bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B63: Therapeutic potential of GPR64 specific CAR T cells in pediatric sarcomas
Authors: Storz Isabel , Schirmer David , Wisskirchen Karin , Feederle Regina , Schmidt Oxana , Abken Hinrich , Protzer Ulrike , Burdach Stefan , Richter Günther HS 
Published: March 2017

Abstract
Ewing Sarcoma (ES) is the second most common bone malignancy in children and young adolescents with a high potential of dissemination into lung and bones. Patients with localized disease receiving current treatment, have an approximate long-term survival of &gt;65%. Patients with disseminated disease into the bone have an approximate long-term survival rate of only 10%, compelling the search for new therapeutic treatment modalities like engineered T cell therapy. Here the therapeutic potential of chimeric antigen receptor (CAR) transgenic T cells directed against G-protein coupled receptor 64 (GPR64), an orphan receptor with normal expression restricted to human epididymis and significant overexpression in ES, was examined. Therefore, two different monoclonal antibodies (mAb) directed against the extracellular region of GPR64 were generated and characterized. Subsequently, retroviral constructs containing second generation CARs together with the scFv fragments of the respective mAbs were designed. Primary lymphocytes were transduced and tested in vitro via flow cytometry, ELISpot and xCelligence assay. Antibodies specifically stained ES cells as determined by flow cytometry. The signal intensity was reduced after RNAi mediated down-regulation of GPR64 in ES cell lines confirming specificity of mAbs. Following sequence determination of those mAbs two different CAR constructs were designed. Retroviruses containing such CARs transduced primary lymphocytes with good efficiency. The CAR transgenic T cells could be enriched for CD8+CAR+ cells via microbead isolation and showed strong proliferative capacities in vitro. Furthermore, target structures were specifically recognized as determined by ELISpot and xCelligence assays. CAR transgenic T cells targeting GPR64 show a promising approach to transfer the success of CARs in hematological malignancies to solid tumors. The cells generated in this study show strong specificity towards GPR64 and are able to control tumor cell growth in vitro. Since GPR64 expression is not restricted to ES but also up-regulated in a number of carcinomas derived from prostate, kidney or lung, GPR64-specific CARs may also be a future treatment option for other tumor entities.
Citation Format: Isabel Storz, David Schirmer, Karin Wisskirchen, Regina Feederle, Oxana Schmidt, Hinrich Abken, Ulrike Protzer, Stefan Burdach, Günther HS Richter. Therapeutic potential of GPR64 specific CAR T cells in pediatric sarcomas. [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 B63.
Abstract IA20: PET imaging of the immune system using new nucleoside analog probes
Authors: Radu Caius G. 
Published: March 2017

Abstract
Similar to other major metabolic networks, nucleotide metabolism consists of redundant and convergent biosynthetic pathways. Thus, nucleotides can be produced both de novo, from glucose and amino acids, and by salvage pathways, via scavenging and re-utilization of preformed nucleosides and nucleobases. The differential utilization of de novo and salvage nucleotide biosynthetic pathways in normal and malignant is poorly understood. We are studying this process in lymphocytes and cancer cells using newly developed mass spectrometry and positron emission tomography (PET) approaches. Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside salvage pathway, is significantly upregulated following T cell activation and therefore represents a promising PET imaging target. PET probes for dCK have been previously developed by our group and shown to be effective in mice but their specificity and sensitivity in humans remained suboptimal. Recently we have identified [18F]CFA (2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosyl-adenine) as a suitable third generation nucleoside analog probe for clinical dCK PET imaging. First-in-human [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The potential use of [18F]CFA PET for imaging systemic immune activation induced by various cancer immunotherapies will be discussed.
Citation Format: Caius G. Radu. PET imaging of the immune system using new nucleoside analog probes. [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 IA20.
Abstract IA24: T cell recognition and tumor resistance in human cancer
Authors: Schumacher Ton 
Published: March 2017

