bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association Between Generalized Anxiety Disorder and Resting-State Prefrontal Cortex Oxygenation Is Modified by Self-Reported Physical Activity: Results From The Irish Longitudinal Study on Ageing
Authors: McDowell Cillian P , Newman Louise , Monroe Derek C , O’Connor John D , Knight Silvin P , Kenny Rose Anne , Herring Matt P
Published: March 2021

Individuals with anxiety disorders exhibit lower intrinsic functional connectivity between prefrontal cortical areas and subcortical regions. The prefrontal cortex (PFC) is sensitive to the acute and chronic effects of physical activity (PA), while the anxiolytic effects of PA are well known. The current study examined the association of generalized anxiety disorder (GAD) and its interaction with PA, with resting-state, left PFC oxygenation. This cross-sectional study used data from participants (N = 2444) from The Irish Longitudinal Study on Ageing, a nationally representative prospective study of community-living adults aged 50 and older in Ireland. The Composite International Diagnostic Interview Short-Form determined fulfillment of criteria for GAD. The short-form International Physical Activity Questionnaire determined adherence to the World Health Organization PA guidelines. Resting-state, left PFC oxygenation was continuously measured via a Portalite. Tissue saturation index (TSI) was calculated as the ratio of oxygenated hemoglobin to total tissue hemoglobin (expressed as a percentage) for the final minute of a 5-minute supine-rest period. Multivariable linear regression quantified associations of GAD with TSI in the total population and population stratified by PA status. Participants with GAD had lower TSI (b = −1.416, p = .008) compared to those without GAD. However, this association was modified by PA. Among participants who met the PA guidelines, TSI did not differ according to GAD status (b = −0.800, p = .398). For participants who did not meet the guidelines, TSI was significantly lower among those with GAD (b = −1.758, p = .004). These findings suggest that PA may help to protect brain health among older adults with GAD.
“Don’t Talk to Them About Goals of Care”: Understanding Disparities in Advance Care Planning
Authors: Ashana Deepshikha Charan , D’Arcangelo Noah , Gazarian Priscilla K , Gupta Avni , Perez Stephen , Reich Amanda J , Tjia Jennifer , Halpern Scott D , Weissman Joel S , Ladin Keren
Published: March 2021

Background

Structurally marginalized groups experience disproportionately low rates of advance care planning (ACP). To improve equitable patient-centered end-of-life care, we examine barriers and facilitators to ACP among clinicians as they are central participants in these discussions.

Method

In this national study, we conducted semi-structured interviews with purposively selected clinicians from 6 diverse health systems between August 2018 and June 2019. Thematic analysis yielded themes characterizing clinicians’ perceptions of barriers and facilitators to ACP among patients, and patient-centered ways of overcoming them.

Results

Among 74 participants, 49 (66.2%) were physicians, 16.2% were nurses, and 13.5% were social workers. Most worked in primary care (35.1%), geriatrics (21.1%), and palliative care (19.3%) settings. Clinicians most frequently expressed difficulty discussing ACP with certain racial and ethnic groups (African American, Hispanic, Asian, and Native American) (31.1%), non-native English speakers (24.3%), and those with certain religious beliefs (Catholic, Orthodox Jewish, and Muslim) (13.5%). Clinicians were more likely to attribute barriers to ACP completion to patients (62.2%), than to clinicians (35.1%) or health systems (37.8%). Three themes characterized clinicians’ difficulty approaching ACP (preconceived views of patients’ preferences, narrow definitions of successful ACP, and lack of institutional resources), while the final theme illustrated facilitators to ACP (acknowledging bias and rejecting stereotypes, mission-driven focus on ACP, and acceptance of all preferences).

Conclusions

Most clinicians avoided ACP with certain racial and ethnic groups, those with limited English fluency, and persons with certain religious beliefs. Our findings provide evidence to support development of clinician-level and institutional-level interventions and to reduce disparities in ACP.
Crustal Lg-wave attenuation in Southeast Asia and its implications for regional tectonic evolution
Authors: Luo Yi , Zhao Lian-Feng , Ge Zeng-Xi , Xie Xiao-Bi , Yao Zhen-Xing
Published: March 2021

