bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible roles for ATP release from RBCs exclude the cAMP-mediated Panx1 pathway
Authors: Keller Alexander S. , Diederich Lukas , Panknin Christina , DeLalio Leon J. , Drake Joshua C. , Sherman Robyn , Jackson Edwin Kerry , Yan Zhen , Kelm Malte , Cortese-Krott Miriam M. , Isakson Brant E.
Published: August 2017

Red blood cell (RBC)-derived adenosine triphosphate (ATP) has been proposed as an integral component in the regulation of oxygen supply to skeletal muscle. In ex vivo settings RBCs have been shown to release ATP in response to a number of stimuli, including stimulation of adrenergic receptors. Further evidence suggested that ATP release from RBCs was dependent on activation of adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)-dependent pathways and involved the pannexin 1 (Panx1) channel. Here we show that RBCs express Panx1 and confirm its absence in Panx1 knockout (−/−) RBCs. However, Panx1−/− mice lack any decrease in exercise performance, challenging the assumptions that Panx1 plays an essential role in increased blood perfusion to exercising skeletal muscle and therefore in ATP release from RBCs. We therefore tested the role of Panx1 in ATP release from RBCs ex vivo in RBC suspensions. We found that stimulation with hypotonic potassium gluconate buffer resulted in a significant increase in ATP in the supernatant, but this was highly correlated with RBC lysis. Next, we treated RBCs with a stable cAMP analog, which did not induce ATP release from wild-type or Panx1−/− mice. Similarly, multiple pharmacological treatments activating AC in RBCs increased intracellular cAMP levels (as measured via mass spectrometry) but did not induce ATP release. The data presented here question the importance of Panx1 for exercise performance and dispute the general assumption that ATP release from RBCs via Panx1 is regulated via cAMP.
Novel therapeutic roles for surfactant-inositols and -phosphatidylglycerols in a neonatal piglet ARDS model: a translational study
Authors: Spengler Dietmar , Winoto-Morbach Supandi , Kupsch Sarah , Vock Christina , Blöchle Katharina , Frank Susanna , Rintz Nele , Diekötter Marie , Janga Harshavardhan , Weckmann Markus , Fuchs Sabine , Schromm Andra B. , Fehrenbach Heinz , Schütze Stefan , Krause Martin F.
Published: August 2017

The biological and immune-protective properties of surfactant-derived phospholipids and phospholipid subfractions in the context of neonatal inflammatory lung disease are widely unknown. Using a porcine neonatal triple-hit acute respiratory distress syndrome (ARDS) model (repeated airway lavage, overventilation, and LPS instillation into airways), we assessed whether the supplementation of surfactant (S; poractant alfa) with inositol derivatives [inositol 1,2,6-trisphosphate (IP3) or phosphatidylinositol 3,5-bisphosphate (PIP2)] or phosphatidylglycerol subfractions [16:0/18:1-palmitoyloleoyl-phosphatidylglycerol (POPG) or 18:1/18:1-dioleoyl-phosphatidylglycerol (DOPG)] would result in improved clinical parameters and sought to characterize changes in key inflammatory pathways behind these improvements. Within 72 h of mechanical ventilation, the oxygenation index (S+IP3, S+PIP2, and S+POPG), the ventilation efficiency index (S+IP3 and S+POPG), the compliance (S+IP3 and S+POPG) and resistance (S+POPG) of the respiratory system, and the extravascular lung water index (S+IP3 and S+POPG) significantly improved compared with S treatment alone. The inositol derivatives (mainly S+IP3) exerted their actions by suppressing acid sphingomyelinase activity and dependent ceramide production, linked with the suppression of the inflammasome nucleotide-binding domain, leucine-rich repeat-containing protein-3 (NLRP3)-apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-caspase-1 complex, and the profibrotic response represented by the cytokines transforming growth factor-β1 and IFN-γ, matrix metalloproteinase (MMP)-1/8, and elastin. In addition, IκB kinase activity was significantly reduced. S+POPG and S+DOPG treatment inhibited polymorphonuclear leukocyte activity (MMP-8 and myeloperoxidase) and the production of interleukin-6, maintained alveolar-capillary barrier functions, and reduced alveolar epithelial cell apoptosis, all of which resulted in reduced pulmonary edema. S+DOPG also limited the profibrotic response. We conclude that highly concentrated inositol derivatives and phosphatidylglycerol subfractions in surfactant preparations mitigate key inflammatory pathways in inflammatory lung disease and that their clinical application may be of interest for future treatment of the acute exudative phase of neonatal ARDS.
The respiratory tract microbial biogeography in alcohol use disorder
Authors: Samuelson Derrick R. , Burnham Ellen L. , Maffei Vincent J. , Vandivier R. William , Blanchard Eugene E. , Shellito Judd E. , Luo Meng , Taylor Christopher M. , Welsh David A.
Published: August 2017

