bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of youth not in education, employment or training: Evidence from Sri Lanka
Authors: Abayasekara Ashani , Gunasekara Neluka 
Published: August 2019

AbstractThe presence of a large proportion of youth neither in education, employment, or training (NEET) signals problems in a country’s education and labor market systems, and has wide‐ranging negative consequences, extending beyond the individual to the economy and society. Using Sri Lankan Labour Force Survey data for the year 2016 and binomial and multinomial logistic regression models, in this paper we provide the first estimates of NEET‐related risk factors in Sri Lanka. Key risk factors of becoming NEET include being female, being of ethnic and religious minorities, belonging to the older 20 to 24 age group, having very low or very high levels of education, being illiterate in English, belonging to a low‐income household or one headed by a male, having young children, and living in more remote areas. Our findings hold several important policy implications for reducing the NEET rate in Sri Lanka and engaging more youth in education and in the labor force.
ASDAS is associated with both the extent and intensity of DW-MRI spinal inflammation in active axial spondyloarthritis
Authors: Chung Ho Yin , Chui Eva Tsz Fung , Lee Kam Ho , Tsang Helen Hoi Lun , Chan Shirley Chiu Wai , Lau Chak Sing 
Published: August 2019

ObjectiveTo investigate the relationship between Ankylosing Spondylitis Disease Activity Score (ASDAS) and intensity of spinal inflammation measured by apparent diffusion coefficient (ADC) in MRI in participants with active axial spondyloarthritis (SpA).MethodsParticipants with axial SpA and back pain were recruited. Clinical, demographic, biochemical and imaging data were collected. ASDAS was calculated based on C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Inflammatory lesions were identified in short tau inversion recovery images and the corresponding ADC maps to determine the maximum apparent diffusion coefficient (ADCmax), normalised maximum ADC, mean apparent diffusion coefficient (ADCmean) and normalised mean ADC by two independent readers. Spondyloarthritis Research Consortium of Canada (SPARCC) spine and sacroiliac (SI) joint MRI indexes were determined. Univariate and multivariate linear regression models were used to determine the associations between of ASDAS with ADC values, SPARCC spine and SI MRI scores.ResultsEighty-two participants had identifiable ADC lesions. Multivariate analyses using ADCmax and SPARCC spine MRI as independent variables showed associations with ASDAS-CRP (ADCmax: B=0.27, p=0.02; SPARCC: B=0.32, p=0.01) and ASDAS-ESR (ADCmax: B=0.24, p=0.03; SPARCC: B=0.36, p<0.01); using ADCmean and SPARCC spine MRI as independent variables also showed an association with ASDAS-ESR (ADCmean: B=0.22, p=0.05; SPARCC: B=0.36, p<0.01) and a tendency to associate with ASDAS-CRP (ADCmean: B=0.21, p=0.07; SPARCC: B=0.34, p<0.01).ConclusionASDAS is associated with both the extent and the intensity of spinal inflammation in patients with detectable inflammatory lesions. Our results showed that ASDAS is an objective disease assessment tool.Trial registration numberHKUCTR-2087.
Subsurface observations of deformation bands and their impact on hydrocarbon production within the Holstein Field, Gulf of Mexico, USA
Authors: Wilkins Scott J. , Davies Russell K. , Naruk Steve J. 
Published: August 2019

Abstract
The Holstein Field consists of poorly lithified turbidite sands deposited during the Pliocene Epoch. Dense arrays of cataclastic deformation bands have been observed in all cores from wells that penetrate the K2 reservoir sand, the highest density of which are located near the hinge of a monocline. The predominant set of deformation bands strikes parallel to the fold axis, and dips at both high and low angles with respect to bedding. Deformation band orientation and offset of marker beds indicate reverse shear and are consistent with a flexural slip origin during folding. Restorations suggest that the monocline and associated deformation bands formed early during the burial process with high pore pressure.
Reservoir permeability estimates from well tests indicate a bulk permeability approximately one-third of the reservoir core permeability in regions with deformation bands, whereas other areas are unaffected. Bulk permeability estimated from the permeability of the reservoir and deformation band network is lower than the reservoir permeability alone, but exceeds the permeability observed in the well tests by a factor of 2. A reduction in permeability of oil relative to water for both the fault and host sand is required to match the well-test permeability with that measured from core.
A knowledge database of hanging-wall traps that are dependent on fault-rock seal
Authors: Bretan Peter G. , Yielding Graham , Sverdrup Einar 
Published: August 2019

