bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVerT2—needling versus non-surgical debridement for the treatment of verrucae: study protocol for a single-centre randomised controlled trial
Authors: Hashmi Farina , Torgerson David , Fairhurst Caroline , Cockayne Sarah , Bell Kerry , Cullen Michelle , Harrison-Blount Michael 
Published: November 2015

IntroductionVerrucae are extremely common, and are experienced by most people at some time during their lives. Although most verrucae will spontaneously disappear without treatment, many patients seek treatment, often because they have persisted for many years, are unsightly or painful or prevent them from doing sports or other activities. There are many different treatments available; including the Falknor's needling procedure. To date, there has only been one small trial evaluating the clinical effectiveness of this treatment and no health economic analysis has been undertaken. The Effective Verruca Treatments (EVerT2) trial aims to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of verrucae.Methods and analysisThis single-centre randomised controlled trial will recruit 58 participants (aged 18 years and over with a plantar verruca) from Salford Podiatry Clinic patient lists and the surrounding area. If the participant presents with multiple verrucae, an ‘index’ verruca (largest and thickest lesion) will be identified and patients will be randomised 1:1 to the intervention group to receive the needling treatment or the control group to have the callus overlying the verruca debrided. The primary outcome is complete clearance of the index verruca at 12 weeks after randomisation. Secondary outcomes include clearance and recurrence of the treated verruca, clearance of all verrucae, number of verrucae remaining, change in size of the index verruca, pain, and participant satisfaction. A cost-effectiveness analysis of the needling versus callus debridement will be carried out from the perspective of health services over a time horizon of 12 weeks.Ethics and disseminationEthical approval has been obtained from the University of Salford, Department of Health Sciences Ethical Approval Committee (HSCR15/24) and the University of York, Department of Health Sciences Research Governance Committee (HSRGC/2014/98/B). Findings will be disseminated through publication and conference presentations.Trial registration numberISRCTN16429440.
An ecological analysis of PM2.5concentrations and lung cancer mortality rates in China
Authors: Fu Jingying , Jiang Dong , Lin Gang , Liu Kun , Wang Qiao 
Published: November 2015

ObjectiveTo explore the association between Particulate Matter (PM)2.5(particles with an aerodynamic diameter less than 2.5 µm) and lung cancer mortality rates and to estimate the potential risk of lung cancer mortality related to exposure to high PM2.5concentrations.DesignGeographically weighted regression was performed to evaluate the relation between PM2.5concentrations and lung cancer mortality for males, females and for both sexes combined, in 2008, based on newly available long-term data. Lung cancer fatalities from long-term exposure to PM2.5were calculated according to studies by Pope IIIet aland the WHO air quality guidelines (AQGs).Setting31 provinces in China.ResultsPM2.5was associated with the lung cancer mortality of males, females and both sexes combined, in China, although there were exceptions in several regions, for males and females. The number of lung cancer fatalities calculated by the WHO AQGs ranged from 531 036 to 532 004, whereas the number calculated by the American Cancer Society (ACS) reached 614 860 after long-term (approximately 3–4 years) exposure to PM2.5concentrations since 2008.ConclusionsThere is a positive correlation between PM2.5and lung cancer mortality rate, and the relationship between them varies across the entire country of China. The number of lung cancer fatalities estimated by ACS was closer to the actual data than those of the WHO AQGs. Therefore, the ACS estimate of increased risk of lung cancer mortality from long-term exposure to PM2.5might be more applicable for evaluating lung cancer fatalities in China than the WHO estimate.
Risk and protective factors for falls on one level in young children: multicentre case–control study
Authors: Benford P , Young B , Coupland C , Watson M , Hindmarch P , Hayes M , Goodenough T , Majsak-Newman G , Kendrick D 
Published: November 2015

