bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathways: Mitochondrial Reprogramming in Tumor Progression and Therapy
Authors: Caino M. Cecilia , Altieri Dario C. 
Published: December 2015

Abstract
Small-molecule inhibitors of the phosphoinositide 3-kinase (PI3K), Akt, and mTOR pathway currently in the clinic produce a paradoxical reactivation of the pathway they are intended to suppress. Furthermore, fresh experimental evidence with PI3K antagonists in melanoma, glioblastoma, and prostate cancer shows that mitochondrial metabolism drives an elaborate process of tumor adaptation culminating with drug resistance and metastatic competency. This is centered on reprogramming of mitochondrial functions to promote improved cell survival and to fuel the machinery of cell motility and invasion. Key players in these responses are molecular chaperones of the Hsp90 family compartmentalized in mitochondria, which suppress apoptosis via phosphorylation of the pore component, Cyclophilin D, and enable the subcellular repositioning of active mitochondria to membrane protrusions implicated in cell motility. An inhibitor of mitochondrial Hsp90s in preclinical development (gamitrinib) prevents adaptive mitochondrial reprogramming and shows potent antitumor activity in vitro and in vivo. Other therapeutic strategies to target mitochondria for cancer therapy include small-molecule inhibitors of mutant isocitrate dehydrogenase (IDH) IDH1 (AG-120) and IDH2 (AG-221), which opened new therapeutic prospects for patients with high-risk acute myelogenous leukemia (AML). A second approach of mitochondrial therapeutics focuses on agents that elevate toxic ROS levels from a leaky electron transport chain; nevertheless, the clinical experience with these compounds, including a quinone derivative, ARQ 501, and a copper chelator, elesclomol (STA-4783) is limited. In light of this evidence, we discuss how best to target a resurgence of mitochondrial bioenergetics for cancer therapy. Clin Cancer Res; 22(3); 540–5. ©2015 AACR.
Disruption ofin vivoChronic Lymphocytic Leukemia Tumor–Microenvironment Interactions by Ibrutinib – Findings from an Investigator-Initiated Phase II Study
Authors: Niemann Carsten U. , Herman Sarah E.M. , Maric Irina , Gomez-Rodriguez Julio , Biancotto Angelique , Chang Betty Y. , Martyr Sabrina , Stetler-Stevenson Maryalice , Yuan Constance M. , Calvo Katherine R. , Braylan Raul C. , Valdez Janet , Lee Yuh Shan , Wong Deanna H. , Jones Jade , Sun Clare , Marti Gerald E. , Farooqui Mohammed Z.H. , Wiestner Adrian 
Published: December 2015

AbstractPurpose: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B-cell receptor (BCR) signaling. Ibrutinib, a Bruton tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. Although the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment.Experimental Design: Patients received single-agent ibrutinib on an investigator-initiated phase II trial. Serial blood and tissue samples were collected pretreatment and during treatment. Changes in cytokine levels, cellular subsets, and microenvironmental interactions were assessed.Results: Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Furthermore, ibrutinib treatment decreased circulating tumor cells and overall T-cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4+ T cells was observed concurrent with reduced expression of activation markers and PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4+ T cells in vitro. Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells.Conclusions: In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the antitumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. Clin Cancer Res; 22(7); 1572–82. ©2015 AACR.See related commentary by Bachireddy and Wu, p. 1547
Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease
Authors: Ma Ruishuang , Zhang Yan , Cao Muhua , Li Tao , Yao Zhipeng , Zhao Lu , Fang Shaohong , Yu Bo , Dong Zengxiang , Thatte Hemant S. , Bi Yayan , Kou Junjie , Yang Shufen , Piao Daxun , He Zhangxiu , Si Yu , Jiang Tao , Hao Lirong , Zhou Jin , Shi Jialan 
Published: December 2015

SummaryInflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. Wright-Giemsa and immunofluorescence staining demonstrated that the elevated NETs were released by activated IBD neutrophils or by control neutrophils treated with IBD sera obtained from patients with the active disease. MPs and MP-origin cells in IBD groups, especially in active stage, markedly shortened coagulation time and had increased levels of fibrin, thrombin and FXa production as assessed by coagulation function assays. Importantly, we found that on stimulated ECs, PS rich membranes provided binding sites for FXa and FVa, promoting fibrin formation while TNF blockage or IgG depletion attenuated this effect. Treatment of control neutrophils with TNF and isolated IgG from PR3-ANCA-positive active IBD patients also resulted in the release of NETs. Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients.
A tecelagem lírica de uma Penélope moderna: a alquimia dos nós, de Yêda Schmaltz
Authors: Vieira Júnior Paulo Antônio 
Published: December 2015

A alquimia dos nós (1979), de Yêda Schmaltz, reinventa o mito de Penélope sob registro de Homero, na Odisseia. Através de uma visão feminina, a voz lírica constante no livro, sobretudo na primeira parte, “Fios (O livro de Penélope)”, desenvolve o relato lírico da sua união com Ulisses, do período em que sofre a ausência do esposo e do retorno dele. A principal modificação na identidade da Penélope yediana decorre da reflexão e do tratamento em relação a sua sexualidade, bem como do desencanto ao divisar o homem amado, quando ele retorna. Os versos que integram essa obra não raro usam da metáfora da tecelagem e do tecido para caracterizar a voz lírica como pertencente à heroína do passado mitológico. Porém, a tecelagem metafórica também alude à sexualidade solitária de Penélope, bem como à atividade por ela exercida, o trabalho com o fio e a escrita poética. O presente estudo empreende leitura dos versos da poeta goiana a partir das considerações desenvolvidas sobre a metáfora da tecelagem e da consciência erótica do literário desenvolvidas por Hughes Liborel (1997), Ana Maria Machado (2001), Octavio Paz (2001) e Angélica Soares (1999).
Tisser la sociabilité, la presse et les imaginaires: Entretien avec Guillaume Pinson (Université Laval - Canada)
Authors: Cerqueira dos Anjos Yuri 
Published: December 2015

Guillaume Pinson, professeur titulaire au Département des Littératures de l’Université Laval, est l’un des plus importants chercheurs de l’histoire de la culture médiatique en Europe et en Amérique du Nord francophones. Dans cet entretien il nous présente les lignes (théoriques, méthodologiques et thématiques) qui traversent son parcours et incarnent un vrai renouveau des études littéraires et médiatiques actuelles. Mettant en relief des corpus traditionnellement considérés comme « mineurs », comme la presse, la mondanité, la mode, etc. il montre qu’il est possible d’envisager un futur très fertile pour les études littéraires dès qu’on adopte un nouveau regard sur le système de circulation textuelle d’une époque.
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Authors: Dubrac Alexandre , Genet Gael , Ola Roxana , Zhang Feng , Pibouin-Fragner Laurence , Han Jinah , Zhang Jiasheng , Thomas Jean-Léon , Chedotal Alain , Schwartz Martin A. , Eichmann Anne 
Published: December 2015

Background—
Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target in a number of diseases, including wet macular degeneration and wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow sprout extension. The adaptor proteins Nck1 and 2 are known regulators of cytoskeletal dynamics and polarity, but their function in angiogenesis is poorly understood. Here, we show that the Nck adaptors are required for endothelial cell front-rear polarity and migration downstream of the angiogenic growth factors VEGF-A and Slit2.

Methods and Results—

Mice carrying inducible, endothelial-specific
Nck1/2
deletions fail to develop front-rear polarized vessel sprouts and exhibit severe angiogenesis defects in the postnatal retina and during embryonic development. Inactivation of
NCK1
and
2
inhibits polarity by preventing Cdc42 and Pak2 activation by VEGF-A and Slit2. Mechanistically, NCK binding to ROBO1 is required for both Slit2- and VEGF-induced front-rear polarity. Selective inhibition of polarized endothelial cell migration by targeting
Nck1/2
prevents hypersprouting induced by Notch or Bmp signaling inhibition, and pathological ocular neovascularization and wound healing, as well.

