bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioaccessible arsenic in soil of thermal areas of Viterbo, Central Italy: implications for human health risk
Authors: Rimondi V. , Costagliola P. , Lattanzi P. , Catelani T. , Fornasaro S. , Medas D. , Morelli G. , Paolieri M.
Published: April 2021

Thermal waters near the city of Viterbo (Central Italy) are known to show high As contents (up to 600 µg/l). Travertine is precipitated by these waters, forming extended plateau. In this study, we determine the As content, speciation and bioaccessibility in soil and travertine samples collected near a recreational area highly frequented by local inhabitants and tourists to investigate the risk of As exposure through accidental ingestion of soil particles. (Pseudo)total contents in the studied soils range from 17 to 528 mg/kg, being higher in soil developed on a travertine substrate (197 ± 127 mg/kg) than on volcanic rocks (37 ± 13 mg/kg). In travertines, most As is bound to the carbonatic fraction, whereas in soil the semimetal is mostly associated with the oxide and residual fractions. Accordingly, bioaccessibility (defined here by the simplified bioaccessibility extraction test, SBET; Oomen et al., 2002.) is maximum (up to 139 mg/kg) for soil developed on a travertine substrate, indicating a control of calcite dissolution on As bioaccessibility. On the other hand, risk analysis suggests a moderate carcinogenic risk associated with accidental soil ingestion, while dermal contact is negligible. By contrast, ingestion of thermal water implies a higher carcinogenic and systemic health risk.
Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study
Authors: Bondonno Catherine P. , Dalgaard Frederik , Blekkenhorst Lauren C. , Murray Kevin , Lewis Joshua R. , Croft Kevin D. , Kyrø Cecilie , Torp-Pedersen Christian , Gislason Gunnar , Tjønneland Anne , Overvad Kim , Bondonno Nicola P. , Hodgson Jonathan M.
Published: April 2021

Whether the vascular effects of inorganic nitrate, observed in clinical trials, translate to a reduction in cardiovascular disease (CVD) with habitual dietary nitrate intake in prospective studies warrants investigation. We aimed to determine if vegetable nitrate, the major dietary nitrate source, is associated with lower blood pressure (BP) and lower risk of incident CVD. Among 53,150 participants of the Danish Diet, Cancer, and Health Study, without CVD at baseline, vegetable nitrate intake was assessed using a comprehensive vegetable nitrate database. Hazard ratios (HRs) were calculated using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. During 23 years of follow-up, 14,088 cases of incident CVD were recorded. Participants in the highest vegetable nitrate intake quintile (median, 141 mg/day) had 2.58 mmHg lower baseline systolic BP (95%CI − 3.12, − 2.05) and 1.38 mmHg lower diastolic BP (95%CI − 1.66, − 1.10), compared with participants in the lowest quintile. Vegetable nitrate intake was inversely associated with CVD plateauing at moderate intakes (~ 60 mg/day); this appeared to be mediated by systolic BP (21.9%). Compared to participants in the lowest intake quintile (median, 23 mg/day), a moderate vegetable nitrate intake (median, 59 mg/day) was associated with 15% lower risk of CVD [HR (95% CI) 0.85 (0.82, 0.89)]. Moderate vegetable nitrate intake was associated with 12%, 15%, 17% and 26% lower risk of ischemic heart disease, heart failure, ischemic stroke and peripheral artery disease hospitalizations respectively. Consumption of at least ~ 60 mg/day of vegetable nitrate (~ 1 cup of green leafy vegetables) may mitigate risk of CVD.
Exploiting the transit timing capabilities of Ariel
Authors: Borsato Luca , Nascimbeni Valerio , Piotto Giampaolo , Szabó Gyula
Published: April 2021