The crustal attenuation structure can effectively reveal the rheology and thermal properties of different geological blocks, and can provide seismological constraints on regional tectonic evolution. Based on 11 306 vertical-component Lg-wave seismograms recorded at 111 broad-band stations from 891 crustal earthquakes that occurred between 1994 and 2020, a broad-band Lg-wave attenuation model is obtained for Southeast Asia. This study demonstrates the capability of applying crustal Lg-wave attenuation inversion in a complex region mixed with continents, islands and marginal seas. The resolution approaches 2° in most parts in the study region. Lg blockages are observed at places with sharp Moho depth changes. The resultant Q models are consistent with regional geologic structures provided by previous studies. Prominent low-attenuation anomalies are located in the Sundaland Core containing stable ancient crust, including Indochina, Malay Peninsula, East Sumatra, Sunda Shelf and Borneo Core. Regions with strong attenuation are associated with complex tectonic conditions, such as the Indo–Australian subduction zone, sutures in Sarawak and Sabah. The observed Lg-wave attenuation characteristics provide constraints on the tectonic affinities and evolutions of the geological blocks. The results show that the Borneo Core remained stable since its accretion with the Sundaland Core. Ancient blocks are characterized by weak Lg attenuation, whereas geologically younger terranes are often characterized by strong Lg attenuation, which can be exploited to better understand the separation and convergence of plates during the tectonic evolution.
Crystal rotations and alignment in spatially varying magma flows: 2-D examples of common subvolcanic flow geometries
Authors: Vachon Rémi , Bazargan Mohsen , Hieronymus Christoph F , Ronchin Erika , Almqvist Bjarne
Published: March 2021

Elongate inclusions immersed in a viscous fluid generally rotate at a rate that is different from the local angular velocity of the flow. Often, a net alignment of the inclusions develops, and the resulting shape preferred orientation of the particle ensemble can then be used as a strain marker that allows reconstruction of the fluid’s velocity field. Much of the previous work on the dynamics of flow-induced particle rotations has focused on spatially homogeneous flows with large-scale tectonic deformations as the main application. Recently, the theory has been extended to spatially varying flows, such as magma with embedded crystals moving through a volcanic plumbing system. Additionally, an evolution equation has been introduced for the probability density function of crystal orientations. Here, we apply this new theory to a number of simple, 2-D flow geometries commonly encountered in magmatic intrusions, such as flow from a dyke into a reservoir or from a reservoir into a dyke, flow inside an inflating or deflating reservoir, flow in a dyke with a sharp bend, and thermal convection in a magma chamber. The main purpose is to provide a guide for interpreting field observations and for setting up more complex flow models with embedded crystals. As a general rule, we find that a larger aspect ratio of the embedded crystals causes a more coherent alignment of the crystals, while it has only a minor effect on the geometry of the alignment pattern. Due to various perturbations in the crystal rotation equations that are expected in natural systems, we show that the time-periodic behaviour found in idealized systems is probably short-lived in nature, and the crystal alignment is well described by the time-averaged solution. We also confirm some earlier findings. For example, near channel walls, fluid flow often follows the bounding surface and the resulting simple shear flow causes preferred crystal orientations that are approximately parallel to the boundary. Where pure shear deformation dominates, there is a tendency for crystals to orient themselves in the direction of the greatest tensile strain rate. Where flow impinges on a boundary, for example in an inflating magma chamber or as part of a thermal convection pattern, the stretching component of pure shear aligns with the boundary, and the crystals orient themselves in that direction. In the field, this local pattern may be difficult to distinguish from a boundary-parallel simple shear flow. Pure shear also dominates along the walls of a deflating magma chamber and in places where the flow turns away from the reservoir walls, but in these locations, the preferred crystal orientation is perpendicular to the wall. Overall, we find that our calculated patterns of crystal orientations agree well with results from analogue experiments where similar geometries are available.
Interactive Exploration of Large-Scale UI Datasets with Design Maps
Authors: Leiva Luis A , Hota Asutosh , Oulasvirta Antti
Published: March 2021

Designers are increasingly using online resources for inspiration. How to best support design exploration without compromising creativity? We introduce and study Design Maps, a class of point-cloud visualizations that makes large user interface datasets explorable. Design Maps are computed using dimensionality reduction and clustering techniques, which we analyze thoroughly in this paper. We present concepts for integrating Design Maps into design tools, including interactive visualization, local neighborhood exploration and functionality to integrate existing solutions to the design at hand. These concepts were implemented in a wireframing tool for mobile apps, which was evaluated with actual designers performing realistic tasks. Overall, designers find Design Maps supporting their creativity (avg. CSI score of 74/100) and indicate that the maps producing consistent whitespacing within cloud points are the most informative ones.
Labour Rights in Special Economic Zones: Between Unilateralism and Transnational Law Diffusion
Authors: Cotula Lorenzo , Mouan Liliane
Published: March 2021