Abstract
The T cell-based immune system has evolved to recognize and destroy cells that differ from self on the basis of the antigens they express. Many human tumors contain large numbers of mutations, of which many hundreds can be present within expressed genes. As the resulting altered protein sequences are foreign to the immune system, immune recognition of such ‘neo-antigens’ has been proposed as a major factor in the activity of clinically used immunotherapeutics such as anti-CTLA-4 and anti-PD-1.
In support of this hypothesis, using in-house developed technologies we have demonstrated that both CD4 and CD8 T cell recognition of the consequences of DNA damage is a common feature in human melanoma and can be boosted by therapy. Furthermore, to extend these data to other tumor types, we have benchmarked the foreign antigenic space in a variety of human cancers against a series of human pathogens. Collectively, these data, and data from other groups, establish tumor foreignness as one of the critical determinants in effective cancer immunotherapy. However, the sensitivity of tumor cells to this T cell attack forms an obvious additional requirement. To address this issue, we are currently determining mechanisms of immune escape upon T cell targeting of human tumors. Results from this analysis are expected to contribute to the further definition of biomarkers that predict the outcome of the interaction between human tumors and the T cell-based immune system.
Citation Format: Ton Schumacher. T cell recognition and tumor resistance in human cancer. [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 IA24.
Serial Measurement of High-Sensitivity Troponin I and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the EXAMINE Trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care)
Authors: Cavender Matthew A. , White William B. , Jarolim Petr , Bakris George L. , Cushman William C. , Kupfer Stuart , Gao Qi , Mehta Cyrus R. , Zannad Faiez , Cannon Christopher P. , Morrow David A. 
Published: March 2017

Background:
We aimed to describe the relationship between changes in high-sensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes.

Methods:
The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized ≥30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point.

Results:

At baseline, hsTnI was detectable (≥1.9 ng/L) in 93% of patients and >99
th
percentile upper reference limit in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months (
P
<0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future cardiovascular events. Stable patients with hsTnI ≥99th percentile upper reference limit at 6 months were at increased risk of cardiovascular death, myocardial infarction, or stroke compared with patients with hsTnI <99 percentile upper reference limit irrespective of whether hsTnI was newly elevated (28.1% versus 8.8%; adjusted hazard ratio, 2.65; 95% confidence interval, 1.64–4.28;
P
<0.001) or persistently so (22.5% versus 8.8%; adjusted hazard ratio, 1.90; 95% confidence interval, 1.33–2.70;
P
<0.001). Alogliptin neither increased nor decreased the risk of cardiovascular events compared with placebo in patients with high baseline hsTnI (22.3% versus 23.0%; hazard ratio, 0.87; 95% confidence interval, 0.60–1.25;
P
=0.44).

Conclusions:
Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00968708.
Dynamic Arterial Compression in Pediatric Vertebral Arterial Dissection
Authors: Rollins Nancy , Braga Bruno , Hogge Amy , Beavers Stefanie , Dowling Michael 
Published: March 2017

Background and Purpose—
The pathogenesis of spontaneous pediatric vertebral artery dissections (VAD) is poorly understood but most often involves the V3 segment where C1 rotates on C2. We studied children with VAD with provocative digital catheter angiography and found an association between VAD and rotational compression.

Methods—
Seven boys (12 months to 9 years; median 4 years) presented over 38 consecutive months with V3 VAD and underwent digital catheter angiography with provocative passive bilateral neck rotation.

Results—
VAD were bilateral in 2 patients and unilateral in 5. Provocative digital catheter angiography showed dynamic V3 compression in 6 of 9 dissections, most pronounced or seen only with head rotation to the contralateral side. Two patients had VAD without dynamic compression; both returned 4 months later with a new dissection in a previously normal VA and worsening VAD in 1 patient each. Dynamic compression was also seen in 2 nondissected VA. Surgical management was C1/2 posterior fusion in 5 of 7 patients; 1 underwent unilateral C2 decompression with recurrent VAD and was subsequently fused.

Conclusions—
The association of dynamic VA compression and VAD at the same level suggests that the compression may contribute to the VAD. However, as dynamic compression was observed in nondissected VA and some VAD were not associated with dynamic compression, VAD may be multifactorial.
A new combination in Tulista, T. kingiana (Asphodeloideae, Xanthorrhoeaceae / Alooideae, Asphodelaceae)
Authors: SMITH GIDEON F. , FIGUEIREDO ESTRELA , MOLTENO STEVEN 
Published: March 2017

