bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMAC Mimetic Birinapant plus Radiation Eradicates Human Head and Neck Cancers with Genomic Amplifications of Cell Death GenesFADDandBIRC2
Authors: Eytan Danielle F. , Snow Grace E. , Carlson Sophie , Derakhshan Adeeb , Saleh Anthony , Schiltz Stephen , Cheng Hui , Mohan Suresh , Cornelius Shaleeka , Coupar Jamie , Sowers Anastasia L. , Hernandez Lidia , Mitchell James B. , Annunziata Christina M. , Chen Zhong , Van Waes Carter 
Published: July 2016

AbstractComparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporting their functional importance in promoting proliferation. Birinapant, a novel SMAC mimetic, sensitized multiple HNSCC lines to cell death by agonists TNFα or TRAIL and inhibited cIAP1&gt;XIAP&gt;IAP2. Combination of birinapant and TNFα induced sub-G0 DNA fragmentation in sensitive lines and birinapant alone also induced significant G2–M cell-cycle arrest and cell death in UM-SCC-46 cells. Gene transfer and expression of FADD sensitized resistant UM-SCC-38 cells lacking FADD amplification to birinapant and TNFα, supporting a role for FADD in sensitization to IAP inhibitor and death ligands. HNSCC varied in mechanisms of cell death, as indicated by reversal by inhibitors or protein markers of caspase-dependent apoptosis and/or RIPK1/MLKL-mediated necroptosis. In vivo, birinapant inhibited tumor growth and enhanced radiation-induced TNFα, tumor responses, and host survival in UM-SCC-46 and -11B xenograft models displaying amplification and overexpression of FADD+/− BIRC2. These findings suggest that combination of SMAC mimetics such as birinapant plus radiation may be particularly active in HNSCC, which harbor frequent FADD/BIRC2 genomic alterations. Cancer Res; 76(18); 5442–54. ©2016 AACR.
Forma urbana de Belém e seus desdobramentos para a formação de um sistema de espaços livres acessível à população
Authors: Cardoso Ana Claudia Duarte , Lima José Julio Ferreira , Ventura Neto Raul , Rodrigues Roberta Menezes , Ximenes Juliano Pamplona , Gomes Taynara Do Vale 
Published: August 2016

Este texto apresenta uma caracterização do espaço construído de Belém, destacando sua condição estuarina, fisiografia e evolução socioespacial, mas iluminando elementos de desarticulação nas estratégias de operação dos agentes envolvidos na produção da cidade e da gestão urbanística para a estruturação de um Sistema de Espaços Livres e a forma limitada como os mesmos são apropriados pela população. O artigo baseia-se nas conclusões da Oficina Quapá SEL realizada em Belém em maio de 2015, na qual professores e estudantes da Universidade Federal do Pará e a equipe de professores e bolsistas da Universidade de São Paulo realizaram a avaliação dos espaços públicos da cidade. Observou-se que há notável diferenciação da paisagem da área central em oposição/contraposição à área de expansão da cidade e comprometimento de Áreas de Preservação Permanente (APPs) nas margens dos rios internos e das ilhas, principais espaços verdes do município e elementos de conexão com o bioma amazônico que, embora possua potencial paisagístico, vem sendo apropriado de forma socialmente desigual.
Is Mitral Valve Repair Superior to Mitral Valve Replacement in Elderly Patients? Comparison of Short‐ and Long‐Term Outcomes in a Propensity‐Matched Cohort
Authors: Silaschi Miriam , Chaubey Sanjay , Aldalati Omar , Khan Habib , Uzzaman Mohammed Mohsin , Singh Mrinal , Baghai Max , Deshpande Ranjit , Wendler Olaf 
Published: July 2016

Background

Because of demographic changes, a growing number of elderly patients present with mitral valve (
MV
) disease. Although mitral valve repair (
MV
‐repair) is the “gold standard” treatment for
MV
disease, in elderly patients, there is controversy about whether
MV
‐repair is superior to mitral valve replacement. We reviewed results after
MV
surgery in elderly patients treated over the past 20 years.