The Transit Timing Variation (TTV) technique is a powerful dynamical tool to measure exoplanetary masses by analysing transit light curves. We assessed the transit timing performances of the Ariel Fine Guidance Sensors (FGS1/2) based on the simulated light curve of a bright, 55 Cnc, and faint, K2-24, planet-hosting star. We estimated through a Markov-Chain Monte-Carlo analysis the transit time uncertainty at the nominal cadence of 1 second and, as a comparison, at a 30 and 60-s cadence. We found that at the nominal cadence Ariel will be able to measure the transit time with a precision of about 12s and 34s, for a star as bright as 55 Cnc and K2-24, respectively. We then ran dynamical simulations, also including the Ariel timing errors, and we found an improvement on the measurement of planetary masses of about 20-30% in a K2-24-like planetary system through TTVs. We also simulated the conditions that allow us to detect the TTV signal induced by an hypothetical external perturber within the mass range between Earth and Neptune using 10 transit light curves by Ariel.
Adipose-Derived Mesenchymal Stem Cells-Derived Exosomes Carry MicroRNA-671 to Alleviate Myocardial Infarction Through Inactivating the TGFBR2/Smad2 Axis
Authors: Wang Xue , Zhu Yuhai , Wu Chengcheng , Liu Wennan , He Yujie , Yang Qing
Published: April 2021

Abstract

Mesenchymal stem cells (MSCs) and their derived extracellular vesicles have been reported as promising tools for the management of heart disease. The aim of this study was to explore the function of adipose-derived MSCs (adMSCs)-derived exosomes (Exo) in the progression of myocardial infarction (MI) and the molecules involved. Mouse cardiomyocytes were treated with oxygen-glucose deprivation (OGD) to mimic an MI condition in vitro. The adMSCs-derived Exo were identified and administrated into the OGD-treated cardiomyocytes, and then the viability and apoptosis of cells, and the secretion of fibrosis- and inflammation-related cytokines in cells were determined. Differentially expressed microRNAs (miRNAs) in cells after Exo treatment were screened using a microarray analysis. The downstream molecules regulated by miR-671 were explored through bioinformatic analysis. Involvements of miR-671 and transforming growth factor beta receptor 2 (TGFBR2) in the exosome-mediated events were confirmed by rescue experiments. A murine model with MI was induced and treated with Exo for functional experiments in vivo. Compared to phosphate-buffered saline treatment, the Exo treatment significantly enhanced viability while reduced apoptosis of cardiomyocytes, and in reduced myocardial fibrosis and inflammation both in vitro and in vivo. miR-671 was significantly upregulated in cells after Exo treatment. Downregulation of miR-671 blocked the protective functions of Exo. miR-671 targeted TGFBR2 and suppressed phosphorylation of Smad2. Artificial downregulation of TGFBR2 enhanced viability of the OGD-treated cardiomyocytes. This study suggested that adMSC-derived exosomal miR-671 directly targets TGFBR2 and reduces Smad2 phosphorylation to alleviate MI-like symptoms both in vivo and in vitro.
Veganism, Moral Motivation and False Consciousness
Authors: Pickett Susana
Published: April 2021

Despite the strength of arguments for veganism in the animal rights literature, alongside environmental and other anthropocentric concerns posed by industrialised animal agriculture, veganism remains only a minority standpoint. In this paper, I explore the moral motivational problem of veganism from the perspectives of moral psychology and political false consciousness. I argue that a novel interpretation of the post-Marxist notion of political false consciousness may help to make sense of the widespread refusal to shift towards veganism. Specifically, the notion of false consciousness fills some explanatory gaps left by the moral psychological notion ofakrasia, often understood to refer to a weakness of will. Central to my approach is the idea that animal exploitation is largely systemic and the assumption that moral motivation is inseparable from moral thinking. In this light, the primary obstacle to the adoption of veganism arises not so much from a failure to put genuine beliefs into action, but rather in a shared, distorted way of thinking about animals. Thus, common unreflective objections to veganism may be said to be manifestations of false consciousness.
Latex Metabolome of Euphorbia Species: Geographical and Inter-Species Variation and its Proposed Role in Plant Defense against Herbivores and Pathogens
Authors: Salomé-Abarca Luis Francisco , Gođevac Dejan , Kim Min Sun , Hwang Geum-Sook , Park Sang Cheol , Jang Young Pyo , Van Den Hondel Cees A. M. J. J. , Verpoorte Robert , Klinkhamer Peter G. L. , Choi Young Hae
Published: April 2021