Phylogenetic studies in the Xanthorrhoeaceae subfam. Asphodeloideae (alternatively Asphodelaceae subfam. Alooideae) (Treutlein et al. 2003a, b; Grace et al. 2013; Manning et al. 2014) indicated that the genus Haworthia Duval (1809: 7) sensu lato should be split into three genera. The three haworthioid genera established and widely accepted for the three groups of species are: Haworthia sensu stricto, Haworthiopsis Rowley (2013: 4), and Tulista Rafinesque (1840: 137). In terms of number of species, Tulista is the smallest of the three genera and is widely considered to include five species. For four of these, T. marginata (Lamarck 1783: 89) Rowley (2013: 6), T. minima (Aiton 1789: 468) Boatwright & Manning in Manning et al. (2014: 70), T. opalina (Hayashi 2001: 17) Breuer (2016: 7), and T. pumila (Linnaeus 1753: 322) Rowley (2013: 6), combinations have been validly published. However, for the fifth species, Haworthia kingiana Von Poellnitz (1937: 203), a valid combination has yet to be published in Tulista. We do so here.
Characterization of Extreme Storm Events Using a Numerical Model–Based Precipitation Maximization Procedure in the Feather, Yuba, and American River Watersheds in California
Authors: Ohara Noriaki , Kavvas M. Levent , Anderson Michael L. , Chen Z. Q. , Ishida Kei 
Published: March 2017

Abstract
Improvements on nonhydrostatic atmospheric models such as MM5 in the last few decades have enhanced our understanding of the precipitation mechanism affected by topography and nonlinear dynamics of the atmosphere. This study addresses the use of such a regional atmospheric model to estimate physical maximum precipitation rates for the next generation of flood management strategies under evolving climate conditions. First, 48 significant historical storm events were selected based on the continuous reconstructed precipitation conditions on the Feather, Yuba, and American River watersheds in California. Then, the boundary conditions of the numerical atmospheric model were modified with the fully saturated atmospheric layers (100% relative humidity) to generate the atmospheric conditions that maximize the precipitation over the three watersheds. Surprisingly, maximizing the atmospheric moisture supply at the model boundary does not always increase the precipitation in the watersheds of interest. A rain-shadow effect of the topography seemed to be intensified by the abundance of the atmospheric moisture in some cases. Consequently, although the linkage between the precipitable water in the atmosphere and the ground precipitation is generally proportional, the alignment of the topography and the wind field can modulate their relationship. Finally, a methodology to maximize the steady-state precipitation rate was discussed to characterize the conceptual continuous heavy storm event in the Feather, Yuba, and American River basins.
Improving Polarimetric C-Band Radar Rainfall Estimation with Two-Dimensional Video Disdrometer Observations in Eastern China
Authors: Chen Gang , Zhao Kun , Zhang Guifu , Huang Hao , Liu Su , Wen Long , Yang Zhonglin , Yang Zhengwei , Xu Lili , Zhu Wenjian 
Published: March 2017

Abstract
In this study, the capability of using a C-band polarimetric Doppler radar and a two-dimensional video disdrometer (2DVD) to estimate monsoon-influenced summer rainfall during the Observation, Prediction and Analysis of Severe Convection of China (OPACC) field campaign in 2014 and 2015 in eastern China is investigated. Three different rainfall R estimators, for reflectivity at horizontal polarization [R(Zh)], for reflectivity at horizontal polarization and differential reflectivity factor [R(Zh, Zdr)], and for specific differential phase [R(KDP)], are derived from 2-yr 2DVD observations of summer precipitation systems. The radar-estimated rainfall is compared to gauge observations from eight rainfall episodes. Results show that the two polarimetric estimators, R(Zh, Zdr) and R(KDP), perform better than the traditional Zh–R relation [i.e., R(Zh)]. The KDP-based estimator [i.e., R(KDP)] produces the best rainfall accumulations. The radar rainfall estimators perform differently across the three organized convective systems (mei-yu rainband, typhoon rainband, and squall line). Estimator R(Zh) overestimates rainfall in the mei-yu rainband and squall line, and R(Zh, Zdr) mitigates the overestimation in the mei-yu rainband but has a large bias in the squall line. QPE from R(KDP) is the most accurate among the three estimators, but it possesses a relatively large bias for the squall line compared to the mei-yu case. The high variability of drop size distribution (DSD) related to the precipitation microphysics in different types of rain is largely responsible for the case-dependent QPE performance using any single radar rainfall estimator. The squall line has a distinct ice-phase process with a large mean size of raindrops, while the mei-yu rainband and typhoon rainband are composed of smaller raindrops. Based on the statistical QPE error in the ZH–ZDR space, a new composite rainfall estimator is constructed by combining R(Zh), R(Zh, Zdr), and R(KDP) and is proven to outperform any single rainfall estimator.
A randomised controlled trial of a web-based multi-modal therapy program to improve executive functioning in children and adolescents with acquired brain injury
Authors: Piovesana Adina , Ross Stephanie , Lloyd Owen , Whittingham Koa , Ziviani Jenny , Ware Robert S , McKinlay Lynne , Boyd Roslyn N 
Published: March 2017