BackgroundChildhood falls are an important global public health problem, but there is lack of evidence about their prevention. Falls on one level result in considerable morbidity and they are costly to health services.ObjectiveTo estimate ORs for falls on one level in children aged 0–4 years for a range of safety behaviours, safety equipment use and home hazards.Design, setting and participantsMulticentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Participants included 582 children less than 5 years of age with a medically attended fall injury occurring at home and 2460 controls matched on age, sex, calendar time and study centre.Main outcome measureFall on one level.ResultsCases’ most common injuries were bangs on the head (52%), cuts or grazes not needing stitches (29%) or cuts or grazes needing stitches (17%). Comparing cases to community controls in the adjusted analyses, significant findings were observed for only two exposures. Injured children were significantly less likely to live in a household without furniture corner covers (adjusted OR (AOR) 0.72, 95% CI 0.55 to 0.95), or without rugs and carpets firmly fixed to the floor (AOR 0.76, 95% CI 0.59 to 0.98).ConclusionsWe did not find any safety practices, use of safety equipment or home hazards associated with a reduced risk of fall on one level. Our findings do not provide evidence to support changes to current injury prevention practice.
Headway Duo microcatheter for cerebral arteriovenous malformation embolization with n-BCA
Authors: Heit Jeremy J , Faisal Abigail G S , Telischak Nicholas A , Choudhri Omar , Do Huy M 
Published: November 2015

BackgroundCerebral arteriovenous malformations (AVMs) are uncommon vascular lesions, and hemorrhage secondary to AVM rupture results in significant morbidity and mortality. AVMs may be treated by endovascular embolization, and technical advances in microcatheter design are likely to improve the success and safety of endovascular embolization of cerebral AVMs.ObjectiveTo describe our early experience with the Headway Duo microcatheter for embolization of cerebral AVMs with n-butyl-cyanoacrylate (n-BCA).MethodsConsecutive patients treated by endovascular embolization of a cerebral AVM with n-BCA delivered intra-arterially through the Headway Duo microcatheter (167 cm length) were identified. Patient demographic information, procedural details, and patient outcome were determined from electronic medical records.ResultsTen consecutive patients undergoing cerebral AVM embolization using n-BCA injected through the Headway Duo microcatheter were identified. Presenting symptoms included headache, hemorrhage, seizures, and weakness. Spetzler Martin grades ranged from 1 to 5, and AVMs were located in the basal ganglia (2 patients), parietal lobe (4 patients), frontal lobe (1 patient), temporal lobe (1 patient), an entire hemisphere (1 patient), and posterior fossa (1 patient). 50 arterial pedicles were embolized, and all procedures were technically successful. There was one post-procedural hemorrhage that was well tolerated by the patient, and no other complications occurred. Additional AVM treatment was performed by surgery and radiation therapy.ConclusionsThe Headway Duo microcatheter is safe and effective for embolization of cerebral AVMs using n-BCA. The trackability and high burst pressure of the Headway Duo make it an important and useful tool for the neurointerventionalist during cerebral AVM embolization.
Republished: Lung consequences in adults born prematurely
Authors: Bolton Charlotte E , Bush Andrew , Hurst John R , Kotecha Sailesh , McGarvey Lorcan 
Published: November 2015

ABSTRACT
Although survival has improved significantly in recent years, prematurity remains a major cause of infant and childhood mortality and morbidity. Preterm births (&lt;37 weeks of gestation) account for 8% of live births representing &gt;50 000 live births each year in the UK. Preterm birth, irrespective of whether babies require neonatal intensive care, is associated with increased respiratory symptoms, partially reversible airflow obstruction and abnormal thoracic imaging in childhood and in young adulthood compared with those born at term. Having failed to reach their optimal peak lung function in early adulthood, there are as yet unsubstantiated concerns of accelerated lung function decline especially if exposed to noxious substances leading to chronic respiratory illness; even if the rate of decline in lung function is normal, the threshold for respiratory symptoms will be crossed early. Few adult respiratory physicians enquire about the neonatal period in their clinical practice. The management of these subjects in adulthood is largely evidence free. They are often labelled as asthmatic although the underlying mechanisms are likely to be very different. Smoking cessation, maintaining physical fitness, annual influenza immunisation and a general healthy lifestyle should be endorsed irrespective of any symptoms. There are a number of clinical and research priorities to maximise the quality of life and lung health in the longer term not least understanding the underlying mechanisms and optimising treatment, rather than extrapolating from other airway diseases.
DNA-PKcs and PARP1 Bind to Unresected Stalled DNA Replication Forks Where They Recruit XRCC1 to Mediate Repair
Authors: Ying Songmin , Chen Zhihui , Medhurst Annette L. , Neal Jessica A. , Bao Zhengqiang , Mortusewicz Oliver , McGouran Joanna , Song Xinming , Shen Huahao , Hamdy Freddie C. , Kessler Benedikt M. , Meek Katheryn , Helleday Thomas 
Published: November 2015