Special economic zones (SEZs) have spread rapidly over the past 20 years, including in many low- and middle-income countries keen to attract private investment for industrial development. But while much debate has focused on their economic performance and success factors and on links with the wider architecture of international economic law, there are enduring concerns over respect for labour rights in SEZs. These concerns are partly rooted in features of the legal regimes that underpin SEZs, such as arrangements that qualify the application of ordinary labour law, or ineffective systems to ensure compliance. This article discusses the law governing labour rights in SEZs, drawing on the case studies of Bangladesh, Ethiopia, and Kenya—three countries reflecting different generations of SEZ legislation, types of SEZs, and regulatory approaches. The article explores the complex interplay of different ‘unilateral’ and international legal regimes, the structural features that affect labour rights in SEZs, and possible ways forward for research and practice.
When Does Competition Become Conflict? Technology, Geography, and the Offense–Defense Balance
Authors: Blagden David
Published: March 2021

Is there a meaningful offense–defense balance of technological, geographical, and human factors that substantially affects war likelihood and severity? Key contemporary policy debates are certainly infused with the notion, from the dangers of crisis instability in East Asia to the possible first-move advantages of cyber weaponry. Defensive realist theory, meanwhile, raises the possibility of inferring intent from external posture choices. Yet for offensive realists, such signaling is a doomed hope, because of aggressors’ incentives to conceal their hostile intentions before turning extant military technology to offensive ends. This article suggests that both perspectives misstate the causal role of the offense–defense balance. Competition may be a general condition of international politics—but it only manifests itself as a military conflict, defined as “cold” or ultimately “hot” war, under certain conditions. Specifically, the feasibility of advancing political goals via aggression rests on prevailing military technology, taken in its geographical context—that is, offense–defense calculations. Via three sub-theoretical cases—the “stopping power of water,” conventional blitzkrieg, and nuclear counterforce innovation—the article shows that the offense–defense balance affects conflict likelihood and severity even within offensive realism, specifically by affecting deterrence prospects. But this does not mean, as defensive realism posits, that the distinguishability of defense dominance promises a route out of the security dilemma.
Toll-like receptor-7/8 agonist kill Leishmania amazonensis by acting as pro-oxidant and pro-inflammatory agent
Authors: Kaushik Deepender , Granato Juliana T , Macedo Gilson C , Dib Paula R B , Piplani Sakshi , Fung Johnson , da Silva Adilson D , Coimbra Elaine S , Petrovsky Nikolai , Salunke Deepak B
Published: March 2021

Objectives

Evaluation of the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists.

Methods

TLR7/8-active imidazoquinolines (2 and 3) were synthesized and assessed for activity against Leishmania amazonensis-intracellular amastigotes using mouse peritoneal macrophages. The production of reactive oxygen species (ROS), nitric oxide (NO) and cytokines was determined in infected and non-infected macrophages.

Key findings

The imidazoquinolines, 2 and 3, were primarily agonists of TLR7 with compound 3 also showing modest TLR8 activity. Docking studies showed them to occupy the same binding pocket on TLR7 and 8 as the known agonists, imiquimod and resiquimod. Compounds 2 and 3 inhibited the growth of L. amazonensis-intracellular amastigotes with the most potent compound (3, IC50 = 5.93 µM) having an IC50 value close to miltefosine (IC50 = 4.05 µM), a known anti-Leishmanial drug. Compound 3 induced macrophages to produce ROS, NO and inflammatory cytokines that likely explain the anti-Leishmanial effects.

Conclusions

This study shows that activating TLR7 using compounds 2 or 3 induces anti-Leishmanial activity associated with induction of free radicals and inflammatory cytokines able to kill the parasites. While 2 and 3 had a very narrow cytotoxicity window for macrophages, this identifies the possibility to further develop this chemical scaffold to less cytotoxic TLR7/8 agonist for potential use as anti-Leishmanial drug.
Neurological Deficits Following Carotid Endarterectomy
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

While carotid endarterectomy can be enormously effective in preventing recurrent stroke, this chapter illustrates the potential adverse effects of the procedure.
Monocular Visual Loss
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

When ophthalmological causes of monocular blindness have been excluded, retinal ischemia, ischemic optic neuritis, and demyelinating optic neuritis must be considered.
Cauda Equina Syndrome
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Key historical details and exam findings help point to cauda equina syndrome, which requires urgent attention. A review of the various causes and management are reviewed.
Rapidly Progressive Dementia
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Encephalopathy which presents subacutely with no other neurological findings, is daunting and includes rapid dementias and more indolent encephalitidies.
Acute Myopathy
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Myopathy is an underrecognized cause of weakness with a growing number of differential diagnoses. Expanded testing and treatment options make this disorder a don’t-miss diagnosis.
Recurring Transient Ischemic Attack
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

A review of transient ischemic attack, prediction of future stroke, and methods to reduce that risk, including carotid endarterectomy and stenting.
Intractable Migraine
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Migraine pain, particularly if long-lasting and accompanied by nausea can be disabling. Effective acute therapy includes intravenous neuroleptics and other medications.
Acute Stroke Up to 24 Hours
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

