bluuebunny/crossref_metadata_2025 huggingface dataset:
Citation classics in neurointerventional research: a bibliometric analysis of the 100 most cited articles
Authors: Kim Eun Soo , Yoon Dae Young , Kim Hye Jeong , Jeon Hong Jun , Lee Jong Young , Cho Byung-Moon , Lee Kwanseop
Published: April 2016

Background and purpose

The number of citations that an article has received can be used to evaluate its impact on the scientific community. This study aimed to identify the 100 most cited articles in the field of neurointervention and to analyze their characteristics.

Materials and methods

We selected the 669 journals that were considered potentially to publish neurointervention articles based on the database of Journal Citation Reports. Using the Web of Science citation search tool, we identified the 100 most cited articles relevant to neurointervention within the selected journals. Each article was evaluated for several characteristics including publication year, journal, journal category, impact factor, number of citations, number of citations per year, authorship, department, institution, country, type of article, and topic.

Results

The number of citations for the top 100 articles ranged from 1912 to 170 (mean 363.4) and citations per year ranged from 271.0 to 4.1 (mean 40.0). The majority of articles were published in clinical neurology journals (63%), were published in 2000–2009 (39%), originated in the USA (45%), were original articles (95%), and dealt with endovascular treatment of cerebral aneurysm (42%). The Department of Radiology, University of California School of Medicine (n=12) was the leading institution and Viñuela F (n=11) was the most prolific author.

Conclusions

Our study presents a detailed list and analysis of the 100 most cited articles in the field of neurointervention and provides a historical perspective on the scientific progress in this field.
Interpreting angina: symptoms along a gender continuum
Authors: Kreatsoulas Catherine , Crea-Arsenio Mary , Shannon Harry S , Velianou James L , Giacomini Mita
Published: April 2016

Background

‘Typical’ angina is often used to describe symptoms common among men, while ‘atypical’ angina is used to describe symptoms common among women, despite a higher prevalence of angina among women. This discrepancy is a source of controversy in cardiac care among women.

Objectives

To redefine angina by (1) qualitatively comparing angina symptoms and experiences in women and men and (2) to propose a more meaningful construct of angina that integrates a more gender-centred approach.

Methods

Patients were recruited between July and December 2010 from a tertiary cardiac care centre and interviewed immediately prior to their first angiogram. Symptoms were explored through in-depth semi-structured interviews, transcribed verbatim and analysed concurrently using a modified grounded theory approach. Angiographically significant disease was assessed at ≥70% stenosis of a major epicardial vessel.

Results

Among 31 total patients, 13 men and 14 women had angiograpically significant CAD. Patients describe angina symptoms according to 6 symptomatic subthemes that array along a ‘gender continuum’. Gender-specific symptoms are anchored at each end of the continuum. At the centre of the continuum, are a remarkably large number of symptoms commonly expressed by both men and women.

Conclusions

The ‘gender continuum’ offers new insights into angina experiences of angiography candidates. Notably, there is more overlap of shared experiences between men and women than conventionally thought. The gender continuum can help researchers and clinicians contextualise patient symptom reports, avoiding the conventional ‘typical’ versus ‘atypical’ distinction that can misrepresent gendered angina experiences.
E11 and exceptional field theory
Authors: Tumanov Alexander G. , West Peter
Published: April 2016

We argue that the exceptional field theory is a truncation of the nonlinear realisation of the semi-direct product of [Formula: see text] and its first fundamental as proposed in 2003. Evaluating the simple equations of the [Formula: see text] approach, and using the commutators of the [Formula: see text] algebra, we find the local variations of the fields of exceptional field theory after making a radical truncation. This procedure does not respect any of the higher level [Formula: see text] symmetries and so these are lost. We suggest that the need for the section condition in the exceptional field theory could be a consequence of the truncation.
Pulse evolution in mid-infrared femtosecond optical parametric oscillator based on silicon-on-insulator waveguides
Authors: Wen Jin
Published: April 2016

The pulse evolution of mid-infrared optical parametric oscillator based on silicon-on-insulator (SOI) waveguides is numerically investigated. The properties of pulse evolution in the process of optical parametric oscillation have been described. The numerical results show that the threshold of the optical parametric oscillation cavity can be lowered due to the high nonlinearity of the waveguide. The parametric signals initiate to oscillate when the circle trip number is 5 with the appropriate length of the SOI waveguide 7 mm. Meanwhile the peak power of the output signal pulse can be reached to 400 W at the stable situation when the circle trip number is over 10 with the conversion efficiency as high as 5%. This research can supply a kind of way to generate the mid-infrared femtosecond pulse at the highly stable on-chip integration level.
OPEN INNOVATION AND THE CHALLENGES OF HUMAN RESOURCE MANAGEMENT
Authors: LENZ SABRINA , PINHANEZ MONICA , DE CÉSARIS LUIS ENRIQUE URTUBEY , JACOBS CHARLOTTE
Published: April 2016

