bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Master Neural Transcription Factor BRN2 Is an Androgen Receptor–Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer
Authors: Bishop Jennifer L. , Thaper Daksh , Vahid Sepideh , Davies Alastair , Ketola Kirsi , Kuruma Hidetoshi , Jama Randy , Nip Ka Mun , Angeles Arkhjamil , Johnson Fraser , Wyatt Alexander W. , Fazli Ladan , Gleave Martin E. , Lin Dong , Rubin Mark A. , Collins Colin C. , Wang Yuzhuo , Beltran Himisha , Zoubeidi Amina 
Published: October 2016

AbstractMechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor–resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo. Mechanistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2. Underscoring its inverse correlation with classic AR activity in clinical samples, BRN2 expression was highest in NEPC tumors and was significantly increased in castration-resistant prostate cancer compared with adenocarcinoma, especially in patients with low serum PSA. These data reveal a novel mechanism of AR-dependent control of NEPC and suggest that targeting BRN2 is a strategy to treat or prevent neuroendocrine differentiation in prostate tumors.Significance: Understanding the contribution of the AR to the emergence of highly lethal, drug-resistant NEPC is critical for better implementation of current standard-of-care therapies and novel drug design. Our first-in-field data underscore the consequences of potent AR inhibition in prostate tumors, revealing a novel mechanism of AR-dependent control of neuroendocrine differentiation, and uncover BRN2 as a potential therapeutic target to prevent emergence of NEPC. Cancer Discov; 7(1); 54–71. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1
CD70 limits atherosclerosis and promotes macrophage function
Authors: Lievens Dirk , Engel David , Spitz Charlotte , Bürger Christina , Rinne Petteri , Beckers Linda , Dandl Angelika , Reim Sigrid , Ahmadsei Maiwand , Van den Bossche Jan , Holdt Lesca M. , Megens Remco T. A. , Schmitt Martin M. , de Winther Menno , Biessen Eric A. , Borst Jannie , Faussner Alexander , Weber Christian , Winkels Holger , Meiler Svenja , Smeets Esther , Lutgens Esther , Gerdes Norbert 
Published: October 2016

SummaryThe costimulatory molecule CD70 is expressed on activated immune cells and is known to modulate responses of T, B, and NK cells via its receptor CD27. Until now, there is only limited data describing the role of CD70 in atherosclerosis. We observed that ruptured human carotid atherosclerotic plaques displayed higher CD70 expression than stable carotid atherosclerotic plaques, and that CD70 expression in murine atheroma localized to macrophages. Lack of CD70 impaired the inflammatory capacity (e. g. reactive oxygen species and nitric oxide production) of bone marrow-derived macrophages, increased both M1-like and M2-like macrophage markers, and rendered macrophages meta-bolically inactive and prone to apoptosis. Moreover, CD70-deficient macrophages expressed diminished levels of scavenger receptors and ABC-transporters, impairing uptake of oxidised low-density lipoprotein (oxLDL) and cholesterol efflux, respectively. Hyperlipidaemic Apoe −/− mice reconstituted with CD70-deficient bone marrow displayed a profound increase in necrotic core size, plaque area, and number of lesional macrophages as compared to mice receiving control bone marrow. Accordingly, 18 week-old, chow diet-fed CD70-deficient Apoe−/−mice displayed larger atheroma characterised by lower cellularity and more advanced plaque phenotype than Apoe−/− mice. In conclusion, CD70 promotes macrophage function and viability and is crucial for effective phagocytosis and efflux of oxLDL. Deficiency in CD70 results in more advanced atheroma. Our data suggest that CD70 mitigates atherosclerosis at least in part by modulating macrophage function.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.
Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice
Authors: Manthey Helga D. , Cochain Clement , Busch Martin , Chaudhari Sweena M. , Stegner David , Yepes Manuel , Lorenz Kristina , Nolte Marc W. , Nieswandt Bernhard , Vorlova Sandra , Koch Miriam , Zernecke Alma 
Published: October 2016

