bluuebunny/crossref_metadata_2025_split huggingface dataset:
Price and expenditure elasticity of cigarette demand in El Salvador: a household-level analysis and simulation of a tax increase
Authors: Paraje Guillermo , Araya Daniel , De Paz Adonay , Nargis Nigar 
Published: June 2020

BackgroundIn El Salvador, 8.8% of adults 15 years and older smoke cigarettes. Little is known about the sensitivity of cigarette consumption among the adults in El Salvador to tax and price increases and income growth.MethodsElasticities are estimated using Deaton’s Almost Ideal Demand System model applied to data from the National Household Income and Expenditure Survey 2005/2006 for the total population and separately for income groups. The estimates are then used to simulate the effects of a proposed change in tobacco tax policy on cigarette consumption and tax revenue.FindingsThe estimated price elasticities (−0.77 for the total population) are within the range of price elasticity estimates available for low and middle-income countries. Given the estimated elasticities, a tobacco tax increase is expected to reduce the number of smokers (by almost 20%) and increase tobacco tax revenue (by more than 50%).ConclusionsIncreasing tobacco taxes has the potential to decrease consumption in El Salvador and raise fiscal revenues. The tobacco tax burden in El Salvador is one of the lowest in Latin America and the social costs of tobacco consumption largely exceed the tobacco tax revenues. An increase in tobacco tax could significantly decrease the number of smokers and reduce the burden of tobacco-related diseases and deaths.
Oddity in nonrelativistic, strong gravity
Authors: Ergen Mert , Hamamcı Efe , Van den Bleeken Dieter 
Published: June 2020

AbstractWe consider the presence of odd powers of the speed of light c in the covariant nonrelativistic expansion of General Relativity (GR). The term of order c in the relativistic metric is a vector potential that contributes at leading order in this expansion and describes strong gravitational effects outside the (post-)Newtonian regime. The nonrelativistic theory of the leading order potentials contains the full non-linear dynamics of the stationary sector of GR.
Rapakivi granite in the architecture of St Petersburg: a potential Global Heritage Stone from Finland and Russia
Authors: Bulakh Andrey , Härmä Paavo , Panova Elena , Selonen Olavi 
Published: June 2020

Abstract
Rapakivi granites were in use during the Middle Ages in Finland. Their most spectacular use, however, was for structures built in St Petersburg between 1760 and 1917. Remarkable examples are the majestic and slender Alexander Column and the 112 columns of St Isaac's Cathedral. All Rapakivi granite was extracted from the Wiborg Rapakivi granite batholith in several quarries around the municipality of Virolahti in SE Finland (old Russia). Today, the 1640 Ma-old Wiborg batholith is the most important area for natural stone production in Finland and in the Leningrad region, Russian Federation. The main quarried stone varieties of Rapakivi granite (Baltic Brown, Baltic Green, Carmen Red, Karelia Red, Eagle Red and Balmoral Red) are regularly produced in large quantities in Finland for the global stone market due to the stone's unique qualities. Examples of applications in Rapakivi granite from Finland can be found in the USA, China, South Africa, the UK, Italy, Austria, Ireland, Spain and Germany as well as in Scandinavia and Russia. There are also quarries near Vyborg, the Russian Federation: Vozrozhdenie and Ala-Noskua.
Collecting women in geology: opening the international case of a Scottish ‘cabinétière’, Eliza Gordon Cumming (
c.
1798–1842)
Authors: Orr Mary 
Published: June 2020

Abstract
The double meanings of ‘case’ in the subtitle pinpoint the dual investigations of this chapter. It first puts the case for better understanding of women's contributions to ‘serious’ geology in international, as well as national, contexts by overtly collecting British women collectors in the field who contributed to French geological knowledge. It can then unpack the pivotal importance of women's geology collections and women collectors ‘at home’ in the establishment of new global subfields of geological work in the 1840s, despite more famous names being given national and international recognition for key discoveries. Our examination of the geology case in point – the collection and its expert collector, Lady Eliza Gordon Cumming – discloses her international geological expertise but also longer transnational heritage of women's scientific collecting practice. By proposing the French term ‘cabinétière’ to name its clearer status, this chapter investigates the implications of serious retrospective relabelling for geology when a woman discoverer-collector is restored and reconnected to her world collections.
Female students of geology in Victorian Dublin
Authors: Hegarty Susan 
Published: June 2020