This paper considers challenges of human resource management (HRM) in open innovation (OI) processes. It examines which strategies managers use to overcome these problems. By conducting an inductive case study of the Brazilian oil and gas company Petrobras based on grounded theory, we developed a framework explaining these challenges and strategies. The paper argues that the most important HR challenges are (a) interpersonal relationships, (b) power shifting inside the organization, and (c) creating a sense of value among workers, and explains how managers tackled all these challenges to build a better working environment. The deep analysis of HRM challenges in OI contributes to a better understanding of management problems these processes can cause and how these could be overcome.
ORGANISATIONAL CULTURE AND LEADERSHIP AS MEDIATORS OF SERVICE INNOVATION AND FIRM COMPETITIVENESS: A STUDY OF AN EMERGING ECONOMY
Authors: ANNING-DORSON THOMAS
Published: April 2016

It has become imperative for researchers to mark out the institutional limits and conditions within which innovation is the most useful strategy and to establish the extent to which its efficacy is conditioned by innovative culture and leadership of the service firm. This paper makes contribution to the service innovation literature by showing the internal boundary conditions under which service innovation can effectively enhance the competitiveness of the service firm. An empirical research design comprised two sets of data collected from service managers; the first for validation and the second for structural analysis of our framework. Five service innovation dimensions were found and that innovation leadership partially mediated the relationship between the service innovations and a service firm’s competitiveness. Innovative culture also mediates the service innovations and competitiveness. In contrast to previous studies which examined the direct effect of innovation on competitiveness, our study found that the mediating role of internal conditions brings about complementarity of strategic assets which produces sustainable competitive advantage to the service firm. The practical implication is that service firms must be equally interested in creating a fundamental service philosophy through their culture and leadership to build competitive advantages.
DETERMINANTS OF FINANCIAL REWARDS FROM INDUSTRY–UNIVERSITY COLLABORATION IN SOUTH KOREA
Authors: HAN JUNGHEE , HESHMATI ALMAS
Published: April 2016

The external circumstances for universities have been changing rapidly. In order to be competitive, survive and flourish, universities have turned to external sources to generate revenues. The literature refers to this phenomenon as academic capitalism, defined as the involvement of colleges and their faculty in market-like behaviours, which has become a key feature of higher education finances in most countries. As a result, technology transfer, technological commercialisation, and patents via industry–university collaboration represent a source of financial rewards. This paper explores the determinants of financial rewards of universities sourced from academic engagement through industry–university collaboration in South Korea. We have found that technology transfer per employees working at technology licensing offices, participation of engineering faculty, patent approvals, and the number of firms with incubators within universities significantly contributes to university revenues. The following determinants of financial performance are unexpectedly not contributors to revenue: technological commercialisation using technology transfer, distinguished faculty and incentive rules for inventors. In the light of these findings, it appears that an entrepreneurial university program is likely to play a strong role in university finances in Korea.
DEVELOPMENT OF AN OPEN INNOVATION MODEL FOR R&D COLLABORATION BETWEEN LARGE FIRMS AND SMALL-MEDIUM ENTERPRISES (SMES) IN MANUFACTURING INDUSTRIES
Authors: JANG HYEJIN , LEE KEEEUN , YOON BYUNGUN
Published: April 2016

Mutual growth in the relation between large firms and small-medium enterprises (SMEs) has been an important issue that can be overcome with the concept of open innovation, which is the most continuous research topic in technology innovation. However, most previous studies on open innovation barely analyse both firm types, focusing only on one party. The aim of this study is to develop open innovation models for complementary cooperation between both types of firms in manufacturing industry. Based on a basic understanding of open innovation in each firm type, this study suggests open innovation typology with two main concepts of open innovation: knowledge interaction and technology innovation. Finally, open innovation models are developed, considering the cooperative participants, their relationships in open innovation processes, and open innovation activities illustrated through case studies. The results contribute to manage strategic open innovation between large firms and SMEs through various approaches of cooperation.
Transcriptional modulation of SLC26A3 (DRA) by sphingosine-1-phosphate
Authors: Anbazhagan Arivarasu N. , Priyamvada Shubha , Alakkam Anas , Kumar Anoop , Borthakur Alip , Saksena Seema , Gill Ravinder K. , Alrefai Waddah A. , Dudeja Pradeep K.
Published: April 2016