Abstract
Hanging-wall traps are successful trapping styles with discoveries made in many sedimentary basins worldwide. Examples of hanging-wall traps are documented in the literature but very few describe the role played by fault-rock seal on trap integrity. This contribution focuses on hanging-wall traps that are dependent on fault-rock seal. Analysis of 18 examples of hanging-wall traps has revealed that the hydrocarbon column height trapped by fault-rock seal is typically less than 190 m. Cross-plots of shale gouge ratio (SGR) and buoyancy pressure from hanging-wall traps have a similar data distribution to published SGR–buoyancy pressure calibration plots. The similarity in data distribution indicates a similarity in the overall fault-sealing mechanism: namely, the capillary fault sealing through the incorporation of clay/shale material into the fault zone. Published ‘global’ calibration plots of SGR v. buoyancy pressure can be used to evaluate the sealing or non-sealing risk of hanging-wall traps in the same manner as for footwall traps.
Validation and analysis procedures for juxtaposition and membrane fault seals in oil and gas exploration
Authors: Murray Titus A. , Power William L. , Johnson Anthony J. , Christie Greg J. , Richards David R. 
Published: August 2019

Abstract
We propose and validate methods for risk analysis of fault-bounded hydrocarbon traps in exploration. We concentrate on cross-fault leakage and consider lateral seals due to (1) juxtaposition and (2) high capillary-entry-pressure fault rock (membrane seal). We conclude that stochastic methods for fault seal analysis are essential, due to the large number of structural and stratigraphic parameters and the uncertainties. Central to the methods proposed is a Monte Carlo simulation which models geometrical and stratigraphic uncertainty. Multiple Allan maps (fault-parallel cross-sections) are produced and analysed for juxtaposition and shale gouge ratio (SGR). For validation, known discoveries with independently observed hydrocarbon–water contacts (IHWC) have been back-analysed. We present two case studies in this paper, and an additional 40 case studies are summarized (four public domain and 36 confidential case studies). The model outputs were compared with the IHWC. Juxtaposition analysis with no SGR contribution gives the smallest error. The inclusion of any fault rock seal mechanisms (such as SGR) matches or increases predicted hydrocarbon column heights compared to juxtaposition and gives larger errors. We conclude there is no reason to include fault rock membrane seals in exploration prospect risking.
Effect of varying chemoreflex stress on sympathetic neural recruitment strategies during apnea
Authors: Ott Elizabeth P. , Baker Sarah E. , Holbein Walter W. , Shoemaker J. Kevin , Limberg Jacqueline K. 
Published: August 2019

