bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression
Authors: Kaneda Megan M. , Cappello Paola , Nguyen Abraham V. , Ralainirina Natacha , Hardamon Chanae R. , Foubert Philippe , Schmid Michael C. , Sun Ping , Mose Evangeline , Bouvet Michael , Lowy Andrew M. , Valasek Mark A. , Sasik Roman , Novelli Francesco , Hirsch Emilio , Varner Judith A. 
Published: May 2016

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8+ T-cell–mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type.
Significance: We report here that PI3Kγ regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kγ restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kγ represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870–85. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 803
Expanded and Activated Natural Killer Cells for Immunotherapy of Hepatocellular Carcinoma
Authors: Kamiya Takahiro , Chang Yu-Hsiang , Campana Dario 
Published: May 2016

Abstract
Viral infection of the liver is a major risk factor for hepatocellular carcinoma (HCC). Natural killer (NK) cells recognize virally infected and oncogenically transformed cells, suggesting a therapeutic role for NK-cell infusions in HCC. Using the K562-mb15-41BBL cell line as a stimulus, we obtained large numbers of activated NK cells from the peripheral blood of healthy donors. Expanded NK cells exerted remarkably high cytotoxicity against HCC cell lines, which was generally much higher than that of unstimulated or IL2-activated NK cells. In immunodeficient NOD/scid IL2RGnull mice engrafted with Hep3B, treatment with expanded NK cells markedly reduced tumor growth and improved overall survival. HCC cells exposed for 48 hours to 5 μmol/L of sorafenib, a kinase inhibitor currently used for HCC treatment, remained highly sensitive to expanded NK cells. HCC cell reductions of 39.2% to 53.8% caused by sorafenib in three cell lines further increased to 80.5% to 87.6% after 4 hours of culture with NK cells at a 1:1 effector-to-target ratio. NK-cell cytotoxicity persisted even in the presence of sorafenib. We found that NKG2D, an NK-cell–activating receptor, was an important mediator of anti-HCC activity. We therefore enhanced its signaling capacity with a chimeric NKG2D-CD3ζ-DAP10 receptor. This considerably increased the anti-HCC cytotoxicity of expanded NK cells in vitro and in immunodeficient mice. The NK expansion and activation method applied in this study has been adapted to clinical-grade conditions. Hence, these results warrant clinical testing of expanded NK-cell infusions in patients with HCC, possibly after genetic modification with NKG2D-CD3ζ-DAP10. Cancer Immunol Res; 4(7); 574–81. ©2016 AACR.
Prolonged Benefit from Ipilimumab Correlates with Improved Outcomes from Subsequent Pembrolizumab
Authors: Shreders Amanda , Joseph Richard , Peng Chengwei , Ye Fei , Zhao Shilin , Puzanov Igor , Sosman Jeffrey A. , Johnson Douglas B. 
Published: May 2016

Abstract
Patients with metastatic melanoma whose disease progresses on ipilimumab can clearly derive benefit from subsequent anti–programmed death-1 (PD-1). However, patients experience heterogeneous outcomes with ipilimumab, including rapid or delayed progression, and it is unclear whether patterns of ipilimumab progression influence subsequent clinical responses to anti–PD-1. We retrospectively reviewed data from 116 patients with metastatic melanoma who progressed on ipilimumab and were subsequently treated with pembrolizumab. The study objectives were to determine whether progression-free survival (PFS) with ipilimumab was associated with PFS, objective response rate (ORR), and clinical benefit rate (CBR; ORR + stable disease) with pembrolizumab. Patients with PFS ≥90 days after treatment with ipilimumab generally had superior outcomes with subsequent pembrolizumab treatment compared with patients with PFS &lt;90 days (ORR, 49% vs. 35%, P = 0.12; CBR, 66% vs. 46%, P = 0.03). Patients with prolonged ipilimumab benefit (PFS ≥ 180 days) had excellent outcomes with pembrolizumab compared with rapid progressors (PFS &lt; 45 days; ORR, 55% vs. 25%; CBR, 80% vs. 25%; median PFS, 249 vs. 50 days). Using logistic regression models, PFS with ipilimumab was independently correlated with response to pembrolizumab (odds ratio, 1.22; 95% CI, 1.02–1.51). This study shows that prolonged PFS with ipilimumab predicts excellent outcomes with subsequent pembrolizumab treatment, offering valuable prognostic information for clinicians. Cancer Immunol Res; 4(7); 569–73. ©2016 AACR.
The Role of Surface Drag in Tornadogenesis within an Idealized Supercell Simulation
Authors: Roberts Brett , Xue Ming , Schenkman Alexander D. , Dawson Daniel T. 
Published: May 2016