This case outlines the dramatic shift in the treatment of acute ischemic stroke and the updated time window for endovascular therapy.
Post-Cardiac Arrest Management
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Targeted temperature management is increasingly used for neuroprotection in patients who remain unresponsive after a cardiac arrest. The indications for this therapy and tools for prognostication are discussed.
Acute Migraine in a Child
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Childhood migraine differs from the adult version in some ways, and management also must be targeted specifically to the needs of children.
Concussion in an Adolescent
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

The epidemic of concussion is particularly poignant as it relates to children and adolescents. There is much yet to learn about the mechanisms and consequences of traumatic brain injury (TBI), but this case discussion attempts to codify a useful clinical approach.
Acute Stroke in an Adolescent
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Stroke is an important cause of morbidity and mortality in the young, with key considerations that differ from adults.
Impact of 3-deazapurine nucleobases on RNA properties
Authors: Bereiter Raphael , Himmelstoß Maximilian , Renard Eva , Mairhofer Elisabeth , Egger Michaela , Breuker Kathrin , Kreutz Christoph , Ennifar Eric , Micura Ronald
Published: March 2021

Deazapurine nucleosides such as 3-deazaadenosine (c3A) are crucial for atomic mutagenesis studies of functional RNAs. They were the key for our current mechanistic understanding of ribosomal peptide bond formation and of phosphodiester cleavage in recently discovered small ribozymes, such as twister and pistol RNAs. Here, we present a comprehensive study on the impact of c3A and the thus far underinvestigated 3-deazaguanosine (c3G) on RNA properties. We found that these nucleosides can decrease thermodynamic stability of base pairing to a significant extent. The effects are much more pronounced for 3-deazapurine nucleosides compared to their constitutional isomers of 7-deazapurine nucleosides (c7G, c7A). We furthermore investigated base pair opening dynamics by solution NMR spectroscopy and revealed significantly enhanced imino proton exchange rates. Additionally, we solved the X-ray structure of a c3A-modified RNA and visualized the hydration pattern of the minor groove. Importantly, the characteristic water molecule that is hydrogen-bonded to the purine N3 atom and always observed in a natural double helix is lacking in the 3-deazapurine-modified counterpart. Both, the findings by NMR and X-ray crystallographic methods hence provide a rationale for the reduced pairing strength. Taken together, our comparative study is a first major step towards a comprehensive understanding of this important class of nucleoside modifications.
The interplay of Western diet and binge drinking on the onset, progression, and outlook of liver disease
Authors: Skinner R Chris , Hagaman Joel A
Published: March 2021

Non-alcoholic fatty liver disease and alcoholic liver disease, the two most prevalent liver diseases worldwide, share a common pathology but have largely been considered disparate diseases. Liver diseases are widely underestimated, but their prevalence is increasing worldwide. The Western diet (high-fat, high-sugar) and binge drinking (rapid consumption of alcohol in a short period of time) are two highly prevalent features of standard life in the United States, and both are linked to the development and progression of liver disease. Yet, few studies have been conducted to elucidate their potential interactions. Data shows binge drinking is on the rise in several age groups, and poor dietary trends continue to be prevalent. This review serves to summarize the sparse findings on the hepatic consequences of the combination of binge drinking and consuming a Western diet, while also drawing conclusions on potential future impacts. The data suggest the potential for a looming liver disease epidemic, indicating that more research on its progression as well as its prevention is needed on this critical topic.
Conscience and the Burden Inquiry—What Should Be Investigated in Exemption Cases, and Why?
Authors: Ciszewski Wojciech
Published: March 2021

The article focuses on a crucial segment of a discussion regarding the legitimacy of conscientious exemptions, namely the burden inquiry. The controversy around this issue involves different ways of identifying the proper object of the inquiry, and the types of evidence that should be considered in the assessment. I claim that there are three main approaches in the discussion regarding these issues: the incommensurable religious costs account, the subjective religious costs account, and the objective religious costs account. In the article, the peculiarity of each position is highlighted and the evaluation of main arguments is provided. I argue that the main justifications advanced for the incommensurable religious costs account and the subjective religious costs account do not stand up to critical scrutiny, and that the objective religious costs account is the most plausible position in this debate.
High-intensity short-duration grazing during spring is not an effective habitat management tool for Northern Bobwhites in Colorado
Authors: Behney Adam C
Published: March 2021

