bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B88: TGF-β pathway-mediated escape from VEGF blockade is linked with angiogenesis and immune-suppression in murine glioma models
Authors: Mangani Davide , Weller Michael , Sadr Emad Seyed , Willscher Edith , Seystahl Katharina , Reifenberger Guido , Tabatabai Ghazaleh , Binder Hans , Schneider Hannah 
Published: March 2017

Abstract
The vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β are key target molecules in glioblastoma that are interdependently regulated. Both pathways drive key malignant features in glioma cells such as angiogenesis, invasiveness and immunosuppression. Here we explore whether TGF-β acts as an escape pathway from VEGF inhibition using gene expression profiling and in vitro and in vivo studies in a panel of syngeneic mouse glioma models. In vivo, single agent activity was observed for the VEGF antibody B20-4.1.1 in three (SMA-540, SMA-560 and GL-261), and for the TGF-β receptor I antagonist LY2157299 in two (SMA-540 and SMA-560) of four mouse glioma models. Transcriptomic profiling of the four mouse glioma models revealed that SMA-497 and GL-261, while unresponsive to LY2157299, were the most immunogenic tumors as defined by Gene Ontology; specifically, up-regulation of chemokine/chemoreceptors genes involved in immune cell recruitment and interferon-related genes were found. Co-targeting of VEGF and TGF-β was ineffective in one refractory model (SMA-497), in which no major changes in tumor immune-infiltrating cells were detected upon mono- or co-treatment settings. Significant prolongation of survival in the GL-261 model was associated with early stage increased infiltration of CD8+ cells, lower numbers of CD11b+ macrophages/microglia and sustained suppression of angiogenesis compared to anti-VEGF treatment alone. Phosphorylated SMAD2 was increased in both tumor cells and CD45+ leukocytes during anti-angiogenic treatment pointing to the possibility of a TGF-β-induced immunosuppressive micro-milieu that is efficiently counteracted by concomitant administration of LY2157299. In conclusion, our study highlights the biological heterogeneity of glioblastoma even among simple mouse models and illustrates that co-targeting of the VEGF and TGF-β pathways might lead to improved tumor control in subsets of glioblastoma linked with angiogenesis impairment and general reduction of the immune-suppressive phenotype.
Note: This abstract was not presented at the conference.
Citation Format: Davide Mangani, Michael Weller, Emad Seyed Sadr, Edith Willscher, Katharina Seystahl, Guido Reifenberger, Ghazaleh Tabatabai, Hans Binder, Hannah Schneider. TGF-β pathway-mediated escape from VEGF blockade is linked with angiogenesis and immune-suppression in murine glioma models. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B88.
Abstract IA21: Profiling immune cell subsets and immune responses using immunoPET
Authors: Wu Anna M. 
Published: March 2017

Abstract
The field of immuno-oncology is seeing striking successes, yet suffers from ongoing diagnostic challenges that are hampering progress in the development of novel and combination immunotherapies in patients. Non-invasive imaging using PET enables profiling tumor and immune system biology throughout the body. In vivo imaging provides a powerful and complementary approach to in vitro diagnostics, allowing profiling of biology in the context of an intact living organism. Given the challenges of tumor heterogeneity, as well as variability of immune responses, molecular imaging approaches are poised to provide essential information to enhance our understanding of immune responses and immunotherapy.
We have developed engineered antibody fragments to provide a versatile platform for non-invasive imaging of cells and tissues based on cell surface phenotype. Recombinant fragments such as minibodies and diabodies have been developed with accelerated clearance (enabling same-day or next-day imaging), limited or no biological activity (lacking complement/Fc receptor binding), and permitting site-specific conjugation. When labeled with positron-emitting radionuclides (such as I-124, Zr-89, Cu-64, F-18), minibodies and diabodies can be employed for high resolution, sensitive, quantitative imaging by immunoPET and provide highly specific molecular assessments of tumor biology and response to treatment. For example, an I-124 prostate stem cell antigen (PSCA)-specific minibody demonstrates sensitive imaging in mouse models of prostate cancer and provides a PET imaging readout of response to anti-androgens. Antibody-based targeting and imaging of CD markers (CD4 or CD8 on T lymphocytes; CD20 on B lymphocytes) broadens applications to assessment of immune cell subsets and monitoring responses to cancer immunotherapy. A Zr-89 anti-CD8 cys-diabody has been used to detect and image tumor infiltrating CD8+ T lymphocytes in tumor treatment models using anti-CD137 or anti-PD-L1 antibodies, and to detect adoptively-transferred OT-I T cells in mice. Applications extend beyond oncology, with recent visualization of CD4+ T lymphocytes in a mouse model of colitis.
Importantly, immunoPET using engineered antibody fragments can be readily translated, and can provide highly sensitive imaging of cell surface biomarkers in patients. ImmunoPET provides a broad approach for noninvasive, whole-body monitoring of key factors such as target expression in vivo, response to therapy, and immune responses, and stands to play an expanding role in the detection and management of cancer.
Citation Format: Anna M. Wu. Profiling immune cell subsets and immune responses using immunoPET. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA21.
Abstract PR07: Use of a novel mouse model to investigate immune related adverse events arising from immunotherapies
Authors: Blake Stephen J. , Liu Jing , Heidi Harjunpaa , Smyth Mark J. , Teng Michele W.L. 
Published: March 2017