Based on the hypothesis that the variation of the metabolomes of latex is a response to selective pressure and should thus be affected differently from other organs, their variation could provide an insight into the defensive chemical selection of plants. Metabolic profiling was used to compare tissues of threeEuphorbiaspecies collected in diverse regions. The metabolic variation of latexes was much more limited than that of other organs. In all the species, the levels of polyisoprenes and terpenes were found to be much higher in latexes than in leaves and roots of the corresponding plants. Polyisoprenes were observed to physically delay the contact of pathogens with plant tissues and their growth. A secondary barrier composed of terpenes in latex and in particular, 24-methylenecycloartanol, exhibited antifungal activity. These results added to the well-known role of enzymes also present in latexes, show that these are part of a cooperative defense system comprising biochemical and physical elements.
Validation of EFFTRAN for efficiency transfer to distant geometries and volume sources
Authors: Ramebäck H. , Jonsson S. , Vidmar T.
Published: April 2021

The efficiency transfer procedure from a geometry where a volume source was placed directly on the endcap of a germanium detector to three different distant geometries was carried out using the EFFTRAN code. One of these distant geometries included absorbers consisting of poly(methyl methacrylate). The efficiency transfer to this geometry therefore had to be realized as a two-stage transfer, since a direct efficiency transfer is not possible using EFFTRAN in such a case. Efficiency transfer to all three distant geometries yielded results which can be considered as fit-for-purpose in e.g. most of the applications of gamma ray spectrometry.
Silver as a capturing material for iodine released from lead–bismuth eutectic in various conditions
Authors: Karlsson Erik , Neuhausen Jörg , Eichler Robert , Danilov Ivan I. , Vögele Alexander , Türler Andreas
Published: April 2021

The usage of silver as a filtering material for removal of iodine from the gas phase of a lead–bismuth eutectic based nuclear reactor was investigated in various atmospheres representing normal operation as well as accident conditions. Thermochromatography experiments were performed to quantify the retention experienced on a silver surface by iodine species evaporated from a lead–bismuth eutectic sample. Measured adsorption enthalpies ranged from −171 to − 208 kJ mol−1 with observed differences attributed to various surface effects rather than a change in iodine speciation. The postulated adsorption mechanism is chemisorption of iodine atoms on the silver surface. Metallic silver fulfills the desired criteria for a capturing material in water-free filtering systems to be used as an alternative to traditional alkaline scrubbers commonly used in LWR systems.
Thermochromatographic behavior of iodine in 316L stainless steel columns when evaporated from lead–bismuth eutectic
Authors: Karlsson Erik , Neuhausen Jörg , Eichler Robert , Danilov Ivan I. , Vögele Alexander , Türler Andreas
Published: April 2021

Iodine evaporated from lead–bismuth eutectic (LBE) has been examined with respect to its adsorption behavior on stainless steel in various gases to establish a base for safety evaluations on LBE based nuclear reactors. In inert conditions the iodine forms a single species with an adsorption enthalpy between − 97 and − 106 kJ/mol. The adsorbed species is tentatively identified as bismuth monoiodide, BiI. Addition of moisture to the inert gas has no substantial influence on the adsorption behaviour. For the reducing hydrogen carrier gas depositions with adsorption enthalpies ranging from − 87 to − 134 kJ/mol were observed in dry and water saturated conditions. The larger variation of adsorption enthalpies compared to analogous experiments in helium likely result from surface effects induced by the reactive gas. Formation of highly volatile species such as hydrogen iodide HI was not observed. In oxidizing conditions multiple iodine species with adsorption enthalpies ranging from − 67 to − 83 kJ/mol were observed, with the exception of one experiment where only a lower limit of –ΔHads < 64 kJ/mol could be determined due to high volatility. The species occurring in oxidizing atmosphere are most likely monatomic iodine, iodine oxides and hydroxides. While oxygen as a carrier gas changes the speciation of iodine to more volatile compounds, it also introduces a retentive effect on the evaporation of iodine from the LBE sample. These results provide important information that establish a better understanding of safety related aspects pertaining to iodine transport in an LBE reactor. The determined thermodynamic data can be used for safety assessments of LBE-based nuclear facilities in normal operation conditions as well as for accident scenarios.
Proposed definition of competencies for surgical neuro-oncology training
Authors: Kamp Marcel A. , Malzkorn Bastian , von Sass Christiane , DiMeco Francesco , Hadjipanayis Constantinos G. , Senft Christian , Rapp Marion , Gepfner-Tuma Irina , Fountas Konstantinos , Krieg Sandro M. , Neukirchen Martin , Florian Ioan Ștefan , Schnell Oliver , Mijderwijk Hendrik-Jan , Perin Alessandro , Baumgarten Peter , van Lieshout Jasper H. , Thon Niklas , Renovanz Miriam , Kahlert Ulf , Spoor Jochem K. H. , Hänggi Daniel , McLean Aaron Lawson , Mäurer Matthias , Sarrubbo Silvio , Freyschlag Christian F. , Schmidt Nils O. , Vergani Francesco , Jungk Christine , Stein Marco , Forster Marie-Therese , Weinberg Jeffrey S. , Sinclair John , Belykh Evgenii , Bello Lorenzo , Mandonnet Emmanuel , Moiyadi Aliasgar , Sabel Michael
Published: April 2021

Objective

The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established.