Conclusions—
These data reveal a novel signal integration mechanism involving NCK1/2, ROBO1/2, and VEGFR2 that controls endothelial cell front-rear polarity during sprouting angiogenesis.
Probabilistic Seasonal Forecasts in the North American Multimodel Ensemble: A Baseline Skill Assessment
Authors: Becker Emily , van den Dool Huug 
Published: December 2015

Abstract
The North American Multimodel Ensemble (NMME) forecasting system has been continuously producing seasonal forecasts since August 2011. The NMME, with its suite of diverse models, provides a valuable opportunity for characterizing forecast confidence using probabilistic forecasts. The current experimental probabilistic forecast product (in map format) presents the most likely tercile for the seasonal mean value, chosen out of above normal, near normal, or below normal categories, using a nonparametric counting method to determine the probability of each class. The skill of the 3-month-mean probabilistic forecasts of 2-m surface temperature (T2m), precipitation rate, and sea surface temperature is assessed using forecasts from the 29-yr (1982–2010) NMME hindcast database. Three forecast configurations are considered: a full six-model NMME; a “mini-NMME” with 24 members, four each from six models; and the 24-member CFSv2 alone. Skill is assessed on the cross-validated hindcasts using the Brier skill score (BSS); forecast reliability and resolution are also assessed. This study provides a baseline skill assessment of the current method of creating probabilistic forecasts from the NMME system.
For forecasts in the above- and below-normal terciles for all variables and geographical regions examined in this study, BSS for NMME forecasts is higher than BSS for CFSv2 forecasts. Niño-3.4 forecasts from the full NMME and the mini-NMME receive nearly identical BSS that are higher than BSS for CFSv2 forecasts. Even systems with modest BSS, such as T2m in the Northern Hemisphere, have generally high reliability, as shown in reliability diagrams.
Intensification of the Western North Pacific Anticyclone Response to the Short Decaying El Niño Event due to Greenhouse Warming
Authors: Chen Wei , Lee June-Yi , Ha Kyung-Ja , Yun Kyung-Sook , Lu Riyu 
Published: December 2015

Abstract
Two types of El Niño evolution have been identified in terms of the lengths of their decaying phases: the first type is a short decaying El Niño that terminates in the following summer after the mature phase, and the second type is a long decaying one that persists until the subsequent winter. The responses of the western North Pacific anticyclone (WNPAC) anomaly to the two types of evolution are remarkably different. Using experiments from phase 5 of the Coupled Model Intercomparison Project (CMIP5), this study investigates how well climate models reproduce the two types of El Niño evolution and their impacts on the WNPAC in the historical period (1950–2005) and how they will change in the future under anthropogenic global warming. To reduce uncertainty in future projection, the nine best models are selected based on their performance in simulating El Niño evolution. In the historical run, the nine best models’ multimodel ensemble (B9MME) well reproduces the enhanced (weakened) WNPAC that is associated with the short (long) decaying El Niño. The comparison between results of the historical run for 1950–2005 and the representative concentration pathway 4.5 run for 2050–99 reveals that individual models and the B9MME tend to project no significant changes in the two types of El Niño evolution for the latter half of the twenty-first century. However, the WNPAC response to the short decaying El Niño is considerably intensified, being associated with the enhanced negative precipitation anomaly response over the equatorial central Pacific. This enhancement is attributable to the robust increase in mean and interannual variability of precipitation over the equatorial central Pacific under global warming.
Accumulation Variability in the Antarctic Peninsula: The Role of Large-Scale Atmospheric Oscillations and Their Interactions*
Authors: Goodwin Bradley P. , Mosley-Thompson Ellen , Wilson Aaron B. , Porter Stacy E. , Sierra-Hernandez M. Roxana 
Published: December 2015