Abstract
While immunotherapy is rapidly growing as an excellent treatment for many cancer types, most immunotherapies, particularly in combination can induce immune related adverse events (irAEs) which are generally caused by immune cell activation and expansion. Although most irAEs are low grade (1-2), higher grade events (3-4) can prevent patients from completing therapy and can also be life threatening. Thus, there is a strong need to develop pre-clinical mouse models to identify which immunotherapeutic combinations induce the best anti-tumor responses without inducing severe irAEs. To replicate irAEs associated with immunotherapies in humans, we utilized the FoxP3-DTR mouse model where regulatory T-cell (Treg) depletion can be achieved by injecting diphtheria toxin (DT), releasing Treg associated immune suppression. Transient Treg depletion by a single dose of DT induced mild T-cell activation and increased T-cell immune checkpoint expression, making mice more sensitive to irAEs development from clinically relevant immunotherapies. In three tumor models, we demonstrated that transient Treg depletion with anti-PD-1 or TIM-3 had a good anti-tumor efficacy and mild irAEs. Conversely, combining transient Treg depletion with an antibody targeting the co-stimulatory receptor CD137 had a lower therapeutic window due to increased irAEs. This combination was effective in suppressing established tumors, but induced severe irAEs including elevated serum cytokines and acute liver inflammation. These irAEs were similar to those seen in clinical trials of anti-CD137 antibodies where liver toxicity was a major concern and were driven by a rapid systemic CD8+ T-cell expansion. We also demonstrated that irAEs from anti-CD137 therapy could be mitigated by neutralising TNF without impacting on anti-tumor efficacy. We believe this model can provide valuable data on the efficacy and irAEs associated with novel combination immunotherapies which may aid clinicians and pharmaceutical companies in clinical trial design. We are currently utilizing this model to predict the therapeutic irAEs and efficacy of other novel immunotherapies that are in pre-clinical and early stage clinical trials.
This abstract is also being presented as Poster B58.
Citation Format: Stephen J. Blake, Jing Liu, Harjunpaa Heidi, Mark J. Smyth, Michele W.L. Teng. Use of a novel mouse model to investigate immune related adverse events arising from immunotherapies. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr PR07.
Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion
Authors: Adeeb Nimer , Griessenauer Christoph J. , Moore Justin M. , Foreman Paul M. , Shallwani Hussain , Motiei-Langroudi Rouzbeh , Gupta Raghav , Baccin Carlos E. , Alturki Abdulrahman , Harrigan Mark R. , Siddiqui Adnan H. , Levy Elad I. , Ogilvy Christopher S. , Thomas Ajith J. 
Published: March 2017

Background and Purpose—
Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement.

Methods—
A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis.

Results—
Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis.

Conclusions—
Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke.
The Role of Media Usage on Building Social Capital: Multiculturalism in Korea Case
Authors: Jin Chang-Hyun 
Published: March 2017

Abstract
The purpose of this study was to explore the relationship between the use of mass media by immigrant women in Korea and their capacity to form and build social capital, centering on their use of media such as; television, newspapers and the Internet. To achieve this research goal, the concept of social capital was reviewed and the relationship between trust, civic engagement and socio-political participation, which are components of social capital, were investigated.
The study (n=335) measured the effects of consuming major media types on the formation of social capital within the sample population and identified the relationship between generic consumption patterns associated with individual media and the formation of social capital. In addition, this paper sheds light on the notion that a person’s socio-demographic background affects the formation and building of social capital and that trust and civic engagement affects socio-political participation.
On Shifting Grounds of ‘Citizen Journalism’ in Egypt
Authors: Onodera Henri 
Published: March 2017