Individuals with alcohol use disorders (AUDs) are at an increased risk of pneumonia and acute respiratory distress syndrome. Data of the lung microbiome in the setting of AUDs are lacking. The objective of this study was to determine the microbial biogeography of the upper and lower respiratory tract in individuals with AUDs compared with non-AUD subjects. Gargle, protected bronchial brush, and bronchoalveolar lavage specimens were collected during research bronchoscopies. Bacterial 16S gene sequencing and phylogenetic analysis was performed, and the alterations to the respiratory tract microbiota and changes in microbial biogeography were determined. The microbial structure of the upper and lower respiratory tract was significantly altered in subjects with AUDs compared with controls. Subjects with AUD have greater microbial diversity [ P < 0.0001, effect size = 16 ± 1.7 observed taxa] and changes in microbial species relative abundances. Furthermore, microbial communities in the upper and lower respiratory tract displayed greater similarity in subjects with AUDs. Alcohol use is associated with an altered composition of the respiratory tract microbiota. Subjects with AUDs demonstrate convergence of the microbial phylogeny and taxonomic communities between distinct biogeographical sites within the respiratory tract. These results support a mechanistic pathway potentially explaining the increased incidence of pneumonia and lung diseases in patients with AUDs.
Adenosine A1receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels
Authors: Soni Hitesh , Peixoto-Neves Dieniffer , Buddington Randal K. , Adebiyi Adebowale
Published: August 2017

Adenosine, a regulator of cardiovascular development and renal function, constricts renal afferent arterioles by inducing intracellular Ca2+concentration ([Ca2+]i) elevation in smooth muscle cells (SMCs) via activation of its cognate A1receptors (A1Rs). Mechanisms that underlie A1R-dependent [Ca2+]ielevation in renal vascular SMCs are not fully resolved. Whether A1R expression and function in preglomerular microvessels are dependent on postnatal kidney maturation is also unclear. In this study, we show that selective activation of A1Rs by 2-chloro- N6-cyclopentyladenosine (CCPA) does not stimulate store-operated Ca2+entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca2+]ielevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca2+]iwas unchanged in afferent arterioles isolated from newborn (0-day-old) pigs compared with their 20-day-old counterparts. By contrast, CCPA treatment resulted in significantly larger [Ca2+]iin afferent arterioles from 20-day-old pigs. A1R protein expression levels in the kidneys and afferent arterioles were unaltered in 0- vs. 20-day-old pigs. However, the TRPC3 channel protein expression level was ~92 and 78% higher in 20-day-old pig kidneys and afferent arterioles, respectively. These data suggest that activation of A1Rs elicits receptor-operated Ca2+entry in porcine afferent arterioles, the level of which is dependent on postnatal maturation of TRPC3 channels. We propose that TRPC3 channels may contribute to the physiology and pathophysiology of A1Rs.
The neural basis of temporal individuation and its capacity limits in the human brain
Authors: Naughtin Claire K. , Tamber-Rosenau Benjamin J. , Dux Paul E.
Published: August 2017

Individuation refers to individualsʼ use of spatial and temporal properties to register objects as distinct perceptual events relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations have been restricted to the spatial domain and at relatively late stages of information processing. Here, we used univariate and multivoxel pattern analyses of functional MRI data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood-oxygen-level-dependent activity across the cortex discriminated between instances where repeated and nonrepeated stimuli were successfully individuated—conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression or other stimulus-related factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Contrary to current theoretical models, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation—instances of RB—lead to changes in the spatial patterns within this network, as well as amplitude changes in the left hemisphere premotor cortex, superior medial frontal cortex, anterior cingulate cortex, and bilateral parahippocampal place area. These findings could not be attributed to response conflict/ambiguity and likely reflect the core brain regions and mechanisms that underlie the capacity-limited process that gives rise to RB.

NEW & NOTEWORTHY We present novel findings into the neural bases of temporal individuation and repetition blindness (RB)—the perceptual deficit that arises when this process reaches its capacity limit. Specifically, we found that temporal individuation is a widely distributed process in the brain and identified a number of candidate brain regions that appear to underpin RB. These findings enhance our understanding of how these fundamental perceptual processes are reflected in the human brain.
Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies
Authors: Chang Che-Jui , Tu Yu-Kang , Chen Pau-Chung , Yang Hsiao-Yu
Published: August 2017