Methods and Results

Our in‐hospital database was explored for patients who underwent
MV
surgery between 1994 and 2015. Survival data, obtained from the National Health Service central register, were complete for all patients. Of 1776 patients with
MV
disease, 341 were aged ≥75 years. Patients with repeat cardiac surgery, endocarditis, and concomitant aortic valve replacement were excluded. This yielded 221
MV
‐repair and 120 mitral valve replacement patients. Concomitant procedures included coronary artery bypass grafting in 135 patients (39.6%) and tricuspid valve surgery in 50 patients (14.7%). Thirty‐day mortality was 5.4% (
MV
‐repair) versus 9.2% (mitral valve replacement,
P
=0.26). Overall 1‐ and 5‐year survival was 90.7%, 74.2% versus 81.3%, 61.0% (
P
<0.01). Median survival after
MV
‐repair was 7.8 years, close to 8.5 years (95%
CI
: 8.2–9.4) in the age‐matched
UK
population (ratio 0.9). Rate of re‐operation for
MV
‐dysfunction was 2.3% versus 2.5% (mitral valve replacement,
P
=1.0). After propensity matching, patients after
MV
‐repair still had improved survival at 1, 2, and 5 years (93.4%, 91.6%, 76.9% versus 77.2%, 75.2%, 58.7%,
P
=0.03).

Conclusions

Excellent outcomes can be achieved after
MV
surgery in elderly patients. Long‐term survival is superior after
MV
‐repair and the re‐operation rate is low.
MV
‐repair should be the preferred surgical approach in elderly patients.
Tumor-Like Presentation of Primary Angiitis of the Central Nervous System
Authors: de Boysson Hubert , Boulouis Grégoire , Dequatre Nelly , Godard Sophie , Néel Antoine , Arquizan Caroline , Detante Olivier , Bloch-Queyrat Coralie , Zuber Mathieu , Touzé Emmanuel , Bienvenu Boris , Aouba Achille , Guillevin Loïc , Naggara Olivier , Pagnoux Christian 
Published: July 2016

Background and Purpose—
We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system.

Methods—
We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort.

Results—

The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30–48] years versus 46 [18–79] years;
P
=0.008; 9 [90%] with seizures versus 22 [29%],
P
<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12–130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification.

Conclusions—
Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide.
Defining Hazards
Authors: Bertrand Darrian , Shafer Mark 
Published: August 2016

Abstract
State hazard mitigation plans guide state and local agencies in actions they may take to reduce their vulnerability to extreme events. However, because they are written for a general audience, they must be written in a way for a layperson to understand. In many cases, the people writing these plans are not meteorologists or do not have access to meteorological expertise. Consequently, descriptions of hazards may be taken from websites, other documents, or perhaps authoritative sources. This leads to inconsistencies in the way hazards are portrayed in the plans, which increases the difficulty of translating proposed actions to local governments or to other states.
This article delves into the issue of these variances and how it affects those who write state hazard mitigation plans. For this brief text, the hazards discussed in state plans that fall in the National Oceanic and Atmospheric Administration (NOAA) Regional Integrated Sciences and Assessments (RISA) Southern Climate Impacts Planning Program (SCIPP)’s region are covered with a comparison of definitions from the National Weather Service (NWS) and the American Meteorological Society (AMS). States within the SCIPP region include Oklahoma, Texas, Arkansas, Louisiana, Mississippi, and Tennessee. This study found that it is more common for states to use key words from NWS and AMS hazard definitions than to use exact definitions. The goal of this article is to prompt a discussion about the inconsistency of terminology used in state hazard mitigation plans and to spread awareness of this issue so that future plans can keep their unique elements while providing a better description and understanding of the included hazards.
The Impact of Vertical Measurement Depth on the Information Content of Soil Moisture for Latent Heat Flux Estimation
Authors: Qiu Jianxiu , Crow Wade T. , Nearing Grey S. 
Published: July 2016

Abstract
This study aims to identify the impact of vertical support on the information content of soil moisture (SM) for latent heat flux estimation. This objective is achieved via calculation of the mutual information (MI) content between multiple soil moisture variables (with different vertical supports) and current/future evaporative fraction (EF) using ground-based soil moisture and latent/sensible heat flux observations acquired from the AmeriFlux network within the contiguous United States. Through the intercomparison of MI results from different SM–EF pairs, the general value (for latent heat flux estimation) of superficial soil moisture observations , vertically integrated soil moisture observations , and vertically extrapolated soil moisture time series [soil wetness index (SWI) from a simple low-pass transformation of ] are examined. Results suggest that, contrary to expectations, 2-day averages of and have comparable mutual information with regards to EF. That is, there is no clear evidence that the information content for flux estimation is enhanced via deepening the vertical support of superficial soil moisture observations. In addition, the utility of SWI in monitoring and forecasting EF is partially dependent on the adopted parameterization of time-scale parameter T in the exponential filter. Similar results are obtained when analyses are conducted at the monthly time scale, only with larger error bars. The contrast between the results of this paper and past work focusing on utilizing soil moisture to predict vegetation condition demonstrates that the particular application should be considered when characterizing the information content of soil moisture time series measurements.
Spectral Characteristics of Convective-Scale Precipitation Observations and Forecasts
Authors: Wong May , Skamarock William C. 
Published: July 2016