SLC26A3 or Downregulated in adenoma (DRA) is the major Cl−/HCO3− exchanger involved in electroneutral NaCl absorption in the mammalian intestine. Alterations in DRA function and expression have been implicated in diarrheal diseases associated with inflammation or infection. Therefore, agents that upregulate DRA activity may serve as potential antidiarrheals. In this regard, sphingosine-1-phosphate (S1P), a member of the bioactive sphingolipid family, has been shown to modulate various cellular processes including improvement of intestinal barrier function. However, the role of S1P in modulating intestinal chloride absorption by regulating DRA is not known. Therefore, the present studies were designed to examine the direct effects of S1P on apical Cl−/HCO3− exchange activity and DRA expression. S1P significantly increased Cl−/HCO3− exchange activity and also significantly increased DRA mRNA and protein expression. Increased DRA mRNA by S1P was accompanied by enhanced DRA promoter activity, indicating involvement of transcriptional mechanisms. The specific S1P receptor subtype-2 (S1PR2) antagonist JTE-013 blocked the stimulatory effects of S1P on DRA promoter activity, indicating the involvement of S1PR2. S1P-mediated increase in DRA promoter activity involved PI3K/Akt pathway. Progressive deletions of the DRA promoter indicated that the putative S1P-responsive elements are present in the −790/−398 region of the DRA promoter. Furthermore, results obtained from electrophoretic mobility shift assay showed that S1P stimulated DRA promoter activity via increased binding of Ying-Yang1 (YY1) in the S1P-responsive region. In conclusion, transcriptional modulation of DRA expression and function in response to S1P through a PI3/Akt pathway represents a novel role of S1P as a potential proabsorptive agent.
The hemodynamic effects of acute aortic regurgitation into a stiffened left ventricle resulting from chronic aortic stenosis
Authors: Okafor Ikechukwu , Raghav Vrishank , Midha Prem , Kumar Gautam , Yoganathan Ajit
Published: April 2016

Acute aortic regurgitation (AR) post-chronic aortic stenosis is a prevalent phenomenon occurring in patients who undergo transcatheter aortic valve replacement (TAVR) surgery. The objective of this work was to characterize the effects of left ventricular diastolic stiffness (LVDS) and AR severity on LV performance. Three LVDS models were inserted into a physiological left heart simulator. AR severity was parametrically varied through four levels (ranging from trace to moderate) and compared with a competent aortic valve. Hemodynamic metrics such as average diastolic pressures (DP) and reduction in transmitral flow were measured. AR index was calculated as a function of AR severity and LVDS, and the work required to make up for lost volume due to AR was estimated. In the presence of trace AR, higher LVDS had up to a threefold reduction in transmitral flow (13% compared with 3.5%) and a significant increase in DP (2-fold). The AR index ranged from ∼42 to 16 (no AR to moderate AR), with stiffer LVs having lower values. To compensate for lost volume due to AR, the low, medium, and high LVDS models were found to require 5.1, 5.5, and 6.6 times more work, respectively. This work shows that the LVDS has a significant effect on the LV performance in the presence of AR. Therefore, the LVDS of potential TAVR patients should be assessed to gain an initial indication of their ability to tolerate post-procedural AR.
Dysfunction of the β2-spectrin-based pathway in human heart failure
Authors: Smith Sakima A. , Hughes Langston D. , Kline Crystal F. , Kempton Amber N. , Dorn Lisa E. , Curran Jerry , Makara Michael , Webb Tyler R. , Wright Patrick , Voigt Niels , Binkley Philip F. , Janssen Paul M. L. , Kilic Ahmet , Carnes Cynthia A. , Dobrev Dobromir , Rasband Matthew N. , Hund Thomas J. , Mohler Peter J.
Published: April 2016

