bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive Measurement of mTORC1 Signaling with 89Zr-Transferrin
Authors: Truillet Charles , Cunningham John T. , Parker Matthew F.L. , Huynh Loc T. , Conn Crystal S. , Ruggero Davide , Lewis Jason S. , Evans Michael J. 
Published: December 2016

Abstract
Purpose: mTOR regulates many normal physiological processes and when hyperactive can drive numerous cancers and human diseases. However, it is very challenging to detect and quantify mTOR signaling noninvasively in clinically relevant animal models of disease or man. We hypothesized that a nuclear imaging tool measuring intracellular mTOR activity could address this unmet need.
Experimental Design: Although the biochemical activity of mTOR is not directly amenable to nuclear imaging probe development, we show that the transferrin receptor can be used to indirectly measure intracellular changes in mTOR activity.
Results: After verifying that the uptake of radiolabeled transferrin (the soluble ligand of the transferrin receptor) is stimulated by active mTORC1 in vitro, we showed that 89Zr-labeled transferrin (Tf) can measure mTORC1 signaling dynamics in normal and cancerous mouse tissues with PET. Finally, we show that 89Zr-Tf can detect the upregulation of mTORC1 by tumor cells to escape the antitumor effects of a standard-of-care antiandrogen, which is to our knowledge the first example of applying PET to interrogate the biology of treatment resistant cancer.
Conclusions: In summary, we have developed the first quantitative assay to provide a comprehensive measurement of mTOR signaling dynamics in vivo, in specific normal tissues, and during tumor development in genetically engineered animal models using a nuclear imaging tool that is readily translatable to man. Clin Cancer Res; 23(12); 3045–52. ©2016 AACR.
Os romances de Sérgio Sant'Anna e de Osman Lins: respostas ficcionais à "morte do autor", de Barthes e Foucault?
Authors: Tavares Enéias Farias 
Published: December 2016

O ápice das discussões que colocaram em xeque a importância autoral na obra literária ocorreu na década de 1960, quando as reflexões de Roland Barthes e de Michel Foucault, em textos como A morte do autor e O que é o autor?, resultaram numa reavaliação crítica da figura autoral bem como promoveram uma maior valorização do texto literário e da interpretação do leitor. O objetivo deste artigo é contrastar as idéias dos dois pensadores sobre a problemática do autor com os romances brasileiros Confissões de Ralfo, de Sergio Sant’Anna, e A rainha dos cárceres da Grécia, de Osman Lins, textos nos quais a oposição à morte do autor se apresenta.
Debate: experiências de revistas produzidas por estudantes
Authors: Tommaso Mario , Santos Ana Lúcia Lins B. dos 
Published: December 2016

A equipe de Opiniães convidou colegas de outras revistas discentes para trocar ideias sobre o trabalho de edição no contexto acadêmico. O leitor encontrará relatos de experiências diversas, que muitas vezes perpassam dificuldades comuns: a fundamentação e a continuidade dos projetos, a burocracia, o envolvimento do corpo editorial. Sob outros aspectos, como relações institucionais, política editorial e avaliação da universidade, o leitor poderá observar certas divergências. Participaram do debate membros da comissão editorial das revistas: Opiniães (Mario Tommaso, DLCV-USP), Angelus Novus (Fernando Ribeiro, DH-USP), Cadernos de Campo (André-Kees Schouten, DA-USP), Criação & Crítica (Samira Murad, DLM-USP), Desassossego (Fernanda Suely Muller, DLCV-USP) e Magma (Tiago Pinheiro, DTLLC-USP)
Em defesa de um ensino (planejado) de literatura pelos direitos do leitor
Authors: Bulgarelli Marcello 
Published: December 2016

Este artigo busca elaborar e colocar em prática uma alternativa metodológica – que considere os direitos do leitor – para que o ensino de literatura possa, ao menos, formar leitores literários autônomos críticos, capazes de fazer as suas escolhas de leitura, sabendo que o aprendido do texto literário não é um todo absoluto, mas passível de ser constantemente ressignificado.
Literatura e sexo por Gérard Dessons
Authors: Lima Bruno Ribeiro de 
Published: December 2016