Methods

We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology.

Result

In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families.

Conclusions and Relevance

The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.
Solid bitumen in shales from the Middle to Upper Jurassic Sargelu and Naokelekan Formations of northernmost Iraq: implication for reservoir characterization
Authors: Omar Nagham , McCann Tom , Al-Juboury Ali I. , Suárez-Ruiz Isabel
Published: April 2021

Petrographic, organic, and inorganic geochemical analysis of the solid bitumen and host shales from the Middle and Late Jurassic-age Sargelu and Naokelekan Formations of the Banik section, northernmost Iraq, was undertaken. The aim was to understand their derivation and preservation, as well as examine the carbon and oxygen isotopes, and paleoredox proxies under which the solid bitumen and host sediments were deposited. Petrographic analysis of both formations revealed the presence of solid bitumen high reflectance (first phase) and solid bitumen low reflectance (second phase). The equivalent vitrinite reflectance indicates that the solid bitumen of the two formations probably accumulated within the shale reservoirs following oil migration from source rocks located within the same formations. Mineralogical study (XRD and SEM - EDX) revealed that the shales hosting the solid bitumen also contain clay minerals (illite, rectorite, chlorite, montmorillonite, and kaolinite) as well as carbonate minerals, quartz, alkali feldspar, and pyrite. Carbon and oxygen isotope data along with paleoredox indicators suggest that both the solid bitumen sources and host shales in both formations formed within a shallow-marine setting, most probably under anoxic conditions where water circulation was restricted.
An Early Warning Tool for Predicting Mortality Risk of COVID-19 Patients Using Machine Learning
Authors: Chowdhury Muhammad E. H. , Rahman Tawsifur , Khandakar Amith , Al-Madeed Somaya , Zughaier Susu M. , Doi Suhail A. R. , Hassen Hanadi , Islam Mohammad T.
Published: April 2021

COVID-19 pandemic has created an extreme pressure on the global healthcare services. Fast, reliable, and early clinical assessment of the severity of the disease can help in allocating and prioritizing resources to reduce mortality. In order to study the important blood biomarkers for predicting disease mortality, a retrospective study was conducted on a dataset made public by Yan et al. in [1] of 375 COVID-19 positive patients admitted to Tongji Hospital (China) from January 10 to February 18, 2020. Demographic and clinical characteristics and patient outcomes were investigated using machine learning tools to identify key biomarkers to predict the mortality of individual patient. A nomogram was developed for predicting the mortality risk among COVID-19 patients. Lactate dehydrogenase, neutrophils (%), lymphocyte (%), high-sensitivity C-reactive protein, and age (LNLCA)—acquired at hospital admission—were identified as key predictors of death by multi-tree XGBoost model. The area under curve (AUC) of the nomogram for the derivation and validation cohort were 0.961 and 0.991, respectively. An integrated score (LNLCA) was calculated with the corresponding death probability. COVID-19 patients were divided into three subgroups: low-, moderate-, and high-risk groups using LNLCA cutoff values of 10.4 and 12.65 with the death probability less than 5%, 5–50%, and above 50%, respectively. The prognostic model, nomogram, and LNLCA score can help in early detection of high mortality risk of COVID-19 patients, which will help doctors to improve the management of patient stratification.
Contradictions and Interventions in Health IS
Authors: Weeger Andy , Wagner Heinz-Theo , Gewald Heiko , Weitzel Tim
Published: April 2021