Many wildlife species, like Northern Bobwhite (Colinus virginianus), are reliant on periodic environmental disturbance to maintain heterogeneity in vegetation patterns. The Northern Bobwhite is a species of conservation concern requiring different vegetation types for nesting and brood-rearing stages, as well as for protection from predators and extreme weather. In northeastern Colorado, there are few management options to increase disturbance, other than domestic livestock grazing, to manage Northern Bobwhite habitat. As high-intensity short-duration grazing has shown promise as a mode of disturbance to manage Northern Bobwhite habitat in other regions, I used a randomized block design to test the effect of spring high-intensity short-duration grazing on Northern Bobwhites and their habitat in northeastern Colorado from 2016 to 2019. Specifically, I monitored Northern Bobwhite nest and brood survival and habitat selection in relation to grazing treatments over 3 years. I found that grazing had no effect on nest or brood survival or brood habitat selection, but Northern Bobwhites selected against grazed plots for nesting. Nest survival was negatively influenced by percent litter around the nest, and Northern Bobwhites selected nest sites with more grass cover and less bare ground. Broods selected habitat with less bare ground and more woody vegetation. Grazing affected vegetation immediately after grazing, but these effects weakened or disappeared by the end of the growing season. One exception to this overall pattern was forbs, which tended to be more abundant on grazed plots throughout the growing season. Overall, I found neutral effects of grazing on Northern Bobwhite nest and brood survival and habitat selection and neutral to positive benefits to the vegetation. Spring high-intensity short-duration grazing does not appear to be an effective tool to manage Northern Bobwhite nest or brood habitat in northeastern Colorado.
Article 310 TFEU
Authors: Killmann Bernd-Roland
Published: March 2021

Article 268 EC All items of revenue and expenditure of the Union shall be included in estimates to be drawn up for each financial year and shall be shown in the budget.
Recklessness
Authors: Hamer Kenneth
Published: March 2021

In 2000, B and R were practising as solicitors from premises in Watford, Hertfordshire. B was the sole equity partner and R was a salaried partner, having no managerial or administrative responsibilities. On 29 August 2000, the Forensic Investigation Unit of the Office for the Supervision of Solicitors (OSS) carried out an inspection of the firm’s books and accounts. Its report revealed a shortfall on clients’ funds of £46,971.57 as at 31 July 2000, of which £36,205.75 related to relatively small client ledger credit balances that had been improperly transferred to the office bank account. B gave evidence to the Solicitors Disciplinary Tribunal (SDT) that the firm’s new accountant had drawn attention to the credit balances on client account and said that, unless they were removed, he would not sign the accountant’s report. Accordingly, B caused lists to be prepared of the credit balances.
Patenting of Genes, Plants, and Animals
Authors: Grubb Philip W , Thomsen Peter R , Hoxie Tom , Wright Gordon
Published: March 2021

This chapter considers the law governing the patentability of human genes, plants, and animals. Here one can no longer stay at the objective level of scientific findings and patent laws, but must consider the broader issues of ethics, social policy, and politics. Many persons, for different reasons, are opposed to the granting of patents for living organisms; the same persons believe that someone who patents a human gene somehow acquires control of human life, or even of an individual from whose tissue the gene was isolated. Where the invention can be useful in the diagnosis or treatment of disease, the majority of the public may accept the need for such patents, but opposition to genetic modification of food crops and to patents on the resulting transgenic plants is more widespread.
Preparation and photocatalytic performance of metallic Nb0.9Ta0.1S2/2D-C3N4 composite
Authors: Chen Hanxiang , Yi Jianjian , Mo Zhao , Song Yanhua , Yang Wenshu , Liu Jingyuan , Zhu Xianglin , Li Huaming , Xu Hui
Published: March 2021

Photocatalysis technology has potential application in the field of energy and environment. How to expand visible light utilization and promote the separation efficiency of the carriers are the key issues for the high active photocatalysts preparation and future practical applications. In this work, a ternary metal sulfide Nb0.9Ta0.1S2 was prepared and used as an electron collector in the photocatalytic application. As a result, the generated electrons are quickly transferred to the surface of the composite to participate in the reaction. It was demonstrated that the photocatalytic activity of 2D-C3N4 was enhanced after the modification of Nb0.9Ta0.1S2. The Nb0.9Ta0.1S2/2D-C3N4 composite material was synthesized by solvothermal method. The composition of 5% Nb0.9Ta0.1S2/2D-C3N4 showed the highest H2 evolution rate of 1961.6 μmolg−1h−1, which was 6.6 times that of 2D-C3N4. The 15% Nb0.9Ta0.1S2/2D-C3N4 exhibited the best activity in Rhodamine B degradation rate of 97% in 2 h, which is 50% higher than that of 2D-C3N4. Nb0.9Ta0.1S2/2D-C3N4 can be used as electron trap to promote the effective separation of electron–hole pairs. This work provides benchmarks in exploring low-cost and efficient cocatalyst.
COVID-19 impact on learners: challenges and responses
Authors: del Castillo Fides A
Published: March 2021

