bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex VivoExpanded Adaptive NK Cells Effectively Kill Primary Acute Lymphoblastic Leukemia Cells
Authors: Liu Lisa L. , Béziat Vivien , Oei Vincent Y.S. , Pfefferle Aline , Schaffer Marie , Lehmann Sören , Hellström-Lindberg Eva , Söderhäll Stefan , Heyman Mats , Grandér Dan , Malmberg Karl-Johan 
Published: June 2017

AbstractManipulation of human natural killer (NK) cell repertoires promises more effective strategies for NK cell–based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIR), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL). Culture of polyclonal NK cells together with feeder cells expressing HLA-E, the ligand for the activating NKG2C receptor, led to selective expansion of adaptive NK cells with enhanced alloreactivity against HLA-mismatched targets. The ex vivo expanded adaptive NK cells gradually obtained a more differentiated phenotype and were specific and highly efficient killers of allogeneic pediatric T- and precursor B-cell acute lymphoblastic leukemia (ALL) blasts, previously shown to be refractory to killing by autologous NK cells and the NK-cell line NK92 currently in clinical testing. Selective expansion of NK cells that express one single inhibitory KIR for self-HLA class I would allow exploitation of the full potential of NK-cell alloreactivity in cancer immunotherapy. In summary, our data suggest that adaptive NK cells may hold utility for therapy of refractory ALL, either as a bridge to transplant or for patients that lack stem cell donors. Cancer Immunol Res; 5(8); 654–65. ©2017 AACR.
Molecular signature of coronary stent thrombosis: oxidative stress and innate immunity cells
Authors: Cubedo Judit , Blasco Ana , Padró Teresa , Ramaiola Ilaria , Juan-Babot Oriol , Goicolea Javier , Fernández-Díaz José , Oteo Juan , Badimon Lina 
Published: June 2017

SummaryThe clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed on native coronary arteries (CT) to identify a differential molecular signature. The study included 45 patients with ST-elevation-myocardial-infarction (STEMI) treated by primary-percutaneous-intervention and thrombus aspiration: 21 had IST and 24 had CT. Thrombi were characterised by morphologic immunohistochemical analysis and differential proteomic profiling (2-DE+MALDI-TOF/TOF). Bioinformatic analysis revealed differences in proteins related to oxidative-stress and cell death/survival. IST showed a higher content of structural proteins (gelsolin, actin-cytoplasmic-1, tropomyosin, and myosin) together with an imbalance in redox-homeostasis related proteins (increased superoxide-dismutase and decreased peroxiredoxin-2 thrombus content), and a coordinated increase of chaperones (HSP60 and HSC70) and cellular quality control-related proteins (26S–protease-regulatory-subunit-7). These changes were reflected into a significant decrease in HSC70 systemic levels and a significant increase in advanced-oxidation-protein-products (AOPP) indicative of increased oxidative stress-mediated protein damage in IST. Our results reveal an imbalance in redox-related proteins indicative of an exacerbated oxidative-stress that leads to an accumulation of AOPP serum levels in IST. Moreover, the coordinated increase in chaperones and regulatory proteins reflects the activation of intracellular protection mechanisms to maintain protein integrity in IST. The failure to counterbalance the stress situation could trigger cellular apoptosis leading to the destabilization of the thrombus and to a worse prognosis of IST-STEMI-patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
Targeting of Extracellular RNA Reduces Edema Formation and Infarct Size and Improves Survival After Myocardial Infarction in Mice
Authors: Stieger Philipp , Daniel Jan‐Marcus , Thölen Christiane , Dutzmann Jochen , Knöpp Kai , Gündüz Dursun , Aslam Muhammad , Kampschulte Marian , Langheinrich Alexander , Fischer Silvia , Cabrera‐Fuentes Hector , Wang Yong , Wollert Kai C. , Bauersachs Johann , Braun‐Dullaeus Rüdiger , Preissner Klaus T. , Sedding Daniel G. 
Published: June 2017

Background
Following myocardial infarction (MI), peri‐infarct myocardial edema formation further impairs cardiac function. Extracellular RNA (eRNA) released from injured cells strongly increases vascular permeability. This study aimed to assess the role of eRNA in MI‐induced cardiac edema formation, infarct size, cardiac function, and survival after acute MI and to evaluate the therapeutic potential of ribonuclease 1 (RNase‐1) treatment as an eRNA‐degrading intervention.