AbstractA new ice core drilled in 2010 to bedrock from the Bruce Plateau (BP) on the Antarctic Peninsula (AP) provides a high temporal resolution record of environmental conditions in this region. The extremely high annual accumulation rate at this site facilitates analysis of the relationships between annual net accumulation An on the BP and large-scale atmospheric oscillations. Over the last ~45 years, An on the BP has been positively correlated with both the southern annular mode (SAM) and Southern Oscillation index (SOI). Extending this analysis back to 1900 reveals that these relationships are not temporally stable, and they exhibit major shifts in the late-1940s and the mid-1970s that are contemporaneous with phase changes in the Pacific decadal oscillation (PDO). These varying multidecadal characteristics of the An–oscillation relationships are not apparent when only data from the post-1970s era are employed. Analysis of the longer ice core record reveals that the influence of the SAM on An depends not only on the phase of the SAM and SOI but also on the phase of the PDO. When the SAM’s influence on BP An is reduced, such as under negative PDO conditions, BP An is modulated by variability in the tropical and subtropical atmosphere through its impacts on the strength and position of the circumpolar westerlies in the AP region. These results demonstrate the importance of using longer-term ice core–derived proxy records to test conventional views of atmospheric circulation variability in the AP region.
mCLOUD: A Multiview Visual Feature Extraction Mechanism for Ground-Based Cloud Image Categorization
Authors: Xiao Yang , Cao Zhiguo , Zhuo Wen , Ye Liang , Zhu Lei 
Published: December 2015

AbstractIn this paper, a novel Multiview CLOUD (mCLOUD) visual feature extraction mechanism is proposed for the task of categorizing clouds based on ground-based images. To completely characterize the different types of clouds, mCLOUD first extracts the raw visual descriptors from the views of texture, structure, and color simultaneously, in a densely sampled way—specifically, the scale invariant feature transform (SIFT), the census transform histogram (CENTRIST), and the statistical color features are extracted, respectively. To obtain a more descriptive cloud representation, the feature encoding of the raw descriptors is realized by using the Fisher vector. This is followed by the feature aggregation procedure. A linear support vector machine (SVM) is employed as the classifier to yield the final cloud image categorization result. The experiments on a challenging cloud dataset termed the six-class Huazhong University of Science and Technology (HUST) cloud demonstrate that mCLOUD consistently outperforms the state-of-the-art cloud classification approaches by large margins (at least 6.9%) under all the different experimental settings. It has also been verified that, compared to the single view, the multiview cloud representation generally enhances the performance.
Updating Perceptions of (In)Justice
Authors: Augustyn Megan Bears 
Published: December 2015

Objectives: This study evaluates the malleability of judgments of procedural justice. Drawing upon various literatures, five factors are hypothesized to be related to changes in procedural justice: (1) prior judgments of procedural justice, (2) direct experiences of arrest, (3) vicarious experiences of arrest, (4) individual arrest history, and (5) age. Methods: Using 11 waves of data from the Pathways to Desistance Study ( N = 1,354), multilevel models relate within-person covariates including individual, family, and peer arrests, and age to changes in procedural justice, controlling for stable, individual characteristics. Results: Judgments of procedural justice are anchored in prior perceptions. They are also a function of direct and vicarious experiences of arrests with the effect of individual arrests varying across individual arrest history. Evidence also suggests a developmental component. Age has a direct effect on judgments of procedural justice and conditions the effect of individual arrests on changes in procedural justice. Conclusions: Judgments of procedural justice are not static. Given these results, future research should continue to investigate the varying effects of other interactions with legal authorities on changes in judgments of procedural justice in order to form stronger policies aimed at increasing citizen cooperation.
Early and Intermediate Hospital-to-Home Transition Outcomes of Older Adults Diagnosed With Diabetes
Authors: LaManna Jacqueline B. , Bushy Angeline , Norris Anne E. , Chase Susan K. 
Published: December 2015