β2-Spectrin is critical for integrating membrane and cytoskeletal domains in excitable and nonexcitable cells. The role of β2-spectrin for vertebrate function is illustrated by dysfunction of β2-spectrin-based pathways in disease. Recently, defects in β2-spectrin association with protein partner ankyrin-B were identified in congenital forms of human arrhythmia. However, the role of β2-spectrin in common forms of acquired heart failure and arrhythmia is unknown. We report that β2-spectrin protein levels are significantly altered in human cardiovascular disease as well as in large and small animal cardiovascular disease models. Specifically, β2-spectrin levels were decreased in atrial samples of patients with atrial fibrillation compared with tissue from patients in sinus rhythm. Furthermore, compared with left ventricular samples from nonfailing hearts, β2-spectrin levels were significantly decreased in left ventricle of ischemic- and nonischemic heart failure patients. Left ventricle samples of canine and murine heart failure models confirm reduced β2-spectrin protein levels. Mechanistically, we identify that β2-spectrin levels are tightly regulated by posttranslational mechanisms, namely Ca2+- and calpain-dependent proteases. Furthermore, consistent with this data, we observed Ca2+- and calpain-dependent loss of β2-spectrin downstream effector proteins, including ankyrin-B in heart. In summary, our findings illustrate that β2-spectrin and downstream molecules are regulated in multiple forms of cardiovascular disease via Ca2+- and calpain-dependent proteolysis.
Increased lethality and defective pulmonary clearance of Streptococcus pneumoniae in microsomal prostaglandin E synthase-1-knockout mice
Authors: Dolan Jennifer M. , Weinberg Jason B. , O'Brien Edmund , Abashian Anya , Procario Megan C. , Aronoff David M. , Crofford Leslie J. , Peters-Golden Marc , Ward Lindsay , Mancuso Peter
Published: April 2016

The production of prostaglandin E2 (PGE2) increases dramatically during pneumococcal pneumonia, and this lipid mediator impairs alveolar macrophage (AM)-mediated innate immune responses. Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme involved in the synthesis of PGE2, and its expression is enhanced during bacterial infections. Genetic deletion of mPGES-1 in mice results in diminished PGE2 production and elevated levels of other prostaglandins after infection. Since PGE2 plays an important immunoregulatory role during bacterial pneumonia we assessed the impact of mPGES-1 deletion in the host defense against pneumococcal pneumonia in vivo and in AMs in vitro. Wild-type (WT) and mPGES-1 knockout (KO) mice were challenged with Streptococcus pneumoniae via the intratracheal route. Compared with WT animals, we observed reduced survival and increased lung and spleen bacterial burdens in mPGES-1 KO mice 24 and 48 h after S. pneumoniae infection. While we found modest differences between WT and mPGES-1 KO mice in pulmonary cytokines, AMs from mPGES-1 KO mice exhibited defective killing of ingested bacteria in vitro that was associated with diminished inducible nitric oxide synthase expression and reduced nitric oxide (NO) synthesis. Treatment of AMs from mPGES-1 KO mice with an NO donor restored bacterial killing in vitro. These results suggest that mPGES-1 plays a critical role in bacterial pneumonia and that genetic ablation of this enzyme results in diminished pulmonary host defense in vivo and in vitro. These results suggest that specific inhibition of PGE2 synthesis by targeting mPGES-1 may weaken host defense against bacterial infections.
Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension
Authors: Crnkovic Slaven , Schmidt Albrecht , Egemnazarov Bakytbek , Wilhelm Jochen , Marsh Leigh M. , Ghanim Bahil , Klepetko Walter , Olschewski Andrea , Olschewski Horst , Kwapiszewska Grazyna
Published: April 2016

Adaptation of the right ventricle (RV) to increased afterload is crucial for survival in pulmonary hypertension (PH), but it is challenging to assess RV function and identify associated molecular mechanisms. The aim of the current study was to analyze the relationship between invasive and noninvasive parameters of RV morphology and function and associated molecular changes. The response of mice to normobaric hypoxia was assessed by hechocardiography, invasive hemodynamics, and histological and molecular analyses. Plasma levels of possibly novel markers of RV remodeling were measured by ELISA in patients with idiopathic pulmonary arterial hypertension (IPAH) and matched healthy controls. Chronic hypoxia-induced PH was accompanied by significantly decreased tricuspid annular plane systolic excursion (TAPSE) and unchanged RV contractility index and tau. RV hypertrophy was present without an increase in fibrosis. There was no change in α- and β-major histocompatibility class or natriuretic peptides expression. Comparative microarray analysis identified two soluble factors, fibroblast growth factor-5 (FGF5) and interleukin-22 receptor alpha-2 (IL22RA2), as being possibly associated with RV remodeling. We observed significantly higher plasma levels of IL22RA2, but not FGF5, in patients with IPAH. Hypoxic pulmonary hypertension in a stage of RV remodeling with preserved systolic function is associated with decreased pulmonary vascular compliance, mild diastolic RV dysfunction, and significant decrease in TAPSE. Subtle gene expression changes in the RV vs. the left ventricle upon chronic hypoxia suggest that the majority of changes are due to hypoxia and not due to changes in afterload. Increased IL22RA2 levels might represent a novel RV adaptive mechanism.
Protein kinase A induces UCP1 expression in specific adipose depots to increase energy expenditure and improve metabolic health
Authors: Dickson Lorna M. , Gandhi Shriya , Layden Brian T. , Cohen Ronald N. , Wicksteed Barton
Published: April 2016