Abstract
The science of geology began to thrive during the middle of the nineteenth century, with the expansion and consolidation of geological mapping of the Geological Survey of Great Britain and Ireland, and the foundation of geological societies across the islands of Britain and Ireland. As the desire for geological knowledge and understanding among the general public grew, so did the provision of lectures and courses open to the public. These public lecture series proved popular with a wide cross-section of men and women of Victorian Britain and Ireland.
This paper explores the provision of geological lectures by officers of the Geological Survey of Ireland through the Museum of Irish Industry in Dublin, and the women who took these courses during the 1850s and 1860s, and completed geological examinations for London's Science and Art Department in Dublin as a result of these lectures. It provides a glimpse into the scientific and, specifically, geological interests and activities of these women at a time when it was not possible for them to become members of the geological societies in the cities in which they lived.
Network-level Design Space Exploration of Resource-constrained Networks-of-Systems
Authors: Zhao Zhuoran , Barijough Kamyar Mirzazad , Gerstlauer Andreas 
Published: June 2020

Driven by recent advances in networking and computing technologies, distributed application scenarios are increasingly deployed on resource-constrained processing platforms. This includes networked embedded and cyber-physical systems as well as edge computing in mobile applications and the Internet of Things (IoT). In such resource-constrained Networks-of-Systems (NoS), computation and communication workloads need to be carefully co-optimized yet are tightly coupled. How to optimally partition and schedule application tasks among an appropriately designed NoS architecture requires a simultaneous consideration of design parameters from applications and processing platforms all the way to network configurations. Traditionally, however, systems and networks are designed in isolation and combined in an ad hoc manner, which ignores joint effects and optimization opportunities. To systematically explore and optimize NoS design spaces, a higher level of design abstraction on top of traditional system and network design is required.
In this article, we propose a novel network-level design methodology for resource-constrained NoS optimization and design space exploration. A key component in such a design flow is fast yet accurate network/system co-simulation to rapidly evaluate NoS parameters with high fidelity. We first introduce a novel NoS simulator (NoSSim) that integrates source-level simulation models of applications with a host-compiled system simulation platform and a reconfigurable network simulation backplane to accurately capture system and network interactions. The co-simulation platform is further combined with model generation tools and a multi-objective genetic search algorithm to provide a comprehensive and fully automated NoS design space exploration framework. Finally, we apply our network-level design flow on several state-of-art IoT/mobile design case studies. Results show that NoSSim can achieve more than 86% simulation accuracy on average as compared to a real-world edge device cluster, where sensitivities to various design parameters are faithfully captured with high fidelity. When applying our network-level design space exploration methodology, design decisions are automatically optimized, where non-obvious NoS configurations are discovered outperforming manually designed solutions by more than 45%.
Where to Next? The Impact of COVID-19 on Human-Robot Interaction Research
Authors: Feil-Seifer David , Haring Kerstin S. , Rossi Silvia , Wagner Alan R. , Williams Tom 
Published: June 2020

The COVID-19 pandemic will have a profound and long-lasting impact on the entire scientific endeavor. Scientists already are adapting research programs to adapt to changes in what is prioritized—and what is possible; educators are changing the way that the next generation of researchers are trained, and flagship conferences in many fields are being cancelled, postponed, and fundamentally transformed.
These broad-reaching changes are particularly impactful to human-oriented domains such as human-robot interaction (HRI). Because in-person human-subject experiments can take a year or more to conduct, the research we will see published in the field in the immediate future may appear to be “business as usual,” with accounts of laboratory studies with large numbers of in-person participants. The research currently being performed, however, is of course a different story entirely. Studies that were under way when the current crisis began will be truncated, resulting either in work that cannot be published or in work whose true impact is difficult to accurately assess. Yet HRI research performed in the coming years will be changed in fundamentally different ways; the inability to perform—or expect future performance of—in-person human subjects research, especially research involving tactile or multiparty interaction, will change both the dominant methodological techniques employed by HRI researchers and the very research questions that the field chooses to—and is able to—address.
These challenges demand that HRI researchers identify precisely how the field can maintain research quality and impact while the ability to conduct human-subject studies is severely impaired for an undetermined amount of time. A natural inclination may be simply to wait the crisis out in the hope of a speedy return to normalcy; however, in this article, we argue that the community can also take this opportunity to reevaluate and refocus how research in this field is conducted and how students are mentored in ways that will yield benefits for years to come after the current crisis has ended.
Deletion of Glutathione S-Transferase Omega 1 Activates Type I Interferon Genes and Downregulates Tissue Factor
Authors: Xu Yibin , Bankhead Armand , Tian Xiaoli , Tang Jianming , Ljungman Mats , Neamati Nouri 
Published: June 2020