Objective. Talc is widely used in industrial applications. Previous meta-analyses of carcinogenic effects associated with inhaled talc included publications before 2004, with a lack of data in China, the largest talc-producing country. The safety of workers exposed to talc was unclear due to limited evidence. The objective of this study was to reevaluate the association between inhaled talc and lung cancer. Setting, Participants, and Outcome Measures. A meta-analysis was performed to calculate the meta-SMR of lung cancer. We searched the MEDLINE, EMBASE, CNKI, and Wanfang Data databases through March 2017. Data from observational studies were pooled using meta-analysis with random effects models. Results. Fourteen observational cohort studies (13 publications) were located via literature search. The heterogeneity of the included data was high (I-squared = 72.9%). Pooling all the cohorts yielded a meta-SMR of 1.45 (95% CI: 1.22–1.72, p<0.0001) for lung cancer among the study subjects exposed to talc. Subgroup analysis for asbestos contamination showed no significant difference in lung cancer death between subjects exposed to talc with and without asbestos (p=0.8680), indicating that this confounding factor may have no significance. Conclusions. This study provides evidence that nonasbestiform talc might still increase the risk of lung cancer. Further epidemiological studies are required to evaluate the safety of workers with occupational talc exposure.
Expression Levels and Clinical Significance of miR-21-5p, miR-let-7a, and miR-34c-5p in Laryngeal Squamous Cell Carcinoma
Authors: Re Massimo , Magliulo Giuseppe , Gioacchini Federico M. , Bajraktari Arisa , Bertini Andrea , Çeka Artan , Rubini Corrado , Ferrante Luigi , Procopio Antonio D. , Olivieri Fabiola
Published: August 2017

Objective. Altered microRNAs (miRNAs) expression has been found in many cancer types, including laryngeal squamous cell carcinoma (LSCC). The aim of this study was to determine the role and clinical value of three LSCC-related miRs, such as miR-21-5p, miR-let-7a, and miR-34c-5p in a homogeneous cohort of patients with primary LSCC treated by primary surgery. Methods. Expression levels of miR-21-5p, miR-let-7a, and miR-34c-5p were detected in 43 pairs of LSCC and adjacent normal tissues by reverse-transcription quantitative PCR. Overall survival and disease-free survival were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results. miR-21-5p is significantly upregulated, while miR-let-7a is significantly downregulated in LSCC tumor tissues compared with the corresponding adjacent normal tissues. The downregulation of miR-34c-5p expression significantly correlated with a shorter disease-free survival and, in the multivariate analysis, low miR-34c-5p expression was associated with an increased risk of recurrence. Conclusions. miR-21-5p, miR-let-7a, and miR-34c-5p seem to play a critical role in LSCC carcinogenesis and might have a diagnostic and prognostic clinical value. The miR-let-7a levels could have a predictive role for lymph node metastases and miR-34c-5p might be a promising biomarker of patient outcome.
CT Scanning in Identification of Sheep Cystic Echinococcosis
Authors: Mao Rui , Qi Hongzhi , Pei Lei , Hao Jie , Dong Jian , Jiang Tao , Ainiwaer Abudula , Shang Ge , Xu Lin , Shou Xi , Zhang Songan , Wu Ge , Lu Pengfei , Bao Yongxing , Li Haitao
Published: August 2017

Objective. We aim to determine the efficiency of CT in identification of cystic echinococcosis in sheep. Methods. Fifty-three sheep with liver cysts confirmed by ultrasonography were subject to CT scan to evaluate the number, size, and type of the cysts in liver and lung, confirmed using necropsy. The correlation of numbers between liver cysts and lung cysts was calculated using Pearson analysis. Results. Necropsy indicated a 98% consensus on size, location, number, and activity compared with CT scan. The viable cysts were 53.1% and 50.6% in the liver and lung, respectively. Among the cysts in liver, 35.5%, 9.5%, 5.7%, 10.2%, and 39.1% were Types CE1, CE2, CE3, CE4, and CE5, respectively. The cysts in the lungs, 17.4%, 26.9%, 12.1%, 11.6%, and 32.1%, were Types CE1, CE2, CE3, CE4, and CE5, respectively. A significant correlation was noticed between the number of cysts in liver and those in lung (R=0.770, P<0.001). Conclusions. CT scan is a suitable tool in determining the size and type of cystic hydatid cysts in both liver and lung of sheep. A significant correlation was noticed between the numbers in liver and lung, indicating that lung infection was likely due to the expansion of liver cyst burden pressure.
Multi-Input Convolutional Neural Network for Flower Grading
Authors: Sun Yu , Zhu Lin , Wang Guan , Zhao Fang
Published: August 2017

Flower grading is a significant task because it is extremely convenient for managing the flowers in greenhouse and market. With the development of computer vision, flower grading has become an interdisciplinary focus in both botany and computer vision. A new dataset named BjfuGloxinia contains three quality grades; each grade consists of 107 samples and 321 images. A multi-input convolutional neural network is designed for large scale flower grading. Multi-input CNN achieves a satisfactory accuracy of 89.6% on the BjfuGloxinia after data augmentation. Compared with a single-input CNN, the accuracy of multi-input CNN is increased by 5% on average, demonstrating that multi-input convolutional neural network is a promising model for flower grading. Although data augmentation contributes to the model, the accuracy is still limited by lack of samples diversity. Majority of misclassification is derived from the medium class. The image processing based bud detection is useful for reducing the misclassification, increasing the accuracy of flower grading to approximately 93.9%.
Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587
Authors: Figueroa Javier , Phillips Lynette M. , Shahar Tal , Hossain Anwar , Gumin Joy , Kim Hoon , Bean Andrew J. , Calin George A. , Fueyo Juan , Walters Edgar T. , Kalluri Raghu , Verhaak Roel G. , Lang Frederick F.
Published: August 2017