Adipose tissue PKA has roles in adipogenesis, lipolysis, and mitochondrial function. PKA transduces the cAMP signal downstream of G protein-coupled receptors, which are being explored for therapeutic manipulation to reduce obesity and improve metabolic health. This study aimed to determine the overall physiological consequences of PKA activation in adipose tissue. Mice expressing an activated PKA catalytic subunit in adipose tissue (Adipoq-caPKA mice) showed increased PKA activity in subcutaneous, epididymal, and mesenteric white adipose tissue (WAT) depots and brown adipose tissue (BAT) compared with controls. Adipoq-caPKA mice weaned onto a high-fat diet (HFD) or switched to the HFD at 26 wk of age were protected from diet-induced weight gain. Metabolic health was improved, with enhanced insulin sensitivity, glucose tolerance, and β-cell function. Adipose tissue health was improved, with smaller adipocyte size and reduced macrophage engulfment of adipocytes. Using metabolic cages, we found that Adipoq-caPKA mice were shown to have increased energy expenditure, but no difference to littermate controls in physical activity or food consumption. Immunoblotting of adipose tissue showed increased expression of uncoupling protein-1 (UCP1) in BAT and dramatic UCP1 induction in subcutaneous WAT, but no induction in the visceral depots. Feeding a HFD increased PKA activity in epididymal WAT of wild-type mice compared with chow, but did not change PKA activity in subcutaneous WAT or BAT. This was associated with changes in PKA regulatory subunit expression. This study shows that adipose tissue PKA activity is sufficient to increase energy expenditure and indicates that PKA is a beneficial target in metabolic health.
DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance
Authors: Caron Alexandre , Labbé Sébastien M. , Mouchiroud Mathilde , Huard Renaud , Richard Denis , Laplante Mathieu
Published: April 2016

We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection.
Response properties of MST parafoveal neurons during smooth pursuit adaptation
Authors: Ono Seiji , Mustari Michael J.
Published: April 2016

Visual motion neurons in the posterior parietal cortex play a critical role in the guidance of smooth pursuit eye movements. Initial pursuit (open-loop period) is driven, in part, by visual motion signals from cortical areas, such as the medial superior temporal area (MST). The purpose of this study was to determine whether adaptation of initial pursuit gain arises because of altered visual sensitivity of neurons at the cortical level. It is well known that the visual motion response in MST is suppressed after exposure to a large-field visual motion stimulus, showing visual motion adaptation. One hypothesis is that foveal motion responses in MST are associated with smooth pursuit adaptation using a small target spot. We used a step-ramp tracking task with two steps of target velocity (double-step paradigm), which induces gain-down or gain-up adaptation. We found that after gain-down adaptation 58% of our MST visual neurons showed a significant decrease in firing rate. This was the case even though visual motion input (before the pursuit onset) from target motion was constant. Therefore, repetitive visual stimulation during the gain-down paradigm could lead to adaptive changes in the visual response. However, the time course of adaptation did not show a correlation between the visual response and pursuit behavior. These results indicate that the visual response in MST may not directly contribute to the adaptive change in pursuit initiation.
Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin
Authors: Patel Ryan , Dickenson Anthony H.
Published: April 2016

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity.
Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue
Authors: Pravenec Michal , Mlejnek Petr , Zídek Václav , Landa Vladimír , Šimáková Miroslava , Šilhavý Jan , Strnad Hynek , Eigner Sebastian , Eigner Henke Kateřina , Škop Vojtěch , Malínská Hana , Trnovská Jaroslava , Kazdová Ludmila , Drahota Zdeněk , Mráček Tomáš , Houštěk Josef
Published: April 2016

Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin ( Retn) transgene specifically in adipose tissue (SHR- Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR- Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR- Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced18F-FDG uptake in BAT induced by exposure to cold in SHR- Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat.
Relaciones universidad-empresa: Hacia una productividad basada en innovación
Authors: Jiménez Alejandro
Published: April 2016