Methods and Results
C57BL/6J mice were subjected to MI by permanent ligation of the left anterior descending coronary artery. Plasma eRNA levels were significantly increased compared with those in controls starting from 30 minutes after ligation. Systemic application of RNase‐1, but not DNase, significantly reduced myocardial edema formation 24 hours after ligation compared with controls. Consequently, eRNA degradation by RNase‐1 significantly improved the perfusion of collateral arteries in the border zone of the infarcted myocardium 24 hours after ligation of the left anterior descending coronary artery, as detected by micro–computed tomography imaging. Although there was no significant difference in the area at risk, the area of vital myocardium was markedly larger in mice treated with RNase‐1 compared with controls, as detected by Evans blue and 2,3,5‐triphenyltetrazolium chloride staining. The increase in viable myocardium was associated with significantly preserved left ventricular function, as assessed by echocardiography. Moreover, RNase‐1 significantly improved 8‐week survival following MI.

Conclusions
eRNA is an unrecognized permeability factor in vivo, associated with myocardial edema formation after acute MI. RNase‐1 counteracts eRNA‐induced edema formation and preserves perfusion of the infarction border zone, reducing infarct size and protecting cardiac function after MI.
Two new species of Nullana from southern Brazil (Hemiptera: Cicadellidae: Gyponini) with key to males
Authors: DOMAHOVSKI ALEXANDRE CRUZ , CAVICHIOLI RODNEY RAMIRO 
Published: June 2017

Two new species of Nullana DeLong, 1980 are described and illustrated: N. albinoi sp. nov. and N. sakakibarai sp. nov., both from the state of Paraná, Brazil. Two new synonyms and a new combination are proposed. A key to the 10 known species of Nullana are presented and Nullana gelbana is newly recorded from Paraná State, Brazil.
An evaluation of Health of the Nation Outcome Scales data to inform psychiatric morbidity following the Canterbury earthquakes
Authors: Beaglehole Ben , Frampton Chris M , Boden Joseph M , Mulder Roger T , Bell Caroline J 
Published: June 2017

Objective: Following the onset of the Canterbury, New Zealand earthquakes, there were widespread concerns that mental health services were under severe strain as a result of adverse consequences on mental health. We therefore examined Health of the Nation Outcome Scales data to see whether this could inform our understanding of the impact of the Canterbury earthquakes on patients attending local specialist mental health services. Method: Health of the Nation Outcome Scales admission data were analysed for Canterbury mental health services prior to and following the Canterbury earthquakes. These findings were compared to Health of the Nation Outcome Scales admission data from seven other large District Health Boards to delineate local from national trends. Percentage changes in admission numbers were also calculated before and after the earthquakes for Canterbury and the seven other large district health boards. Results: Admission Health of the Nation Outcome Scales scores in Canterbury increased after the earthquakes for adult inpatient and community services, old age inpatient and community services, and Child and Adolescent inpatient services compared to the seven other large district health boards. Admission Health of the Nation Outcome Scales scores for Child and Adolescent community services did not change significantly, while admission Health of the Nation Outcome Scales scores for Alcohol and Drug services in Canterbury fell compared to other large district health boards. Subscale analysis showed that the majority of Health of the Nation Outcome Scales subscales contributed to the overall increases found. Percentage changes in admission numbers for the Canterbury District Health Board and the seven other large district health boards before and after the earthquakes were largely comparable with the exception of admissions to inpatient services for the group aged 4–17 years which showed a large increase. Conclusion: The Canterbury earthquakes were followed by an increase in Health of the Nation Outcome Scales scores for attendees of local mental health services compared to other large district health boards. This suggests that patients presented with greater degrees of psychiatric distress, social disruption, behavioural change and impairment as a result of the earthquakes.
Rates and Correlates of Binge Drinking Among College Students With Disabilities, United States, 2013
Authors: West Steven L. , Graham Carolyn W. , Temple Peter 
Published: June 2017

Objective: Our objective was to provide the first comprehensive picture of alcohol use and binge drinking by US college students with disabilities (SWDs), who represent at least 11% (1.6 million) of the US college student population. Methods: In fall 2013, we used a stratified random sampling technique to identify and recruit 2440 SWDs from 122 US colleges and universities. A total of 1285 (53%) SWDs from 61 (50%) colleges and universities completed a survey of alcohol and other drug use and the use of substances by student peers. We conducted 4 multiple logistic regression analyses to compare binge-drinking and non–binge-drinking SWDs by potential correlates of such use and a final model that included only significant variables. Results: SWDs aged <21 vs ≥21 (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.82-0.99) who spent more time vs less time socializing (OR = 1.24; 95% CI, 1.11-1.38), who spent less time vs more time studying (OR = –0.89; 95% CI, –0.80 to –0.99), and who used vs did not use marijuana (OR = 1.44; 95% CI, 1.18-1.75) or amphetamines (OR = 1.82; 95% CI, 1.15-2.89) were significantly more likely to binge drink. SWDs who reported using barbiturates were less likely to binge drink than were those who did not use barbiturates (OR = –0.36; 95% CI, –0.21 to –0.61). In the final model, use of amphetamines (OR = 1.74; 95% CI, 1.15-2.65) or marijuana (OR = 1.60; 95% CI, 1.32-1.94) was the highest predictor of binge drinking. Conclusion: SWDs’ reported rates of binge drinking, although high, were not as high as those of nondisabled college students. Nevertheless, prevention efforts should be targeted toward college SWDs.
Entrapment of Cultured Pancreas Islets in Three-Dimensional Collagen Matrices
Authors: Chao Seh-Huang , Peshwa Madhusudan V. , Sutherland David E.R. , Hu Wei-Shou 
Published: June 2017