Abstract
A series of critical pathways are responsible for the detection, signaling, and restart of replication forks that encounter blocks during S-phase progression. Small base lesions may obstruct replication fork progression and processing, but the link between repair of small lesions and replication forks is unclear. In this study, we investigated a hypothesized role for DNA-PK, an important enzyme in DNA repair, in cellular responses to DNA replication stress. The enzyme catalytic subunit DNA-PKcs was phosphorylated on S2056 at sites of stalled replication forks in response to short hydroxyurea treatment. Using DNA fiber experiments, we found that catalytically active DNA-PK was required for efficient replication restart of stalled forks. Furthermore, enzymatically active DNA-PK was also required for PARP-dependent recruitment of XRCC1 to stalled replication forks. This activity was enhanced by preventing Mre11-dependent DNA end resection, suggesting that XRCC1 must be recruited early to an unresected stalled fork. We also found that XRCC1 was required for effective restart of a subset of stalled replication forks. Overall, our work suggested that DNA-PK and PARP-dependent recruitment of XRCC1 is necessary to effectively protect, repair, and restart stalled replication forks, providing new insight into how genomic stability is preserved. Cancer Res; 76(5); 1078–88. ©2015 AACR.
Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models
Authors: Benito Juliana , Ramirez Marc S. , Millward Niki Zacharias , Velez Juliana , Harutyunyan Karine G. , Lu Hongbo , Shi Yue-xi , Matre Polina , Jacamo Rodrigo , Ma Helen , Konoplev Sergej , McQueen Teresa , Volgin Andrei , Protopopova Marina , Mu Hong , Lee Jaehyuk , Bhattacharya Pratip K. , Marszalek Joseph R. , Davis R. Eric , Bankson James A. , Cortes Jorge E. , Hart Charles P. , Andreeff Michael , Konopleva Marina 
Published: November 2015

Abstract
Purpose: To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models.
Experimental Design: Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models.
Results: Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a “hypoxia index” compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo. In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells.
Conclusions: These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins. Clin Cancer Res; 22(7); 1687–98. ©2015 AACR.
First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies
Authors: Munster Pamela , Aggarwal Rahul , Hong David , Schellens Jan H.M. , van der Noll Ruud , Specht Jennifer , Witteveen Petronella O. , Werner Theresa L. , Dees E. Claire , Bergsland Emily , Agarwal Neeraj , Kleha Joseph F. , Durante Michael , Adams Laurel , Smith Deborah A. , Lampkin Thomas A. , Morris Shannon R. , Kurzrock Razelle 
Published: November 2015