Tumor–stromal communications impact tumorigenesis in ways that are incompletely understood. Here, we show that glioma-associated human mesenchymal stem cells (GA-hMSC), a newly identified stromal component of glioblastoma, release exosomes that increase the proliferation and clonogenicity of tumor-initiating glioma stem-like cells (GSC). This event leads to a significantly greater tumor burden and decreased host survival compared with untreated GSCs in orthotopic xenografts. Analysis of the exosomal content identified miR-1587 as a mediator of the exosomal effects on GSCs, in part via downregulation of the tumor-suppressive nuclear receptor corepressor NCOR1. Our results illuminate the tumor-supporting role for GA-hMSCs by identifying GA-hMSC–derived exosomes in the intercellular transfer of specific miRNA that enhance the aggressiveness of glioblastoma. Cancer Res; 77(21); 5808–19. ©2017 AACR.
CD73 Promotes Resistance to HER2/ErbB2 Antibody Therapy
Authors: Turcotte Martin , Allard David , Mittal Deepak , Bareche Yacine , Buisseret Laurence , José Vinu , Pommey Sandra , Delisle Vincent , Loi Sherene , Joensuu Heikki , Kellokumpu-Lehtinen Pirkko-Liisa , Sotiriou Christos , Smyth Mark J. , Stagg John
Published: August 2017

Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome. In immunocompetent mouse models of HER2/ErbB2–driven breast cancer, CD73 expression by tumor cells and host cells significantly suppressed immune-mediated responses mediated by anti-ErbB2 mAb. Furthermore, anti-CD73 mAb therapy enhanced the activity of anti-ErbB2 mAb to treat engrafted or spontaneous tumors as well as lung metastases. Gene ontology enrichment analysis from gene-expression data revealed a positive association of CD73 expression with extracellular matrix organization, TGFβ genes, epithelial-to-mesenchymal transition (EMT) transcription factors and hypoxia-inducible-factor (HIF)-1 gene signature. Human mammary cells treated with TGFβ or undergoing EMT upregulated CD73 cell-surface expression, confirming roles for these pathways. In conclusion, our findings establish CD73 in mediating resistance to trastuzumab and provide new insights into how CD73 is regulated in breast cancer. Cancer Res; 77(20); 5652–63. ©2017 AACR.
Bone-Induced Expression of Integrin β3 Enables Targeted Nanotherapy of Breast Cancer Metastases
Authors: Ross Michael H. , Esser Alison K. , Fox Gregory C. , Schmieder Anne H. , Yang Xiaoxia , Hu Grace , Pan Dipanjan , Su Xinming , Xu Yalin , Novack Deborah V. , Walsh Thomas , Colditz Graham A. , Lukaszewicz Gabriel H. , Cordell Elizabeth , Novack Joshua , Fitzpatrick James A. J. , Waning David L. , Mohammad Khalid S. , Guise Theresa A. , Lanza Gregory M. , Weilbaecher Katherine N.
Published: August 2017

Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site. Cancer Res; 77(22); 6299–312. ©2017 AACR.
Shrimp miR-S8 Suppresses the Stemness of Human Melanoma Stem-like Cells by Targeting the Transcription Factor YB-1
Authors: Yang Fan , Wei Jun , Zhang Song , Zhang Xiaobo
Published: August 2017

Cross-species regulation of gene expression by microRNA is a possible untapped opportunity for miRNA-based therapy. In this study, we report a novel approach to ablate melanoma stem-like cells by targeting the transcription factor YB-1, which is significantly and selectively upregulated in these cells in melanoma. Silencing YB-1 expression was sufficient to significantly inhibit the stemness of melanoma stem-like cells. In exploring YB-1 targeting, we discovered that the shrimp microRNA miR-S8 could suppress human YB-1 expression in melanoma stem-like cells. Mechanistic investigations revealed that miR-S8 recognized the 3′UTR of YB-1 mRNA and mediated its degradation. In tumor cell and xenograft experiments, miR-S8 suppressed the tumorigenic capacity of melanoma stem-like cells by targeting human YB-1. Overall, our results illuminated a novel aspect of miRNA-mediated cross-species gene expression and its use in regulating cancer stem-like cells. Cancer Res; 77(20); 5543–53. ©2017 AACR.
Chemogenomic Landscape of RUNX1-mutated AML Reveals Importance of RUNX1 Allele Dosage in Genetics and Glucocorticoid Sensitivity
Authors: Simon Laura , Lavallée Vincent-Philippe , Bordeleau Marie-Eve , Krosl Jana , Baccelli Irène , Boucher Geneviève , Lehnertz Bernhard , Chagraoui Jalila , MacRae Tara , Ruel Réjean , Chantigny Yves , Lemieux Sébastien , Marinier Anne , Hébert Josée , Sauvageau Guy
Published: August 2017

Purpose: RUNX1-mutated (RUNX1mut) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Toward this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup.

Experimental Design: RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML.

