 to 3.49). The predominant features at hospital admission were those of raised ICP: between 1.17 per 100 person-months (95% CI 1.08 to 1.26) in newborns to 4-year-olds and 0.77 (0.67 to 0.88) in 19-year-olds to 24-year-olds.ConclusionsNon-localising symptoms and signs were more than twice as common as focal neurological signs. An intracranial tumour should be considered in patients with relevant symptoms that do not resolve or that progress rapidly.
A pre–postintervention study to evaluate the impact of dose calculators on the accuracy of gentamicin and vancomycin initial doses
Authors: Hamad Anas , Cavell Gillian , Hinton James , Wade Paul , Whittlesea Cate 
Published: June 2015

ObjectivesGentamicin and vancomycin are narrow-therapeutic-index antibiotics with potential for high toxicity requiring dose individualisation and continuous monitoring. Clinical decision support (CDS) tools have been effective in reducing gentamicin and vancomycin dosing errors. Online dose calculators for these drugs were implemented in a London National Health Service hospital. This study aimed to evaluate the impact of these calculators on the accuracy of gentamicin and vancomycin initial doses.MethodsThe study used a pre–postintervention design. Data were collected using electronic patient records and paper notes. Random samples of gentamicin and vancomycin initial doses administered during the 8 months before implementation of the calculators were assessed retrospectively against hospital guidelines. Following implementation of the calculators, doses were assessed prospectively. Any gentamicin dose not within ±10% and any vancomycin dose not within ±20% of the guideline-recommended dose were considered incorrect.ResultsThe intranet calculator pages were visited 721 times (gentamicin=333; vancomycin=388) during the 2-month period following the calculators’ implementation. Gentamicin dose errors fell from 61.5% (120/195) to 44.2% (95/215), p<0.001. Incorrect vancomycin loading doses fell from 58.1% (90/155) to 32.4% (46/142), p<0.001. Incorrect vancomycin first maintenance doses fell from 55.5% (86/155) to 33.1% (47/142), p<0.001. Loading and first maintenance vancomycin doses were both incorrect in 37.4% (58/155) of patients before and 13.4% (19/142) after calculator implementation, p<0.001.ConclusionsThis study suggests that gentamicin and vancomycin dose calculators significantly improved the prescribing of initial doses of these agents. Therefore, healthcare organisations should consider using such CDS tools to support the prescribing of these high-risk drugs.
Pivotal clinical trials of novel ophthalmic drugs and medical devices: retrospective observational study, 2002–2012
Authors: Hwang Jenny , Hwang Thomas J , Ciolino Joseph B 
Published: June 2015

ObjectivesNovel therapeutics are an important part of ophthalmologists’ armamentarium, and the risks and benefits of these therapies must be carefully evaluated. We sought to quantify the characteristics of the pivotal clinical trials supporting the regulatory approval of new ophthalmic drugs and medical devices.DesignRetrospective observational study.Setting and data sourceMedical review dossiers for new ophthalmic drug and high-risk device approvals released publicly by the US Food and Drug Administration (FDA).Main outcome measuresProportion of pivotal trials with randomisation, masking, active or placebo controls and subgroup analyses; total and median number of trial enrollees; and the number of drugs and devices approved with required postapproval studies.ResultsFrom 2002 to 2012, the FDA approved 11 ophthalmic drugs and 25 devices. The pivotal trials underlying the approvals of ophthalmic drugs in our study cohort enrolled a median of 809 patients. Virtually all drug trials were randomised and masked (91%), of which 7 (70%) used a placebo control. Pivotal trials for ophthalmic devices enrolled 324 patients on average, and significantly fewer trials for ophthalmic devices versus drugs were randomised (16% vs 91%; p<0.001) or masked (12% vs 91%; p<0.001). 8 (32%) ophthalmic devices and 6 (55%) ophthalmic drugs were approved with required postapproval studies.ConclusionsOphthalmic therapeutics were approved based on varying levels of evidence. Postapproval studies could be used to confirm or refute early indications of safety and effectiveness of these therapeutics, with the study results accessible to patients and clinicians who need to make informed treatment decisions.
Arterial hypoxaemia and its impact on coagulation: significance of altered redox homeostasis
Authors: Fall Lewis , New Karl J , Evans Kevin A , Bailey Damian M 
Published: June 2015