The effects of coronavirus disease 2019 pandemic among the learners are shown in the rising cases of mental health issues. Young people are forced to stay at home and limit their physical and social interaction with peers. This paper contributes to address the well-being of the young learners.
Two-Dimensional Locally Nash Groups
Authors: Baro ElÍas , De Vicente Juan , Otero Margarita
Published: March 2021

We give a classification of connected abelian locally (real) Nash groups of dimension two. We first consider Painlevé’s description of meromorphic maps admitting an algebraic addition theorem and analyse the algebraic dependence of such maps. We then give a classification of connected abelian locally complex Nash groups of dimension two, from which we deduce the corresponding real classification. As a consequence, we obtain a classification of two-dimensional abelian irreducible algebraic groups defined over $\mathbb{R}$.
Willing, Caring and Capable: Gendered Ideals of Vernacular Preparedness in Finland
Authors: Hart Linda
Published: March 2021

This article analyzes women’s own emergency preparedness courses within voluntary defense training Finland as a site of “vernacular security”. The article introduces a subcategory of vernacular security, “vernacular preparedness” to illustrate what woman citizens familiar with voluntary defense training make of security and defense policies where they are seen as key actors in producing grass-roots security, both as private citizens and when serving state institutions. The interviewees, both participants and course leaders, situate themselves within a gendered division of security labor characterized by male conscription. This produces a civic ideal of a psychologically resilient, altruistically caring, and physically capable civilian whose preparedness covers concerns ranging from emergencies and disasters to potential wartime efforts.
Transcriptomic and Functional Analyses Reveal Roles of AclR, a luxR-type Global Regular, in Regulating Motility and Virulence of Acidovorax citrulli
Authors: Guan Wei , Wang Tielin , Huang Qi , Zhao Mei , Tian Eryuan , Liu Yanfeng , Liu Bo , Yang Yuwen , Zhao Tingchang
Published: March 2021

LuxR-type transcriptional regulators are essential for many physiological processes in bacteria, including pathogenesis. Acidovorax citrulli is a seedborne bacterial pathogen responsible for bacterial fruit blotch, which causes great losses in melon and watermelon worldwide. However, the LuxR-type transcriptional factors in A. citrulli have not been well studied, except for the previously reported LuxR-type regulatory protein, AcrR, involved in regulating virulence and motility. Here, we characterized a second LuxR-type regulator, AclR, in the group II strain Aac-5 of A. citrulli by mutagenesis, virulence and motility assays, and transcriptomic analysis. Deletion of aclR resulted in impaired twitching and swimming motility and flagellar formation and diminished virulence but increased biofilm formation. Transcriptomic analysis revealed that 1,379 genes were differentially expressed in the aclR mutant strain, including 29 genes involved in flagellar assembly and 3 involved in pili formation, suggesting a regulatory role for AclR in multiple important biological functions of A. citrulli. Together, our results not only indicate that AclR plays a global role in transcriptional regulation in A. citrulli influencing motility, biofilm formation, and virulence but also provide perspective regarding the regulatory network of biological functions in A. citrulli.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Three Common Symbiotic ABC Subfamily B Transporters inMedicago truncatulaAre Regulated by a NIN-Independent Branch of the Symbiosis Signaling Pathway
Authors: Roy Sonali , Breakspear Andrew , Cousins Donna , Torres-Jerez Ivone , Jackson Kirsty , Kumar Anil , Su Yangyang , Liu Cheng-Wu , Krom Nick , Udvardi Michael , Xu Ping , Murray Jeremy D.
Published: March 2021

Several ATP-binding cassette (ABC) transporters involved in the arbuscular mycorrhizal symbiosis and nodulation have been identified. We describe three previously unreported ABC subfamily B transporters, named AMN1, AMN2, and AMN3 (ABCB for mycorrhization and nodulation), that are expressed early during infection by rhizobia and arbuscular mycorrhizal fungi. These ABCB transporters are strongly expressed in symbiotically infected tissues, including in root-hair cells with rhizobial infection threads and arbusculated cells. During nodulation, the expression of these genes is highly induced by rhizobia and purified Nod factors and is dependent on DMI3 but is not dependent on other known major regulators of infection, such as NIN, NSP1, or NSP2. During mycorrhization their expression is dependent on DMI3 and RAM1 but not on NSP1 and NSP2. Therefore, they may be commonly regulated through a distinct branch of the common symbiotic pathway. Mutants with exonic Tnt1-transposon insertions were isolated for all three genes. None of the single or double mutants showed any differences in colonization by either rhizobia or mycorrhizal fungi, but the triple amn1 amn2 amn3 mutant showed an increase in nodule number. Further studies are needed to identify potential substrates of these transporters and understand their roles in these beneficial symbioses.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Sweet Taste Perceptions and Preferences May Not Be Associated With Food Intakes or Obesity
Authors: Kamil Alison , Wilson Alissa R.
Published: March 2021