Abstract
Purpose: GSK2126458 (GSK458) is a potent inhibitor of PI3K (α, β, γ, and δ), with preclinical studies demonstrating broad antitumor activity. We performed a first-in-human phase I study in patients with advanced solid tumors.
Materials and Methods: Patients received oral GSK458 once or twice daily in a dose-escalation design to define the maximum tolerated dose (MTD). Expansion cohorts evaluated pharmacodynamics, pharmacokinetics, and clinical activity in histologically and molecularly defined cohorts.
Results: One hundred and seventy patients received doses ranging from 0.1 to 3 mg once or twice daily. Dose-limiting toxicities (grade 3 diarrhea, n = 4; fatigue and rash, n = 1) occurred in 5 patients (n = 3 at 3 mg/day). The MTD was 2.5 mg/day (MTD with twice daily dosing undefined). The most common grade ≥3 treatment-related adverse events included diarrhea (8%) and skin rash (5%). Pharmacokinetic analyses demonstrated increased duration of drug exposure above target level with twice daily dosing. Fasting insulin and glucose levels increased with dose and exposure of GSK458. Durable objective responses (ORs) were observed across multiple tumor types (sarcoma, kidney, breast, endometrial, oropharyngeal, and bladder cancer). Responses were not associated with PIK3CA mutations (OR rate: 5% wild-type vs. 6% mutant).
Conclusions: Although the MTD of GSK458 was 2.5 mg once daily, twice-daily dosing may increase duration of target inhibition. Fasting insulin and glucose levels served as pharmacodynamic markers of drug exposure. Select patients achieved durable responses; however, PIK3CA mutations were neither necessary nor predictive of response. Combination treatment strategies and novel biomarkers may be needed to optimally target PI3K. Clin Cancer Res; 22(8); 1932–9. ©2015 AACR.
Inflammatory Marker Changes in Postmenopausal Women after a Year-long Exercise Intervention Comparing High Versus Moderate Volumes
Authors: Friedenreich Christine M. , O'Reilly Rachel , Shaw Eileen , Stanczyk Frank Z. , Yasui Yutaka , Brenner Darren R. , Courneya Kerry S. 
Published: November 2015

Abstract
This randomized dose comparison trial examined if higher exercise volume decreased inflammatory biomarkers, associated with postmenopausal breast cancer risk, more than moderate exercise volume. The Breast Cancer and Exercise Trial in Alberta was a two-center, two-armed randomized trial in 400 inactive, healthy, postmenopausal women, aged 50 to 74 years, with a body mass index of 22 to 40 kg/m2. Participants were randomized to high (300 minutes/week) or moderate (150 minutes/week) volumes of aerobic exercise while maintaining usual diet. Fasting blood concentrations of C-reactive protein (CRP), IL6, and TNFα were measured at baseline, 6 and 12 months. Intention-to-treat (ITT) analysis was performed using linear mixed models adjusted for baseline biomarker concentrations. ITT analyses of 386 (97%) participants showed no statistically significant group differences for changes in biomarker levels at 6 and 12 months. In addition, we did not observe any modification of this effect by baseline characteristics of participants. In post hoc analyses based on self-selected exercise level (measured in minutes/week), CRP decreased by 22.45% for participants who exercised &gt;246 minutes/week (highest quintile) and increased by 0.07% for those who exercised &lt;110 minutes/week (lowest quintile, Ptrend = 0.04), adjusted for baseline covariates. When this analysis was restricted to include exercise time in the target heart rate zone only, statistically significant trends were observed for both CRP (P &lt; 0.01) and IL6 (P = 0.04). Prescribing 300 minutes/week of moderate-to-vigorous aerobic exercise did not improve inflammatory markers compared with 150 minutes/week in postmenopausal women. Decreases in CRP were observed with higher self-selected exercise volume. Cancer Prev Res; 9(2); 196–203. ©2015 AACR.
Contexto comunicativo: pensando um operador para análise de estratégias comunicativas no telejornalismo
Authors: Gutmann Juliana Freire 
Published: November 2015

<p>O artigo discute a produtividade do contexto comunicativo enquanto operador analítico para o estudo do lugar configurador de comunicabilidade no telejornalismo. Busca-se entender como se constroem posições e vínculos com o espectador, movimento que remete a disputas de sentido e relações de poder. Os resultados analíticos sugerem que o contexto comunicativo seja apropriado como referência para a operacionalização analítica, no interior de formatos industriais, das relações inscritas no mapa das mediações de Jesús Martín Barbero, entre instâncias de produção e consumo midiático.</p>
Imagem e jornalismo de revista: fotografia e representação feminina no Manifesto Tpm
Authors: Reginato Gisele Dotto 
Published: November 2015