AbstractAs an alternative to traditional precipitation analysis and forecast verification, 1D and 2D spectral decompositions of NCEP/Stage IV and Multi-Radar Multi-Sensor (MRMS) precipitation products and convective-scale model forecasts are examined. Both the stage IV and MRMS analyses and the model forecasts show a similar weak power-law behavior in 1D spectral decompositions, although the MRMS analysis does not drop off in power at wavelengths less than approximately 20 km as found in the stage IV analysis. The convective-scale forecasts produce similar behavior to the MRMS when the forecast model’s effective resolution is sufficient. Neither the MRMS analyses nor the forecasts suggest the existence of a break in the spectral slope at the scales for which the analyses and forecasts are valid. The 2D spectra of both observations and forecasts, expressed in terms of an absolute wavenumber and azimuthal angle, show power varying significantly as a function of azimuthal angle for a given wavenumber. This azimuthal anisotropy is significant, and is dominated by the second mode (wavenumber 2). The phase of the mode is the result of the orientation of precipitation features and, hence, convective system orientations and propagation. Observations show a shift in orientation (phase) over May–June–July. The convective forecasts reproduce this shift in phase, although with a consistent but small phase error.
NAQFC Developmental Forecast Guidance for Fine Particulate Matter (PM2.5)
Authors: Lee Pius , McQueen Jeffery , Stajner Ivanka , Huang Jianping , Pan Li , Tong Daniel , Kim Hyuncheol , Tang Youhua , Kondragunta Shobha , Ruminski Mark , Lu Sarah , Rogers Eric , Saylor Rick , Shafran Perry , Huang Ho-Chun , Gorline Jerry , Upadhayay Sikchya , Artz Richard 
Published: July 2016

Abstract
The National Air Quality Forecasting Capability (NAQFC) upgraded its modeling system that provides developmental numerical predictions of particulate matter smaller than 2.5 μm in diameter (PM2.5) in January 2015. The issuance of PM2.5 forecast guidance has become more punctual and reliable because developmental PM2.5 predictions are provided from the same system that produces operational ozone predictions on the National Centers for Environmental Prediction (NCEP) supercomputers.
There were three major upgrades in January 2015: 1) incorporation of real-time intermittent sources for particles emitted from wildfires and windblown dust originating within the NAQFC domain, 2) suppression of fugitive dust emissions from snow- and/or ice-covered terrain, and 3) a shorter life cycle for organic nitrate in the gaseous-phase chemical mechanism. In May 2015 a further upgrade for emission sources was included using the U.S. Environmental Protection Agency’s (EPA) 2011 National Emission Inventory (NEI). Emissions for ocean-going ships and on-road mobile sources will continue to rely on NEI 2005.
Incremental tests and evaluations of these upgrades were performed over multiple seasons. They were verified against the EPA’s AIRNow surface monitoring network for air pollutants. Impacts of the three upgrades on the prediction of surface PM2.5 concentrations show large regional variability: the inclusion of windblown dust emissions in May 2014 improved PM2.5 predictions over the western states and the suppression of fugitive dust in January 2015 reduced PM2.5 bias by 52%, from 6.5 to 3.1 μg m−3 against a monthly average of 9.4 μg m−3 for the north-central United States.
Student- and school-level belonging and commitment and student smoking, drinking and misbehaviour
Authors: Bonell Christopher , Shackleton Nichola , Fletcher Adam , Jamal Farah , Allen Elizabeth , Mathiot Anne , Markham Wolfgang , Aveyard Paul , Viner Russell 
Published: July 2016

Objectives: It has been suggested that students are healthier in schools where more students are committed to school. Previous research has examined this only using a proxy measure of value-added education (a measure of whether school-level attendance and attainment are higher than predicted by students’ social profile), finding associations with smoking tobacco, use of alcohol and illicit drugs, and violence. These findings do not provide direct insights into the associations between school-level aggregate student commitment and health behaviours, and may simply reflect the proxy measure being residually confounded by unmeasured student characteristics. We examined the previously used proxy measure of value-added education, as well as direct measures at the level of the school and the student of lack of student commitment to school to see whether these were associated with students’ self-reported smoking tobacco, alcohol use and school misbehaviour. Design: Cross-sectional survey. Setting: A total of 40 schools in south-east England. Methods: Multi-level analyses. Results: There were associations between school- and student-level measures of lack of commitment to school and tobacco smoking, alcohol use and school misbehaviour outcomes, but the proxy measure of school-level commitment, value-added education, was not associated with these outcomes. A sensitivity analysis focused only on violent aspects of school misbehaviour found a pattern of associations identical to that found for the measure of misbehaviour. Conclusion: Our study provides the first direct evidence in support of the Theory of Human Functioning and School Organisation.
Palliative Care in Undergraduate Medical Education—How Far Have We Come?
Authors: Fitzpatrick Danielle , Heah Rebecca , Patten Simon , Ward Helena 
Published: July 2016

Purpose: There is an increasing demand for quality palliative care teaching within undergraduate medical education. Studies suggest that many junior doctors feel underprepared to perform end-of-life care. Previous systematic reviews on palliative care teaching within medical schools have identified significant variability and lack of consistency in teaching. This review aims to update the literature on the current status of palliative care teaching to undergraduates within medical schools. Method: A systematic review was undertaken on articles published from December 2001 to November 2015 on palliative care teaching for undergraduate medical students. In all, 650 abstract citations were obtained, of which 126 were relevant to the research questions. Thematic analysis was performed on remaining articles according to whether they discussed content and/or methodology of palliative care education, and data collated. Results: There is greater consistency in the content being delivered as part of end-of-life care education within medical schools. The most frequently taught topics include attitudes to death and dying, communication skills, and pain management. Pediatric care and religious/cultural issues are less frequently addressed. Teaching institutions are also utilising a broader range of teaching modalities. Conclusion: There is significant progress in palliative care education within medical schools. Ongoing challenges relate to correlating our current practice in medical education to professional recommendations and the expressed needs of junior doctors to practice competent end-of-life care.
Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden
Authors: Arkema Elizabeth V. , Grunewald Johan , Kullberg Susanna , Eklund Anders , Askling Johan 
Published: July 2016

Our objective was to estimate the contemporary incidence and prevalence of sarcoidosis using Swedish population-based register data.Adults with any sarcoidosis-coded visit were identified from the National Patient Register (hospitalisations 1964–2013 and outpatient care 2001–2013). Demographic and medication dispensing data were retrieved from national registers. We estimated the prevalence of sarcoidosis in 2013 overall and by county of residence. The incidence of sarcoidosis during 2003–2012 was estimated by sex, age, education level and year of diagnosis. Case definitions were varied to test their robustness.More than 16 000 individuals had a history of sarcoidosis in 2013. When defined as two or more sarcoidosis-coded visits, the prevalence was 160 per 100 000. Using different definitions, the prevalence ranged from 152 (requiring a specialist visit) to 215 per 100 000 (only one visit required). The highest prevalence was observed in northern less densely populated counties. The incidence was 11.5 per 100 000 per year and varied by −10% to +30% depending on case definition. The incidence peaked in males aged 30–50 years and in females aged 50–60 years, but did not differ by education level and was stable over time.This study represents the largest epidemiological investigation of sarcoidosis using population-based individual-level data. Age at diagnosis in men was 10 years younger than in women and geographical variation was observed.
Notch1 signalling regulates endothelial proliferation and apoptosis in pulmonary arterial hypertension
Authors: Dabral Swati , Tian Xia , Kojonazarov Baktybek , Savai Rajkumar , Ghofrani Hossein Ardeschir , Weissmann Norbert , Florio Monica , Sun Jan , Jonigk Danny , Maegel Lavinia , Grimminger Friedrich , Seeger Werner , Savai Pullamsetti Soni , Schermuly Ralph Theo 
Published: July 2016

Pulmonary arterial hypertension (PAH) is characterised by excessive pulmonary vascular remodelling involving deregulated proliferation of cells in intima, media as well as adventitia. Pulmonary arterial endothelial cell (PAEC) hyperproliferation and survival underlies the endothelial pathobiology of the disease.The indispensable involvement of Notch1 in the arterial endothelial phenotype and angiogenesis provides intriguing prospects for its involvement in the pathogenesis of PAH.We observed an increased expression of Notch1 in lungs of idiopathic PAH (IPAH) patients and hypoxia/SU5416 (SUHx) rats compared with healthy subjects.In vitroloss- and gain-of-function studies demonstrated that Notch1 increased proliferation of human PAECs (hPAECs)viadownregulation of p21 and inhibited apoptosisviaBcl-2 and Survivin. Inhibition of Notch signalling using the γ-secretase inhibitor dibenzazepine dose-dependently decreased proliferation and migration of hPAECs. Notably, Notch1 expression and transcriptional activity were increased under hypoxia in hPAECs and knockdown of Notch1 inhibited hypoxia-induced proliferation of the cells. Furthermore,in vivotreatment with a γ-secretase inhibitor (AMG2008827) significantly reduced the right ventricular systolic pressure and right heart hypertrophy in SUHx rats.Here, we conclude that Notch1 plays a critical role in PAH and Notch inhibitors may be a promising therapeutic option for PAH.