We sought to examine the effect of varying chemoreflex stress on sympathetic neural recruitment strategies during end-expiratory apnea. We hypothesized that increases in the firing frequency and probability of low-threshold axons at the asphyxic “break point” would be exaggerated during hypoxia and attenuated during hyperoxia. Multiunit muscle sympathetic nervous system activity (MSNA) (peroneal nerve microneurography) was measured in 10 healthy male subjects (31 ± 2 yr, 25 ± 1 kg/m2). Individuals completed maximal voluntary end-expiratory apnea under normoxic, hypoxic (inspired O2 fraction: 0.17 ± 0.01), and hyperoxic (inspired O2 fraction: 0.92 ± 0.03) conditions. Action potential (AP) patterns were examined from the filtered raw signal with wavelet-based methodology. Multiunit MSNA was increased ( P ≤ 0.05) during normoxic apnea, because of an increase in the frequency and incidence of AP spikes (243 ± 75 to 519 ± 134 APs/min, P = 0.048; 412 ± 133 to 733 ± 185 APs/100 heartbeats, P = 0.02). Multiunit MSNA increased from baseline ( P < 0.01) during hypoxic apnea, which was due to an increase in the frequency and incidence of APs (192 ± 59 to 952 ± 266 APs/min, P < 0.01; 326 ± 89 to 1,212 ± 327 APs/100 heartbeats, P < 0.01). Hypoxic apnea also resulted in an increase in the probability of a particular AP cluster firing more than once per burst ( P < 0.01). Hyperoxia attenuated any increase in MSNA with apnea, such that no changes in multiunit MSNA or frequency or incidence of AP spikes were observed ( P > 0.05). We conclude that increases in frequency and incidence of APs during apnea are potentiated during hypoxia and suppressed when individuals are hyperoxic, highlighting the important impact of chemoreflex stress in AP discharge patterns. The results may have implications for neural control of the circulation in recreational activities and/or clinical conditions prone to apnea. NEW & NOTEWORTHY Our results demonstrate that, compared with normoxic end-expiratory apnea, hypoxic apnea increases the frequency and incidence of action potential spikes as well as the probability of multiple firing. We further show that this response is suppressed when individuals are hyperoxic. These data highlight the potentially important role of chemoreflex stress in neural firing and recruitment and may have implications for neural control of the circulation in recreational and/or clinical conditions prone to apnea.
Abstract 118: GPR68, a proton-sensing GPCR that mediates interaction of pancreatic cancer associated fibroblasts and cancer cells, is a potential therapeutic target for pancreatic cancer
Authors: Wiley Shu Z. , Sriram Krishna , Salmeron-Salvador Cristina , Nishihara Hiroshi , French Randall , Lowy Andrew M. , Insel Paul A. 
Published: August 2019

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) that is generated by pancreatic cancer associated fibroblasts (PCAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). We discovered that GPR68, a proton-sensing GPCR, has much higher expression in PCAFs compared to either PFs or PSCs. GPR68 activation in PCAFs enhances interleukin-6 (IL-6) expression via a cAMP/PKA/CREB signaling pathway. GPR68 knockdown with siRNA decreased low pH-induced IL-6 production by PCAFs and increased the proliferation of PDAC cells by PCAF conditioned media. Ogerin, a GPR68 positive allosteric modulator, enhanced the pH-dependent increase in cAMP in PCAFs. A pilot screening of 96 GPCR-specific compounds tested with GPR68-overexpressing HEK293 cells identified two compounds (C1 and C2) that decrease intracellular cAMP at pH6.4, but not isoproterenol (β-adrenergic receptor)-induced cAMP, implying their selective antagonism of GPR68. Furthermore, compound C2 decreased low pH-induced IL-6 levels in the conditioned media of GPR68-overexpressing HEK293 cells We conclude that GPR68 in PCAFs detects low pH, contributes to PDAC cell-PCAF interaction and may be a novel therapeutic target for pancreatic cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Shu Z. Wiley, Krishna Sriram, Cristina Salmeron-Salvador, Hiroshi Nishihara, Randall French, Andrew M. Lowy, Paul A. Insel. GPR68, a proton-sensing GPCR that mediates interaction of pancreatic cancer associated fibroblasts and cancer cells, is a potential therapeutic target for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 118.
Abstract 1193: S100A proteins play immune regulatory roles in tumor microenvironment
Authors: Tanaka Nobuyuki , Kodake Natsumi , Ogama Naoko 
Published: August 2019

Abstract
S100A proteins are Ca2+ binding multifunctional molecule in different cellular compartments. Dysregulated expression of S100A is often observed in many types of human cancers, and is assoiciated with cancer pathogenesis. Inside a cell, S100A proteins respond to various stimuli, and some typical intracellular functions such as cytoskeleton control and motility have been extensively studied. Extracellular functions of S100A proteins have recently emerged, and they bind innate immune receptors such as TLR4 and RAGE. Nevertheless, the mode of S100A secretion has been obscure. We designed a secretion system to induce spontaneous S100A release from the cell, and examined their roles towards tumor microenvironment. We found S100A proteins are included in exosomes, and the stability of S100A contributes to their extracellular functions. Using a syngeneic tumor model, we investigated some S100A proteins show immune regulatory functions on tumor-associated macrophages. These results suggest that S100A secretion affects tumor immune environment.
Note: This abstract was not presented at the meeting.
Citation Format: Nobuyuki Tanaka, Natsumi Kodake, Naoko Ogama. S100A proteins play immune regulatory roles in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1193.
Abstract 1240: Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy
Authors: Arora Loukik , Tan Chris Soon Heng , Sobota Radoslaw M. , Sethi Gautam 
Published: August 2019