Abstract
To investigate the effect of surface drag on tornadogenesis, a pair of idealized simulations is conducted with 50-m horizontal grid spacing. In the first experiment (full-wind drag case), surface drag is applied to the full wind; in the second experiment (environmental drag case), drag is applied only to the background environmental wind, with storm-induced perturbations unaffected. The simulations are initialized using a thermal bubble within a horizontally homogeneous background environment that has reached a balance between the pressure gradient, Coriolis, and frictional forces. The environmental sounding is derived from a prior simulation of the 3 May 1999 Oklahoma tornado outbreak but modified to account for near-ground frictional effects. In the full-wind drag experiment, a tornado develops around 25 min into the simulation and persists for more than 10 min; in the environmental-only drag experiment, no tornado occurs. Three distinct mechanisms are identified by which surface drag influences tornadogenesis. The first mechanism is the creation by drag of near-ground vertical wind shear (and associated horizontal vorticity) in the background environment. The second mechanism is generation of near-ground crosswise horizontal vorticity by drag on the storm scale as air accelerates into the low-level mesocyclone; this vorticity is subsequently exchanged into the streamwise direction and eventually tilted into the vertical. The third mechanism is frictional enhancement of horizontal convergence, which strengthens the low-level updraft and stretching of vertical vorticity. The second and third mechanisms are found to work together to produce a tornado, while baroclinic vorticity plays a negligible role.
Bulk modulus evolution of thermoset resins during crosslinking: Is a direct and accurate measurement possible?
Authors: Péron Mael , Sobotka Vincent , Boyard Nicolas , Le Corre Steven 
Published: May 2016

The determination of the mechanical properties of thermoset resin and their evolution during transformation still represents a scientific issue in the composite materials community. A homemade apparatus named PvTα has recently been adapted to the measurement of neat resin bulk modulus evolution during cure and has been presented in a previous study. Several assumptions were used to directly obtain this value but they cannot be checked in situ. A multi-physic modelling of the system is proposed for this purpose in this paper. It accounts for the thermal, chemical and mechanical behaviours of the different components of the apparatus as well as their interactions during an experiment. This model is thoroughly validated thanks to several comparisons with experimental results. This study shows that the early assumptions are not verified during the whole cure in the case of RTM6 resin. It leads to 40% error in the bulk modulus estimation, thus making impossible a direct measurement of the resin bulk modulus using the simple protocol proposed by Nawab et al. A new procedure, which is based on the developed model, is proposed to improve the analysis accuracy.
Relative Difference and Burglary Location
Authors: Chamberlain Alyssa W. , Boggess Lyndsay N. 
Published: May 2016

Objectives: Neighborhood characteristics predict burglary targets, but target attractiveness may be colored by the conditions in which a potential offender resides. We test whether relative differences in concentrated disadvantage, racial/ethnic composition, and ethnic heterogeneity influence where burglars offend, controlling for distance. From a relative deprivation perspective, economically advantaged areas make more attractive targets to burglars residing in disadvantage neighborhoods, but a social disorganization perspective predicts areas lower in social cohesion are most attractive, which may be neighborhoods with greater disadvantage. Methods: Drawing upon a unique sample of cleared burglaries in the City of Tampa, Florida from 2000 to 2012, we utilize discrete choice modeling to predict burglar offense destination. Results: Offenders target neighborhoods that are geographically proximate or ecologically similar to their own. When accounting for relative differences, burglars from all neighborhood types are more likely to target highly disadvantaged or heterogeneous neighborhoods. Conclusions: Burglars generally select targets that are similar to their residence. However, when suspects do discriminate, there is evidence that they target neighborhoods that are worse off relative to their own on characteristics such as residential instability, disadvantage, racial composition, and racial/ethnic diversity. These neighborhoods are associated with lower social control and lower risk of detection.
The experience of an increase in the injection of ethylphenidate in Lothian April 2014–March 2015
Authors: Lafferty Con , Smith Linda , Coull Alison , Shanley Jim 
Published: May 2016