Abstract

GST omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. Here we have validated GSTO1 as an impactful target in oncology. Transcriptional profiling coupled with proteomics uncovered novel pharmacodynamic markers and cellular pathways regulated by GSTO1. CRISPR/Cas9 GSTO1 knockout (KO) cell lines failed to form tumors or displayed growth delay in vivo; they also formed smaller 3D spheroids in vitro. Multiomics analysis in GSTO1 KO cells found a strong positive correlation with cell adhesion molecules and IFN response pathways and a strong negative correlation with Myc transcriptional signature. In addition, several clinically used drugs showed significant synthetic lethality with loss or inhibition of GSTO1. Transcription and protein expression of tissue factor (gene name, F3) were downregulated in response to GSTO1 KO. F3 is associated with poor patient survival and promotion of tumor progression in multiple cancers and is a known risk factor for metastasis. Transcription of F3 was regulated by IL1β, whose secretion decreased upon inhibition of GSTO1, suggesting that IL1β links GSTO1 expression and F3 transcription. In summary, our results implicate GSTO1 as a potential therapeutic target in cancer and offer new mechanistic insights into its significant role in cancer progression.

Significance:
These findings validate GSTO1 as a therapeutic target in cancer and implicate GSTO1 in the modulation of tumor growth, immune responses, and expression of F3.
Improving the Clinical Significance of Preclinical Immunotherapy Studies through Incorporating Tumor Microenvironment–like Conditions
Authors: Maggs Luke , Ferrone Soldano 
Published: June 2020

AbstractFrequently, the results generated when testing novel antitumor immunotherapies in vitro do not correlate with data collected in in vivo models and/or in clinical settings. It is our hypothesis that this discrepancy is caused by the use of in vitro conditions, such as normoxia, a two-dimensional surface, optimal growth media, and lack of cell complexity and heterogeneity. These conditions do not accurately reflect the tumor microenvironment (TME) that the tested immunotherapeutic strategies experience in vivo. While there are many variables which can have an impact upon the antitumor efficacy of an immunotherapy, the immunosuppressive TME is one in which several of the conditions commonly found in vivo can be mimicked in vitro. These conditions, which include hypoxia, low pH, low glucose, presence of adenosine, cell complexity and heterogeneity, as well as the three-dimensional structure of TME, can all affect immune cell–tumor cell interactions. Here, we discuss the impact that these conditions, either individually or in combination, can have on these interactions. Furthermore, we propose that performing in vitro assays under TME-like conditions improves the clinical relevance of the yielded results. This, in turn, contributes to accelerate the speed, reduce the cost, and increase efficiency of screening novel immunotherapies and eventually the development of prospective clinical trials.
Identification of Somatically AcquiredBRCA1/2Mutations by cfDNA Analysis in Patients with Metastatic Breast Cancer
Authors: Vidula Neelima , Dubash Taronish , Lawrence Michael S. , Simoneau Antoine , Niemierko Andrzej , Blouch Erica , Nagy Becky , Roh Whijae , Chirn Brian , Reeves Brittany A. , Malvarosa Giuliana , Lennerz Jochen , Isakoff Steven J. , Juric Dejan , Micalizzi Douglas , Wander Seth , Spring Laura , Moy Beverly , Shannon Kristen , Younger Jerry , Lanman Richard , Toner Mehmet , Iafrate A. John , Getz Gad , Zou Lee , Ellisen Leif W. , Maheswaran Shyamala , Haber Daniel A. , Bardia Aditya 
Published: June 2020