The topic of sweet taste and the relationship to health is one that has been of interest to researchers for many years. Recently, reduced consumption of sweet-tasting foods and beverages, regardless of how they are sweetened (ie, caloric or low/no-calorie sweeteners), has been recommended by some health authorities to encourage reduced sugar consumption. The hypothesized rationale is that human attraction to sweetness could increase the risk of developing less healthy eating patterns. This article summarizes the work presented by Professors Appleton and de Graaf on the topics of sweet taste perceptions and preferences, food intakes and obesity, during an American Society for Nutrition webinar on July 28, 2020, and finds little evidence to support this hypothesis.
Current Use of Cosmetic Toxins to Improve Facial Aesthetics
Authors: Janes Lindsay E. , Connor Lauren M. , Moradi Amir , Alghoul Mohammed
Published: March 2021

Learning Objectives:

After studying this article, the participant should be able to: 1. Compare and contrast the various types of botulinum toxin on the market. 2. Appropriately select patients for treatment with cosmetic botulinum toxin. 3. Understand the common injection patterns for treating various regions of the face with cosmetic botulinum toxin. 4. List the complications associated with treating various regions of the face with cosmetic botulinum toxin.

Nonsurgical rejuvenation of the face with botulinum toxin is one of the most commonly performed procedures in the United States. This article reviews the current evidence in treating different regions of the face: upper face, lower face, masseter, and platysma. Dosing and complications associated with different facial regions are reviewed.
An Effective, Reproducible, and Cost-Effective Approach for Achieving Symmetry in Bicoronal Incisions in Pediatric Patients Undergoing Craniofacial Surgery
Authors: Adetayo Oluwaseun A. , Mountziaris Paschalia M. , Chattha Anmol , Nair Lakshmi , Adamo Matthew A.
Published: March 2021

Bicoronal incisions are frequently used for exposure and access to the craniofacial skeleton. A zigzag design is often used to camouflage the resultant scar. Often, free-hand zigzag drawings require several correction attempts to ensure symmetry because of the need for replication of multiple limbs of the bicoronal incision that need to be similar lengths, distance, and angles from each other. The authors present a novel technique using a template that rapidly and consistently achieves symmetric zigzag bicoronal incisions. The device is a hairstyling device that is inherently geometric in its design. Retrospective results of pediatric craniofacial patients from 2010 to 2018 are presented. Patients undergoing endoscopic reconstructions and patients who had prior operations at other institutions were excluded from the study. Fifty-two patients met inclusion criteria, with age at surgery ranging from 3 to 207 months (mean, 17 months). Follow-up ranged from 1 to 66 months (mean, 26 months). Data collected included demographics, type of surgery, and operative outcomes, including incision-related complications. Using this dynamic hairstyling device in a novel application as a template results in a fast, effective, and easily reproducible symmetric bicoronal zigzag incision in all cases. This technique eliminates the need for adjusting the length and angles of bicoronal incisions, and it can be adapted across a variety of head sizes and shapes in both pediatric and adult populations.
Uncertainty quantification in classical molecular dynamics
Authors: Wan Shunzhou , Sinclair Robert C. , Coveney Peter V.
Published: March 2021

Molecular dynamics simulation is now a widespread approach for understanding complex systems on the atomistic scale. It finds applications from physics and chemistry to engineering, life and medical science. In the last decade, the approach has begun to advance from being a computer-based means of rationalizing experimental observations to producing apparently credible predictions for a number of real-world applications within industrial sectors such as advanced materials and drug discovery. However, key aspects concerning the reproducibility of the method have not kept pace with the speed of its uptake in the scientific community. Here, we present a discussion of uncertainty quantification for molecular dynamics simulation designed to endow the method with better error estimates that will enable it to be used to report actionable results. The approach adopted is a standard one in the field of uncertainty quantification, namely using ensemble methods, in which a sufficiently large number of replicas are run concurrently, from which reliable statistics can be extracted. Indeed, because molecular dynamics is intrinsically chaotic, the need to use ensemble methods is fundamental and holds regardless of the duration of the simulations performed. We discuss the approach and illustrate it in a range of applications from materials science to ligand–protein binding free energy estimation.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
The fundamental principles of reproducibility
Authors: Gundersen Odd Erik
Published: March 2021

Reproducibility is a confused terminology. In this paper, I take a fundamental view on reproducibility rooted in the scientific method. The scientific method is analysed and characterized in order to develop the terminology required to define reproducibility. Furthermore, the literature on reproducibility and replication is surveyed, and experiments are modelled as tasks and problem solving methods. Machine learning is used to exemplify the described approach. Based on the analysis, reproducibility is defined and three different degrees of reproducibility as well as four types of reproducibility are specified.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Collective knowledge: organizing research projects as a database of reusable components and portable workflows with common interfaces
Authors: Fursin Grigori
Published: March 2021