AimsArterial hypoxaemia stimulates free radical formation. Cellular studies suggest this may be implicated in coagulation activation though human evidence is lacking. To examine this, an observational study was designed to explore relationships between systemic oxidative stress and haemostatic responses in healthy participants exposed to inspiratory hypoxia.ResultsActivated partial thromboplastin time and international normalised ratio were measured as routine clinical biomarkers of coagulation and ascorbate free radical (A•−) as a direct global biomarker of free radical flux. Six hours of hypoxia activated coagulation, and increased formation of A•−, with inverse correlations observed against oxyhaemoglobin saturation.ConclusionsThis is the first study to address the link between free radical formation and coagulation in vivo. This ‘proof-of-concept’ study demonstrated functional associations between hypoxaemia and coagulation that may be subject to redox activation of the intrinsic pathway. Further studies are required to identify precisely which intrinsic factors are subject to redox activation.
Palaeomagnetism, geochronology and geochemistry of the Palaeoproterozoic Rabbit Creek and Powder River dyke swarms: implications for Wyoming in supercraton Superia
Authors: Kilian Taylor M. , Bleeker Wouter , Chamberlain Kevin , Evans David A. D. , Cousens Brian 
Published: June 2015

Abstract

It is likely that Archaean cratons of Laurentia had different palaeogeographic histories prior to their amalgamation. New palaeomagnetic, geochronological and geochemical evidence supports a reconstruction of the Wyoming craton adjacent to the southern margin of the Superior craton at 2.16 Ga, before rifting (
c.
2.1–2.0 Ga) and eventual reamalgamation after the Hudsonian Orogeny (
c.
1.8 Ga). U–Pb ages (TIMS on baddeleyite) from five dykes yield two groups of ages at
c.
2164 and 2155 Ma. The younger group of ages defines the Rabbit Creek swarm at 2161–2152 Ma and precisely dates its palaeomagnetic pole. Two large and differentiated dykes (>100 m) in the Bighorn and Wind River uplifts are geographically related to the Rabbit Creek swarm but have slightly different orientations and yield slightly older ages at 2171–2157 Ma. These dykes may be parts of a single intrusion (the ‘Great Dyke of Wyoming’) that spans over 200 km between uplifts, possibly representing a different magmatic event. This older event does not have enough distinct intrusions to provide a correctly averaged palaeomagnetic pole, but correlates with magmatism in the Superior craton and has a palaeomagnetic remanence comparable to the Rabbit Creek dykes. With minor tilt corrections, the palaeomagnetic data from the Rabbit Creek swarm and Powder River–South Pass dykes support a reconstruction of the southeastern Wyoming craton against the southern Superior craton. This fit juxtaposes the Palaeoproterozoic Huronian and Snowy Pass Supergroups along two passive margins that experienced a prolonged period of mafic magmatism (>100 myr) and rift basin development. Although there are slight geochemical variations across the Rabbit Creek swarm, all dykes fit into two distinct groups that are independently dated and internally consistent.

Supplementary material:

Supporting figures and locality tables are available at
www.geolsoc.org.uk/SUP18824
Clinical Outcomes According to Diabetic Status in Patients Treated With Biodegradable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents
Authors: Franzone Anna , Pilgrim Thomas , Heg Dik , Roffi Marco , Tüller David , Vuilliomenet André , Muller Olivier , Cook Stéphane , Weilenmann Daniel , Kaiser Christoph , Jamshidi Peiman , Räber Lorenz , Stortecky Stefan , Wenaweser Peter , Jüni Peter , Windecker Stephan 
Published: June 2015

Background—
Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus.

Methods and Results—

BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27–2.56;
P
=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67–2.10;
P
=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58–1.33;
P
=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49–3.41;
P
=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39–1.25;
P
=0.23, in nondiabetics).

Conclusions—
In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01443104.
Suppression of the soybean cyst nematode, Heterodera glycines, using water extract of bean sprout residue
Authors: Ito Daisuke , Toyota Koki , Sedrati Ghalia Missous 
Published: June 2015

The soybean cyst nematode (SCN),Heterodera glycines, is a widespread pest in most soybean-producing areas, causing serious damage to soybean crops and resulting in economic losses. We have previously reported that bean sprout residue might function as an environmentally-friendly control agent against SCN. In order to understand the role of water extracted from bean sprout residue as a possible factor in lowering the number of SCN, either water extract of bean sprout residue (WE) or water (W) was applied to pots containing soil infested with SCN, and komatsuna plants, a leafy vegetable, were grown in these pots. After 2 months, the number of SCN, estimated with real-time PCR, was 80% lower in WE than in W and the biomass of komatsuna plants was 100% higher in WE than in W, suggesting that WE has not only an SCN eradication effect but also a fertilisation effect. In field experiments, WE or W was applied ten times during the experimental period from July 2010 to June 2011. The number of SCN decreased by 82% in WE and by 36% in W; however, the marked decrease was observed only between July and September and between April and June. Green soybean plants were grown in the field where WE or W had been applied and the yield was markedly higher in WE (750 g m−2) than in W (200 g m−2). The hatching stimulation of SCN eggs by WE was tested at four different temperatures (10, 20, 25, 30°C) and was observed only at 25°C. These results show that water extract of bean sprout residue decreases the density of SCN and thereby damage to green soybeans, and that the suppressive effect depends on soil temperature.
Thunderstorms Do Not Get Butterflies
Authors: Durran Dale R. , Weyn Jonathan A. 
Published: June 2015