AbstractPurpose:Plasma genotyping may identify mutations in potentially “actionable” cancer genes, such as BRCA1/2, but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired BRCA1/2 mutations in patients with metastatic breast cancer (MBC).Experimental Design:Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting a new therapy were included. Somatic BRCA1/2 mutations were classified as known germline pathogenic mutations or novel variants, and linked to clinicopathologic characteristics. The effect of the PARP inhibitor, olaparib, was assessed in vitro, using cultured circulating tumor cells (CTCs) from a patient with a somatically acquired BRCA1 mutation and a second patient with an acquired BRCA2 mutation.Results:Among 215 patients with MBC, 29 (13.5%) had somatic cfDNA BRCA1/2 mutations [nine (4%) known germline pathogenic and rest (9%) novel variants]. Known germline pathogenic BRCA1/2 mutations were common in younger patients (P = 0.008), those with triple-negative disease (P = 0.022), and they were more likely to be protein-truncating alterations and be associated with TP53 mutations. Functional analysis of a CTC culture harboring a somatic BRCA1 mutation demonstrated high sensitivity to PARP inhibition, while another CTC culture harboring a somatic BRCA2 mutation showed no differential sensitivity. Across the entire cohort, APOBEC mutational signatures (COSMIC Signatures 2 and 13) and the “BRCA” mutational signature (COSMIC Signature 3) were present in BRCA1/2-mutant and wild-type cases, demonstrating the high mutational burden associated with advanced MBC.Conclusions:Somatic BRCA1/2 mutations are readily detectable in MBC by cfDNA analysis, and may be present as both known germline pathogenic and novel variants.
Population-based Screening for BRAFV600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis
Authors: Chu Jenny E. , Johnson Benny , Kugathasan Laveniya , Morris Van K. , Raghav Kanwal , Swanson Lucas , Lim Howard J. , Renouf Daniel J. , Gill Sharlene , Wolber Robert , Karsan Aly , Kopetz Scott , Schaeffer David F. , Loree Jonathan M. 
Published: June 2020

Abstract

Purpose:
BRAF V600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF sequencing.

Experimental Design:
We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and BRAFV600E testing. Outcomes among IHC-detected BRAFV600E mCRC (BRAFIHC) were compared with patients with next-generation sequencing (NGS)–identified BRAFV600E-mutated mCRC from two institutions (BRAFNGS) with patients spanning from 2004 to 2018.

Results:
All-stage population prevalence of BRAFV600E was 12.5% (238/1,898) and did not differ between early and metastatic stages (P = 0.094). Prevalence among mCRC was 10.6% (61/575), of whom 51 (83.6%) were referred to oncology and 26 (42.6%) had NGS testing. BRAFIHC had worse median overall survival (mOS) than BRAFNGS [5.5 vs. 20.4 months; HR, 2.90; 95% confidence interval (CI), 1.89–4.45; P &lt; 0.0001], which persisted in multivariate analysis (P &lt; 0.0001). Across a combined NGS and IHC cohort, BRAFV600E tumors with deficient MMR showed worse mOS compared with MMR proficient tumors (8.9 vs. 17.2 months; HR, 1.46; 95% CI, 0.96–2.27; P = 0.043). In this combined cohort, first-line progression-free survival was 5.9 months, with minimal differences between regimens. Within the population-based cohort, attrition between treatment lines was high with only 60.7% receiving first-line chemotherapy and 26.2% receiving second line.

Conclusions:
Patients with BRAFV600E-mutated mCRC have a worse prognosis than previously suggested, potentially arising from referral bias for testing. High attrition between lines of therapy suggests efficacious therapies need to be prioritized early for patients to benefit.
Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification
Authors: Furmanik Malgorzata , Chatrou Martijn , van Gorp Rick , Akbulut Asim , Willems Brecht , Schmidt Harald , van Eys Guillaume , Bochaton-Piallat Marie-Luce , Proudfoot Diane , Biessen Erik , Hedin Ulf , Perisic Ljubica , Mees Barend , Shanahan Catherine , Reutelingsperger Chris , Schurgers Leon 
Published: June 2020

Rationale:
Vascular calcification, the formation of calcium phosphate crystals in the vessel wall, is mediated by vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms remain elusive, precluding mechanism-based therapies.

