bluuebunny/crossref_metadata_2025 huggingface dataset:
Xiyanping Plus Azithromycin Chemotherapy in Pediatric Patients with Mycoplasma pneumoniae Pneumonia: A Systematic Review and Meta-Analysis of Efficacy and Safety
Authors: Li Qiao , Li Zhi-Yong , Zhang Jie , Guo Wen-Na , Xu Xiao-Meng , Sun Fa-Xin , Xu Hui
Published: August 2019

Background. Xiyanping injection (XYP) is a well-known Chinese medicinal preparation reputed as a most effective alternative to antibiotics. XYP has been widely used in combination therapies to treat various infectious diseases, among which XYP plus azithromycin (AZM) chemotherapy is often used for the treatment of Mycoplasma pneumoniae pneumonia in pediatric patients (p-MPP) in China. Objective. The present study just aimed to confirm whether XYP can improve the clinical efficacy and safety of AZM chemotherapy for p-MPP by performing meta-analysis and systematic review. Methods. A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The randomized controlled trials (RCTs) concerning XYP plus AZM chemotherapy for p-MPP were selected, for which the main outcomes included overall response rate (ORR), antipyretic time, cough disappearance time, lung wet Rales disappearance time, hospitalization duration, and adverse drug reactions (ADRs). Based on the data extracted, the meta-analysis was conducted by using a standard data extraction form. Results. Nine RCTs involving 963 patients were included for meta-analysis. More concretely, the combination therapy showed the risk ratio (RR) and 95% confidence intervals (CI) of ORR and ADRs as (RR, 1.21 [95% CI, 1.15, 1.28]) and (RR, 0.37 [95% CI, 0.27, 0.51]), respectively. And other major outcomes were as follows: hospitalization durations (standard mean difference (SMD), −1.32 [95% CI, −1.48, −1.16]), antipyretic time (SMD, −1.26 [95% CI, −1.70, −0.83]), cough disappearance time (SMD, −1.07 [95% CI, −1.38, −0.75]), and the disappearance time of lung wet Rales (SMD, −0.83 [95% CI, −1.07, −0.60]). With statistically significant differences in various aspects, the combination therapy plus XYP displayed obvious advantages in contrast to AZM alone. Conclusion. Overall, XYP might reduce the incidence of ADRs and significantly improve the clinical efficacy for p-MPP receiving AZM chemotherapy.
Rare Isolated Pectoralis Minor Tear from a Noncontact Injury: Case Report and Review of the Literature
Authors: Vance Danica D. , Qayyum Usama , Jobin Charles M.
Published: August 2019

Isolated pectoralis minor tears are rare orthopedic injuries often in weightlifters or contact sports and should be included in the differential when evaluating athletes with anterior shoulder pain. These injuries are often mistaken for pectoralis major muscle stains and tears. Advanced imaging with MRI helps define the anatomic location and grade of injury. Treatment is usually conservative with full return to activity after a brief period of rest for a few weeks. The purpose of this article is to present a case report and review of the literature on the clinical evaluation, imaging, and treatment of an isolated pectoralis minor tears.
Effects of Working Medium Gases on Emission Spectral and Temperature Characteristics of a Plasma Igniter
Authors: Chen Gao Cheng , He Li Ming , Zhao Bing Bing , Zhang Hua Lei , Zhao Zi Chen , Zeng Hao , Lei Jian Ping , Liu Xiong
Published: August 2019

Ar, N2, O2, and N2-O2 mixture under different O2 components were separately used as the working medium gas of a plasma igniter to study the influence of working-medium-gas type and O2 concentration on emission spectral and temperature characteristics of a direct-current arc plasma igniter. The emission spectra of the plasma jet were also analyzed using the optical emission spectroscopy method, and the influence rule of working medium gas and O2 concentration on electron temperature and vibrational temperature of the plasma jet was calculated and analyzed. The experimental results show that the emission spectra of the plasma jet had significant differences when diverse working gases were used as the working medium of the igniter. With increasing O2 concentration in the working medium gas, the spectral line intensity of oxygen-containing particles in emission spectra of the plasma jet was significantly enhanced, and the spectral intensities of nitrogen-containing particles, NO molecular bands, the second positive system of N2C3∏u−B3∏g, and the first negative system of N2+B2∑u+−X2∑u+ were also enhanced obviously. Both electron and vibrational temperature of the plasma jet increased gradually with increasing O2 concentration in the working medium gas, and first increased and then decreased with increasing axial distance from the plasma jet.
Synthesis of Bi0.5Li0.5TiO3 Nanoparticles by Sol-Gel Method for Photocatalytic Methylene Blue Degradation and Antibacterial Activity
Authors: Le Thanh T. Hai , Phung Bao Quoc , Dang Dung Duc
Published: August 2019

Facile synthesis of nanomaterials for advanced characterization and application is gaining interest from many researchers. In this study, Bi0.5Li0.5TiO3 nanoparticles were synthesized through the sol-gel method. The photocatalytic activity of the synthesized Bi0.5Li0.5TiO3 was investigated for degradation of methylene blue (MB) under UV irradiation. A photocatalytic efficiency of 74% was found at 150 min when the degradation was performed in the basic media, and the kinetic rate constant was calculated equal to 0.0093 min-1. The antibacterial activity of Bi0.5Li0.5TiO3 nanoparticles was evaluated against E. coli, and the results showed considerable efficiency.
Dynamic Interactions between Intraday Returns and Trading Volume on the CSI 300 Index Futures: An Application of an SVAR Model
Authors: Wang Susheng , Li Guanglu , Wang Junbo
Published: August 2019