Gérard Dessons é professor de literatura francesa na Universidade Paris 8, onde trabalha com teoria da arte, da literatura e da linguagem. A entrevista abaixo busca questionar problemas “morais” e “éticos” a partir da ligação direta entre literatura e sexo. Algumas de suas publicações: La Manière folle (2010); Rembrandt: l’odeur de la peinture (2006); L’Art et la manière (2004), Traité du rythme (com H. Meschonnic) (1998).
Arena conta Tiradentes: dilemas estéticos e ideológicos do Teatro de Arena pós golpe de 1964
Authors: Klafke Mariana Figueiró 
Published: December 2016

Arena conta Tiradentes, de Augusto Boal e Gianfrancesco Guarnieri, utiliza um levante político do período colonial para falar do momento de 1967, refletindo sobre o malogro das expectativas democráticas de inclusão popular que se viviam no Brasil dos anos 1950 e 1960, interrompidas pelo golpe de 1964 e pela ditadura que se instalaria a partir de então. Para o Teatro de Arena, grupo muito ligado à questão nacional-popular e que teve centralidade na produção cultural dos anos anteriores, lidando justamente com uma temática relativa à inclusão do povo no debate sobre os rumos do país, o golpe significou uma ruptura fundamental e exigiu uma revisão significativa dos horizontes ideológicos e estéticos. A partir de 1965, o Arena produziu uma série de musicais utilizando uma nova técnica, o Sistema Coringa, que procurou sintetizar sua trajetória estética e propor rumos para a nova situação política do país. Dentre esses musicais encontra-se Arena conta Tiradentes, objeto deste estudo. Por meio de uma leitura própria e da retomada dos principais estudos sobre a peça, procuramos refletir sobre os dilemas estéticos e ideológicos do grupono conturbado pós-64.
O sonho de Piotr
Authors: Fernandes Thiago 
Published: December 2016

Texto de criação literária que possui gênese no processo criativo do espetáculo “Pequeno-burgueses: rapsódia em duas partes” (2014), no qual a Cia Bruta de Arte (SP) tomava o texto de Maksim Górki como ponto de partida.
A hora e a vez de Iná Camargo Costa: a dramaturgia em cena
Authors: Caldas Juliana , Balista Lígia , Destri Luisa 
Published: December 2016

Entrevista realizada pelas editoras do n. 8 da revista Opiniães com Iná Camargo Costa, professora aposentada do Departamento de Teoria Literária e Literatura Comparada da Universidade de São Paulo. Iná dedicou a vida acadêmica ao estudo da dramaturgia e do teatro, tornando-se referência para os estudos sobre Brecht e o teatro épico no Brasil.
Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II–Induced Aortic Aneurysm and Atherosclerosis
Authors: Krishna Smriti Murali , Seto Sai-Wang , Jose Roby J. , Li Jiaze , Morton Susan K. , Biros Erik , Wang Yutang , Nsengiyumva Vianne , Lindeman Jan H.N. , Loots Gabriela G. , Rush Catherine M. , Craig Jeffrey M. , Golledge Jonathan 
Published: December 2016

Objective—
Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations.

Approach and Results—

SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E–deficient (
ApoE
−/−
) mice (
SOST

Tg

.
ApoE
−/−
) and administration of recombinant mouse Sost inhibited angiotensin II–induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in
SOST

Tg

.
ApoE
−/−
mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and
SOST

Tg

.
ApoE
−/−
mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/β-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of
SOST

Tg

.
ApoE
−/−
mice. SOST expression was downregulated and the wingless-type mouse mammary virus integration site/β-catenin pathway was activated in human AA samples. The cytosine–phosphate–guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated.

Conclusions—
This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.
Loss of Caspase‐Activated DNase Protects Against Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Chao Meng‐Lin , Guo Junhong , Cheng Wen‐Lin , Zhu Xue‐Yong , She Zhi‐Gang , Huang Zan , Ji Yong , Li Hongliang 
Published: December 2016

Background

Atherosclerosis is a chronic disease that is closely related to inflammation and macrophage apoptosis, which leads to secondary necrosis and proinflammatory responses in advanced lesions. Caspase‐activated
DN
ase (
CAD
) is a double‐strand specific endonuclease that leads to the subsequent degradation of chromosome
DNA
during apoptosis. However, whether
CAD
is involved in the progression of atherosclerosis remains elusive.