In vitro culture of islets of Langerhans decreases their immunogenecity, presumably by eliminating passenger leukocytes and other Ia+ presenting cells within the islets. Islets cultivated in petri dishes either at 37°C or at 25°C gradually disintegrate during culture in a time-dependent manner which is related to the free-floating condition of the islets. Also, a fraction of the islets disperse as single cells and beta-cell aggregates or adhere to the bottom of the culture dishes. Thus, the retrieval rate of transplantable islets is dampened due to their disintegration and spontaneous dispersion in conventional petri dish cultures. Entrapment of freshly harvested islets of Langerhans in a three-dimensional collagen matrix was studied as an alternative method for islet cultivation. The contraction of collagen fibrils during in vitro culture counteracts the dispersion of islets and helps in maintaining their integrity while in culture. It was observed that the entrapped islets maintain satisfactory morphology, viability, and capability of glucose-dependent insulin secretion for over 2 wk. The oxygen consumption rate and glucose metabolism of these islets was not deranged when entrapped in collagen. Also, the retrieval of islets is easier and more efficient than that observed in conventional culture systems. Our results indicate that culture of islets in three-dimensional collagen gels can potentially develop into an ideal system applicable to clinical transplantation of cultured islets or beta-cell aggregates.
Assessment of the Reproducibility of Alginate Encapsulation of Pancreatic Islets Using the MTT Colorimetric Assay
Authors: Heald K.A. , Jay T.R. , Downing R. 
Published: June 2017

Radioisotope diffusion experiments demonstrate that alginate/polyaminoacid encapsulation can prevent antibody and cytotoxic cell contact in vitro. The unpredictable outcome of xenotransplantation of encapsulated islets may reflect incomplete encapsulation. We have assessed a cytotoxic/MTT (tetrazolium) assay to test antibody permeability of capsules. Samples of free porcine islet tissue, and islet tissue encapsulated in alginate/poly-l-lysine/alginate microspheres were incubated with fresh autologous pig serum or normal human serum overnight. Cell metabolism was assessed by the MTT assay. Data from eight experiments (10 replicates/experiment) were analyzed using the Mann-Whitney U-test. Values were deemed significant when p < 0.05. Free islets cultured in human serum showed a significant reduction in metabolism when compared with islets cultured in pig serum: percentage reduction 52 ± 23% (mean ± SD). The differences in formazan production were significant in all experiments (p < 0.05). Alginate encapsulation of islets or removal of xeno-reactive antibodies in human serum by adsorption was shown to prevent the effects of complement-mediated lysis. However, in one of the eight experiments, there was a significant reduction in islet metabolism after exposure of encapsulated porcine islets to human serum. In conclusion, it has been shown that alginate encapsulation can prevent complement-mediated lysis. However, the encapsulation process employed was imperfect and did not prevent complement-mediated lysis of porcine islets in all experiments. The cytotoxicity/MTT assay allows investigation of the permeability of capsules to serum antibodies and could be performed to determine the viability of the islets and the integrity of microcapsules prior to transplantation.
Modern Contraceptive Choice Among Patients Seen at the “Cameroon National Planning Association for Family Welfare” Clinic Yaoundé
Authors: Yangsi Tameh Theodore , Florent Fouelifack Ymele , Ngole Mbong Eta , Nelson Fomulu 
Published: June 2017