The study analyzes data collected in two case studies in the healthcare industry, which is characterized by a variety of social and technical elements forming an activity system where all elements interact with each other. The findings indicate that many problems emerging during the implementation of a health information system can be traced back to contradictions between elements of the activity systems that are created or amplified by the new IS. The authors find that some contradictions are latent and become salient when introducing a new IS, while other contradictions are (unintentionally) newly created. Also, the study shows that contradictions are more complex than hitherto assumed and often concern more than two elements of a healthcare activity system. In a similar vein, effective interventions geared toward countering these contradictions are found to account for additional complexity while not always achieving their goal. Drawing on activity theory, the authors develop a framework to coherently synthesize the findings. The study can help increase the understanding of the IS’s role within an activity system and help guide IS implementation projects aimed at avoiding unintended consequences.
Technology Law
Authors: Smith Marcus , Urbas Gregor
Published: April 2021

The regulation of technology is an important and topical area of law, relevant to almost all aspects of society. Technology Law: Australian and International Perspectives presents a thorough exploration of the new legal challenges created by evolving technologies, from the use of facial recognition technology in criminal investigations to the rise and regulation of cryptocurrencies. A well-written and fascinating introduction to technology law in Australia and internationally, Technology Law provides thorough coverage of the theoretical perspectives, legislation, cases and developing issues where technology and the law interact. The text covers data protection and privacy, healthcare technology, criminal justice technology, commercial transactions, cybercrime, social media and intellectual property, and canvasses the future of technology and technology law.
Written by leading experts in the field, Technology Law is an excellent resource for law students and legal professionals with an interest in the area.
Commentary on Thomas Aquinas's Treatise on Divine Law
Authors: Budziszewski J.
Published: April 2021

Thomas Aquinas's classic Treatise on Divine Law is brought to life in this illuminating line-by-line commentary, which acts as a sequel to Budziszewski's Commentary on Thomas Aquinas's Treatise on Law. In this new work, Budziszewski reinvestigates the theory of divine law in Aquinas's Summa Theologiae, exploring questions concerning faith and reason, natural law and revelation, the organization of human society, and the ultimate destiny of human life. This interdisciplinary text includes thorough explanations, applications to life, and ancillary discussions that open up Aquinas's dense body of work, which tends to demand a great deal from readers. More than a half-century has passed since the last commentary on Thomas Aquinas's view of these matters. Budziszewski fills this gap with his consideration of not only the medieval text under examination, but also its immediate relevance to contemporary thought and issues of the modern world.
Prioritizing studies of COVID-19 and lessons learned
Authors: Jayaweera Dushyantha , Flume Patrick A. , Singer Nora G. , Cohen Myron S. , Lachiewicz Anne M. , Cameron Amanda , Kumar Naresh , Thompson Joel , Cabrera Alyssa , Daudelin Denise , Shaker Reza , Bauer Philippe R
Published: April 2021

Introduction:

COVID-19 altered research in Clinical and Translational Science Award (CTSA) hubs in an unprecedented manner, leading to adjustments for COVID-19 research.

Methods:

CTSA members volunteered to conduct a review on the impact of CTSA network on COVID-19 pandemic with the assistance from NIH survey team in October 2020. The survey questions included the involvement of CTSAs in decision-making concerning the prioritization of COVID-19 studies. Descriptive and statistical analyses were conducted to analyze the survey data.

Results:

60 of the 64 CTSAs completed the survey. Most CTSAs lacked preparedness but promptly responded to the pandemic. Early disruption of research triggered, enhanced CTSA engagement, creation of dedicated research areas and triage for prioritization of COVID-19 studies. CTSAs involvement in decision-making were 16.75 times more likely to create dedicated diagnostic laboratories (95% confidence interval [CI] = 2.17–129.39; P < 0.01). Likewise, institutions with internal funding were 3.88 times more likely to establish COVID-19 dedicated research (95% CI = 1.12–13.40; P < 0.05). CTSAs were instrumental in securing funds and facilitating establishment of laboratory/clinical spaces for COVID-19 research. Workflow was modified to support contracting and IRB review at most institutions with CTSAs. To mitigate chaos generated by competing clinical trials, central feasibility committees were often formed for orderly review/prioritization.