Methods and Results

CAD
−/−
ApoE
−/−
and ApoE
−/−
littermates were fed a high‐fat diet for 28 weeks to develop atherosclerosis. Human specimens were collected from coronary heart disease (
CHD
) patients who were not suitable for transplantation.
CAD
expression was increased in the atheromatous lesions of
CHD
patients and high‐fat diet‐treated ApoE‐deficient mice. Further investigation demonstrated that
CAD
deficiency inhibited high‐fat diet‐induced atherosclerosis, as evidenced by decreased atherosclerotic plaques, inhibited inflammatory response, and macrophage apoptosis, as well as enhanced stability of plaques in
CAD
−/−
ApoE
−/−
mice compared to the ApoE
−/−
controls. Bone marrow transplantation verified the effect of
CAD
on atherosclerosis from macrophages. Mechanically, the decrease in the phosphorylated levels of mitogen‐activated protein kinase (MAPK) kinase/extracellular signal‐regulated kinase 1 and 2 (
MEK
‐
ERK
1/2) that resulted from
CAD
knockout and the activation of nuclear factor kappa B signaling mediated by
CAD
stimulation that was suppressed by inhibiting
ERK
1/2 phosphorylation revealed the potential association between the role of
CAD
in atherosclerosis and the
MAPK
signaling pathway.

Conclusions

In conclusion,
CAD
deficiency protects against atherosclerosis through inhibiting inflammation and macrophage apoptosis, which is partially through inactivation of the
MEK
‐
ERK
1/2 signaling pathway. This finding provides a promising therapeutic target for treating atherosclerosis.
Invasive minimal Microvascular Resistance Is a New Index to Assess Microcirculatory Function Independent of Obstructive Coronary Artery Disease
Authors: de Waard Guus A. , Nijjer Sukhjinder S. , van Lavieren Martijn A. , van der Hoeven Nina W. , Petraco Ricardo , van de Hoef Tim P. , Echavarría‐Pinto Mauro , Sen Sayan , van de Ven Peter M. , Knaapen Paul , Escaned Javier , Piek Jan J. , Davies Justin E. , van Royen Niels 
Published: December 2016

Background

Coronary microcirculatory dysfunction portends a poor cardiovascular outcome. Invasive assessment of microcirculatory dysfunction by coronary flow reserve (
CFR
) and hyperemic microvascular resistance (
HMR
) is affected by coronary artery disease (
CAD
). In this study we propose minimal microvascular resistance (m
MR
) as a new measure of microcirculatory dysfunction and aim to determine whether m
MR
is influenced by CAD.

Methods and Results

We obtained 482 simultaneous measurements of intracoronary Doppler flow velocity and pressure. The m
MR
is defined as the ratio between distal coronary pressure and flow velocity during the hyperemic wave‐free period. Measurements were divided into 2 cohorts. Cohort 1 was a paired analysis involving 81 pairs with a vessel with and without
CAD
to investigate whether
HMR
,
CFR
, and m
MR
are modulated by
CAD
.
CFR
was lower, and
HMR
was higher, in vessels with
CAD
than in vessels without
CAD
: 2.12±0.79 versus 2.56±0.63 mm Hg·cm
−1
·s,
P
<0.001, and 2.61±1.22 versus 2.31±0.89 mm Hg·cm
−1
·s,
P
=0.04, respectively. m
MR
was equal in vessels with and without
CAD
: 1.54±0.77 versus 1.53±0.57 mm Hg·cm
−1
·s,
P
=0.90. Differences for
CFR
occurred when
FFR
was 0.60 to 0.80 or ≤0.60 but not when
FFR
≥0.80. For
HMR
, the difference occurred only when
FFR
≤0.60. For m
MR
, no difference was observed in any
FFR
stratum. Cohort 2 was used for validation and showed significant relationships for
CFR
and
HMR
with
FFR
: Pearson r=0.488,
P
<0.001 and −0.159,
P
=0.03, respectively; m
MR
had no association with
FFR
: Pearson r=0.055;
P
=0.32.

Conclusions

mMR
is a novel index to assess microcirculatory dysfunction and is not modified by the presence of obstructive
CAD
.
Early Coronary Reperfusion Facilitates Return of Spontaneous Circulation and Improves Cardiovascular Outcomes After Ischemic Cardiac Arrest and Extracorporeal Resuscitation in Pigs
Authors: Hutin Alice , Lamhaut Lionel , Lidouren Fanny , Kohlhauer Matthias , Mongardon Nicolas , Carli Pierre , Berdeaux Alain , Ghaleh Bijan , Tissier Renaud 
Published: December 2016

Background

Extracorporeal cardiopulmonary resuscitation (
ECPR
) is widely proposed for the treatment of refractory cardiac arrest. It should be associated with coronary angiography if coronary artery disease is suspected. However, the prioritization of care remains unclear in this situation. Our goal was to determine whether coronary reperfusion should be instituted as soon as possible in such situations in a pig model.