Background and aims New psychoactive substances are causing increasing harm across the UK but the use of new psychoactive substance by injecting has become a significant problem within Lothian since the beginning of 2014. Data indicate a rapid rise in the number of existing drug injectors, particularly heroin injectors, moving to new psychoactive substance injecting. This paper reports the experiences within Lothian of a sudden increase in injecting of ethylphenidate over one year. A temporary class drug order was placed on ethylphenidate on 10 April 2015, and as yet the effects of this are unknown. Methods Data specifically relating to new psychoactive substance recorded during injecting equipment provision transactions conducted by the NHS are reported. A survey was utilised to gather more detailed data from new psychoactive substance injectors. Results Injection of new psychoactive substance, including ethylphenidate has had significant adverse effects on physical and mental health. Risky behaviour such as sharing of equipment is known, and there are risks of transmission of infections. Conclusion The rapid increase in injecting ethylphenidate has had a major impact on injecting equipment provision services, health services and public health. More work is required to identify routes to recovery.
A Dystopian Climate for Transitional Justice
Authors: Phillips-Amos Georgia 
Published: May 2016

As Colombia’s asymmetric war has evolved, gravitating toward cities, it has become absorbed by a transitional justice system. In the process, language used to name relevant stakeholders, shape national narratives of collective memory, and activate legal infrastructure is mediated by a symbolic and often duplicitous system of governance. A history of political violence and attempts to impose security focusing on the contemporary population of Comuna 13, the fastest-growing site of urban displacement in the city of Medellín, gives context to stories of violence that are otherwise eclipsed by the process of collective memory making and describes grassroots attempts at retracing a public narrative. Mientras la guerra asimétrica en Colombia ha ido evolucionado, gravitando más y más hacia las ciudades, ésta ha sido absorbida por un sistema de justicia transicional. En este proceso, el lenguaje que se utiliza para nombrar a los actores más importantes, construir narrativas nacionales sobre la memoria colectiva y activar una infraestructura legal está condicionado por un sistema de gobernanza simbólico y a menudo engañoso. La historia sobre la violencia política y los esfuerzos por imponer medidas de seguridad en la Comuna 13—la zona de desplazamiento urbano de más alto crecimiento en la ciudad de Medellín— le da un contexto a las historias de violencia que de otra manera serían eclipsadas por el proceso de construir la memoria colectiva y describe los esfuerzos de base para recrear una narrativa pública.
Bilateral thoracoscopic extended thymectomy versus sternotomy
Authors: Fiorelli Alfonso , Mazzella Antonio , Cascone Roberto , Caronia Francesco Paolo , Arrigo Ettore , Santini Mario 
Published: May 2016

Background Complete open surgical resection is the standard treatment for thymoma and myasthenia gravis. We evaluated the feasibility of bilateral video-assisted thoracoscopic extended thymectomy, and compared it to surgery via sternotomy. Methods From 2011 to 2014, 43 patients undergoing thymectomy were divided into 2 groups: 23 underwent video-assisted thoracoscopic extended thymectomy, and 20 had thymectomy via sternotomy. The primary outcomes were postoperative pain score (visual analog scale) at 6, 12, 24, 48, and 72 h, and 1-month postoperatively, and morphine consumption in the first 48 h. Secondary outcomes were surgical and clinical results. Results There were no significant differences between the 2 groups in terms of demographics and preoperative clinical data. Compared to the sternotomy group, the video-assisted thoracoscopic thymectomy group had lower pain scores and morphine consumption at all time points, significantly less operative blood loss and chest drainage volume, and shorter hospital stay. The rates of improvement in myasthenia gravis were 85% and 86% in the video-assisted thoracoscopic thymectomy and sternotomy groups, respectively. No recurrence of thymoma was found in either group (median follow-up 27 months). Conclusions Our results seem to confirm that in selected cases, video-assisted thoracoscopic thymectomy allows complete resection of thymus and perithymic tissue, similar to sternotomy but with the known advantages of minimally invasive surgery including less pain and a good cosmetic result.
Similarity of coagulation and inflammation despite different surgical revascularization strategies – a prospective randomized trial
Authors: Gorki Hagen , Hoenicka Markus , Rupp Patricia , Müller-Eising Kristina , Deininger Stefanie , Kunert Andreas , Liebold Andreas 
Published: May 2016

Background: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. Methods: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. Results: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor α (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. Conclusions: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood – recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated. The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/
Efficacy of the RemoweLL cardiotomy reservoir for fat and leucocyte removal from shed mediastinal blood: a randomized controlled trial
Authors: Lagny Marc-Gilbert , Gothot Andre , Hans Gregory A. , Koch Jean-Noël , Blaffart Francine , Hella Dominique , Donneau Anne-Françoise , Roediger Laurence , Lecut Christelle , Pincemaïl Joël , Cheramy-Bien Jean-Paul , Defraigne Jean-Olivier 
Published: May 2016