Background: To understand the low modern contraceptive prevalence in Cameroon, we reviewed the methods chosen and determined their side effects among patients in an urban setting. Methods: We conducted a cross-sectional study at the “Cameroon National Planning Association for Family Welfare (CAMNAFAW) Clinic” in Yaoundé. Data were processed by SPSS software version 20.0 for Windows, and all tests were considered statistically significant at P < .05. Results: Of the 1180 women sampled, the most chosen methods were as follows: depot medroxy progesterone acetate: 72.1% (787 of 1091), followed by oral combined contraceptives: 21.3% (232 of 1091), subcutaneous implants: 3.2% (35 of 1091), and intrauterine contraceptive devices: 1.9% (21 of 1091). A hundred and forty two (14.5%) of the 977 women received at least once (revisits) at the Center, reported at least one side effect. Irregular vaginal bleeding was the most frequent side effect: 44.6% (84 of 188 total documented side effects). Side effects were most common among users of subcutaneous implants: 28% (7 of the 25 implant users). Conclusions: Prescription of contraceptives should reflect not only the desire of couples but also the side effects associated with each method. This would optimize observance and adherence, consequently decreasing the failure rate.
Approach to the Management of Patients With Hidradenitis Suppurativa: A Consensus Document
Authors: Alavi Afsaneh , Lynde Charles , Alhusayen Raed , Bourcier Marc , Delorme Isabelle , George Ralph , Gooderham Melinda , Gulliver Wayne , Kalia Sunil , Marcoux Danielle , Poulin Yves 
Published: June 2017

Background: Hidradenitis suppurativa (HS) is a painful, debilitating, and poorly understood condition, which is suboptimally diagnosed, managed, and treated. Evidence supporting various treatment modalities is sparse. Objectives: To incorporate scientific evidence and expert opinions to develop useful guidance for the evaluation and management of patients with HS. Methods: An expert panel of Canadian dermatologists and surgeons developed statements and recommendations based on available evidence and clinical experience. The statements and recommendations were subjected to analysis and refinement by the panel, and voting was conducted using a modified Delphi technique with a prespecified cutoff agreement of 75%. Results: Ten specific statements and recommendations were accepted by the expert panel. These were grouped into 4 domains: diagnosis and assessment, treatment and management, comorbidities and a multidisciplinary approach, and education. Conclusions: These statements and recommendations will serve to increase awareness of HS and provide a framework for decisions involving diagnosis and management. Evidence suggests that antibacterial and anti–tumour necrosis factor therapies are effective in the treatment of HS. This is supported by the clinical experience of the authors. Further clinical research and the establishment of multidisciplinary management teams will continue to advance management of HS in Canada.
Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
Authors: Chari Ajai , Suvannasankha Attaya , Fay Joseph W. , Arnulf Bertrand , Kaufman Jonathan L. , Ifthikharuddin Jainulabdeen J. , Weiss Brendan M. , Krishnan Amrita , Lentzsch Suzanne , Comenzo Raymond , Wang Jianping , Nottage Kerri , Chiu Christopher , Khokhar Nushmia Z. , Ahmadi Tahamtan , Lonial Sagar 
Published: June 2017

Key PointsNo new safety signals were observed with daratumumab plus pomalidomide and dexamethasone, except for increased neutropenia. Daratumumab plus pomalidomide and dexamethasone induced rapid, deep, and durable responses in heavily treated patients with multiple myeloma.
Automated analysis of retinal imaging using machine learning techniques for computer vision
Authors: De Fauw Jeffrey , Keane Pearse , Tomasev Nenad , Visentin Daniel , van den Driessche George , Johnson Mike , Hughes Cian O , Chu Carlton , Ledsam Joseph , Back Trevor , Peto Tunde , Rees Geraint , Montgomery Hugh , Raine Rosalind , Ronneberger Olaf , Cornebise Julien 
Published: June 2017

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases. Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular (“wet”) age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the ‘back’ of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges. This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients. Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success.
Cambio institucional, discurso y política. Una propuesta de análisis desde el postestructuralismo
Authors: Reynares Juan Manuel 
Published: June 2017

Este artículo contribuye a la discusión sobre el vínculo entre instituciones y discurso en la ciencia política. Para ello, recupera algunos aportes del institucionalismo discursivo que han subrayado cómo la dimensión simbólica de la política permite comprender los cambios institucionales de un modo del que adolece la mayoría de las perspectivas canónicas del lenguaje institucionalista. No obstante dicha contribución, el presente trabajo pretende mostrar cómo sus presupuestos ontológicos y epistemológicos limitan la noción de política a la consecución del consenso y a la provisión de razones por parte de actores provistos de una racionalidad comunicativa, lo que relega su carácter contingente y disputado. Frente a ello, presenta una perspectiva onto-epistemológica postestructuralista que subraya el carácter constitutivamente descentrado y conflictivo de la objetividad social en el marco de la disputa entre proyectos hegemónicos antagónicos. A partir de esta propuesta se enfatiza en los tropos retóricos de la metáfora y la metonimia como recursos discursivos que permiten comprender la dinámica de desplazamiento y de condensación significante mediante la cual se producen los cambios institucionales. En la última parte del texto, se ponen en juego algunos de estos conceptos en el análisis de la Reforma del Estado implementada en la provincia argentina de Córdoba entre 1999 y 2000.