Results: We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the glucocorticoid receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that coassociating mutations as well as GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells.

Conclusions: Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Clin Cancer Res; 23(22); 6969–81. ©2017 AACR.
Independent Risk Factors and 2-Year Outcomes of Acute Kidney Injury after Surgery for Congenital Heart Disease
Authors: Hirano Daishi , Ito Akira , Yamada Akifumi , Kakegawa Daisuke , Miwa Saori , Umeda Chisato , Chiba Kosuke , Takemasa Yoichi , Tokunaga Ai , Ida Hiroyuki
Published: August 2017

Background: Data are limited regarding risk factors for acute kidney injury (AKI) following cardiac surgery in children with congenital heart disease (CHD). This observational study was performed to examine temporal trends in AKI incidence according to the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria, identify independent risk factors for AKI after cardiac surgery, and examine associations between AKI and long-term mortality. Methods: We retrospectively evaluated 418 patients (259 males, 159 females; median age, 5 months) who underwent cardiac surgery for CHD between April 2007 and August 2013. Patients were followed up for 2 years. AKI was defined according to the pRIFLE criteria as ≥25% decrease in estimated creatinine clearance. Results: AKI developed postoperatively in 104 cases (24.9%). Approximately 80% belonged to the “Risk” category according to the pRIFLE criteria, and only 21 cases (5%) required renal replacement therapy (peritoneal dialysis in all cases). Multivariate analysis revealed 3 independent risk factors for onset of AKI: young age (<1 year), surgery in Risk Adjustment in Congenital Heart Surgery (RACHS-1) category ≥4, and long cardiopulmonary bypass (CPB) time (≥90 min). Twenty-three patients (22%) with AKI died during the 2-year follow-up. In multivariate cox hazard regression analysis, the most significant contributor to risk of mortality was AKI. Conclusions: Postoperative AKI was strongly associated with young age, high RACHS-1 category, and prolonged CPB time. In addition, mortality rate was higher in patients who survived after recovery from AKI than in those without AKI, even among the lower pRIFLE categories.
Onívoros digitais em contato perpétuo: a mobilidade das mídias pela ótica ecológica
Authors: Angeluci Alan César Belo , Américo Marcos
Published: August 2017

A rápida configuração do (meio‑ )ambiente digital que ocorre nestas primeiras dé‑ cadas do século XXI tem envolvido o uso de dispositivos utilizados para consumir simultaneamente conteúdos nos espaços domésticos, laborais e também em períodos de trânsito ou mobilidade.O surgimento desta vasta paisagem digital multiplatafor‑ ma estimula a se conhecer as formas de utilização destes dispositivos de natureza ubíqua ou não. “Onívoros digitais” formam um novo grupo de consumidores cuja de‑ nominação refere ‑se às plataformas que esses indivíduos utilizam para ter acesso à Internet, seja de maneira individual ou em multiplataforma. Este artigo propõe uma revisão de literatura sobre os usos e apropriações das mídias móveis pelos onívoros digitais que busque situá‑ las como elemento integrador de um complexo ecossistema midiático contemporâneo. Busca, ainda, apontar como esse ecossistema tem trans‑ formado as práticas sociais em direção ao “contato perpétuo” (Katz & Aakhus, 2004). De forma a abordar os aspectos de impacto das mídias móveis por uma perspectiva socio ‑científica, autores como Haddon (2001), Ling& Donner (2009), Hartmann (2013) e Chen (2015) devem compor o arcabouço teórico ‑conceitual da discussão proposta, retomando a ideia de consumo da mídia a partir do paradigma da mobilidade.
Internet no campo: direitos humanos e políticas públicas de inclusão digital
Authors: Fornasier Mateus De Oliveira , Scarantti Danielli Regina
Published: August 2017

O presente trabalho tece algumas considerações sobre a (r)evolução tecnológica na pós-modernidade, enfatizando o problema da exclusão digital no campo e a afronta que isso significa aos direitos humanos. Nesse sentido, o texto trata da importância do direito de acesso à internet para a busca de informações imprescindíveis na efetivação dos direitos - civis, políticos, socioeconômicos e de solidariedade internacional - do homem. O trabalho discute, ainda, que o desenvolvimento tecnológico se expandiu em maior escala nas cidades, sendo que apenas 15% da população residente na zona rural possui computador conectado à rede. Portanto, torna-se necessário analisar a ampliação das políticas públicas existentes nestas áreas de maior desigualdade entre a afirmação da norma e sua devida execução.
Occurrence and genetic characterization of Staphylococcus aureus in milk samples of cattle with mastitis, and in the Veterinary Hospital personnel and dairy workers
Authors: Leigue Lucianne , Hilgert Ayrton Rodrigo , Fiorini Adriana , Santos Marise Fonseca dos , Vendruscolo Eliane Cristina Gruzka
Published: August 2017