Abstract
Cancer is complex disease involving complex genetic and epigenetic heterogeneity making it the second leading cause of death globally after heart disease. While conventional treatments like surgery, radiotherapy, chemotherapy are principal strategies, the focus is shifting to therapies that can target multiple pathways to treat cancers. In the present report, we hypothesized that Tris DBA, an organometallic compound, can inhibit proliferation, tumor growth, and induce apoptosis in multiple myeloma (MM) and hepatocellular carcinoma (HCC) cells, thereby potentially exhibiting significant anticancer effects. Our preliminary results clearly indicated that Tris DBA could substantially inhibit both constitutive as well as IL-6 inducible STAT3 activation and abrogate proliferation/survival in MM and HCC cells. A phospho-proteomic profiling revealed several key phosphorylation changes induced by Tris DBA treatment which further indicate broad anticancer potential of the compound. Additionally, the agent exhibited potent antitumor actvitiy in vivo, with little adverse effects. The ongoing work is aimed at investigating the possible binding target(s) of Tris DBA and further characterize the molecular mechanism(s) underlying STAT3 inhibitory effects of the drug.
Citation Format: Loukik Arora, Chris Soon Heng Tan, Radoslaw M. Sobota, Gautam Sethi. Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1240.
Abstract 1470: Development & characterization of a new oncolytic immunotherapy platform based on herpes simplex virus type 1
Authors: Thomas Suzanne , Juncheria Linta , Roulstone Victoria , Kyula Joan N. , Kaufman Howard L. , Harrington Kevin J. , Coffin Robert S. 
Published: August 2019

Abstract
A number of oncolytic viruses have shown single agent clinical activity and evidence of clinical synergy with immune checkpoint blockade. However, not all patients respond, and as yet most of the promising clinical data have been generated in patients with melanoma. With the objective of maximally activating a patient's immune system against their own cancer which will then provide enhanced synergy with anti-PD1/L1 blockade, we developed a new oncolytic immunotherapy platform based on herpes simplex virus (HSV). This has the dual objectives of killing tumor to provide abundant release of tumor antigens, and potently activating immune responses against these antigens once released. To augment the natural ability of the virus to kill tumors and activate the immune system, these viruses are each armed with multiple therapeutic genes. Initially, we screened 29 new clinical strains of HSV isolated from volunteers who suffer from cold sores across a panel of human tumor cell lines to select a candidate for further development. This strain was then engineered to provide tumor selective replication (deletion of the genes encoding ICP34.5 and ICP47) and to express a potent fusogenic glycoprotein (GALV-GP R-). These modifications greatly enhance both local and systemic antitumor effects, increase immunogenic cell death, potently activate anti-tumor immunity, and are synergistic with PD-1 blockade in pre-clinical models. A virus expressing both GALV-GP R- and human GM-CSF is currently in a Phase 1/2 clinical trial in approximately 150 patients as a single-agent and combined with PD1 blockade in four solid tumor types. Further viruses express additional immune-activating proteins expected to act at the site of immune response initiation in tumors and draining lymph nodes, in particular an anti-CTLA-4 antibody-like molecule and immune co-stimulatory pathway-activating ligands. Each of these demonstrated increased activity in pre-clinical models, particularly an enhanced anenestic effect. The anti-CTLA-4 expressing virus (RP2) is targeted to enter clinical trials in the first half of 2019. Thus, a modular approach to oncolytic immunotherapy development can rapidly generate multiple clinical candidates with multiple mechanisms of action intended to act synergistically with other approaches to cancer therapy. The latest pre-clinical data utilizing this platform will be presented.
Citation Format: Suzanne Thomas, Linta Juncheria, Victoria Roulstone, Joan N. Kyula, Howard L. Kaufman, Kevin J. Harrington, Robert S. Coffin. Development & characterization of a new oncolytic immunotherapy platform based on herpes simplex virus type 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1470.
Abstract 1489: Increased levels of systemic LPS-positive bacterial extracellular vesicles in cancer patients with chemotherapy-induced intestinal barrier dysfunction
Authors: Tulkens Joeri , Wever Olivier De , Hendrix An 
Published: August 2019