SummaryAtherosclerosis is considered a chronic inflammatory disease of the vessel wall. Coagulation pathways and immune responses contribute to disease development. The role of coagulation factor XII (FXII) in vascular inflammation, however, remains controversial. We here investigated the function of FXII in atherosclerosis using apolipoprotein E and FXII-deficient (F12−/−Apoe −/−) mice. Compared to F12 +/+ Apoe −/− controls, atherosclerotic lesion formation was reduced in F12−/−Apoe −/− mice. This was associated with a decrease in serum interleukin (IL)-1β and IL-12 levels and reduced expression of pro-inflammatory cytokines in the aorta in atherosclerotic F12−/−Apoe −/− mice, as well as diminished Th1-cell differentiation in the aorta, blood, and lymphoid organs. No changes in circulating bradykinin, thrombin-antithrombin-complexes or plasminogen were observed. Mechanistically, activated FXII (FXIIa) was revealed to directly induce bone marrow-derived macrophages to secrete pro-inflammatory cytokines, including tumour necrosis factor-α, IL-1β, IL-12, and IL-6. Exposure of bone marrow-derived antigen presenting cells to FXIIa similarly induced pro-inflammatory cytokines, and an enhanced capacity to trigger antigen-specific interferon γ-production in CD4+ T cells. Notably, bone-marrow derived macrophages were capable of directly activating FXII. Moreover, the induction of cytokine expression by FXIIa in macrophages occurred independently of FXII protease enzymatic activity and was decreased upon phospholipase C treatment, suggesting urokinase-type plasminogen activator receptor (uPAR) to confer FXIIa-induced cell signalling. These data reveal FXII to play an important role in atherosclerotic lesion formation by functioning as a strong inducer of pro-inflammatory cytokines in antigen-presenting cells. Targeting of FXII may thus be a promising approach for treating cardiovascular disease.Supplementary Material to this article is available online at www.thrombosis-online.com.
Serum 25-hydroxyvitamin D and the risk of stroke in Hong Kong Chinese
Authors: Sing Chor-Wing , Cheung Bernard M. Y. , Wong Ian C. K. , Tan Kathryn C. B. , Kung Annie W. C. , Leung Raymond Y. H. , Han Yi , Cheung Ching-Lung 
Published: October 2016

SummaryLow vitamin D levels have been associated with various cardiovascular diseases; however, whether it is associated with stroke remains inconclusive. We aimed to evaluate the association between serum 25-hydroxyvitamin D and risk of stroke. We conducted a cohort study consisting of 3,458 participants from the Hong Kong Osteoporosis Study aged ≥45 at baseline, examined between 1995 and 2010 and followed up using electronic medical records. Ischaemic and haemorrhagic stroke were defined using the ICD-9 code. In multivariable Cox-proportional hazard regression, quintiles 1 and 4 were significantly associated with increased risk of stroke when compared to the highest quintile (Quintile 1: HR, 1.78; 95 % CI, 1.16–2.74 and quintile 4: HR, 1.61; 95 % CI, 1.07–2.43). A similar association was observed in both men and women. In subgroup analysis, the association was specifically observed for ischaemic stroke, but not haemorrhagic stroke. Using a penalized regression spline, the association between vitamin D and risk of stroke was in a reverse J-shape, with the lowest risk of stroke being observed at 25(OH)D levels between 70 and 80 nmol/l. In conclusion, a low vitamin D level is associated with increased risk of ischaemic stroke; however, whether high vitamin D level is also associated with increased risk of stroke requires further study.Supplementary Material to this article is available at www.thrombosis-online.com.
AVALIAÇÃO DA SATISFAÇÃO DOS USUÁRIOS DE UM SERVIÇO DE SAÚDE PÚBLICO-PRIVADO NO NORDESTE DO BRASIL E A JUDICIALIZAÇÃO DA SAÚDE
Authors: Silva Junior Geraldo Bezerra da , Dias Eduardo Rocha 
Published: October 2016