Staphylococcus aureus está entre os microrganismos que apresentam as maiores taxas de morbidade e mortalidade em seres humanos e animais. Linhagens de S. aureus resistentes a meticilina podem causar surtos de infecção em todo o mundo, o que contribui para a escassez de arsenal terapêutico. Este trabalho analisou o perfil epidemiológico de estirpes de S. aureus isoladas de pessoas que trabalham em contato com animais em um hospital veterinário com gado leiteiro e também em amostras de leite de vacas acometidas por mastite. As estirpes de S. aureus isoladas foram caracterizadas fenotipicamente por meio de antibiograma, testes de catalase e coagulase, e pelo teste de Voges-Proskauer. As amostras também foram caracterizadas genotipicamente pela técnica de Analise de Restricao de DNA Ribossomico Amplificado (ARDRA-PCR). Das 218 estirpes isoladas, 27 foram identificados como S. aureus (12%). Entre essas, quatro estirpes foram resistentes a oxacilina e duas classificadas como SARM (S. aureus resistente a meticilina). A ocorrência de estirpes de S.aureus isoladas entre o pessoal que trabalha em contato com os animais foi baixa (2%), mas estirpes identificadas como SARM foram encontradas na equipe clínica. As análises de ARDRA realizadas com as enzimas de restrição HindIII e HinfII demonstraram que S. aureus isolados de diferentes indivíduos que trabalhavam com animais foram agrupados no mesmo cluster. Quando a ARDRA foi realizada com HaeIII foi observada formação de dois grupos, mas os isolados não se correlacionaram. Conclusão: a ocorrência de estirpes de S. aureus isoladas foi maior na equipe clínica, apresentando também correlação de 100% nos ensaios bioquímicos e moleculares.
Relações de poder no exame Celpe-Bras
Authors: Villela Ana Maria Nápoles , Neves Liliane De Oliveira , Tosatti Natália Moreira
Published: August 2017

Neste artigo, discutiremos as relações de poder existentes no exame que confere o Certificado de Proficiência em Língua Portuguesa para Estrangeiros (Celpe-Bras), o único instrumento de avaliação da proficiência em língua portuguesa para estrangeiros reconhecido oficialmente pelo governo brasileiro. O exame, que é estruturado em duas partes, escrita e oral, tem como propósito aferir o desempenho dos examinandos no uso da língua portuguesa. Considerando-se que avaliações, sobretudo as de alta relevância, como é o caso do Celpe-Bras, são instrumentos de poder, apresentaremos, neste trabalho, reflexões a respeito de como as situações de poder se dão durante as interações entre os sujeitos que participam do exame.
Reducing the Global Burden of Cardiovascular Disease, Part 1
Authors: Joseph Philip , Leong Darryl , McKee Martin , Anand Sonia S. , Schwalm Jon-David , Teo Koon , Mente Andrew , Yusuf Salim
Published: August 2017

Current global health policy goals include a 25% reduction in premature mortality from noncommunicable diseases by 2025. In this 2-part review, we provide an overview of the current epidemiological data on cardiovascular diseases (CVD), its risk factors, and describe strategies aimed at reducing its burden. In part 1, we examine the global epidemiology of cardiac conditions that have the greatest impact on CVD mortality; the predominant risk factors; and the impact of upstream, societal health determinants (eg, environmental factors, health policy, and health systems) on CVD. Although age-standardized mortality from CVD has decreased in many regions of the world, the absolute number of deaths continues to increase, with the majority now occurring in middle- and low-income countries. It is evident that multiple factors are causally related to CVD, including traditional individual level risk factors (mainly tobacco use, lipids, and elevated blood pressure) and societal level health determinants (eg, health systems, health policies, and barriers to CVD prevention and care). Both individual and societal risk factors vary considerably between different regions of the world and economic settings. However, reliable data to estimate CVD burden are lacking in many regions of the world, which hampers the establishment of nationwide prevention and management strategies. A 25% reduction in premature CVD mortality globally is feasible but will require better implementation of evidence-based policies (particularly tobacco control) and integrated health systems strategies that improve CVD prevention and management. In addition, there is a need for better health information to monitor progress and guide health policy decisions.
Follicle‐Stimulating Hormone, Its Association with Cardiometabolic Risk Factors, and 10‐Year Risk of Cardiovascular Disease in Postmenopausal Women
Authors: Wang Ningjian , Shao Hongfang , Chen Yi , Xia Fangzhen , Chi Chen , Li Qin , Han Bing , Teng Yincheng , Lu Yingli
Published: August 2017

Background

Cardiovascular disease is the leading cause of mortality in postmenopausal women. Follicle‐stimulating hormone (
FSH
) shows negative associations with obesity and diabetes mellitus in postmenopausal women. We aimed to study the associations between
FSH
and 10‐year risk of atherosclerotic cardiovascular disease (
ASCVD
) in postmenopausal women.