Before and after the January 25 uprisings in Egypt, public and scholarly attention moved from the early political bloggers to today’s citizen journalists who use not only blogs but any available means to disseminate alternative information. The use of new ‘information and communication technologies’ (ICTs) is no longer an asset for the secular-civil opposition only. Since 2011, various groups, including the Salafists and the military, have resorted to the use of ICTs to establish their influence in public life. In this article, I offer an examination of citizen journalism as political practice and public debate in the Middle East and North Africa. This research may shed light on the everyday appropriations of this traveling concept and the meanings it engenders through actual practices in given socio-cultural contexts. I also argue that the ambiguities around the Arabic translations of citizen journalism provide a way to examine the uneasy processes of state transformation in today’s Egypt.
Non-Gaussian Analysis of Observations from the Atmospheric Infrared Sounder Compared with ERA and MERRA Reanalyses
Authors: De Souza-Machado Sergio , Tangborn Andrew , Sura Philip , Hepplewhite Christopher , Strow L. Larrabee 
Published: March 2017

AbstractStatistical relationships between higher-order moments of probability density functions (PDFs) are used to analyze top-of-atmosphere radiance measurements made by the Atmospheric Infrared Sounder (AIRS) and radiance calculations from the ECMWF Re-Analysis (ERA) and the Modern-Era Retrospective Analysis for Research and Applications (MERRA) over a 10-yr period. The statistical analysis used in this paper has previously been applied to sea surface temperature, and here the authors show that direct satellite radiance observations of atmospheric variability also exhibit stochastic forcing characteristics. The authors have chosen six different AIRS channels based on the sensitivity of their measured radiances to a variety of geophysical properties. In each of these channels, the authors have found evidence of correlated additive and multiplicative (CAM) stochastic forcing. In general, channels sensitive to tropospheric humidity and surface temperature show the strongest evidence of CAM forcing, while those sensitive to stratospheric temperature and ozone exhibit the weakest forcing. Radiance calculations from ERA and MERRA agree well with AIRS measurements in the Gaussian part of the PDFs but show some differences in the tails, indicating that the reanalyses may be missing some extrema there. The CAM forcing is investigated through numerical simulation of simple stochastic differential equations (SDEs). The authors show how measurements agree better with weaker CAM forcing, achieved by reducing the multiplicative forcing or by increasing the spatial correlation of the added noise in the case of an SDE with one spatial dimension. This indicates that atmospheric models could be improved by adjusting nonlinear terms that couple long and short time scales.
Intermittency in Precipitation: Duration, Frequency, Intensity, and Amounts Using Hourly Data
Authors: Trenberth Kevin E. , Zhang Yongxin , Gehne Maria 
Published: March 2017

Abstract
Intermittency is a core characteristic of precipitation, not well described by data and very poorly modeled. Detailed analyses are made of near-global gridded (about 1°) hourly or 3-hourly precipitation rates from two updated observational datasets [3-hourly TRMM 3B42, version 7, and hourly CMORPH, version 1.0, bias corrected (CRT)] and from special runs of CESM from January 1998 to December 2013 to obtain hourly values. The analyses explore the intermittency of precipitation: the frequency, intensity, duration, and amounts. A comparison is made for all products using several metrics with a focus on the duration of events, and a new metric is proposed based on the ratio of the frequency of precipitation at certain rates (0.2–2 mm h−1) for hourly versus 3-hourly versus daily data. For all seasons and rain rates, TRMM values are similar in pattern to CMORPH, but durations are about 80%–85%. It is mainly over land in the monsoons that CMORPH exceeds TRMM rain durations. Observed duration of precipitation events in CMORPH over oceans are 12–15 h in the tropics and subtropics, much less than the ~20 h for CESM. Hence, the observational results differ somewhat but both are considerably different from the model, which has too much precipitation overall, and it precipitates far too often at low rates and not enough for intense rates, with the divide about 1–2 mm h−1. There is a need to properly represent precipitation phenomena and processes either explicitly or implicitly (parameterized).
On Cost Functions in the Hybrid Variational–Ensemble Method
Authors: Duc Le , Saito Kazuo 
Published: March 2017

Abstract
In the hybrid variational–ensemble data assimilation schemes preconditioned on the square root of background covariance , is a linear map from the model space to a higher-dimensional space. Because of the use of the nonsquare matrix , the transformed cost function still contains the inverse of . To avoid this inversion, all studies have used the diagonal quadratic form of the background term in practice without any justification. This study has shown that this practical cost function belongs to a class of cost functions that come into play whenever the minimization problem is transformed from the model space to a higher-dimension space. Each such cost function is associated with a vector in the kernel of (Ker), leading to an infinite number of these cost functions in which the practical cost function corresponds to the zero vector. These cost functions are shown to be the natural extension of the transformed one from the orthogonal complement of Ker to the full control space.
In practice, these cost functions are reduced to a practical form where calculation does not require a predefined vector in Ker, and are as valid as the transformed one in the control space. That means the minimization process is not needed to be restricted to any subspace, which is contrary to the previous studies. This was demonstrated using a real observation data assimilation system. The theory justifies the use of the practical cost function and its variant in the hybrid variational–ensemble data assimilation method.
Effect of Discontinuation of Manganese Supplementation From Home Parenteral Nutrition Solutions on Whole‐Blood Levels and Magnetic Resonance Imaging of the Brain: A 5‐Year Cohort Study
Authors: Jin Jennifer , Saqui Olivia , Allard Johane P. 
Published: March 2017