<p>Este artigo analisa a representação da mulher na revista Tpm por meio da fotografia jornalística e problematiza em que medida ela ajuda a desvelar os sentidos sobre liberdade feminina no Manifesto Tpm. O corpus de análise é constituído pelas edições da revista de maio, junho, julho e agosto de 2012. A partir da análise, foram encontradas quatro matrizes de representação da mulher na revista: maternidade, trabalho, moda e corpo. Elas indicam que, apesar do Manifesto Tpm apresentar imagens contra-hegemônicas em relação à mulher, as “eternas funções femininas” de mãe e de esposa ainda estão presentes no texto e nas imagens da revista.</p>
Association of Hospital and Physician Characteristics and Care Processes With Racial Disparities in Procedural Outcomes Among Contemporary Patients Undergoing Coronary Artery Bypass Grafting Surgery
Authors: Mehta Rajendra H. , Shahian David M. , Sheng Shubin , O’Brien Sean M. , Edwards Fred H. , Jacobs Jeffery P. , Peterson Eric D. 
Published: November 2015

Background—
Previous studies have reported that black patients undergoing coronary artery bypass surgery had worse outcomes than white patients, even after accounting for patient factors. The degree to which clinician, hospital, and care factors account for these outcome differences remains unclear.

Methods and Results—

We evaluated procedural outcomes in 11 697 blacks and 136 362 whites undergoing isolated coronary artery bypass surgery at 663 Society of Thoracic Surgery Database participating sites (January 1, 2010 to June 30, 2011) adjusted for patients’ clinical and socioeconomic features, hospital and surgeon effects, and care processes (internal mammary artery graft and perioperative medications use). Relative to whites, blacks undergoing coronary artery bypass surgery were younger, yet had higher comorbidities and more adverse presenting features. Blacks were also more likely to be treated at hospitals with higher risk-adjusted mortality. The use of internal mammary artery was marginally lower in blacks than in whites (93.3% versus 92.2%,
P
<0.0001). Unadjusted mortality and major morbidity rates were higher in blacks than in whites (1.8% versus 2.5%,
P
<0.0001) and (13.6% versus 19.4%,
P
<0.0001), respectively. These racial differences in outcomes narrowed but still persisted after adjusting for surgeon, hospital, and care processes in addition to patient and socioeconomic factors (odds ratio, 1.17; 95% confidence interval, 1.00–1.36 and odds ratio, 1.26; 95% confidence interval, 1.19–1.34, respectively).

Conclusions—
The risks of procedural mortality and morbidity after coronary artery bypass surgery were higher among black patients than among white patients. These differences were in part accounted for by patient comorbidities, socioeconomic status, and surgeon, hospital, and care factors, as well, as suggested by the reduction in the strength of the race-outcomes association. However, black race remained an independent predictor of outcomes even after accounting for these differences.
The MJO as a Dispersive, Convectively Coupled Moisture Wave: Theory and Observations
Authors: Adames Ángel F. , Kim Daehyun 
Published: November 2015

Abstract
A linear wave theory for the Madden–Julian oscillation (MJO), previously developed by Sobel and Maloney, is extended upon in this study. In this treatment, column moisture is the only prognostic variable and the horizontal wind is diagnosed as the forced Kelvin and Rossby wave responses to an equatorial heat source/sink. Unlike the original framework, the meridional and vertical structure of the basic equations is treated explicitly, and values of several key model parameters are adjusted, based on observations. A dispersion relation is derived that adequately describes the MJO’s signal in the wavenumber–frequency spectrum and defines the MJO as a dispersive equatorial moist wave with a westward group velocity. On the basis of linear regression analysis of satellite and reanalysis data, it is estimated that the MJO’s group velocity is ~40% as large as its phase speed. This dispersion is the result of the anomalous winds in the wave modulating the mean distribution of moisture such that the moisture anomaly propagates eastward while wave energy propagates westward. The moist wave grows through feedbacks involving moisture, clouds, and radiation and is damped by the advection of moisture associated with the Rossby wave. Additionally, a zonal wavenumber dependence is found in cloud–radiation feedbacks that cause growth to be strongest at planetary scales. These results suggest that this wavenumber dependence arises from the nonlocal nature of cloud–radiation feedbacks; that is, anomalous convection spreads upper-level clouds and reduces radiative cooling over an extensive area surrounding the anomalous precipitation.