Este artigo tem por escopo analisar o grau de satisfação dos usuários de um serviço público-privado de saúde do Nordeste do Brasil, bem como o nível de conhecimento sobre seus direitos e a procura pelo Judiciário para garanti-los. Foram avaliadas as respostas dadas a um questionário aplicado junto a 67 pacientes atendidos pelo Núcleo de Assistência Médica Integrada, da Universidade de Fortaleza, conveniado ao Sistema Único de Saúde (SUS). Os pacientes entrevistados mostraram satisfação com os serviços oferecidos, considerando-os como bons ou excelentes. O principal problema evidenciado foi a dificuldade de acesso a medicações fornecidas pelo SUS e a falta de conhecimento dos direitos relacionados à saúde. Observou-se uma baixa procura pela Justiça para questões ligadas à saúde, o que pode se explicar, por um lado, pelo reduzido grau de conhecimento dos direitos relacionados a tal campo e pela baixa escolaridade da maior parte dos entrevistados. A melhora do grau de satisfação pode contribuir para reduzir a judicialização, muito embora usuários mais bem informados possam se mostrar mais exigentes e recorrer mais à Justiça. Soluções alternativas de resolução de conflitos, como a mediação e a justiça restaurativa, podem contribuir para diminuir a busca pelo Judiciário.
BREVES CONSIDERAÇÕES ACERCA DO CONTROLE JURISDICIONAL DE POLÍTICAS PÚBLICAS EM FACE DO DIREITO FUNDAMENTAL AO MEIO AMBIENTE ECOLOGICAMENTE EQUILIBRADO
Authors: Myszczuk Ana Paula , Meirelles Jussara Maria Leal de 
Published: October 2016

O presente artigo tem por objetivo realizar um breve comento sobre o Recurso Especial n. 1.367.549 – MG (2011/0132513-5), julgado pelo Superior Tribunal de Justiça, que analisa a possibilidade da utilização do controle judicial de políticas públicas em face de falta de prestações positivas por parte da Administração Pública na área ambiental. Dessa forma, o artigo apresenta um resumo comentado da decisão e traça algumas considerações sobre as políticas públicas municipais. Além disso, discute a possibilidade do uso do controle judicial de políticas públicas em face de direitos fundamentais e, por fim, o papel do Ministério Público no controle social de políticas públicas.
TODO, PARA TODOS Y GRATIS: COORDENADAS PARA GARANTIZAR LA INVIABILIDAD DE UN SISTEMA DE SALUD
Authors: Pregno Elian 
Published: October 2016

El presente trabajo pretende anotar el fallo de la Corte Suprema de Justicia de la Nación Argentina recaído en autos caratulados: "Asociación Civil para la Defensa en el Ámbito Federal e Internacional de Derechos c/ Instituto Nacional de Servicios Sociales para Jubilados y Pensionados s/ amparo", en febrero de 2015. En primer término, se ofrece -en apretada síntesis- una referencia al caso, esclareciendo: las partes en litigio; la pretensión de la parte actora; el medio procesal interpuesto y la secuencia seguida en las sucesivas instancias, como así también los argumentos esgrimidos en cada una de ellas. A este último respecto, cabe destacar que el máximo tribunal argentino ha sentado como doctrina que resultan procedentes las acciones de clase interpuestas con el objeto de que el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados brinde cobertura integral de prestaciones a personas con discapacidad, beneficiarias de pensiones no contributivas. En segundo lugar, se presenta la integración del sistema de salud en la Argentina y una serie de conjeturas en orden a la tensa relación que exhiben la justicia y la utilidad a la hora de fundamentar los derechos humanos -en general- y el derecho a la atención de la salud -en particular-.
ACIDENTES DE TRÂNSITO E DIREITO À SAÚDE: PREVENÇÃO DE VIDAS E ECONOMIA PÚBLICA
Authors: Massaú Guilherme Camargo , Rosa Rosana Gomes da 
Published: October 2016

Os acidentes de trânsito constituem significativa fonte de despesas na gestão da saúde pública brasileira. Em contrapartida, sua prevenção representa importante ato de gestão da saúde pública, tanto pela redução de gastos diretos no Sistema Único de Saúde (SUS), como pela redução das despesas indiretas junto ao sistema de seguridade social, às vítimas e seus familiares e ao sistema econômico em geral. Este artigo tem como objetivo demonstrar que a garantia do direito à saúde é um desafio agravado pelas despesas destinadas ao atendimento e tratamento das vítimas de acidentes de trânsito. Busca, ainda, estabelecer a importância da efetivação das dimensões da prevenção, enquanto dever do Estado, em termos jurídicos de acesso à saúde. O método utilizado é a análise bibliográfica, a fim de situar o problema da efetivação do direito à saúde de forma preventiva, com impacto no orçamento do Estado-Administração. O método quantitativo contribuiu para que se pudesse visualizar a importância da prevenção como política social de saúde pública, principalmente no trânsito e nas estradas brasileiras. Assim, foi possível estabelecer uma projeção de gastos públicos para recuperação da saúde, bem como demonstrar a repercussão dos acidentes de trânsito nas contas públicas, de modo a relacionar as políticas públicas preventivas de acidentes com a manutenção e a preservação da saúde dos indivíduos. Trata-se de uma prevenção com duplo viés: economia financeira e economia de recursos humanos.
AUTONOMIA DA VONTADE DO PACIENTE E CAPACIDADE PARA CONSENTIR: UMA REFLEXÃO SOBRE A COAÇÃO IRRESISTÍVEL
Authors: Beltrão Silvio Romero 
Published: October 2016