Los centros de investigación son importantes en la generación de innovaciones en países industrializados, en donde existe una sólida institucionalidad público-privada, incentivos para los investigadores y un interés empresarial por financiar la I+D. En Chile y Latinoamérica la realidad es diferente. La universidad está desvinculada de la industria y la investigación es financiada mayoritariamente con fondos públicos, lo que ha complejizado la protección de los resultados económicos surgidos de la I+D. Este artículo propone esfuerzos para modificar la actual normativa favoreciendo la creación de empresas (spin-offs) y entregando incentivos que mejoren la transferencia tecnológica desde la universidad al sector productivo.
Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer
Authors: Ciarloni Laura , Ehrensberger Sahar Hosseinian , Imaizumi Natsuko , Monnier-Benoit Sylvain , Nichita Cristina , Myung Seung-Jae , Kim Joo Sung , Song Si Young , Kim Tae Il , van der Weg Boudewijn , Meier Rémy , Borovicka Jan , Beglinger Christoph , Vallet Cédric , Maerten Philippe , Rüegg Curzio , Dorta Gian
Published: April 2016

Purpose: A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer–related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy.

Experimental Design: A case–control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) ≥1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I–II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers.

Results: The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively.

Conclusions: We report the validation of a novel blood test, Colox®, for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy. Clin Cancer Res; 22(18); 4604–11. ©2016 AACR.
SIRPα-Antibody Fusion Proteins Selectively Bind and Eliminate Dual Antigen-Expressing Tumor Cells
Authors: Piccione Emily C. , Juarez Silvia , Tseng Serena , Liu Jie , Stafford Melissa , Narayanan Cyndhavi , Wang Lijuan , Weiskopf Kipp , Majeti Ravindra
Published: April 2016

Purpose: CD47 is highly expressed on a variety of tumor cells. The interaction of CD47 with signal regulatory protein alpha (SIRPα), a protein on phagocytic cells, transmits a “don't eat me” signal that negatively regulates phagocytosis. CD47–SIRPα antagonists enable phagocytosis by disrupting the inhibitory signal and can synergize with Fc-mediated pro-phagocytic signals for potent elimination of tumor cells. A potential limitation of therapeutic CD47–SIRPα antagonists is that expression of CD47 on normal cells may create sites of toxicity or an “antigen sink.” To overcome these limitations and address selective tumor targeting, we developed SIRPabodies to improve the therapeutic benefits of CD47–SIRPα blockade specifically toward tumor.

Experimental Design: SIRPabodies were generated by grafting the wild-type SIRPα either to the N-terminus or to the C-terminus of the heavy chain of rituximab. Selective tumor binding was tested using CFSE-labeled human primary CLL cells in the presence of 20-fold excess of human RBCs. NSG mice were transplanted with Raji-luciferase cells and were assigned to controls versus SIRPabody treatment. Cynomolgus nonhuman primates were administered a single intravenous infusion of SIRPabody at 3, 10, or 30 mg/kg.

Results: SIRPabodies selectively bound to dual antigen-expressing tumor cells in the presence of a large antigen sink. SIRPabody reduced tumor burden and extended survival in mouse xenograft lymphoma models. SIRPabody caused no significant toxicity in nonhuman primates.

Conclusions: These findings establish SIRPabodies as a promising approach to deliver the therapeutic benefit of CD47–SIRPα blockade specifically toward tumor cells. SIRPabodies may be applied to additional cancer types by grafting SIRPα onto other tumor-specific therapeutic antibodies. Clin Cancer Res; 22(20); 5109–19. ©2016 AACR.
Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients
Authors: Tada Kohei , Kitano Shigehisa , Shoji Hirokazu , Nishimura Takashi , Shimada Yasuhiro , Nagashima Kengo , Aoki Kazunori , Hiraoka Nobuyoshi , Honma Yoshitaka , Iwasa Satoru , Okita Natsuko , Takashima Atsuo , Kato Ken , Yamada Yasuhide , Katayama Naoyuki , Boku Narikazu , Heike Yuji , Hamaguchi Tetsuya
Published: April 2016

It remains unclear whether the immunologic status of cells in peripheral blood can be used as a prognostic indicator of response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunologic status of 40 patients with MCRC who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4+ TEM, or low CD8+ TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) was correlated with significantly shorter progression-free survival compared with none or one (n = 19, 47.5%; P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% confidence interval, 2.5–34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of patients with MCRC treated with first-line chemotherapy. Cancer Immunol Res; 4(7); 592–9. ©2016 AACR.
A Psychometric Evaluation of the Threadgold Communication Tool for Persons with Dementia
Authors: Strøm Benedicte Sørensen , Engedal Knut , Grov Ellen-Karine
Published: April 2016