Introduction: Re-transfusion of lipid particles and activated leucocytes with shed mediastinal blood (SMB) can aggravate cardiopulmonary bypass-associated inflammation and increase the embolic load. This study evaluated the fat and leucocyte removal capacity of the RemoweLL cardiotomy reservoir. Methods: Forty-five patients undergoing elective on-pump cardiac surgery were randomly allocated to filtration of SMB using the RemoweLL or the Admiral cardiotomy reservoir. The primary outcome was a drop in leucocytes and lipid particles obtained with the two filters. The effect of the filters on other blood cells and inflammatory mediators, such as myeloperoxidase (MPO), was also assessed. Results: The RemoweLL cardiotomy filter removed 16.5% of the leucocytes (p<0.001) while no significant removal of leucocytes was observed with the Admiral (p=0.48). The percentage reductions in lipid particles were similar in the two groups (26% vs 23%, p=0.2). Both filters similarly affected the level of MPO (p=0.71). Conclusion: The RemoweLL filter more effectively removed leucocytes from SMB than the Admiral. It offered no advantage in terms of lipid particle clearance.
Factors affecting optimal linear endovenous energy density for endovenous laser ablation in incompetent lower limb truncal veins – A review of the clinical evidence
Authors: Cowpland Christine A , Cleese Amy L , Whiteley Mark S 
Published: May 2016

Objectives The objective is to identify the factors that affect the optimal linear endovenous energy density (LEED) to ablate incompetent truncal veins. Methods We performed a literature review of clinical studies, which reported truncal vein ablation rates and LEED. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow diagram documents the search strategy. We analysed 13 clinical papers which fulfilled the criteria to be able to compare results of great saphenous vein occlusion as defined by venous duplex ultrasound, with the LEED used in the treatment. Results Evidence suggests that the optimal LEED for endovenous laser ablation of the great saphenous vein is >80 J/cm and <100 J/cm in terms of optimal closure rates with minimal side-effects and complications. Longer wavelengths targeting water might have a lower optimal LEED. A LEED <60 J/cm has reduced efficacy regardless of wavelength. The optimal LEED may vary with vein diameter and may be reduced by using specially shaped fibre tips. Laser delivery technique and type as well as the duration time of energy delivery appear to play a role in determining LEED. Conclusion The optimal LEED to ablate an incompetent great saphenous vein appears to be >80 J/cm and <95 J/cm based on current evidence for shorter wavelength lasers. There is evidence that longer wavelength lasers may be effective at LEEDs of <85 J/cm.
Obesity and lower limb venous disease – The epidemic of phlebesity
Authors: Davies Huw OB , Popplewell Matthew , Singhal Rishi , Smith Neil , Bradbury Andrew W 
Published: May 2016

Introduction Lower limb venous disease affects up to one half, and obesity up to one quarter, of the adult population. Many people are therefore affected by, and present to health services for the treatment of both conditions. This article reviews the available evidence of pathophysiological and clinical relationship between obesity and varicose veins, chronic venous insufficiency and ulceration and deep vein thrombosis. Methods A literature search of PubMed and Cochrane libraries was performed in accordance with PRISMA statement from 1946 to 2015, with further article identification from following cited references for articles examining the relationship between obesity and venous disease. Search terms included obesity, overweight, thrombosis, varicose veins, CEAP, chronic venous insufficiency, treatment, endovenous, endothermal, sclerotherapy, bariatric surgery and deep vein thrombosis. Results The proportion of the population suffering from lower limb venous disease and obesity is increasing. Obesity is an important risk factor for all types of lower limb venous disease, and obese patients with lower limb venous disease are more likely to be symptomatic as a result of their lower limb venous disease. The clinical diagnosis, investigation, imaging and treatment of lower limb venous disease in obese people present a number of challenges. The evidence base underpinning medical, surgical and endovenous management of lower limb venous disease in obese people is limited and such treatment may be associated with worse outcomes and increased risks when compared to patients with a normal body mass index. Conclusion Lower limb venous disease and obesity are both increasingly common. As such, phlebologists will be treating ever greater numbers of obese patients with lower limb venous disease, and clinicians in many other specialties are going to be treating a wide range of obesity-related health problems in people with or at risk of lower limb venous disease. Unfortunately, obese people have been specifically excluded from many, if not most, of the pivotal studies. As such, many basic questions remain unanswered and there is an urgent need for research in this challenging and increasingly prevalent patient group.