The results of data description using ten samples of high‐frequency data to describe the intraday characteristics of the CSI 300 index futures show that there is no significant summit and fat tail phenomenon. The Granger causality test shows that there is not only a two‐way Granger causality between returns and trading volume but also an instantaneous causality relationship. Therefore, the A‐type SVAR models are identified and estimated after setting up constraints, and all the models are tested stable. Subsequent variance decomposition results show that the residual disturbance of returns can be explained more than 99.9% by its lagged terms; the residual disturbance of trading volume explained by its lagged terms and returns is quite different, and the range of interpretation is very wide. The impulse response results show that the market responds very quickly to new information. When a shock is reached, the market can reach a new equilibrium point after about three observation time periods. This shows that the market is able to digest new information quickly, and arbitrage trading becomes very difficult in this market.
Characterizing Software Stability via Change Propagation Simulation
Authors: Pan Weifeng , Jiang Haibo , Ming Hua , Chai Chunlai , Chen Bi , Li Hao
Published: August 2019

Software stability means the resistance to the amplification of changes in software. It has become one of the most important attributes that affect maintenance cost. To control the maintenance cost, many approaches have been proposed to measure software stability. However, it is still a very difficult task to evaluate the software stability especially when software becomes very large and complex. In this paper, we propose to characterize software stability via change propagation simulation. First, we propose a class coupling network (CCN) to model software structure at the class level. Then, we analyze the change propagation process in the CCN by using a simulation way, and by doing so, we develop a novel metric, SS (software stability), to measure software stability. Our SS metric is validated theoretically using the widely accepted Weyuker’s properties and empirically using a set of open source Java software systems. The theoretical results show that our SS metric satisfies most of Weyuker’s properties with only two exceptions, and the empirical results show that our metric is an effective indicator for software quality improvement and class importance. Empirical results also show that our approach has the ability to be applied to large software systems.
TAS6417/CLN-081 Is a Pan-Mutation–Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically Relevant EGFR Mutations
Authors: Udagawa Hibiki , Hasako Shinichi , Ohashi Akihiro , Fujioka Rumi , Hakozaki Yumi , Shibuya Mikiko , Abe Naomi , Komori Toshiharu , Haruma Tomonori , Terasaka Miki , Fujita Ryoto , Hashimoto Akihiro , Funabashi Kaoru , Yasuda Hiroyuki , Miyadera Kazutaka , Goto Koichi , Costa Daniel B. , Kobayashi Susumu S.
Published: August 2019

Despite the worldwide approval of three generations of EGFR tyrosine kinase inhibitors (TKI) for advanced non–small cell lung cancers with EGFR mutations, no TKI with a broad spectrum of activity against all clinically relevant mutations is currently available. In this study, we sought to evaluate a covalent mutation-specific EGFR TKI, TAS6417 (also named CLN-081), with the broadest level of activity against EGFR mutations with a prevalence of ≥1%. Lung cancer and genetically engineered cell lines, as well as murine xenograft models were used to evaluate the efficacy of TAS6417 and other approved/in-development EGFR TKIs (erlotinib, afatinib, osimertinib, and poziotinib). We demonstrate that TAS6417 is a robust inhibitor against the most common EGFR mutations (exon 19 deletions and L858R) and the most potent against cells harboring EGFR-T790M (first/second-generation TKI resistance mutation). In addition, TAS6417 has activity in cells driven by less common EGFR-G719X, L861Q, and S768I mutations. For recalcitrant EGFR exon 20 insertion mutations, selectivity indexes (wild-type EGFR/mutant EGFR ratio of inhibition) favored TAS6417 in comparison with poziotinib and osimertinib, indicating a wider therapeutic window. Taken together, we demonstrate that TAS6417 is a potent EGFR TKI with a broad spectrum of activity and a wider therapeutic window than most approved/in-development generations of EGFR inhibitors.

Implications:

TAS6417/CLN-081 is a potent EGFR TKI with a wide therapeutic window and may be effective in lung cancer patients with clinically relevant EGFR mutations.
Principal Component Analysis Based on Graph Laplacian and Double Sparse Constraints for Feature Selection and Sample Clustering on Multi-View Data
Authors: Wu Ming-Juan , Gao Ying-Lian , Liu Jin-Xing , Zhu Rong , Wang Juan
Published: August 2019