Methods and Results

SPECT
‐China (the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors) is a 22‐site, population‐based study conducted during 2014–2015. This study included 2658 postmenopausal women. A newly developed effective tool for 10‐year
ASCVD
risk prediction among Chinese was adopted. Regression analyses were performed to assess the relationship among
FSH
, 10‐year
ASCVD
risk, and multiple cardiometabolic risk factors. With the increase in
FSH
quartiles, the mean 10‐year
ASCVD
risk in postmenopausal women decreased from 4.9% to 3.3%, and most metabolic parameters were significantly ameliorated (all
P
for trend <0.05). In regression analyses, a 1‐
SD
increment in ln‐
FSH
was negatively associated with continuous (B −0.12, 95% confidence interval, −0.16, −0.09,
P
<0.05) and categorical (odds ratio 0.65, 95% confidence interval, 0.49, 0.85,
P
<0.05) 10‐year
ASCVD
risk. These significant associations existed in subgroups with or without medication use, obesity, diabetes mellitus, hypertension, and dyslipidemia. Body mass index and waist circumference (both B −0.35, 95% confidence interval, −0.40, −0.30,
P
<0.05) had the largest associations of all metabolic measures, and blood pressure had the smallest association.

Conclusions

Serum
FSH
levels were negatively associated with 10‐year
ASCVD
risk in postmenopausal women. Among cardiometabolic factors, obesity indices had the largest associations with
FSH
. These results indicated that a low
FSH
might be a risk factor or a biomarker for cardiovascular disease risk in postmenopausal women.
Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer
Authors: Addison Daniel , Seidelmann Sara B. , Janjua Sumbal A. , Emami Hamed , Staziaki Pedro V. , Hallett Travis R. , Szilveszter Bálint , Lu Michael T. , Cambria Richard P. , Hoffmann Udo , Chan Annie W. , Wirth Lori J. , Neilan Tomas G.
Published: August 2017

Background

Radiation therapy (
RT
) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (
CVEs
; stroke or transient ischemic attack). Human papillomavirus (
HPV
) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether
HPV
confers an increased risk of
CVE
s after
RT
is unknown.

Methods and Results

Using an institutional database, we identified all consecutive patients treated with
RT
from 2002 to 2012 for head and neck cancer who were tested for
HPV
. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between
HPV
and
CVE
s was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent
RT
for head and neck cancer were tested for
HPV
(age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for
CVEs
were similar between HPV‐positive and ‐negative patients. Over a median follow‐up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the
HPV
‐positive patients compared with the HPV‐negative patients (2.6% versus 0.9%,
P
=0.002). In a multivariable model, HPV‐positive status was associated with a >4 times increased risk of
CVEs
(hazard ratio: 4.4; 95% confidence interval, 1.5–13.2;
P
=0.008).

Conclusions

In this study, HPV‐positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer.
Sensitivity of Global Warming to Carbon Emissions: Effects of Heat and Carbon Uptake in a Suite of Earth System Models
Authors: Williams Richard G. , Roussenov Vassil , Goodwin Philip , Resplandy Laure , Bopp Laurent
Published: August 2017

Climate projections reveal global-mean surface warming increasing nearly linearly with cumulative carbon emissions. The sensitivity of surface warming to carbon emissions is interpreted in terms of a product of three terms: the dependence of surface warming on radiative forcing, the fractional radiative forcing from CO2, and the dependence of radiative forcing from CO2on carbon emissions. Mechanistically each term varies, respectively, with climate sensitivity and ocean heat uptake, radiative forcing contributions, and ocean and terrestrial carbon uptake. The sensitivity of surface warming to fossil-fuel carbon emissions is examined using an ensemble of Earth system models, forced either by an annual increase in atmospheric CO2or by RCPs until year 2100. The sensitivity of surface warming to carbon emissions is controlled by a temporal decrease in the dependence of radiative forcing from CO2on carbon emissions, which is partly offset by a temporal increase in the dependence of surface warming on radiative forcing. The decrease in the dependence of radiative forcing from CO2is due to a decline in the ratio of the global ocean carbon undersaturation to carbon emissions, while the increase in the dependence of surface warming is due to a decline in the ratio of ocean heat uptake to radiative forcing. At the present time, there are large intermodel differences in the sensitivity in surface warming to carbon emissions, which are mainly due to uncertainties in the climate sensitivity and ocean heat uptake. These uncertainties undermine the ability to predict how much carbon may be emitted before reaching a warming target.
Extreme Warming in the Kara Sea and Barents Sea during the Winter Period 2000–16
Authors: Kohnemann Svenja H. E. , Heinemann Günther , Bromwich David H. , Gutjahr Oliver
Published: August 2017