Methods and Results

Anesthetized pigs were instrumented and submitted to coronary artery occlusion and ventricular fibrillation. After 5 minutes of untreated cardiac arrest, conventional cardiopulmonary resuscitation (
CPR
) was started. Fifteen minutes later,
ECPR
was initiated for a total duration of 240 minutes. Animals randomly underwent either early or late coronary reperfusion at 20 or 120 minutes of
ECPR
, respectively. This timing was adapted to the kinetic of infarct extension in pigs. Return of spontaneous circulation was determined as organized electrocardiogram rhythm with systolic arterial pressure above 80 mm Hg. During conventional
CPR
, hemodynamic parameters were not different between groups. Carotid blood flow then increased by 70% after the onset of
ECPR
in both groups. No animal (0 of 7) elicited return of spontaneous circulation after late reperfusion versus 4 of 7 after early reperfusion (
P
=0.025). The hemodynamic parameters, such as carotid blood flow, were also improved in early versus late reperfusion groups (113±20 vs 43±17 mL/min after 240 minutes of
ECPR
, respectively;
P
=0.030), along with infarct size decrease (71±4% vs 84±2% of the risk zone, respectively;
P
=0.013).

Conclusions

Early reperfusion improved hemodynamic status and facilitated return of spontaneous circulation in a porcine model of ischemic cardiac arrest treated by
ECPR
.
Impact of Retinal Vein Occlusion on Stroke Incidence: A Meta‐Analysis
Authors: Li Min , Hu Xiaolan , Huang Jiangtao , Tan Yuan , Yang Baoping , Tang Zhenyu 
Published: December 2016

Background

Considerable controversy exists on the association between retinal vein occlusion (
RVO
) and stroke risk. Therefore, we conducted a meta‐analysis to assess the relationship between
RVO
and stroke risk.

Methods and Results

PubMed,
EMBASE
, and the Cochrane library databases were searched for cohort studies with data on
RVO
and stroke risk. Studies that reported adjusted relative risks (
RR
s) with 95%
CI
s of stroke associated with
RVO
were included. Stratified analyses were conducted according to key characteristics. A total of 5 articles including results from 6 prospective cohort studies with 431 cases of stroke and 37 471 participants were included in the meta‐analysis. Overall, after adjustment for established cardiovascular risk factors, participants with
RVO
at baseline were considerably more associated with a greater incidence of stroke risk (combined
RR
: 1.50, 95%
CI
: 1.19–1.90), compared to participants without
RVO
. The results were more pronounced for stroke (
RR
: 1.72, 95%
CI
: 1.24–2.37) in the stratified with a stroke history. The risk of stroke was nonsignificant in male subjects (
RR
: 1.20, 95%
CI
: 0.96–1.49) and in female subjects (
RR
: 0.93, 95%
CI
: 0.64–1.34). The presence of both central
RVO
(
RR
: 1.90, 95%
CI
: 1.46–2.48) and branch
RVO
(
RR
: 1.79, 95%
CI
: 1.18–2.72) was associated with increased risk of stroke. Stratifying by age, the associations between
RVO
and risk of stroke were similar between the age range in the cohorts that ranged from 50 to 59 years and 60 to 69 years.

Conclusions

Exposure to
RVO
was associated with an increased risk of stroke, especially in subjects aged between 50 and 69 years. Future studies on the effect of
RVO
treatment and modifiable risk factor reduction on stroke risk in
RVO
patients are warranted.
Revisiting the “Christmas Holiday Effect” in the Southern Hemisphere
Authors: Knight Josh , Schilling Chris , Barnett Adrian , Jackson Rod , Clarke Phillip 
Published: December 2016

Background
A “Christmas holiday effect” showing elevated cardiovascular mortality over the Christmas holidays (December 25 to January 7) was demonstrated previously in study from the United States. To separate the effect of seasonality from any holiday effect, a matching analysis was conducted for New Zealand, where the Christmas holiday period falls within the summer season.