O presente trabalho pretende investigar a validade da manifestação de vontade do paciente, no momento em que o mesmo está influenciado pela dor e pelo sofrimento e necessita declarar se irá se submeter ou não a determinado tratamento. A pesquisa tem caráter interdisciplinar e se utiliza dos elementos da Teoria Geral do Direito Civil para a declaração de validade do negócio jurídico. A relação médico-paciente necessita de uma visão completa quanto aos elementos e requisitos que constituem sua validade na ordem jurídica. Como ponto de partida, analisa a relação do médico com os pacientes adeptos da religião Testemunha de Jeová para, em seguida, verificar os requisitos de validade da declaração de vontade. Investiga a manifestação da vontade como principal elemento do negócio jurídico para, no final, definir os conflitos que envolvem o estudo da autonomia da vontade e a dificuldade de solução dos casos concretos.
Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat
Authors: Fu Jinjuan , Han Yu , Wang Jialiang , Liu Yukai , Zheng Shuo , Zhou Lin , Jose Pedro A. , Zeng Chunyu 
Published: October 2016

Background
Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure.

Methods and Results

Blood pressures of male Wistar‐Kyoto (
WKY)
rats and spontaneously hypertensive rats (
SHR
s) were monitored through the carotid artery. Our study found that acute intravenous injection of irisin reduced blood pressure in
SHR
s, but not
WKY
rats. Irisin, by itself, had no direct vasorelaxing effect in phenylephrine‐preconstricted mesenteric arteries from
SHR
s. However, irisin augmented the acetylcholine‐induced vasorelaxation in mesenteric arteries from
SHR
s that could be reversed by Nω‐nitro‐
l
‐arginine‐methyl ester (L‐
NAME;
100 μmol/L), indicating a role of nitric oxide (
NO)
in this action. Indeed, irisin increased
NO
production and phosphorylation of endothelial nirtic oxide synthase (
eNOS)
in endothelial cells. 5′‐
AMP
‐activated protein kinase (
AMPK
) was involved in the vasorelaxing effect of irisin because compound C (20 μmol/L), an
AMPK
inhibitor, blocked the irisin‐mediated increase in phosphorylation of
eNOS
and protein kinase B (Akt) in endothelial cells and vasodilation in mesenteric arteries.

Conclusions

We conclude that acute administration of irisin lowers blood pressure of
SHR
s by amelioration of endothelial dysfunction of the mesenteric artery through the
AMPK
‐Akt‐
eNOS
‐
NO
signaling pathway.
Knockdown of Inhibitory Guanine Nucleotide Binding Protein Giα‐2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats
Authors: Ali El‐Basyuni Yousra , Li Yuan , Anand‐Srivastava Madhu B. 
Published: October 2016

Background

We previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (
SHRs
) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in
SHRs
. The aim of the present study was to determine the specific contributions of Giα‐2 and Giα‐3 proteins to the development of hypertension.

Methods and Results

Antisense oligodeoxynucleotide of Giα‐2 and Giα‐3 encapsulated in
PEG
/
DOTAP
/
DOPE
cationic liposomes were administrated intravenously into 3‐week‐old prehypertensive
SHRs
and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and
SHRs
received PBS, empty liposomes, or sense. The knockdown of Giα‐2 but not Giα‐3 protein attenuated tachycardia and prevented the development of hypertension up to age 6 weeks; thereafter, blood pressure started increasing and reached the same level as that of untreated
SHRs
at 9 weeks. Furthermore, Giα‐2 and Giα‐3 antisense oligodeoxynucleotide treatments significantly decreased the enhanced levels of Giα‐2 and Giα‐3 proteins, respectively, and enhanced levels of superoxide anion and
NADPH
oxidase activity in heart, aorta, and kidney and hyperproliferation of vascular smooth muscle cells from SHRs aged 6 weeks. In addition, antisense oligodeoxynucleotide treatment with Giα‐2 but not Giα‐3 restored enhanced inhibition of adenylyl cyclase by oxotremorine to WKY levels.