Background: The objective of this study was to investigate the psychometric properties of the Threadgold Communication Tool (TCT). Method: Internal consistency reliability was measured using Cronbach's α coefficient and inter-item correlation. Test-retest was performed to examine the instrument's stability. Exploratory principal component analysis (PCA) with oblimin rotation was carried out to evaluate construct validity. Finally, the score on each item of the TCT was correlated with the person's Mini Mental State Examination (MMSE) and Barthel Index of activities of daily living scores. Results: A total of 51 persons participated, with a mean age of 86.7 (SD 6.6) years, of whom 46 were women with moderate-to-severe dementia [mean MMSE score 7.5 (SD 6.7)]. There were two measurement points 2 weeks apart. The results showed a satisfactory level for internal consistency and a high test-retest reliability (r = 0.76). The corrected item-total correlation ranged between 0.50 and 0.87, and a two-factor structure was revealed at the PCA. ‘Vocalizing' seemed to measure another aspect of communication and was the only item which was negatively loaded. Conclusion: Despite the low sample size in this study, the results revealed the TCT as a reliable and valid instrument, suitable for measuring communication among people with dementia. We suggest clarifying the understanding of ‘vocalizing' before considering removing it from the scale.
Idiopathic Atrial Fibrillation and Coronary Arteriovenous Fistulae: Is There a Link?
Authors: Jamali Hina K. , Raza Umara , Waqar Fahad
Published: April 2016

Despite being one of the most prevalent cardiac arrhythmias, the cause of atrial fibrillation (AF) in a vast majority of patients remains unknown. There is growing evidence of associated AF in patients diagnosed with coronary arteriovenous fistula. In this discussion, we have included an example of a patient who presented with new-onset AF and was subsequently diagnosed with an anomalous fistula between the right coronary artery and the superior vena cava. Definitive treatment of the fistula resulted in permanent resolution of the AF. Based on this case and a similar case reported in the literature, it is proposed that further research will unmask this possibly underdiagnosed and very treatable cause of AF.
Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model
Authors: Kao Chi-Ya , He Zhisong , Henes Kathrin , Asara John M. , Webhofer Christian , Filiou Michaela D. , Khaitovich Philipp , Wotjak Carsten T. , Turck Christoph W.
Published: April 2016

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo 15N metabolic labeling combined with mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus between shocked and nonshocked (control) mice, with and without fluoxetine treatment. In silico pathway analyses revealed an upregulation of the citric acid cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic fluoxetine treatment prevented decreased citric acid cycle activity in NAc and ACC and ameliorated conditioned fear response in shocked mice. Our results shed light on the role of energy metabolism in PTSD pathogenesis and suggest potential therapy through mitochondrial targeting.
Cauda Equina Syndrome Secondary to Leptomeningeal Carcinomatosis of Gastroesophageal Junction Cancer
Authors: Alkhotani Amal , Alrishi Nouf , Alhalabi M. Salem , Hamid Tahira
Published: April 2016

Leptomeningeal carcinomatosis (LMC) is a diffuse or multifocal malignant infiltration of the pia matter and arachnoid membrane. The most commonly reported cancers associated with LMC are breast, lung, and hematological malignancies. Patients with LMC commonly present with multifocal neurological symptoms. We report a case of LMC secondary to gastroesophageal junction cancer present initially with cauda equina syndrome. A 51-year-old male patient with treated adenocarcinoma of the gastroesophageal junction presented with left leg pain, mild weakness, and saddle area numbness. Initial radiological examinations were unremarkable. Subsequently, he had worsening of his leg weakness, fecal incontinence, and urine retention. Two days later, he developed rapidly progressive cranial neuropathies including facial diplegia, sensorineural hearing loss, dysarthria, and dysphagia. MRI with and without contrast showed diffuse enhancement of leptomeninges surrounding the brain, spinal cord, and cauda equina extending to the nerve roots. Cerebrospinal fluid cytology was positive for malignant cells. The patient died within 10 days from the second presentation. In cancer patients with cauda equina syndrome and absence of structural lesion on imaging, LMC should be considered. To our knowledge, this is the first case of LMC secondary to gastroesophageal cancer presenting with cauda equina syndrome.
Re-significação da identidade cultural dos Terêna de Ekeruá: uma abordagem da produção cultural subalterna
Authors: Losnak Sérgio Ricardo
Published: April 2016