Methods and Results

New Zealand mortality data for a 25‐year period (1988–2013) was analyzed based on the same methodology used in the previous study. Locally weighted smoothing was used to calculate an “expected” number of deaths for each day of the year. The expected value was compared with the actual number of deaths. In addition, mean age at death was estimated and used to assess the life‐years lost due to excess mortality. There were 738 409 deaths (197 109 coded as cardiac deaths) during the period. We found evidence of a Christmas holiday effect in our of medical facility's cardiac deaths, with an excess event rate of 4.2% (95%
CI
0.7–7.7%) leading to ≈4 additional deaths per annum. The average age of those with fatal cardiac deaths was 76.8 years (
SD
13.5) during the Christmas holiday period, resulting in 148 to 222 years of life lost per annum.

Conclusions

Cardiac mortality is elevated during the Christmas holiday period relative to surrounding time periods. Our findings are consistent with a previously reported study conducted in the
United States
, suggesting that cardiac mortality does not take a “summer break.”
Intracranial Carotid Artery Calcification Relates to Recanalization and Clinical Outcome After Mechanical Thrombectomy
Authors: Hernández-Pérez María , Bos Daniel , Dorado Laura , Pellikaan Karlijn , Vernooij Meike W. , López-Cancio Elena , Pérez de la Ossa Natalia , Gomis Meritxell , Castaño Carlos , Munuera Josep , Puig Josep , Millán Mònica , Dávalos Antoni 
Published: December 2016

Background and Purpose—
Intracranial carotid artery calcification (ICAC) is a surrogate marker of intracranial arteriosclerosis, which may impact the revascularization and clinical outcome of acute stroke patients who undergo mechanical thrombectomy.

Methods—
We included 194 patients admitted to our Stroke Unit between January 2009 and September 2015 who underwent mechanical thrombectomy for an anterior circulation occlusion. ICAC was quantified in both intracranial carotid arteries on the nonenhanced computed tomographic scan that was acquired before thrombectomy. Complete arterial revascularization was defined as a Thrombolysis in Cerebral Infarction ≥2b on the final angiographic examination. Poor functional outcome was defined as a modified Rankin Scale score of >2 at 90 days. We assessed the independent effect of ICAC volume on complete arterial revascularization, functional outcome, and mortality using logistic regression models adjusted for relevant confounders.

Results—

ICAC was present in 164 (84.5%) patients, with a median volume of 87.1 mm
3
(25th–75th quartile: 18.9–254.6 mm
3
). We found that larger ICAC volumes were associated with incomplete arterial revascularization (adjusted odds ratio per unit increase in ln-transformed ICAC volume 0.73 [95% confidence interval, 0.57–0.93]) and with poorer functional outcome (adjusted odds ratio per unit increase in ln-transformed ICAC volume 1.31 [95% confidence interval, 1.04–1.66]).

Conclusions—
A larger amount of ICAC before mechanical thrombectomy in acute stroke patients is an indicator of worse postprocedural arterial revascularization and poorer functional outcome.
Review of the mirine plant bug genus Pachylygus (Heteroptera: Miridae: Mirinae), with description of a new species from Japan
Authors: Yasunaga Tomohide , Schwartz Michael D. 
Published: December 2016

The little-known plant bug genus Pachylygus Yasunaga, 1994, now considered nearly endemic to Japan proper and to include five monophagous species, is reviewed, diagnosed, and discussed. A new species, P. luteonotatus, is described on the basis of specimens recently collected from Nikko, central Honshu. All known congeners are diagnosed and an identification key to them is included. A checklist, with known distributions, is also provided. The Asian genus Peltidolygus Poppius, 1915 is proposed as the most closely related sister taxon of Pachylygus.
A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework
Authors: Thurston George D. , Kipen Howard , Annesi-Maesano Isabella , Balmes John , Brook Robert D. , Cromar Kevin , De Matteis Sara , Forastiere Francesco , Forsberg Bertil , Frampton Mark W. , Grigg Jonathan , Heederik Dick , Kelly Frank J. , Kuenzli Nino , Laumbach Robert , Peters Annette , Rajagopalan Sanjay T. , Rich David , Ritz Beate , Samet Jonathan M. , Sandstrom Thomas , Sigsgaard Torben , Sunyer Jordi , Brunekreef Bert 
Published: December 2016

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.