Conclusions

These results suggested that the enhanced expression of Giα‐2 but not Giα‐3 protein plays an important role in the pathogenesis of hypertension and tachycardia in
SHRs
.
Tracing the Evolution and Economic Potential of Konjac Glucomannan in Amorphophallus species (Araceae) using Molecular Phylogeny and RAPD Markers
Authors: MEKKERDCHOO ORACHORN , BOROMPICHAICHARTKUL CHALEEDA , PERRIGO ALLISON , SRZEDNICKI GEORGE , PRAKITCHAIWATTANA CHEUNJIT , ANTONELLI ALEXANDRE 
Published: October 2016

The genus Amorphophallus is an economically important taxon that is abundant in Old World tropical forests (Asia, Oceania and Africa). It includes many species that are used with increasing frequency as a source of food and pharmaceutical products worldwide. Amorphophallus konjac is an important economic crop and has been used widely in China and Japan for commercial konjac glucomannan (KGM) production. However, the species’ range does not extend to Thailand, where other closely related species may be more suitable for commercial KGM production. Present understanding of genetic relationships among Thai Amorphophallus species is still limited, and the connection between evolutionary history and KGM content is unknown. Here, the genetic relationships among various accessions of Amorphophallus spp. collected in Thailand are investigated using the chloroplast trnL-trnF spacer, nuclear ribosomal internal transcribed spacer (ITS) region and the second intron of LEAFY (FLint2) together with genome-wide DNA variation analysis, Randomly Amplified Polymorphic DNA (RAPD) technique. RAPD primers are also developed to quickly and efficiently identify species producing high levels of KGM. This study finds that two monophyletic clades include high KGM content species. RAPD analyses indicate that primer AC-10 generates specific bands identifying species belonging only to the high and medium KGM content clades. These primers can be used as a screening tool for economical species, aiming at improving the industrial production of KGM in Thailand and the world.
Event-Based Validation of Swell Arrival Time
Authors: Jiang Haoyu , Babanin Alexander V. , Chen Ge 
Published: October 2016

AbstractThe arrival time of ocean swells is an important factor for offshore and coastal engineering and naval and recreational activities, which can also be used in evaluating the numerical wave model. Using the continuity and pattern of wave heights during the same swell event, a methodology is developed for identifying swell events and verifying swell arrival time in models from buoy data. The swell arrival time in a WAVEWATCH III hindcast database is validated with in situ measurements. The results indicate that the model has a good agreement with the observations but usually predicts an early arrival of swell, about 4 h on average. A histogram shows that about one-quarter of swell events arrive early and three-quarters late by comparison with the model. Many processes that may be responsible for the arrival time errors are discussed, but at this stage it is not possible to distinguish between them from the available data.
Spectral and Structure Function Estimates of Turbulence Dissipation Rates in a High-Flow Tidal Channel Using Broadband ADCPs
Authors: McMillan Justine M. , Hay Alex E. 
Published: October 2016

AbstractSpectral and structure function methods are implemented to compute the dissipation rate ε from broadband, diverging-beam acoustic Doppler current profiler (ADCP) data collected at four sites in a high-flow tidal channel. This paper shows that middepth estimates of ε obtained from spectral and second-order structure function (SF2) methods are both lognormally distributed with comparable means and variances. Speed bin–averaged ε values agree to within 16%, depending on the site and tidal phase (ebb/flood). The close agreement between the two independent methods provides further support for the argument put forward by McMillan et al.: that is, that the factor-of-2 difference between shear probe and (spectral) ADCP estimates of ε was likely caused by spatial differences in turbulence levels. The agreement between the spectral and both second- and third-order structure function methods also supports the use of for the SF2 universal constant. Notably, however, the SF3 method was less robust for these data. Two additional aspects of the SF2 approach are examined in some detail: 1) the differences from upstream- and downstream-facing beams are shown to arise from the Reynolds stress and 2) the inability of the ADCP to resolve small-scale motions does not affect the estimates of ε but yields apparent Doppler noise levels that—counterintuitively—decrease with increasing flow speed and increasing dissipation rate. A modified SF2 method that accounts for the variance associated with the unresolved scales removes the flow speed dependence and yields noise level estimates that agree with the spectral values.