AbstractBackground: Manganese (Mn) is included in current premixed multiple trace element (TE) additives for home parenteral nutrition (HPN). However, there is a risk of oversupplementation of Mn due to contamination from PN additives. Oversupplementation can produce Mn toxicity with neurologic symptoms and abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported that whole‐blood Mn levels were above the upper limit of normal in 16 HPN patients, with 81% having MRI findings. Subsequently, we removed Mn supplementation from all our HPN patients. We present a 5‐year follow‐up here. Methods: This is a prospective cohort study on 11 of the surviving 16 patients on HPN. All patients had Mn removed from PN and had yearly monitoring of blood Mn levels. Eight patients had a repeat MRI to evaluate for resolution of basal ganglia deposits. Patient demography, clinical history, and bloodwork were recorded. Results: Five of 6 patients who initially had elevated Mn levels had normal levels on follow‐up. All patients who had Mn levels measured serially had a decrease in levels; the mean percent decrease of Mn was 38.1% (range, 10.1%–53.8%). Two patients had elevated Mn despite the absence of supplementation. Six of 8 patients who had repeat MRIs had complete resolution abnormalities. Conclusions: Removal of Mn as an additive in HPN solutions resulted in resolution of MRI abnormalities in most patients. Over 5 years, all patients except for 1 maintained normal blood Mn levels. Therefore, Mn levels should be monitored and supplementation be individualized.
Joint dysfunction associated with venous malformations of the limbs: Which patients are at high risk?
Authors: Hu Li , Chen Hui , Yang Xi , Liu Ming , Yan Mengning , Lin Xiaoxi 
Published: March 2017

Objectives Joint dysfunction occurs frequently in patients with venous malformations of the extremities. This study aims to describe the risk factors of joint dysfunction in these patients. Method We retrospectively collected clinical and radiological aspects of 168 patients with extremity venous malformations from January 2013 to August 2015. Patients were categorized into “with joint dysfunction” or “without joint dysfunction” groups according to the symptoms. Results Forty-four (26%) patients were assigned into with joint dysfunction group. Univariate analysis showed that the significant variables were age (P = 0.008), location (P = 0.005), size (P < 0.001), involved tissue (P < 0.001), visual analogue scale scores of pain (P = 0.004), pain duration (P = 0.018), and therapy history (P < 0.001). Multivariate analysis showed that the factors associated with joint dysfunction were age below 10 years (adjusted odds ratio = 2.70, P = 0.004), lower limb (adjusted odds ratio = 2.72, P = 0.042), pain duration over 1 year (adjusted odds ratio = 3.47, P = 0.001) and therapy history (yes) (adjusted odds ratio = 3.71, P = 0.004). Conclusion This study provides preliminary evidence indicating which patients are at high risk for joint dysfunction associated with limb venous malformations.
Prevalence and patterns of antidepressant switching amongst primary care patients in the UK
Authors: Mars Becky , Heron Jon , Gunnell David , Martin Richard M , Thomas Kyla H , Kessler David 
Published: March 2017

Objective: Non-response to antidepressant treatment is a substantial problem in primary care, and many patients with depression require additional second-line treatments. This study aimed to examine the prevalence and patterns of antidepressant switching in the UK, and identify associated demographic and clinical factors. Method: Cohort analysis of antidepressant prescribing data from the Clinical Practice Research Datalink, a large, anonymised UK primary care database. The sample included 262,844 patients who initiated antidepressant therapy between 1 January 2005 and 31 June 2011. Results: 9.3% of patients switched to a different antidepressant product, with most switches (60%) occurring within 8 weeks of the index date. The proportion switching was similar for selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants (9.3%, 9.8% and 9.2%, respectively). Most switches were to an SSRI (64.5%), and this was the preferred option regardless of initial antidepressant class. Factors predictive of switching included male gender, age, and history of self-harm and psychiatric illness. Conclusion: Over one in every 11 patients who initiates antidepressant therapy will switch medication, suggesting that initial antidepressant treatment has been unsatisfactory. Evidence to guide choice of second-line treatment for individual patients is currently limited. Additional research comparing different pharmacological and psychological second-line treatment strategies is required in order to inform guidelines and improve patient outcomes.