Principal component analysis (PCA) is a widely used method for evaluating low-dimensional data. Some variants of PCA have been proposed to improve the interpretation of the principal components (PCs). One of the most common methods is sparse PCA which aims at finding a sparse basis to improve the interpretability over the dense basis of PCA. However, the performances of these improved methods are still far from satisfactory because the data still contain redundant PCs. In this paper, a novel method called PCA based on graph Laplacian and double sparse constraints (GDSPCA) is proposed to improve the interpretation of the PCs and consider the internal geometry of the data. In detail, GDSPCA utilizes L2,1-norm and L1-norm regularization terms simultaneously to enforce the matrix to be sparse by filtering redundant and irrelative PCs, where the L2,1-norm regularization term can produce row sparsity, while the L1-norm regularization term can enforce element sparsity. This way, we can make a better interpretation of the new PCs in low-dimensional subspace. Meanwhile, the method of GDSPCA integrates graph Laplacian into PCA to explore the geometric structure hidden in the data. A simple and effective optimization solution is provided. Extensive experiments on multi-view biological data demonstrate the feasibility and effectiveness of the proposed approach.
Acute Stroke Treatment in Patients with Basilar Artery Occlusion: A Single-Center Observational Study
Authors: Francalanza Isabella , Ciacciarelli Antonio , Caragliano Antonio Armando , Casella Carmela , Cotroneo Masina , Dell’Aera Cristina , Fazio Maria Carolina , Grillo Francesco , Pitrone Antonio , Vinci Sergio Lucio , Trimarchi Giuseppe , Musolino Rosa Fortunata , La Spina Paolino
Published: August 2019

Background: Acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) represents 1–4% of all ischemic strokes. BAO results in strokes associated with a high risk of a poor functional outcome and, in 86–95% of the untreated cases, it results in death because of the vital cerebral structures involved. Diagnosis can be delayed because of the variability in presenting symptoms, and acute treatment is often attempted even beyond 6 h from symptoms onset because of the high risk of a fatal prognosis. Objective: In this observational study, we retrospectively analyzed patients with AIS due to BAO referred to the stroke center of the University Hospital of Messina. We aimed to assess prognostic factors and to evaluate the association between clinical outcome and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and collateral status. Method: BAO was confirmed by cerebral computed tomography (CT) angiography or cerebral angiography. All patients underwent CT scan and magnetic resonance imaging (MRI). We assessed the pc-ASPECTS on diffusion-weighted imaging (DWI) MR images and the Posterior Circulation Collateral Score (PC-CS) for every patient. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS). Results: The study population consisted of 27 patients; 16 males and 11 females. The mean age was 66 (±14) years. We observed a favorable outcome (mRS 0–3) in 40.7% of cases, 25.9% reached mRS 0–2, and 29.6% had a poor clinical outcome (mRS 4–5). Patient survival was 70.4%, whereas 8 patients died (29.6%). In 7 patients, pc-ASPECTS was ≥7. According to the PC-CS, 33.3% had moderate collaterals and 63.0% had good collateral status prior to receiving the treatment. Favorable outcome was significantly associated with age, NIHSS score at admission, pc-ASPECTS, hypercholesterolemia, and female sex but not with the other risk factors. Conclusions: In our study, we found that younger age, low NIHSS score at admission, and high pc-ASPECTS, but not onset to treatment time, are associated with a favorable clinical outcome. Transferred patients did not have a significantly poorer outcome. These findings confirm that acute stroke treatment improves clinical outcome in BAO patients, in spite of a delayed diagnosis and an extended therapeutic window, considering lesion volume and localization in DWI MRI.
Condicionantes de la retención estudiantil en «escuelas de segunda oportunidad» en Chile
Authors: Espinoza Óscar , González Luis Eduardo , Castillo Dante , Neut Sebastián
Published: August 2019

(analítico) El artículo busca comprender las percepciones que estudiantes, docentes
y directivos tienen respecto de los aspectos que inciden en la retención de adolescentes atendidos en «escuelas de segunda oportunidad» en Santiago de Chile. La información proviene de 56 entrevistas semiestructuradas, aplicadas a tales actores en los Centros de Educación Integrada de Jóvenes y Adultos seleccionados. Las entrevistas fueron sometidas a un análisis narrativo etnográfico y, para su codificación, se utilizó el software Atlas.ti. Los actores identificaron como las condicionantes más importantes la contextualización en la exigencia académica y evaluativa, el acompañamiento afectivo a estudiantes y que la escuela sea acogedora. Finalmente, se vislumbra la necesidad de revisar los procesos de reinserción escolar para un grupo no menor de niños y jóvenes que no se adaptan a condiciones «normales».
Conceptualizaciones, perspectivas y referentes de la participación en la educación primaria, México
Authors: Serrano-Arenas Denys , Ochoa-Cervantes Azucena , Arcos-Miranda Evaristo
Published: August 2019

(analítico) Se analizan las conceptualizaciones sobre participación que refieren niñas y niños (entre cinco y ocho años de edad), así como las de sus profesores y familiares, en tres escuelas de educación primaria de zonas urbano-marginales en México. El método cuasietnográfico fue utilizado para describir e interpretar los significados obtenidos de las entrevistas individuales, grupos focales y el dibujo infantil. La información fue analizada por medio del análisis de contenido categorial. Los resultados muestran que, conforme la infancia avanza en su escolarización, los significados sobre participación se acotan a emitir opiniones cuando le son solicitadas por los profesores. Se identifica al adultocentrismo y obediencia como los obstáculos de la construcción de escuelas inclusivas, concluyendo que es imperativo generar diálogos entre los referentes conceptuales sobre participación provenientes del espacio familiar y educativo.
Representações de professores e gestores de uma escola que se diz pesquisadora
Authors: Galvão Idelbrando Amália
Published: August 2019