Abstract
One important limitation on the accuracy of weather forecasts is imposed by unavoidable errors in the specification of the atmosphere’s initial state. Much theoretical concern has been focused on the limits to predictability imposed by small-scale errors, potentially even those on the scale of a butterfly. Very modest errors at much larger scales may nevertheless pose a more important practical limitation. We demonstrate the importance of large-scale uncertainty by analyzing ensembles of idealized squall-line simulations. Our results imply that minimizing initial errors on scales around 100 km is more likely to extend the accuracy of forecasts at lead times longer than 3–4 h than efforts to minimize initial errors on much smaller scales. These simulations also demonstrate that squall lines, triggered in a horizontally homogeneous environment with no initial background circulations, can generate a background mesoscale kinetic energy spectrum roughly similar to that observed in the atmosphere.
Symptom Assessment for a Palliative Care Approach in People With Dementia Admitted to Acute Hospitals
Authors: O’Shea Emma , Timmons Suzanne , Kennelly Sean , Siún Anna de , Gallagher Paul , O’Neill Desmond 
Published: June 2015

Context: As the prevalence of dementia increases, more people will need dementia palliative and end-of-life (EOL) care in acute hospitals. Published literature suggests that good quality care is not always provided. Objective: To evaluate the prescription of antipsychotics and performance of multidisciplinary assessments relevant to palliative care for people with dementia, including those at EOL, during hospital admission. Method: As part of a national audit of dementia care, 660 case notes were reviewed across 35 acute hospitals. Results: In the entire cohort, many assessments essential to dementia palliative care were not performed. Of the total sample, 76 patients died, were documented to be receiving EOL care, and/or were referred for specialist palliative care. In this cohort, even less symptom assessment was performed (eg, no pain assessment in 27%, no delirium screening in 68%, and no mood or behavioral and psychological symptoms of dementia in 93%). In all, 37% had antipsychotic drugs during their admission and 71% of these received a new prescription in hospital, most commonly for “agitation.” Conclusion: This study suggests a picture of poor symptom assessment and possible inappropriate prescription of antipsychotic medication, including at EOL, hindering the planning and delivery of effective dementia palliative care in acute hospitals.
Assessment of mental health literacy in patients with breast cancer
Authors: Cheung Yin Ting , Ong Ying Ying , Ng Terence , Tan Yee Pin , Fan Gilbert , Chan Choi Wan , Molassiotis Alex , Chan Alexandre 
Published: June 2015

Introduction Psychosocial distress is often underdiagnosed and undertreated among breast cancer patients due to the poor recognition of the associated symptoms and inadequate knowledge of the treatments available. Objective To evaluate the mental health literacy of breast cancer patients by assessing (1) their ability to recognize the symptoms of anxiety, fatigue, depression, and cognitive disturbances, and (2) their knowledge of help-seeking options and professional treatments. Methods In this multi-center, cross-sectional study, early-stage breast cancer patients receiving chemotherapy underwent four assessments to measure their levels of anxiety, depression, fatigue, and cognitive disturbances. With the aid of cancer-specific vignettes, a questionnaire was administered to evaluate their mental health literacy. Results Fifty-four patients were recruited (77.7% Chinese, aged 52.7 ± 8.5 years). Clinically significant anxiety (15.1%), fatigue (27.8%), and cognitive disturbances (25.9%) were more prevalent than depression (5.6%). Although the majority of the patients could recognize the symptoms of fatigue accurately (75.9%), less than half could identify those of anxiety (35.2%), depression (48.1%), and cognitive disturbances (48.1%). Patients were more receptive to help from their family members (score: 3.39 out of 4.00) and oncologists (score: 3.13) than from other mental health specialists, such as psychiatrists (score: 2.26) and psychologists (score: 2.19) in the management of their psychosocial distress. Approximately half of the patients indicated that embarrassment and fear were their main barriers to seeking professional treatment (55.6%). Conclusions Our results suggest that the mental health literacy of breast cancer patients was inadequate. Intervention and management strategies could be implemented to teach these patients about evidence-based treatments and professional help that are specific to mental disorders.