Este artigo traça a trajetória dos índios Terêna, desde sua origem na região do Chaco à fixação de um de seus grupos na Aldeia de Ekeruá, localizada na Reserva Indígena de Araribá, Centro Oeste Paulista. Os constantes contatos com seus parentes indígenas e com os não indígenas, durante seus deslocamentos em terras brasileiras são mostrados como processos de assimilação, aculturação, re-significação e desterritorialização dos quais foram sujeitos durante estes últimos dois séculos. É neste contexto mais difuso proporcionado pela nova ordem globalizante que se verifica ações marcantes dos indígenas de Ekeruá na reconstrução de sua identidade, na recuperação de seus saberes e fazeres tradicionais, e ao mesmo tempo a transformação de sua produção cultural em produto. Por meio da identificação da diferença e da desigualdade dos quais estes cidadãos brasileiros estão sujeitos é que a pesquisa de campo identificou resultados concretos de empoderamento proporcionados por sua produção cultural rica e diversa, pelo reconhecimento de sua própria identidade re-significada e pelas novas possibilidades de desenvolvimento sustentável do grupo.
Entre páginas policiais e galerias de arte: a poética do olhar de Alberto Bitar em “corte Seco”
Authors: Neves Ivânia Dos Santos , Cardoso Ana Penaforte Shirley
Published: April 2016

O tema central da série fotográfica “Corte Seco”, de Alberto Bitar, é a violência urbana na cidade de Belém. Diferente do que acontece nos cadernos de polícia, de forma poética, ele retrata cenas de pessoas que foram assassinadas e estão à espera de remoção. Neste artigo, tomando como referência o paradigma indiciário, procuramos mostrar como os detalhes registrados por Bitar revelam aspectos da história do presente e das práticas culturais em que estas pessoas estão envolvidas.
Tudo sobre minha mãe e algo sobre a teoria queer e o universo almodovariano: aproximações entre cinema e educação
Authors: Míguez Antón Castro , Fonseca Estrella Da
Published: April 2016

O objetivo deste artigo é apresentar algumas reflexões sobre a relevância da teoria queer para os estudos fílmicos (STAM, 2003; LOPES, 2006), no sentido de se compreender, a partir dos pressupostos de que o cinema exerce uma espécie de “pedagogização da sexualidade” (LOURO, 2008), a importância do cinema queer em problematizar as categorias identitárias de gêneros e sexualidades. Para tanto, apresentamos algumas reflexões sobre as relações entre cinema queer e educação (MÍGUEZ, 2014) e uma proposta de leitura de Tudo sobre minha mãe (Pedro Almodóvar, 1999), em que se destaca sua proximidade (e, em algum momento, seu distanciamento) de uma perspectiva queer.
Specific instruments to evaluate their knowledge of asthma: a systematic review
Authors: Roncada Cristian , Dias Caroline P. , Sarria Edgar E. , Pitrez Paulo M.
Published: April 2016

Introduction: The evaluation of the level of asthma knowledge is one of the major outcomes for studies related to educational programs on asthma. Hence, identifying the particular instrument suitable for this outcome is essential to the success of studies in this field. Objective: To identify specific instruments to assess knowledge of asthma, analyzing the main characteristics and quality criteria for psychometric validation. Methods: A systematic review was performed to identify outcome measures available to assess knowledge of asthma in children, adolescents, guardians and caregivers. We applied the logic of search in Medline, Lilacs, Scopus, DirectScience, PsycINFO, Cochrane and Tripdatabase. Articles were included by description of the development and psychometric testing of the questionnaires on asthma knowledge. Quality criteria for content validity, construct validity, internal consistency and reproducibility were evaluated and assigned as “positive”, “intermediate” or “negative” rating. Results: Twenty-two instruments were included in the study. None of them had a positive review for all four evaluated psychometric properties. Six received positive or intermediate classification, one of these was developed in Portuguese-BR. Conclusion: Currently, there are 22 questionnaires available to assess the level of asthma knowledge, but most of the instruments do not have full psychometric validation
Participação dos cidadãos e saneamento básico: panorama da legislação nacional
Authors: Souza Cezarina Maria Nobre
Published: April 2016

Tendo em vista contribuir para o aprofundamento do estudo sobre a partici­pação dos cidadãos na área de saneamento, temática ainda recente e pouco discutida, este trabalho objetiva identificar, no marco legal nacional do saneamento, referências concer­nentes à participação dos cidadãos, as quais são analisadas à luz dos conceitos de cidadania, empoderamento e cultura política. As dezoito referências identificadas abordam a participa­ção na perspectiva do controle social e podem ser classificadas em dois grupos: 1) promotoras da participação e 2) marcadas pela dubiedade, uma vez que, ao mesmo tempo, incentivam e limitam a ação participativa. Conclui-se que é forçoso reconhecer os avanços alcançados, re­presentados pela existência da legislação em si, sabendo-se que, contudo, são insuficientes e requerem ampliação para a efetividade da par­ticipação