(analítico) O presente texto é parte integrante dos resultados de uma pesquisa em Educação que se propõe a refletir tanto sobre as representações de professores e gestores de uma escola que se autointitula Escola Pesquisadora como também sobre a relação entre suas práticas e a construção de conhecimento de seus alunos. Os procedimentos metodológicos empreendidos foram: entrevistas semiestruturadas com 5 gestores, 8 professores e 10 alunos egressos, bem como análises documentais e observação participante. A perspectiva teórica que se buscou seguir foi a antropologia dialética, a partir da obra de Henri Lefebvre, para quem as representações se formam entre o vivido e o concebido de sujeitos determinados. O desdobramento das ações dessa escola inovadora proporcionou aos professores a ocupação de um lugar diferenciado: o de sujeitos de criação.
Concepciones de niño y modos de relación de cuidadores y profesionales con niños institucionalizados, Colombia
Authors: Sánchez-Reyes José Eduardo , Cantor-Jiménez Jackeline , Castro-Sardi Ximena , Bolaños Yamileth
Published: August 2019

Este artículo explora las diferentes concepciones de niño y las formas
de relación que tienen los profesionales y los cuidadores de niños
y adolescentes en una institución de protección en Colombia. Se
parte del supuesto que tanto las concepciones de sujeto, como los
modos de relación orientan las prácticas de los cuidadores en la institución.
Durante el estudio se analizan 13 entrevistas realizadas a
cuidadores y profesionales de la institución de protección, observaciones
participantes y documentos. Emergen tres concepciones de
niño: el niño como hijo de Bienestar, el niño resiliente, y el niño en
carencia. Los profesionales y cuidadores se encuentran en tensión
entre su labor profesional de restitución de derechos y la labor de
crianza tradicionalmente desempeñada por las familias.
Formação profissional e a relação com a sucessão geracional entre jovens rurais, Brasil
Authors: Breitenbach Raquel , Corazza Graziela
Published: August 2019

O objetivo do estudo foi analisar as perspectivas de permanência no meio rural e sucessão familiar na agricultura dos jovens e das jovens rurais estudantes do Instituto Federal de Educação, Ciência e Tecno-logia do Rio Grande do Sul, Campus Sertão. Este estudo é uma pes-quisa quantitativa. Os dados empíricos foram obtidos com questio-nário que contemplou a totalidade dos jovens e das jovens rurais do Campus e posteriormente foram analisados pelo programa estatísti-co PSPP (análises de frequência e correlação, com teste chi-square). Concluiu-se que os jovens rurais do sexo masculino são mais incenti-vados e têm mais interesse em serem gestores e sucessores das propriedades rurais e em permanecer no campo. Estudar na área de ciências agrárias também aumenta o interesse em serem sucessores, mas não diminui a diferença de gênero.
Significados do mundo do crime para adolescentes em medida socioeducativa de internação, Brasil
Authors: Coscioni Vinicius , Graebin de Farias Bruno , Rosa Edinete Maria , Koller Sílvia Helena
Published: August 2019

O objetivo deste estudo é investigar significados atribuídos ao mundo do crime por adolescentes em medida socioeducativa de internação. Os participantes do estudo foram 25 adolescentes (15 a 19 anos) do sexo masculino internados em quatro unidades socioeducativas nos Estados do Rio Grande do Sul e Espírito Santo, Brasil. Foram realizados dois grupos focais em cada Estado, interpretados por Análise Temática. Os significados expressos pelos participantes revelaram que a vinculação ao mundo do crime atende a necessidades de segurança econômica, fortalecimento da identidade pessoal, reconhecimento social, senso de pertencimento e proteção física, consistindo em um processo de resiliência oculta. A compreensão das perspectivas dos adolescentes sobre o mundo do crime pode informar práticas de atendimento capazes de atender necessidades materiais e simbólicas e prevenir riscos.
DNA Barcoding revealing the occurrence of Isarachnanthus (Cnidaria: Anthozoa: Ceriantharia) in Cape Verde
Authors: Stampar Sérgio Nascimento , Lopes Celine S.S. , Angelis Stefany Archangelo de , Morandini André Carrara
Published: August 2019

The occurrence of Isarachnanthus Carlgren, 1924 (Cnidaria: Anthozoa: Ceriantharia) specimens in Cape Verde Islands is recorded. Identification of the tube anemone species Isarachnanthus maderensis (Johnson, 1861) was possible based on DNA Barcoding. A discussion on biogeographic patterns associated with ocean circulation and life cycle is presented.
A new species of Gnomidolon Thomson, 1864 and taxonomic and geographical notes on Hexoplonini (Coleoptera, Cerambycidae) from Colombia
Authors: García Kimberly
Published: August 2019

A new species of Gnomidolon from Colombia is described and illustrated: Gnomidolon franciscoi sp. nov.; and the previous key for the genus is modified to include the new species. The male of Gnomidolon hamatum Linsley, 1935 is described and illustrated for the first time. Additionally, a chromatic variation in some species of Hexoplonini from Colombia is reported and the geographical distribution of four species is expanded.
Monotony in the consumption of fruits and vegetables and food environment characteristics
Authors: Mendonça Raquel De Deus , Lopes Mariana Souza , Freitas Patrícia Pinheiro , Campos Suellen Fabiane , Menezes Mariana Carvalho de , Lopes Aline Cristine Souza
Published: August 2019