Objective: To examine the efficacy of a multi-modal web-based therapy program, Move it to improve it (Mitii™) delivered at home to improve Executive Functioning (EF) in children with an acquired brain injury (ABI). Design: Randomised Waitlist controlled trial. Setting: Home environment. Participants: Sixty children with an ABI were matched in pairs by age and intelligence quotient then randomised to either 20-weeks of Mitii™ training or 20 weeks of Care As Usual (waitlist control; n=30; 17 males; mean age=11y, 11m (±2y, 6m); Full Scale IQ=76.24±17.84). Fifty-eight children completed baseline assessments (32 males; mean age=11.87±2.47; Full Scale IQ=75.21±16.76). Main Measures: Executive functioning was assessed on four domains: attentional control, cognitive flexibility, goal setting, and information processing using subtests from the Wechsler Intelligence Scale for Children (WISC-IV), Delis-Kaplan Executive Functioning System (D-KEFS), Comprehensive Trail Making Test (CTMT), Tower of London (TOL), and Test of Everyday Attention for Children (Tea-Ch). Executive functioning performance in everyday life was assessed via parent questionnaire (Behaviour Rating Inventory of Executive Functioning; BRIEF). Results: No differences were observed at baseline measures. Groups were compared at 20-weeks using linear regression with no significant differences found between groups on all measures of EF. Out of a potential total dose of 60 hours, children in the Mitii™ group completed a mean of 17 hours of Mitii™ intervention. Conclusion: Results indicate no additional benefit to receiving Mitii™ compared to standard care. Mitii™, in its current form, was not shown to improve EF in children with ABI.
The conundrum of feline trichomonosis: the more we learn the ‘trickier’ it gets
Authors: Gookin Jody L , Hanrahan Katherine , Levy Michael G 
Published: March 2017

Practical relevance: Trichomonosis of the large intestine of the cat was described as a cause of chronic diarrhea over 20 years ago. The trichomonad was identified as Tritrichomonas foetus, with a genotype that is distinct from venereal T foetus of cattle. Clinical challenges: Despite multiple means for diagnosis of the infection, including light microscopy, protozoal culture and PCR amplification using species-specific primers, tests with even greater sensitivity are needed. Feline trichomonosis is resistant to all commonly used antiprotozoal drugs. Ronidazole is currently the only drug demonstrated to be effective in eliminating the infection from cats; however, this drug has a narrow safety margin and clinical resistance is increasingly recognized. The more we learn about trichomonosis in cats, the more complicated and controversial the infection has become, ranging from what we should call the organism to whether we should even bother trying to treat it. Global importance: Feline trichomonosis is recognized to occur worldwide and is regarded as one of the most common infectious causes of colitis in the domestic cat. The infection is widespread in catteries and shelters; and, while remission of diarrhea may occur over time, persistence of the infection is common. Evidence base: This review provides a comprehensive examination of what is currently known about feline trichomonosis and pinpoints areas, based on the authors’ opinion, where further research is needed.
Gaps and barriers in the control of blood glucose in people with type 2 diabetes
Authors: Blonde Lawrence , Aschner Pablo , Bailey Clifford , Ji Linong , Leiter Lawrence A , Matthaei Stephan ,   on behalf of the Global Partnership for Effective Diabetes Management
Published: March 2017

Background: Glycaemic control is suboptimal in a large proportion of people with type 2 diabetes who are consequently at an increased and avoidable risk of potentially severe complications. We sought to explore attitudes and practices among healthcare professionals that may contribute to suboptimal glycaemic control through a review of recent relevant publications in the scientific literature. Methods: An electronic search of the PubMed database was performed to identify relevant publications from January 2011 to July 2015. The electronic search was complemented by a manual search of abstracts from key diabetes conferences in 2014/2015 available online. Results: Recently published data indicate that glycaemic control is suboptimal in a substantial proportion (typically 40%–60%) of people with diabetes. This is the case across geographic regions and in both low- and higher-income countries. Therapeutic inertia appears to be an important contributor to poor glycaemic control in up to half of people with type 2 diabetes. In particular, prescribers are often willing to tolerate extended periods of ‘mild’ hyperglycaemia as well as having low expectations for their patients. There are often delays of 3 years or longer in initiating or intensifying glucose-lowering therapy when needed. Conclusion: Many people with type 2 diabetes are failed by current management, with approximately half not achieving or maintaining appropriate target blood glucose levels, leaving these patients at increased and avoidable risk of serious complications. Review criteria: The methodology of this review article is detailed in the ‘Methods’ section.