Conclusions:

The lessons learned from the COVID-19 pandemic emphasize the pivotal role of CTSAs in prioritizing studies and establishing the necessary research infrastructure, and the importance of prompt and flexible research leadership with decision-making capacity to manage future pandemics.
Treatment of ice-shelf evolution combining flow and flexure
Authors: MacAyeal Douglas R. , Sergienko Olga V. , Banwell Alison F. , Macdonald Grant J. , Willis Ian C. , Stevens Laura A.
Published: April 2021

We develop a two-dimensional, plan-view formulation of ice-shelf flow and viscoelastic ice-shelf flexure. This formulation combines, for the first time, the shallow-shelf approximation for horizontal ice-shelf flow (and shallow-stream approximation for flow on lubricated beds such as where ice rises and rumples form), with the treatment of a thin-plate flexure. We demonstrate the treatment by performing two finite-element simulations: one of the relict pedestalled lake features that exist on some debris-covered ice shelves due to strong heterogeneity in surface ablation, and the other of ice rumpling in the grounding zone of an ice rise. The proposed treatment opens new venues to investigate physical processes that require coupling between the longitudinal deformation and vertical flexure, for instance, the effects of surface melting and supraglacial lakes on ice shelves, interactions with the sea swell, and many others.
Genetics of substance use disorders: a review
Authors: Deak Joseph D. , Johnson Emma C.
Published: April 2021

Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2= ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g.ADH1BandALDH2) affecting alcohol-related traits, and loci within theCHRNA5-CHRNA3-CHRNB4gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.
A self-learning finite element extraction system based on reinforcement learning
Authors: Pan Jie , Huang Jingwei , Wang Yunli , Cheng Gengdong , Zeng Yong
Published: April 2021

Automatic generation of high-quality meshes is a base of CAD/CAE systems. The element extraction is a major mesh generation method for its capabilities to generate high-quality meshes around the domain boundary and to control local mesh densities. However, its widespread applications have been inhibited by the difficulties in generating satisfactory meshes in the interior of a domain or even in generating a complete mesh. The element extraction method's primary challenge is to define element extraction rules for achieving high-quality meshes in both the boundary and the interior of a geometric domain with complex shapes. This paper presents a self-learning element extraction system, FreeMesh-S, that can automatically acquire robust and high-quality element extraction rules. Two central components enable the FreeMesh-S: (1) three primitive structures of element extraction rules, which are constructed according to boundary patterns of any geometric boundary shapes; (2) a novel self-learning schema, which is used to automatically define and refine the relationships between the parameters included in the element extraction rules, by combining an Advantage Actor-Critic (A2C) reinforcement learning network and a Feedforward Neural Network (FNN). The A2C network learns the mesh generation process through random mesh element extraction actions using element quality as a reward signal and produces high-quality elements over time. The FNN takes the mesh generated from the A2C as samples to train itself for the fast generation of high-quality elements. FreeMesh-S is demonstrated by its application to two-dimensional quad mesh generation. The meshing performance of FreeMesh-S is compared with three existing popular approaches on ten pre-defined domain boundaries. The experimental results show that even with much less domain knowledge required to develop the algorithm, FreeMesh-S outperforms those three approaches in essential indices. FreeMesh-S significantly reduces the time and expertise needed to create high-quality mesh generation algorithms.
Making space for resistance: the spatiality of popular protest in the late medieval Southern Low Countries
Authors: Serneels Hannah
Published: April 2021

Using several cities in the late medieval Southern Low Countries as a case-study, this article deals with the relation between urban space and different forms of political protest. Urban commoners were aware of the powerful symbolism of certain places in the late medieval city and used that to their advantage during large-scale revolts. Yet the use of space was not limited to the dramatic occupations during these revolts. This article uncovers a wide range of strategies and tactics that common people used to act within given spaces to make their resistance possible. A spatial analysis of several instances of large- and smaller-scale resistance shows that space was intrinsically connected with how and when any form of resistance developed in late medieval cities. As such, the article aims to contribute to the literature on the importance of space in late medieval urban politics, in which attention to smaller-scale practices has been very limited.
S3-Leitlinie „Screening, Diagnose und Behandlung alkoholbezogener Störungen“
Authors: Kiefer Falk , Batra Anil , Bischof Gallus , Funke Wilma , Lindenmeyer Johannes , Mueller Sebastian , Preuss Ulrich W. , Schäfer Martin , Thomasius Rainer , Veltrup Clemens , Weissinger Volker , Wodarz Norbert , Wurst Friedrich M. , AUD Leitliniengruppe , Hoffmann Sabine
Published: April 2021