OBJECTIVE: To analyze the quantity and diversity in the consumption fruits and vegetables, as well as its relationship with the consumer’s purchase characteristics and food environment. METHODS: Baseline study stemming from a controlled and randomized community trial investigating a sample representative of Primary Health Care services (Health Academy Program) of Belo Horizonte, state of Minas Gerais. The intake of fruits and vegetables was analyzed in servings/day, whereas diversity was assessed by the Food Frequency Questionnaire. Users were also questioned on the frequency, purchase location and availability of these foods at their households. To assess the consumer’s food environment, commercial establishments within a 1.6 km radius around the program unit sampled were audited. RESULTS: 3,414 adults and older adults (88.1% women) were investigated, as well as 336 commercial establishments, in 18 units of the Health Academy Program. The average consumption of fruits and vegetables was adequate [5.4 (SD = 2.1) servings/day] but monotonous, with average daily intake of two different types. In the establishments audited, a good diversity (77.7% and 85.0%) and variety (74.5% and 81.4%) of fruits and vegetables was observed, although with lower quality of vegetables (60.4%). After adjusting for sociodemographic variables, we identified that knowledge on food crops (p = 0.006), increased monthly availability of fruits at households (p < 0.001), and greater variety of fruits (p = 0.03) and quality of vegetables (p = 0.05) in commercial establishments could improve the quantitative intake of fruits and vegetables, whereas a greater variety of fruits (p = 0.008) would increase consumption diversity. CONCLUSIONS: The intake of fruits and vegetables was quantitatively adequate but monotonous, being influences by the consumer environment. Such results highlight the need for improving educational actions in health services and programs, in addition to acting on the consumer environment, aiming to promote and maintain the adequate and diversified consumption, as recommended by Brazilian guidelines for proper and healthy eating.
Maternal characteristics and type of prenatal care associated with peregrination before childbirth
Authors: Mendes Rosemar Barbosa , Santos José Marcos De Jesus , Prado Daniela Siqueira , Gurgel Rosana Queiroz , Bezerra Felipa Daiana , Gurgel Ricardo Queiroz
Published: August 2019

OBJECTIVE: To analyze the maternal characteristics and type of prenatal care associated with peregrination before childbirth among pregnant women in a northeastern Brazilian state. METHODS: Quantitative and transversal study, with descriptive and analytical approaches, part of the Nascer em Sergipe research held between June 2015 and April 2016. A total of 768 puerperal women proportionally distributed across all maternities of the state (n = 11) were evaluated. Data were collected in interviews and from prenatal records. The associations between antepartum peregrination and the exposure variables were described in absolute and relative frequencies, crude and adjusted odds ratios and their respective confidence intervals. RESULTS: Antepartum peregrination was reported by 29.4% (n = 226) of the interviewees, most of whom sought care in a single service before the current one (87.6%; n = 198). It should be noted that antepartum peregrination was less frequent among women aged ≥ 20 years old (OR = 0.50; 95%CI 0.34–0.71), with high education level (OR = 0.42; 95%CI 0.31–0.59) and a paid job (adjusted OR = 0.59; 95%CI 0.41–0.82), who had been instructed during prenatal care about the referral maternity for childbirth (adjusted OR = 0.88; 95%CI 0.42–0.92), and who used the private service to receive prenatal (adjusted OR = 0.44; 95%CI 0.18–0.86) or childbirth (adjusted OR = 0.96; 95%CI 0.66–0.98) care. No statistical evidence of associations between gestational characteristics and the occurrence of peregrination was observed. CONCLUSIONS: Antepartum peregrination suffers interference from the mother’s socioeconomic characteristics, the type of prenatal care received and the source of funding for childbirth.
2018 George Lyman Duff Memorial Lecture
Authors: McPherson Ruth
Published: August 2019

Recent studies have led to a broader understanding of the genetic architecture of coronary artery disease and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on coronary artery disease risk. The tools applied include genome-wide association studies encompassing over 200 000 individuals complemented by bioinformatic approaches including imputation from whole-genome data sets, expression quantitative trait loci analyses, and interrogation of ENCODE (Encyclopedia of DNA Elements), Roadmap Epigenetic Project, and other data sets. Over 160 genome-wide significant loci associated with coronary artery disease risk have been identified using the genome-wide association studies approach, 90% of which are situated in intergenic regions. Here, I will describe, in part, our research over the last decade performed in collaboration with a series of bright trainees and an extensive number of groups and individuals around the world as it applies to our understanding of the genetic basis of this complex disease. These studies include computational approaches to better understand missing heritability and identify causal pathways, experimental approaches, and progress in understanding at the molecular level the function of the multiple risk loci identified and potential applications of these genomic data in clinical medicine and drug discovery.
Plaque Calcification
Authors: Akers Emma J. , Nicholls Stephen J. , Di Bartolo Belinda A.
Published: August 2019

Vascular calcification (VC) is strongly associated with all-cause mortality and is an independent predictor of cardiovascular events. Resulting from its complex, multifaceted nature, targeted treatments for VC have not yet been developed. Lipoproteins are well characterized in the pathogenesis of atherosclerotic plaques, leading to the development of plaque regressing therapeutics. Although their roles in plaque progression are well documented, their roles in VC, and calcification of a plaque, are not well understood. In this review, early in vitro data and clinical correlations suggest an inhibitory role for HDL (high-density lipoproteins) in VC, a stimulatory role for LDL (low-density lipoprotein) and VLDL (very low-density lipoprotein) and a potentially causal role for Lp(a) (lipoprotein [a]). Additionally, after treatment with a statin or PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, plaque calcification is observed to increase. With the notion that differing morphologies of plaque calcification associate with either a more stable or unstable plaque phenotype, uncovering the mechanisms of lipoprotein-artery wall interactions could produce targeted therapeutic options for VC.
Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice
Authors: Li Jianing , Pijut Sonja S. , Wang Yuhuan , Ji Ailing , Kaur Rupinder , Temel Ryan E. , van der Westhuyzen Deneys R. , Graf Gregory A.
Published: August 2019

Objective:

Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice.

Approach and Results:

We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infusion of bile acid. The proximal small bowel was perfused with bile acid micelles. In high-fat, high-cholesterol–fed mice, the presence of a CETP transgene increased biliary cholesterol secretion at the expense of transintestinal cholesterol elimination. The increase in biliary cholesterol secretion was not associated with increases in hepatic SR-BI (scavenger receptor BI) or ABCG5 (ATP-binding cassette G5) ABCG8. The decline in intestinal cholesterol secretion was associated with an increase in intestinal Niemann-Pick disease, type C1, gene-like 1 mRNA. Finally, we followed the delivery of HDL (high-density lipoprotein) or LDL (low-density lipoprotein) cholesteryl esters (CE) from plasma to bile and intestinal perfusates. HDL-CE favored the biliary pathway. Following high-fat feeding, the presence of CETP directed HDL-CE away from the bile and towards the intestine. The presence of CETP increased LDL-CE delivery to bile, whereas the appearance of LDL-CE in intestinal perfusate was near the lower limit of detection.

Conclusions:

Biliary and intestinal cholesterol secretion can be simultaneously measured in mice and used as a model to examine factors that alter cholesterol elimination. Plasma factors, such as CETP, alter the route of cholesterol elimination from the body. Intestinal and biliary cholesterol secretion rates are independent of transhepatic or transintestinal delivery of HDL-CE, whereas LDL-CE was eliminated almost exclusively in the hepatobiliary pathway.
Association of Cognitive Impairment With Treatment and Outcomes in Older Myocardial Infarction Patients: A Report From the NCDR Chest Pain–MI Registry
Authors: Bagai Akshay , Chen Anita Y. , Udell Jacob A. , Dodson John A. , McManus David D. , Maurer Mathew S. , Enriquez Jonathan R. , Hochman Judith , Goyal Abhinav , Henry Timothy D. , Gulati Martha , Garratt Kirk N. , Roe Matthew T. , Alexander Karen P.
Published: August 2019

Background

Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (
MI
) patients with cognitive impairment.

Methods and Results

Patients ≥65 years old with MI in the
NCDR
(National Cardiovascular Data Registry) Chest Pain–
MI
Registry between January 2015 and December 2016 were categorized by presence and degree of chart‐documented cognitive impairment. We evaluated whether cognitive impairment was associated with all‐cause in‐hospital mortality after adjusting for known prognosticators. Among 43 812 ST‐segment–elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non–ST‐segment–elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%;
P
=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%;
P
<0.001). Compared with
NSTEMI
patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (
STEMI
: odds ratio, 2.2, 95%
CI
, 1.8–2.7;
NSTEMI
: odds ratio, 1.7, 95%
CI
, 1.4–2.0) and mild cognitive impairment (
STEMI
:
OR
, 1.3, 95%
CI
, 1.1–1.5;
NSTEMI
: odds ratio, 1.3, 95%
CI
, 1.2–1.5) was associated with higher in‐hospital mortality.

Conclusions

Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in‐hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.
Manipulation of the Sphingolipid Rheostat Influences the Mediator of Flow‐Induced Dilation in the Human Microvasculature
Authors: Schulz Mary E. , Katunaric Boran , Hockenberry Joseph C. , Gutterman David D. , Freed Julie K.
Published: August 2019

Background

Elevated levels of ceramide, a sphingolipid known to cause a transition from nitric oxide (NO)– to hydrogen peroxide–dependent flow‐induced dilation (
FID
) in human arterioles, correlate with adverse cardiac events. However, elevations of ceramide are associated with changed concentrations of other sphingolipid metabolites. The effects of sphingolipid metabolites generated through manipulation of this lipid pathway on microvascular function are unknown. We examined the hypothesis that inhibition or activation of the ceramide pathway would determine the mediator of
FID
.

Methods and Results

Using videomicroscopy, internal diameter changes were measured in human arterioles collected from discarded adipose tissue during surgery. Inhibition of neutral ceramidase, an enzyme responsible for the hydrolysis of ceramide, favored hydrogen peroxide–dependent
FID
in arterioles from healthy patients. Using adenoviral technology, overexpression of neutral ceramidase in microvessels from diseased patients resulted in restoration of
NO
‐dependent
FID
. Exogenous sphingosine‐1‐phosphate, a sphingolipid with opposing effects of ceramide, also restored
NO
as the mediator of
FID
in diseased arterioles. Likewise, exogenous adiponectin, a known activator of neutral ceramidase, or, activation of adiponectin receptors, favored
NO
‐dependent dilation in arterioles collected from patients with coronary artery disease.

Conclusions

Sphingolipid metabolites play a critical role in determining the mediator of
FID
in human resistance arterioles. Manipulating the sphingolipid balance towards ceramide versus sphingosine‐1‐phosphate favors microvascular dysfunction versus restoration of
NO
‐mediated
FID
, respectively. Multiple targets exist within this biolipid pathway to treat microvascular dysfunction and potentially improve patient outcomes.
Blood Pressure Drop and Penumbral Tissue Loss in Nonrecanalized Emergent Large Vessel Occlusion
Authors: Jeong Han-Gil , Kim Beom Joon , Kim Hyeran , Jung Cheolkyu , Han Moon-Ku , Liebeskind David S. , Bae Hee-Joon
Published: August 2019

Background and Purpose—

For patients with emergent large vessel occlusion who may not benefit from timely recanalization treatment, maintaining adequate cerebral perfusion to prevent penumbral tissue loss is a key therapeutic strategy. Cerebral perfusion should be proportional to systemic blood pressure (BP) due to the loss of autoregulation properties in ischemic brain tissue. We hypothesized that acute fluctuations in BP would lead to aggravated penumbral tissue loss in persistent large vessel occlusion.

Methods—

A total of 80 patients with persistent large vessel occlusion of internal carotid artery or middle cerebral artery admitted within 24 hours after onset, and with a baseline, National Institutes of Health Stroke Scale score ≥4-point were included. Baseline and follow-up (median 88 hours) magnetic resonance images were analyzed, and penumbra was defined as the T
max
>6 s region excluding baseline infarction. The hypoperfusion intensity ratio (T
max
>10 s/T
max
>6 s) was calculated within the penumbra. Penumbral tissue loss (%) was defined as the proportion of follow-up infarct in the penumbra. With serial BP measurements in the first 24 hours (median 29, interquartile range 26–35), BP and BP variability parameters, including BP
dropmax
(change from local maxima to minima), were calculated and compared. Generalized linear models were applied to examine the association between BP parameters and the penumbral tissue loss.

Results—

The median penumbral volume was 79.3 mL (interquartile range, 38.2–129.6) and median penumbral tissue loss was 36.7% (interquartile range, 12.0–56.1). In a multivariable analysis, systolic BP (SBP) SBP
dropmax
(β±SE of fourth quartile, 17.82±6.58;
P
value, 0.01) and diastolic BP (DBP) DBP
dropmax
(β±SE of fourth quartile, 14.04±6.38;
P
value, 0.01) were associated with increasing penumbral tissue loss, independently of age, baseline infarction and hypoperfusion intensity ratio. DBP
incmax
, SBP
max
, DBP
max
, SBP
max-min
, DBP
max-min
, and most of the DBP variability indices were associated with penumbral tissue loss.

Conclusions—

BP fluctuations, even a brief and drastic BP drop in the first 24 hours, significantly contributed to penumbral tissue loss irrespective of baseline hypoperfusion.
Extent to Which Network Hubs Are Affected by Ischemic Stroke Predicts Cognitive Recovery
Authors: Aben Hugo P. , Biessels Geert Jan , Weaver Nick A. , Spikman Jacoba M. , Visser-Meily Johanna M.A. , de Kort Paul L.M. , Reijmer Yael D. ,   on behalf of the PROCRAS Study Group*, Jansen Ben P.W.
Published: August 2019

Background and Purpose—

It is uncertain what determines the potential for cognitive recovery after ischemic stroke. The extent to which strategic areas of the brain network, so-called hubs, are affected by the infarct could be a key factor. We developed a lesion impact score, which estimates the damage to network hubs by integrating information on infarct size with healthy brain network topology. We verified whether the lesion impact score indeed reflects global network disturbances in patients and assessed if it could predict cognitive recovery.

Methods—

Seventy-five ischemic stroke patients without signs of a prestroke cognitive disorder were included, all with evidence of a cognitive disorder during hospitalization. A brain magnetic resonance imaging and neuropsychological assessment were performed 5 weeks (±1 week) after stroke. Neuropsychological testing was repeated after 1 year to assess cognitive recovery. Brain networks were reconstructed from diffusion-weighted data and consisted of 90 gray matter regions (ie, network nodes). A standard brain network map, indicating the hub-score of each node, was obtained from network data of 44 cognitively healthy adults. For each patient, we calculated the lesion impact score by multiplying the percentage of node volume affected by the infarct with the node’s corresponding hub-score. The patients’ maximum lesion impact score was used as outcome predictor.

Results—

A higher lesion impact score in patients, indicating an increasing infarct size in nodes with a higher hub-score, was related to lower global brain network efficiency (β=−0.528 [−0.776 to −0.277];
P
<0.001), independent of age, brain volume, infarct volume, and white matter hyperintensity severity. A lower lesion impact score, however, was an independent predictor of cognitive recovery 1 year after stroke (odds ratio=0.434 [0.193–0.978];
P
=0.044).

Conclusions—

We introduced a lesion impact score that combines information on infarct size and network topology to predict long-term recovery after stroke. This score can potentially be used in a clinical setting, also without availability of high-resolution diffusion-weighted magnetic resonance imaging.
Cerebral Blood Flow Predicts the Infarct Core
Authors: Amukotuwa Shalini , Straka Matus , Aksoy Didem , Fischbein Nancy , Desmond Patricia , Albers Gregory , Bammer Roland
Published: August 2019

Background and Purpose—

The aim of this study is to determine the spatial and volumetric accuracy of infarct core estimates from relative cerebral blood flow (rCBF) by comparison with near-contemporaneous diffusion-weighted imaging (DWI), and evaluate whether it is sufficient for patient triage to reperfusion therapies.