Purpose The purpose of this study was to identify factors affecting early and intermediate hospital-to home transition outcomes of older adults with preexisting diabetes mellitus. Methods A mixed-methods design was used. A sample of 96 hospitalized older adults with a prior diagnosis of diabetes were recruited within 4 hours of discharge. Data reflective of general health status, diabetes status, perceived discharge readiness (Readiness for Hospital Discharge Scale), hospitalization, and anticipated postdischarge support were gathered upon enrollment. Transition outcome data including unplanned care encounter occurrences, perceived transition quality (Care Transition Measure-15), and postdischarge difficulty (scale and free responses to the Post-Discharge Coping Difficulty Scale [PDCDS]) were obtained by telephone interview 7 and 30 days after discharge. Three unique, dichotomous variables were created from recurrent subthemes that emerged during content analysis of free-response data and were used in statistical testing. Binary logistic regression was performed to identify predictive factors for an unplanned care encounter within 30 days of discharge. Results Multimorbidity was prevalent in participants. Difficulties managing medications, blood glucose, and chronic illnesses other than diabetes were common problems. Higher PDCDS scores 7 and 30 days following discharge and difficulty managing a nondiabetes chronic health problem were predictive of an unplanned care encounter within 30 days of discharge. Conclusions Multimorbidity complicates home recovery of older adults with diabetes. Diabetes adds complexity to hospital-to-home care transitions. Transition difficulties predict higher risk for an unplanned care encounter. More intensive follow-up of older adults with diabetes during the first month following discharge is recommended.
Endovenous laser ablation of the great saphenous vein – Varying energy may not affect outcome
Authors: Nejm Carlos S , Timi Jorge RR , de Araújo Walter Boim , Caron Filipe C 
Published: December 2015

Objectives To determine great saphenous vein occlusion rate after endovenous laser ablation using the 1470-nm bare-fiber diode laser to supply either 7 W or 15 W and evaluate procedure-related complications. Method Patients with varicose veins of the lower extremities (CEAP class C2–C6) were randomly assigned to undergo either 7-W (18 patients, 30 limbs) or 15-W (18 patients, 30 limbs) endovenous laser ablation. Duplex ultrasound follow-up was at 3–5 days, 1, 6, and 12 months postoperatively. Results Occlusion rate was 100% in both groups at 3–5 days and 1 month and 86.7% in 7-W and 100% in 15-W patients at both 6 and 12 months, with no difference between groups ( p > 0.05). Four (13.3%) 15-W and 3 (10%) 7-W patients had paresthesia at 3–5 days, with no difference between groups ( p > 0.05). Conclusions These preliminary data suggest that both techniques are similarly effective in the treatment of varicose great saphenous veins.
For how long can two emergency medical technicians perform high-quality cardiopulmonary resuscitation?
Authors: Kim Chu Hyun , Kim Gi Woon , Cha Won Chul , Kang Bo Ra , Do Han ho , Seo Jun Seok 
Published: December 2015

Objective To determine the duration and obstacles to prolonged on-scene cardiopulmonary resuscitation (CPR), and establish how long a pair of emergency medical technicians (EMTs) can provide high-quality CPR. Method Intermediate-level EMTs in Gyeonggi-do Province, Republic of Korea completed a survey regarding on-scene CPR. EMTs undergoing routine training took part in a simulation using mannequins. Parameters including compression depth, total number and rate of compressions; occurrence of incorrect hand position and incomplete chest recoil were collected over 16 2-min cycles of CPR (32 min total), with EMTs working in pairs. Result The simulation study included 43 EMTs. The median duration of on-scene CPR was 3.7 min. Fear of decrease in performance was the main obstacle to continued CPR ( n = 188/254 [74.0%]). Standards for high-quality CPR were met at each of the 16 steps of the simulation. Compression rate increased significantly with time. There were no significant changes in any other parameter. Conclusion Pairs of EMTs maintained high-quality CPR for 16 cycles (32 min) with no decrease in performance. Our findings could provide evidence to recommend guidelines for duration of on-scene CPR for cardiac arrest, particularly in countries where the level and number of ambulance crews are limited.