Zusammenfassung. Zielsetzung: Alkoholkonsum ist in Deutschland mit erheblichen gesundheitlichen und wirtschaftlichen Folgen assoziiert. Neben der Prävention spielen die Früherkennung und differentielle Behandlung von Betroffenen eine bedeutende Rolle. Die Leitlinie „Screening, Diagnose und Behandlung alkoholbezogener Störungen“ bildet die Grundlage für die Versorgung betroffener Personen. Die regelmäßigen Updates implementieren evidenzbasiert den aktuellen Forschungsstand von Literatur und klinischer Expertise. Methodik: Unter Federführung der Deutschen Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) und der Deutschen Gesellschaft für Suchtforschung und Suchttherapie e. V. (DG-Sucht) wurde die S3-Leitlinie Alkohol von 2019–2020 in acht Arbeitsgruppen überarbeitet. Am strukturierten Konsensprozess zur Beratung der Empfehlungen beteiligten sich 35 Fachgesellschaften. Potentielle Interessenskonflikte wurden im Vorfeld erfragt, dokumentiert und in der Abstimmung der Empfehlungen berücksichtigt.: Die Leitlinie gibt Empfehlungen zu Screening und Kurzintervention für verschiedene Personengruppen, sowie zur Behandlung von Betroffenen in der akuten und postakuten Phase des Entzugs. Besondere Bedeutung kommt der Behandlung von komorbiden somatischen und psychischen Störungen zu. Außerdem wurden Empfehlungen für bestimmte Personengruppen (z. B. Kinder und Jugendliche, Schwangere) ausgesprochen und auf die deutsche Versorgungslandschaft adapiert.
A Model for Buoyant Tephra Plumes Coupled to Lava Fountains With an Application to the 29th of August 2011 Paroxysmal Eruption at Mount Etna, Italy
Authors: Snee E. , Degruyter W. , Bonadonna C. , Scollo S. , Rossi E. , Freret‐Lorgeril V.
Published: April 2021

Explosive basaltic eruptions pose significant threats to local communities, regional infrastructures and international airspace. They produce tephra plumes that are often associated with a lava fountain, complicating their dynamics. Consequently, source parameters cannot be easily constrained using traditional formulations. Particularly, mass flow rates (MFRs) derived from height observations frequently differ from field deposit‐derived MFRs. Here, we investigate this discrepancy using a novel integral plume model that explicitly accounts for a lava fountain, which is represented as a hot, coarse‐grained inner plume co‐flowing with a finer‐grained outer plume. The new model shows that a plume associated with a lava fountain has higher variability in rise height than a standard plume for the same initial MFR depending on initial conditions. The initial grain‐size distribution and the relative size of the lava fountain compared to the surrounding plume are primary controls on the final plume height as they determine the strength of coupling between the two plumes. We apply the new model to the August 29, 2011 paroxysmal eruption of Mount Etna, Italy. The modeled MFR profile indicates that the field‐derived MFR does not correspond to that at the vent, but rather the MFR just above the lava fountain top. High fallout from the lava fountain results in much of the erupted solid material not reaching the top of the plume. This material deposits to form the proximal cone rather than dispersing in the atmosphere. With our novel model, discrepancies between the two types of observation‐derived MFR can be investigated and understood.
Simultaneous Calibration of Hydrologic Model Structure and Parameters Using a Blended Model
Authors: Chlumsky Robert , Mai Juliane , Craig James R. , Tolson Bryan A.
Published: April 2021

The advent of hydrological modeling frameworks that support multiple model structures using the same software enables both model structure and model parameters to be calibrated and assessed. To date, the identification of optimal model structure has typically been performed manually. Here, a continuous (rather than discrete) treatment of model structure is used, which enables simultaneous automatic calibration of model structure and parameters using a conventional real‐valued decision variable optimization algorithm (the dynamically dimensioned search algorithm, DDS). The method, referred to herein as blended model structure calibration (BMSC), relies upon the calculation of each hydrologic flux (e.g., for infiltration) as a weighted average of fluxes generated from multiple process algorithm options. This method is applied to 12 lumped MOPEX catchment models and compared to the calibration of 108 fixed model structures, representing all possible permutations of fixed model structures with the given process options in this study. The BMSC method consistently identified near‐optimal model structure (as evaluated using average model rank performance) at significantly lower computational cost than calibrating the collective of fixed structure models. The BMSC method also provides a useful tool in identifying dominant processes and model structures in catchments.
Geomojis Translate Geoscience Across Any Language
Authors: Sever Megan
Published: April 2021