Methods—

One hundred ninety-three patients enrolled in the DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) and SENSE 3 (Sensitivity Encoding) stroke studies were screened, and 119 who underwent acute magnetic resonance imaging with DWI and perfusion imaging within 24 hours of onset were included. Infarct core was estimated using reduced rCBF at 12 thresholds (<0.20–<0.44) and compared against DWI (apparent diffusion coefficient <620 10
−6
mm2/s). For each threshold, volumetric agreement between the rCBF and DWI core estimates was assessed using Bland-Altman, correlation, and linear regression analyses; spatial agreement was assessed using receiver operating characteristic analysis.

Results—

An rCBF threshold of 0.32 yielded the smallest mean absolute volume difference (14.7 mL), best linear regression fit (R
2
=0.84), and best spatial agreement (Youden index, 0.38; 95% CI, 0.34–0.41) between rCBF and DWI, with high correlation (
r
=0.91,
P
<0.05), a small mean volume difference (1.3 mL) and no fixed bias (
P
<0.05). At this threshold, 110 of 119 (92.4%) patients were correctly triaged when applying 70 mL as the volume limit for thrombectomy. Spatial agreement was better for prediction of large infarcts (>70 mL) than small infarcts (≤70 mL), with Youden indices of 0.53 (95% CI, 0.49–0.56) and 0.34 (95% CI, 0.30–0.37), respectively.

Conclusions—

Strong correlation and agreement with near-contemporaneous DWI indicate that infarct core estimates obtained using rCBF are sufficiently accurate for patient triage to reperfusion therapies. The identified optimal rCBF threshold of 0.32 closely approximates the threshold currently used in clinical practice.
“My Life Has Become More Absurd Than My Play”: Mi Minör and the Crackdown on Artistic Freedom in Turkey
Authors: Seyben Burcu Yasemin
Published: August 2019

Mi Minör, written by Turkish author Meltem Arıkan and directed by Turkish actor and director Memet Ali Alabora, deals with rising authoritarianism in the age of social media. The play envisaged both the fate of its artists, who were persecuted for ostensibly rehearsing the Gezi uprising through the play, and also the future of Turkey’s performing arts scene, currently struggling under an authoritarian regime.
Dance X Fase X Quad: Choreographic Seeing in Lucinda Childs, Anne Teresa de Keersmaeker, and Samuel Beckett
Authors: van Hensbergen Rosa
Published: August 2019

Minimalist lines often show up in philosophical and theoretical writings to diagram accounts of human perspective. But they also show up to do the opposite: to diagram the possibility of structures that precede or exceed a human perspective. By inhabiting scored lines as bodies in performance and simultaneously imagining what it is to score these lines from above, choreography can animate philosophical and theoretical approaches to perspective to reveal how multiple even minimal lines can become.
Concentration or dispersal of research funding?
Authors: Aagaard Kaare , Kladakis Alexander , Nielsen Mathias W.
Published: August 2019

The relationship between the distribution of research funding and scientific performance is a major discussion point in many science policy contexts. Do high shares of funding handed out to a limited number of elite scientists yield the most value for money, or is scientific progress better supported by allocating resources in smaller portions to more teams and individuals? In this review article, we seek to qualify discussions on the benefits and drawbacks of concentrating research funds on fewer individuals and groups. Based on an initial screening of 3,567 articles and a thorough examination of 92 papers, we present a condensation of central arguments. Further, we juxtapose key findings from 20 years of empirical research on the relation between the size of research grants and scientific performance. Overall, the review demonstrates a strong inclination toward arguments in favor of increased dispersal. A substantial body of empirical research also exhibits stagnant or diminishing returns to scale for the relationship between grant size and research performance. The findings question the rationale behind current funding trends and point toward more efficient ways to allocate resources. In addition, they highlight the need for more research on the interplay between science-internal mechanisms and policy priorities in accelerating concentration of funding.
Large publishing consortia produce higher citation impact research but coauthor contributions are hard to evaluate
Authors: Thelwall Mike
Published: August 2019

This paper introduces a simple agglomerative clustering method to identify large publishing consortia with at least 20 authors and 80% shared authorship between articles. Based on Scopus journal articles from 1996–2018, under these criteria, nearly all (88%) of the large consortia published research with citation impact above the world average, with the exceptions being mainly the newer consortia, for which average citation counts are unreliable. On average, consortium research had almost double (1.95) the world average citation impact on the log scale used (Mean Normalised Log Citation Score). At least partial alphabetical author ordering was the norm in most consortia. The 250 largest consortia were for nuclear physics and astronomy, involving expensive equipment, and for predominantly health-related issues in genomics, medicine, public health, microbiology and neuropsychology. For the health-related issues, except for the first and last few authors, authorship seem to primarily indicate contributions to the shared project infrastructure necessary to gather the raw data. It is impossible for research evaluators to identify the contributions of individual authors in the huge alphabetical consortia of physics and astronomy and problematic for the middle and end authors of health-related consortia. For small-scale evaluations, authorship contribution statements could be used when available.