Objective:
Phenotypic switching denotes a loss of contractile proteins and an increase in migration and proliferation, whereby VSMCs are termed synthetic. We examined how VSMC phenotypic switching influences vascular calcification and the possible role of the uniquely calcium-dependent reactive oxygen species (ROS)-forming Nox5 (NADPH oxidase 5).

Methods and Results:

In vitro cultures of synthetic VSMCs showed decreased expression of contractile markers CNN-1 (calponin 1), α-SMA (α-smooth muscle actin), and SM22-α (smooth muscle protein 22α) and an increase in synthetic marker S100A4 (S100 calcium binding protein A4) compared with contractile VSMCs. This was associated with increased calcification of synthetic cells in response to high extracellular Ca
2+
. Phenotypic switching was accompanied by increased levels of ROS and Ca
2+
-dependent Nox5 in synthetic VSMCs. Nox5 itself regulated VSMC phenotype as siRNA knockdown of Nox5 increased contractile marker expression and decreased calcification, while overexpression of Nox5 decreased contractile marker expression. ROS production in synthetic VSMCs was cytosolic Ca
2+
-dependent, in line with it being mediated by Nox5. Treatment of VSMCs with Ca
2+
loaded extracellular vesicles (EVs) lead to an increase in cytosolic Ca
2+
. Inhibiting EV endocytosis with dynasore blocked the increase in cytosolic Ca
2+
and VSMC calcification. Increased ROS production resulted in increased EV release and decreased phagocytosis by VSMCs.

Conclusions:

We show here that contractile VSMCs are resistant to calcification and identify Nox5 as a key regulator of VSMC phenotypic switching. Additionally, we describe a new mechanism of Ca
2+
uptake via EVs and show that Ca
2+
induces ROS production in VSMCs via Nox5. ROS production is required for release of EVs, which promote calcification. Identifying molecular pathways that control Nox5 and VSMC-derived EVs provides potential targets to modulate vascular remodeling and calcification in the context of mineral imbalance.

Graphic Abstract:

A
graphic abstract
is available for this article.
Health Impact and Cost-Effectiveness of Volume, Tiered, and Absolute Sugar Content Sugar-Sweetened Beverage Tax Policies in the United States
Authors: Lee Yujin , Mozaffarian Dariush , Sy Stephen , Liu Junxiu , Wilde Parke E. , Marklund Matti , Abrahams-Gessel Shafika , Gaziano Thomas A. , Micha Renata 
Published: June 2020

Background:
Sugar-sweetened beverage taxes are a rapidly growing policy tool and can be based on absolute volume, sugar content tiers, or absolute sugar content. Yet, their comparative health and economic impacts have not been quantified, in particular, tiered or sugar content taxes that provide industry incentives for sugar reduction.

Methods:
We estimated incremental changes in diabetes mellitus and cardiovascular disease, quality-adjusted life-years, costs, and cost-effectiveness of 3 sugar-sweetened beverage tax designs in the United States, on the basis of (1) volume ($0.01/oz), (2) tiers (<5 g of added sugar/8 oz: no tax; 5–20 g/8 oz: $0.01/oz; and >20 g/8 oz: $0.02/oz), and (3) absolute sugar content ($0.01 per teaspoon added sugar), each compared with a base case of modest ongoing voluntary industry reformulation. A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey, policy effects and sugar-sweetened beverage-related diseases from meta-analyses, and industry reformulation and health-related costs from established sources.

Results:
Over a lifetime, the volume, tiered, and absolute sugar content taxes would generate $80.4 billion, $142 billion, and $41.7 billion in tax revenue, respectively. From a healthcare perspective, the volume tax would prevent 850 000 cardiovascular disease (95% CI, 836 000–864 000) and 269 000 diabetes mellitus (265 000–274 000) cases, gain 2.44 million quality-adjusted life-years (2.40–2.48), and save $53.2 billion net costs (52.3–54.1). Health gains and savings were approximately doubled for the tiered and absolute sugar content taxes. Results were robust for societal and government perspectives, at 10 years follow-up, and with lower (50%) tax pass-through. Health gains were largest in young adults, blacks and Hispanics, and lower-income Americans.

Conclusions:
All sugar-sweetened beverage tax designs would generate substantial health gains and savings. Tiered and absolute sugar content taxes should be considered and evaluated for maximal potential gains.