Abstract
Bacterial extracellular vesicles (EV) are nanometer-sized membrane particles transporting nucleic acids, metabolites, proteins and endotoxins (lipopolysaccharide (LPS)). As such, bacterial EV that enter the systemic circulation may deliver and elicit a variety of immunological and metabolic responses in different organs including the brain. To date, the systemic presence and activity of bacterial EV in patients with intestinal barrier dysfunction have not been investigated. We combined size exclusion chromatography and density gradient (DG) centrifugation to fractionate plasma LPS in two dimensions to separate bacterial EV-associated LPS from other LPS products. We evaluated plasma from healthy donors asymptomatic of intestinal barrier dysfunction versus cancer patients with radiation- or chemotherapy (with or without gastrointestinal mucositis). We quantitatively measured bacterial EV-associated LPS and other LPS products by performing Limulus Amebocyte Lysate (LAL) and Toll-like receptor 4 (TLR4) reporter assays and qualitatively confirmed the results by immunoelectron microscopy. LAL analysis of DG fractions corresponding to the density of bacterial EV, demonstrated significantly increased LPS activity in patients diagnosed with therapy-induced gastrointestinal mucositis compared to respective controls. In accordance, we detected elevated amounts of microbial pattern recognition receptor (PRR) ligands by determining TLR4 agonistic activity. Immunoelectron microscopy confirmed bacterial EV-associated LPS. In conclusion, LPS-positive bacterial EV are present in plasma, and correlate with impaired barrier integrity in cancer therapy-induced intestinal mucositis. Further studies are needed to understand systemic functions of circulating bacterial EV in cancer patients and cancer therapy-induced conditions.
Citation Format: Joeri Tulkens, Olivier De Wever, An Hendrix. Increased levels of systemic LPS-positive bacterial extracellular vesicles in cancer patients with chemotherapy-induced intestinal barrier dysfunction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1489.
Abstract 1492: Evaluation of combinatorial chemotherapeutics nano-carriers at different dosage regimens in breast cancer model: Tumor immune signaling, inhibit angiogenesis and tumor growth
Authors: Fatease Adel Al , Shah Vidhi , Lopez Kalei , Cote Brianna , Rao Deepa , Alani Adam 
Published: August 2019

Abstract
The objective of this work is to evaluate the effect of individual & combinatorial delivery of Docetaxel (DTX) and Everolimus (EVR) in polymeric micelles at frequent dosing regimen below their maximum tolerated dose on angiogenesis, efficacy & immune signaling in breast cancer animal model. Based on previous in-vivowork in our lab, the maximum tolerated dose (MTDs) for EVR, DTX & combinatorial micelles is 50, 25 and 20 mg/kg respectively. To achieve our goal, two studies have been conducted. First, in-vivo assessment of anti-angiogenic effects of individual & dual DTX-EVR micelles in murine model at 10%, 30%, and 50% MTD, & MTD dose. Second, in-vivo efficacy evaluation of individual & dual DTX EVR micelles at 10%, 30%, 50% MTD, and MTD dose in orthotropic breast cancer murine model. Relative blood vessel invasion & increase in tumor growth will be evaluated for each dosing treatment. We observed that dual DTX EVR polymeric micelles showed significant inhibition of angiogenesis & tumor growth compared to individual agent. The effect of frequent lower dosing schedule is also currently being investigated for its effect immune signaling.
Citation Format: Adel Al Fatease, Vidhi Shah, Kalei Lopez, Brianna Cote, Deepa Rao, Adam Alani. Evaluation of combinatorial chemotherapeutics nano-carriers at different dosage regimens in breast cancer model: Tumor immune signaling, inhibit angiogenesis and tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1492.