The regional climate model COSMO in Climate Limited-Area Mode (COSMO-CLM or CCLM) is used with a high resolution of 15 km for the entire Arctic for all winters 2002/03–2014/15. The simulations show a high spatial and temporal variability of the recent 2-m air temperature increase in the Arctic. The maximum warming occurs north of Novaya Zemlya in the Kara Sea and Barents Sea between March 2003 and 2012 and is responsible for up to a 20°C increase. Land-based observations confirm the increase but do not cover the maximum regions that are located over the ocean and sea ice. Also, the 30-km version of the Arctic System Reanalysis (ASR) is used to verify the CCLM for the overlapping time period 2002/03–2011/12. The differences between CCLM and ASR 2-m air temperatures vary slightly within 1°C for the ocean and sea ice area. Thus, ASR captures the extreme warming as well. The monthly 2-m air temperatures of observations and ERA-Interim data show a large variability for the winters 1979–2016. Nevertheless, the air temperature rise since the beginning of the twenty-first century is up to 8 times higher than in the decades before. The sea ice decrease is identified as the likely reason for the warming. The vertical temperature profiles show that the warming has a maximum near the surface, but a 0.5°C yr−1 increase is found up to 2 km. CCLM, ASR, and also the coarser resolved ERA-Interim data show that February and March are the months with the highest 2-m air temperature increases, averaged over the ocean and sea ice area north of 70°N; for CCLM the warming amounts to an average of almost 5°C for 2002/03–2011/12.
Ensemble-Based Storm Surge Forecasting Models
Authors: Salighehdar Amin , Ye Ziwen , Liu Mingzhe , Florescu Ionut , Blumberg Alan F.
Published: August 2017

Accurate prediction of storm surge is a difficult problem. Most forecast systems produce multiple possible forecasts depending on the variability in weather conditions, possible temperature levels, winds, etc. Ensemble modeling techniques have been developed with the stated purpose of obtaining the best forecast (in some specific sense) from the individual forecasts. In this work a statistical methodology of evaluating the performance of multiple ensemble forecasting models is developed. The methodology is applied to predicting storm surge in the New York Harbor area. Data from three hurricane events collected from multiple locations in the New York Bay area are used. The methodology produces three key findings for the particular test data used. First, it is found that even the simplest possible way of creating an ensemble produces results superior to those of any single forecast. Second, for the data used and the events under study the methodology did not interact with any event at any location studied. Third, based on the methodology results for the data studied selecting the best-performing ensemble models for each specific location may be possible.
Updates in the NCEP GFS Cumulus Convection Schemes with Scale and Aerosol Awareness
Authors: Han Jongil , Wang Weiguo , Kwon Young C. , Hong Song-You , Tallapragada Vijay , Yang Fanglin
Published: August 2017

The current operational NCEP Global Forecast System (GFS) cumulus convection schemes are updated with a scale-aware parameterization where the cloud mass flux decreases with increasing grid resolution. The ratio of advective time to convective turnover time is also taken into account for the scale-aware parameterization. In addition, the present deep cumulus convection closure using the quasi-equilibrium assumption is no longer used for grid sizes smaller than a threshold value. For the shallow cumulus convection scheme, the cloud-base mass flux is modified to be given by a function of mean updraft velocity. A simple aerosol-aware parameterization where rain conversion in the convective updraft is modified by aerosol number concentration is also included in the update. Along with the scale- and aerosol-aware parameterizations, more changes are made to the schemes. The cloud-base mass-flux computation in the deep convection scheme is modified to use convective turnover time as the convective adjustment time scale. The rain conversion rate is modified to decrease with decreasing air temperature above the freezing level. Convective inhibition in the subcloud layer is used as an additional trigger condition. Convective cloudiness is enhanced by considering suspended cloud condensate in the updraft. The lateral entrainment in the deep convection scheme is also enhanced to more strongly suppress convection in a drier environment. The updated NCEP GFS cumulus convection schemes display significant improvements especially in the summertime continental U.S. precipitation forecasts.
Role of Balloon Dilation in the Management of Adult Idiopathic Subglottic Stenosis
Authors: Lee Kenneth H. , Rutter Michael J.
Published: August 2017

Objectives

We evaluated the efficacy of balloon dilation for adjunctive and symptomatic management of isolated idiopathic subglottic stenosis in adults.

Methods

Adults with airway obstruction symptoms classified as idiopathic subglottic stenosis based on history and findings of a single discrete stenotic area on microlaryngoscopy and bronchoscopy were included in this series. Patients who met these criteria underwent dilation with a 10- to 14-mm balloon in a single procedure or in 2 consecutive dilations within 7 days. The patients were followed for up to 30 months after dilation.

Results

Six patients met the criteria. One of the 6 had prior laser treatments and a cricotracheal resection. One patient had a previous scar band lysis procedure. The remaining 4 patients had no prior procedures. The airway sizes prior to dilation ranged from a 2.5 endotracheal tube to a 5.0 endotracheal tube. In all cases the airway was dilated to 2.0 to 3.5 endotracheal tube sizes larger than the initial size. To date, 4 patients have been followed for 10 to 30 months without symptoms of recurrent airway stenosis. One patient was symptom-free for 22 months, then presented with progressive airway difficulty following an upper respiratory tract infection, and has undergone a repeat dilation. No patients had adverse effects or complications from the procedure.

Conclusions

Balloon dilation of idiopathic subglottic stenosis in adults is a relatively safe and effective method to manage this disease entity for cases of isolated and discrete lesions. Patients who underwent a single procedure have remained symptom-free for up to 30 months after balloon dilation.