Newly created pictograms aim to easily communicate geoscience and geohazard terms.
LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target
Authors: Kang Xi , Li Weilin , Liu Weixin , Liang Han , Deng Jingyu , Wong Chi Chun , Zhao Sinan , Kang Wei , To Ka Fai , Chiu Philip Wai Yan , Wang Guiying , Yu Jun , Ng Enders Kwok Wai
Published: April 2021

Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.
Emulating the local Kuramoto model with an injection-locked photonic crystal laser array
Authors: Takemura Naotomo , Takata Kenta , Takiguchi Masato , Notomi Masaya
Published: April 2021

The Kuramoto model is a mathematical model for describing the collective synchronization phenomena of coupled oscillators. We theoretically demonstrate that an array of coupled photonic crystal lasers emulates the Kuramoto model with non-delayed nearest-neighbor coupling (the local Kuramoto model). Our novel strategy employs indirect coupling between lasers via additional cold cavities. By installing cold cavities between laser cavities, we avoid the strong coupling of lasers and realize ideal mutual injection-locking with effective non-delayed dissipative coupling. First, after discussing the limit cycle interpretation of laser oscillation, we demonstrate the synchronization of two indirectly coupled lasers by numerically simulating coupled-mode equations. Second, by performing a phase reduction analysis, we show that laser dynamics in the proposed device can be mapped to the local Kuramoto model. Finally, we briefly demonstrate that a chain of indirectly coupled photonic crystal lasers actually emulates the one-dimensional local Kuramoto chain. We also argue that our proposed structure, which consists of periodically aligned cold cavities and laser cavities, will best be realized by using state-of-the-art buried multiple quantum well photonic crystals.
Risk factors for poor outcome in childhood tuberculous meningitis
Authors: Wang Mao-Shui , Zhao Mei , Liu Xin-Jie
Published: April 2021

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment.
Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient’s lung cells
Authors: George Bijesh , Amjesh Revikumar , Paul Aswathy Mary , Santhoshkumar T. R. , Pillai Madhavan Radhakrishna , Kumar Rakesh
Published: April 2021

Although a defective vitamin D endocrine system has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D endocrine system and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D endocrine system in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes, as potentially modulated by vitamin D endocrine system, were identified in transcriptomic datasets from patient’s cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D endocrine system in SARS-CoV-2-infected cells. Protein–protein interaction network of differentially expressed vitamin D-modulated genes were enriched in the immune system, NF-κB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results presented here povide computational evidence to implicate a dysregulated vitamin D endocrine system in the pathobiology of SARS-CoV-2 infection.
Path integral implementation of relational quantum mechanics
Authors: Yang Jianhao M.
Published: April 2021

Relational formulation of quantum mechanics is based on the idea that relational properties among quantum systems, instead of the independent properties of a quantum system, are the most fundamental elements to construct quantum mechanics. In a recent paper (Yang in Sci Rep 8:13305, 2018), basic relational quantum mechanics framework is formulated to derive quantum probability, Born’s Rule, Schrödinger Equations, and measurement theory. This paper further extends the reformulation effort in three aspects. First, it gives a clearer explanation of the key concepts behind the framework to calculate measurement probability. Second, we provide a concrete implementation of the relational probability amplitude by extending the path integral formulation. The implementation not only clarifies the physical meaning of the relational probability amplitude, but also allows us to elegantly explain the double slit experiment, to describe the interaction history between the measured system and a series of measuring systems, and to calculate entanglement entropy based on path integral and influence functional. In return, the implementation brings back new insight to path integral itself by completing the explanation on why measurement probability can be calculated as modulus square of probability amplitude. Lastly, we clarify the connection between our reformulation and the quantum reference frame theory. A complete relational formulation of quantum mechanics needs to combine the present works with the quantum reference frame theory.
Topical administration of the kappa opioid receptor agonist nalfurafine suppresses corneal neovascularization and inflammation
Authors: Shokirova Hurramhon , Inomata Takenori , Saitoh Tsuyoshi , Zhu Jun , Fujio Kenta , Okumura Yuichi , Yanagawa Ai , Fujimoto Keiichi , Sung Jaemyoung , Eguchi Atsuko , Miura Maria , Nagino Ken , Hirosawa Kunihiko , Kuwahara Mizu , Akasaki Yasutsugu , Nagase Hiroshi , Murakami Akira
Published: April 2021

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans.