bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease
Authors: Jackson Yves , Wyssa Baptiste , Chappuis François 
Published: October 2019

Abstract

Background
Current options for Chagas’ disease treatment are restricted to benznidazole and nifurtimox. To the best of our knowledge, no study has ever compared their tolerance in adults in a non-endemic country.

Objectives
To compare the completion rates and drug tolerance in a cohort of patients treated according to current guidelines.

Patients and methods
We analysed the medical records of all Chagas’ disease patients aged 18 years or over who started antiparasitic treatment at the Geneva University Hospitals, Switzerland, from 2008 to 2016. We recorded treatment duration and all adverse events.

Results
We included 176 patients, 92 and 84 of whom received benznidazole or nifurtimox, respectively. The overall treatment completion rate was 62.5%, without a significant difference between the groups (P=0.436). Most patients (89.8%) suffered at least one adverse event. Those receiving nifurtimox had more events (6.2 versus 3.5, P&lt;0.001). Mucocutaneous symptoms predominated in the benznidazole group, whereas digestive symptoms were most frequent with nifurtimox. Neuropsychiatric events frequently occurred in both groups, most notably in patients receiving nifurtimox. Arthralgia, dyspnoea, sensitive neuropathy and pruritus were independent predictors of treatment interruption.

Conclusions
Currently recommended drug regimens for Chagas’ disease are not well tolerated and entail frequent treatment discontinuation irrespective of the drug used. This highlights the need to improve treatment tolerance in adults with Chagas’ disease with new therapeutic options.
International scope of the Japanese Anti-monopoly Act in cross-border cartel cases: a Japanese approach to ‘extraterritorial application’
Authors: Nishioka Kazuaki 
Published: October 2019

Abstract
Most states have a national anti-trust or competition law to regulate anti-competitive activities. There is no doubt that, in purely domestic cases, where an anti-competitive activity and its anti-competitive effects have occurred within a state, that state’s national competition authority can regulate the activity by applying its competition law. For cross-border cases such as where anti-competitive activities are carried out abroad but have anti-competitive effects on the domestic or internal market of that state or region, it has been gradually accepted that a state can apply its competition law to the activities on the basis of the effects within its territory. However, it should be noted that states have approached such cases differently. In 2017, the Supreme Court of Japan first decided the international scope of the Japanese Anti-Monopoly Act (JAMA) in cross-border cartel cases and clarified that the JAMA could apply to anti-competitive activities conducted outside of Japan if the activities in question disturbed the free competition economic order of Japan. The court did not mention the effects doctrine or the territorial principle. This article examines on what grounds and how far the JAMA can and should apply to cross-border cartel cases by analysing the Supreme Court judgement.
Interleukin-6 confers radio-resistance by inducing Akt mediated glycolysis and reducing mitochondrial damage in cells
Authors: Kumari Neeraj , Das Asmita , Bhatt Anant Narayan 
Published: October 2019

Abstract
Interleukin-6 (IL-6) induced glycolysis and therapeutic resistance is reported in some cell systems; however the mechanism of IL-6 induced glycolysis in radio-resistance is un-explored. Therefore to investigate, we treated Raw264.7 cells with IL-6 (1hr prior to irradiation) and examined the glycolytic flux. Increased expression of mRNA and protein levels of key glycolytic enzymes was observed after IL-6 treatment, which conferred glycolysis dependent resistance from radiation induced cell death. We further established that IL-6 induced glycolysis is activated by Akt signaling and knocking down Akt or inhibition of pan Akt phosphorylation significantly abrogated the IL-6 induced radio-resistance. Moreover, reduction of IL-6 induced pAkt level suppressed the expression of Hexokinase-2 and its translocation to the mitochondria, thereby inhibiting the glycolysis induced resistance to radiation. IL-6 induced glycolysis also minimized the radiation induced mitochondrial damage. These results suggest that IL-6 induced glycolysis observed in cells may be responsible for IL-6 mediated therapeutic radio-resistance in cancer cells, partly by activation of Akt signaling.
Quantifying the Efficacy of an Assessment-Based Pest Management (APM) Program for German Cockroach (L.) (Blattodea: Blattellidae) Control in Low-Income Public Housing Units
Authors: Miller Dini M , Smith Eric P 
Published: October 2019

AbstractOver the last several decades, low-income public housing facilities have been known to be infested with particularly large German cockroach populations. These populations persist even though the housing pest control contracts often require, and pay for, IPM practices to be used in their facilities. When Virginia Tech researchers began reviewing public housing contracts in Virginia and North Carolina, it was easy to see why these ‘IPM programs’ were not successful. Many of these ‘low-bidder’ contracts do not allow the technician enough time in each apartment to assess the size of the pest population. In addition, these pest management contracts did not require German cockroach population monitoring, even though all IPM programs are based on assessments of the pest population. There was a clear need for an effective, easy to apply cockroach management program in U.S. public housing authorities. This study determined the long-term efficacy of an Assessment-based Pest Management (APM) program for German cockroach control in U.S. public housing facilities. Specifically, we evaluated an APM program where the residents were not asked to clean or prepare for treatment, and where overnight cockroach trap counts were used to determine the volume of gel bait that would be applied. The APM baiting program was conducted for 15 mo in three housing authorities. In all three housing authorities, cockroach populations in test units were typically reduced by &gt;90%. German cockroach infestations were even eliminated from 49 of the 65 (75%) test units during this study.
Pediatric Trials for Cancer Therapies With Targets Potentially Relevant to Pediatric Cancers
Authors: Hwang Thomas J , Orenstein Liat , DuBois Steven G , Janeway Katherine A , Bourgeois Florence T 
Published: October 2019

Abstract
The Research to Accelerate Cures and Equity (RACE) for Children Act was enacted in 2017 to authorize the US Food and Drug Administration (FDA) to require pediatric studies for new cancer drugs that have a molecular target relevant to the growth or progression of a pediatric cancer. To assess the possible scope of this new policy, we examined all 78 adult cancer drugs approved by the FDA from 2007 to 2017. Only 17 (21.8%) drugs received any pediatric labeling information. Based on the FDA’s Pediatric Molecular Target List, we found that the RACE Act could have increased the proportion of cancer drugs potentially subject to pediatric study requirements from 0% to 78.2%. However, the actual effect of the legislation will depend on how often regulators require pediatric trials and on timely completion of such trials.
The effects of short-term calorie restriction on mutations in the spleen cells of infant-irradiated mice
Authors: Kakomi Saori , Nakayama Takafumi , Shang Yi , Tsuruoka Chizuru , Sunaoshi Masaaki , Morioka Takamitsu , Shimada Yoshiya , Kakinuma Shizuko , Tachibana Akira 
Published: October 2019

Abstract
The risk of cancer due to exposure to ionizing radiation is higher in infants than in adults. In a previous study, the effect of adult-onset calorie restriction (CR) on carcinogenesis in mice after early-life exposure to X-rays was examined (Shang, Y, Kakinuma, S, Yamauchi, K, et al. Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice. Int J Cancer. 2014; 135: 1038-47). The results showed that the tumor frequency was reduced in the CR group. However, the mechanism of tumor suppression by CR is not yet clear. In this study, we examined the effects of CR on radiation-induced mutations using gpt delta mice, which are useful to analyze mutations in various tissues throughout the whole body. Infant male mice (1-week old) were exposed to 3.8 Gy X-rays and fed a control (95 kcal/week/mouse) or CR (65 kcal/week/mouse) diet from adult stage (7-weeks old). Mice were sacrificed at the age of 7 weeks, 8 weeks and 100 days, and organs (spleen, liver, lung, thymus) were harvested. Mutations at the gpt gene in the DNA from the spleen were analyzed by using a gpt assay protocol that detects primarily point mutations in the gpt gene. The results showed that mutation frequencies were decreased in CR groups compared with non-CR groups. Sequence analysis of the gpt gene in mutants revealed a reduction in the G:C to T:A transversion in CR groups. Since it is known that 8-oxoguanine could result in this base substitution and that CR has an effect of reducing oxidative stress, these results indicate that the suppression of oxidative stress by CR is the cause of the reduction of this transversion.
WUSCHEL-related homeobox gene PagWOX11/12a responds to drought stress by enhancing root elongation and biomass growth in poplar
Authors: Wang Liu-Qiang , Li Zhen , Wen Shuang-Shuang , Wang Jin-Nan , Zhao Shu-Tang , Lu Meng-Zhu 
Published: October 2019

Abstract
In plants, a large root system improves the uptake of water and nutrients and is important for responding to drought stress. The poplar WUSCHEL-related homeobox (WOX) transcription factor promotes adventitious rooting, but its regulation of root growth in response to drought stress remains elusive. In this study, we found that PagWOX11/12a from hybrid poplar 84K (Populus alba×Populus glandulosa) is expressed predominantly in the roots and is strongly induced by drought stress. Compared with nontransgenic 84K plants, transgenic poplar plants overexpressing PagWOX11/12a displayed increased root biomass and enhanced drought tolerance, while opposite phenotypes were observed for PagWOX11/12a dominant repression (DR) plants. PagWOX11/12a functions as a nuclear transcriptional activator with a transactivation domain at the C-terminus. In addition, PagERF35 was found to specifically bind to a dehydration-responsive element (DRE) within the PagWOX11/12a promoter and activate PagWOX11/12a gene expression. These results indicate that PagERF35 may activate PagWOX11/12a expression in response to drought stress by promoting root elongation and biomass, thereby increasing drought tolerance of poplar.
A Common Subject for Ethics
Authors: Schroeder Mark 
Published: October 2019

AbstractThe purpose of this paper is to conceptualize and explore what I shall call the Common Subject Problem for ethics. The problem is that there seems to be no good answer to what property everyone who makes moral claims could be talking and thinking about. The Common Subject Problem is not a new problem; on the contrary, I will argue that it is one of the central animating concerns in the history of both metaethics and normative theory. But despite its importance, the Common Subject Problem is essentially invisible on many contemporary ways of carving up the problems of metaethics and normative ethical theory.My aim, therefore, is to make progress – in part by naming the problem, but also by beginning to sketch out the contours of what gives the problem its force, by distinguishing between different paths of response to the problem and assessing some of their chief merits, and finally, by distinguishing the Common Subject Problem from another problem with which it has come to be conflated. This nearby problem is the Moral Twin Earth Problem. Whereas the Common Subject Problem is a problem about what property ‘wrong’ could refer to, the Moral Twin Earth Problem is a problem about how ‘wrong’ could refer to it.The upshot of the paper, therefore, is to rescue one of the historically significant problems in normative ethics and metaethics – a problem that is essentially about normative semantics – from the illusion that has persisted over the last twenty years that it is really, somehow, a problem about metasemantics. Once we have reclaimed this problem, we can see that it could still be a problem even if there are no distinctively metasemantic problems in metaethics at all, that it is a problem faced by a wider variety of views, and that the space of possible solutions is much wider and more interesting for normative theory, moral psychology, and moral epistemology.
On Westphalian Woodworms and Rhenish Missionaries: The Soest Conductus Fragments and Their Afterlife
Authors: Maschke Eva M 
Published: October 2019

Abstract
Examining the Soest conductus fragments, of which five single leaves have so far been rediscovered, this article analyses the different layers of use and reuse that can be deduced. First, a detailed account of the circumstances under which these manuscript fragments travelled with (or without) their respective host volumes is given. The music manuscript must have been discarded by the fifteenth century, as a bookbinder from the Dominican convent of Soest in Westphalia reused various leaves of it in a series of autographs written by Jacob of Soest, who died in 1438. After the dissolution of the convent’s library in the course of nineteenth-century secularization, further contexts of reuse and dismemberment pertaining to the fragments can be demonstrated. Secondly, the remnants of the original music manuscript are analysed. The use of the two-part conductus O crux ave spes unica (H4) as the opening piece of a fascicle can be connected to the dedication of the Soest Dominican house to the Holy Cross. In comparison to other fragmentary sources that made their way to the German-speaking area, as well as the long-known codices F, W1, and W2, the Soest music manuscript seems closest to W2. While, however, these two codices show significant parallels in terms of mise-en-page and copying process, the choice of repertory might have deliberately differed. This points to production in the same workshop, but for different commissioners.
Reflection spectra of thick accretion discs
Authors: Riaz Shafqat , Ayzenberg Dimitry , Bambi Cosimo , Nampalliwar Sourabh 
Published: October 2019

ABSTRACT
Relativistic reflection features are commonly observed in the X-ray spectra of stellar-mass and supermassive black holes and originate from illumination of the inner part of the accretion disc by a hot corona. All the available relativistic reflection models assume that the disc is infinitesimally thin and the inner edge is at the innermost stable circular orbit or at a larger radius. However, we know that several sources, especially among supermassive black holes, have quite high-mass accretion rates. In such a case, the accretion disc becomes geometrically thick and the inner edge of the disc is expected to be inside the innermost stable circular orbit. In this work, we employ the Polish donut model to describe geometrically thick discs and we study the iron-line shapes from similar systems. We also simulate full reflection spectra and we analyse the simulated observations with a thin disc relativistic reflection model to determine the impact of the disc structure on the estimation of the model parameters, in particular in the case of tests of the Kerr hypothesis.
Sulphur-bearing and complex organic molecules in an infrared cold core
Authors: Beaklini Pedro P B , Mendoza Edgar , Canelo Carla M , Aleman Isabel , Merello Manuel , Kong Shuo , Navarete Felipe , Janot-Pacheco Eduardo , Abraham Zulema , Lépine Jacques R D , de Almeida Amaury A , Friaça Amâncio C S 
Published: October 2019

ABSTRACT
Since the start of ALMA (Atacama Large Millimeter Array) observatory operation, new and important chemistry of infrared cold core was revealed. Molecular transitions at millimetre range are being used to identify and to characterize these sources. We have investigated the 231 GHz ALMA archive observations of the infrared dark cloud region C9, focusing on the brighter source that we called as IRDC-C9 Main. We report the existence of two substructures on the continuum map of this source: a compact bright spot with high chemistry diversity that we labelled as core, and a weaker and extended one, that we labelled as tail. In the core, we have identified lines of the molecules OCS(19−18), 13CS(5−4), and CH3CH2CN, several lines of CH3CHO and the k-ladder emission of 13CH3CN. We report two different temperature regions, while the rotation diagram of CH3CHO indicates a temperature of 25 K, the rotation diagram of 13CH3CN indicates a warmer phase at temperature of ∼450 K. In the tail, only the OCS(19−18) and 13CS(5−4) lines were detected. We used the nautilus and the radex codes to estimate the column densities and the abundances. The existence of hot gas in the core of IRDC-C9 Main suggests the presence of a protostar, which is not present in the tail.
ChiTaRS 5.0: the comprehensive database of chimeric transcripts matched with druggable fusions and 3D chromatin maps
Authors: Balamurali Deepak , Gorohovski Alessandro , Detroja Rajesh , Palande Vikrant , Raviv-Shay Dorith , Frenkel-Morgenstern Milana 
Published: October 2019

Abstract
Chimeric RNA transcripts are formed when exons from two genes fuse together, often due to chromosomal translocations, transcriptional errors or trans-splicing effect. While these chimeric RNAs produce functional proteins only in certain cases, they play a significant role in disease phenotyping and progression. ChiTaRS 5.0 (http://chitars.md.biu.ac.il/) is the latest and most comprehensive chimeric transcript repository, with 111 582 annotated entries from eight species, including 23 167 known human cancer breakpoints. The database includes unique information correlating chimeric breakpoints with 3D chromatin contact maps, generated from public datasets of chromosome conformation capture techniques (Hi–C). In this update, we have added curated information on druggable fusion targets matched with chimeric breakpoints, which are applicable to precision medicine in cancers. The introduction of a new section that lists chimeric RNAs in various cell-lines is another salient feature. Finally, using text-mining techniques, novel chimeras in Alzheimer's disease, schizophrenia, dyslexia and other diseases were collected in ChiTaRS. Thus, this improved version is an extensive catalogue of chimeras from multiple species. It extends our understanding of the evolution of chimeric transcripts in eukaryotes and contributes to the analysis of 3D genome conformational changes and the functional role of chimeras in the etiopathogenesis of cancers and other complex diseases.
RB, p130 and p107 differentially repress G1/S and G2/M genes after p53 activation
Authors: Schade Amy E , Fischer Martin , DeCaprio James A 
Published: October 2019

AbstractCell cycle gene expression occurs in two waves. The G1/S genes encode factors required for DNA synthesis and the G2/M genes contribute to mitosis. The Retinoblastoma protein (RB) and DREAM complex (DP, RB-like, E2F4 and MuvB) cooperate to repress all cell cycle genes during G1 and inhibit entry into the cell cycle. DNA damage activates p53 leading to increased levels of p21 and inhibition of cell cycle progression. Whether the G1/S and G2/M genes are differentially repressed by RB and the RB-like proteins p130 and p107 in response to DNA damage is not known. We performed gene expression profiling of primary human fibroblasts upon DNA damage and assessed the effects on G1/S and G2/M genes. Upon p53 activation, p130 and RB cooperated to repress the G1/S genes. In addition, in the absence of RB and p130, p107 contributed to repression of G1/S genes. In contrast, G2/M genes were repressed by p130 and p107 after p53 activation. Furthermore, repression of G2/M genes by p107 and p130 led to reduced entry into mitosis. Our data demonstrates specific roles for RB, p130-DREAM, and p107-DREAM in p53 and p21 mediated repression of cell cycle genes.
Electro-mechanically controlled assembly of reconfigurable 3D mesostructures and electronic devices based on dielectric elastomer platforms
Authors: Pang Wenbo , Cheng Xu , Zhao Haojie , Guo Xiaogang , Ji Ziyao , Li Guorui , Liang Yiming , Xue Zhaoguo , Song Honglie , Zhang Fan , Xu Zheng , Sang Lei , Huang Wen , Li Tiefeng , Zhang Yihui 
Published: October 2019

AbstractThe manufacture of 3D mesostructures is receiving rapidly increasing attention, because of the fundamental significance and practical applications across wide-ranging areas. The recently developed approach of buckling-guided assembly allows deterministic formation of complex 3D mesostructures in a broad set of functional materials, with feature sizes spanning nanoscale to centimeter-scale. Previous studies mostly exploited mechanically controlled assembly platforms using elastomer substrates, which limits the capabilities to achieve on-demand local assembly, and to reshape assembled mesostructures into distinct 3D configurations. This work introduces a set of design concepts and assembly strategies to utilize dielectric elastomer actuators as powerful platforms for the electro-mechanically controlled 3D assembly. Capabilities of sequential, local loading with desired strain distributions allow access to precisely tailored 3D mesostructures that can be reshaped into distinct geometries, as demonstrated by experimental and theoretical studies of ∼30 examples. A reconfigurable inductive–capacitive radio-frequency circuit consisting of morphable 3D capacitors serves as an application example.
Rethinking the economics of water: an assessment
Authors: Garrick Dustin E , Hanemann Michael , Hepburn Cameron 
Published: October 2019

AbstractWater is rising on the policy agenda as population growth and climate change intensify scarcity, shocks, and access inequalities. The conventional economic policy recommendations—privatization, pricing, and property rights—have struggled due to a failure to account adequately for the politics of water and the associated distributional conflicts. We identify distinctive social and physical characteristics of water supply and demand, and explore their implications for three central areas of water policy: financing infrastructure, pricing, and property rights reform. Growing dependence on groundwater and non-networked water supplies exacerbates these challenges and reinforces the need to rethink the economics of water and tackle the political challenges head on. Meeting the water sustainable development goals would require institutional and technological innovations to supply, allocate, and manage water, as well as a sustained political and financial commitment to address those who might be left behind.