This article provides the motivation and overview of the Collective Knowledge Framework (CK or cKnowledge). The CK concept is to decompose research projects into reusable components that encapsulate research artifacts and provide unified application programming interfaces (APIs), command-line interfaces (CLIs), meta descriptions and common automation actions for related artifacts. The CK framework is used to organize and manage research projects as a database of such components. Inspired by the USB ‘plug and play’ approach for hardware, CK also helps to assemble portable workflows that can automatically plug in compatible components from different users and vendors (models, datasets, frameworks, compilers, tools). Such workflows can build and run algorithms on different platforms and environments in a unified way using the customizable CK program pipeline with software detection plugins and the automatic installation of missing packages. This article presents a number of industrial projects in which the modular CK approach was successfully validated in order to automate benchmarking, auto-tuning and co-design of efficient software and hardware for machine learning and artificial intelligence in terms of speed, accuracy, energy, size and various costs. The CK framework also helped to automate the artifact evaluation process at several computer science conferences as well as to make it easier to reproduce, compare and reuse research techniques from published papers, deploy them in production, and automatically adapt them to continuously changing datasets, models and systems. The long-term goal is to accelerate innovation by connecting researchers and practitioners to share and reuse all their knowledge, best practices, artifacts, workflows and experimental results in a common, portable and reproducible format at
cKnowledge.io
.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantification
in silico
’.
VECMAtk: a scalable verification, validation and uncertainty quantification toolkit for scientific simulations
Authors: Groen D. , Arabnejad H. , Jancauskas V. , Edeling W. N. , Jansson F. , Richardson R. A. , Lakhlili J. , Veen L. , Bosak B. , Kopta P. , Wright D. W. , Monnier N. , Karlshoefer P. , Suleimenova D. , Sinclair R. , Vassaux M. , Nikishova A. , Bieniek M. , Luk Onnie O. , Kulczewski M. , Raffin E. , Crommelin D. , Hoenen O. , Coster D. P. , Piontek T. , Coveney P. V.
Published: March 2021

We present the VECMA toolkit (VECMAtk), a flexible software environment for single and multiscale simulations that introduces directly applicable and reusable procedures for verification, validation (V&V), sensitivity analysis (SA) and uncertainty quantication (UQ). It enables users to verify key aspects of their applications, systematically compare and validate the simulation outputs against observational or benchmark data, and run simulations conveniently on any platform from the desktop to current multi-petascale computers. In this sequel to our paper on VECMAtk which we presented last year [1] we focus on a range of functional and performance improvements that we have introduced, cover newly introduced components, and applications examples from seven different domains such as conflict modelling and environmental sciences. We also present several implemented patterns for UQ/SA and V&V, and guide the reader through one example concerning COVID-19 modelling in detail.

This article is part of the theme issue ‘Reliability and reproducibility in computational science: implementing verification, validation and uncertainty quantificationin silico’.
Whole-exome sequencing in 16,511 individuals reveals a role of the HTRA1 protease and its substrate EGFL8 in brain white matter hyperintensities
Authors: Malik Rainer , Beaufort Nathalie , Frerich Simon , Gesierich Benno , Georgakis Marios K , Rannikmäe Kristiina , Ferguson Amy C , Haffner Christof , Traylor Matthew , Ehrmann Michael , Sudlow Cathie LM , Dichgans Martin
Published: March 2021

White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on WMH volume, the contribution of rare variants to WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of WMH burden in the UK Biobank using publicly available whole-exome sequencing data (N=16,511) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level (c.691+2T>C, beta=-0.74, se=0.13, p=9.7E-9). Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 to associate with increased WMH volume (p=5.5E-6, FDR=0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; beta=0.79, se=0.14, p=9.4E-8). The frequency of such variants in the UK Biobank population was 1 in 450. WMH volume was brought forward by approximately 11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (beta=0.26, se=0.02, p=2.9E-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (beta=0.44, se=0.14, p=0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in a markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (p=1.5E-4, FDR=0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study (PheWAS) mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (OR=12.24, 95%CI [2.54-35.25], p=8.3E-5). Collectively, these findings highlight an important role of rare genetic variation and of the HTRA1 protease in determining WMH burden in the general population.
Some Mathematics for the Method of Pooled PCR Test
Authors: Otsu Nobuyuki ,   Honorable Researcher of AIST
Published: March 2021

At the time of the worldwide COVID-19 disaster, the author learned about the pooled (RT-) PCR test from the news. From the common sense of individual tests, the idea of mixing multiple samples seems taboo, however in fact many samples can be tested with a smaller number of tests by the method. As a retired researcher of mathematical engineering, the author was deeply interested in the idea and absorbed in the mathematical formulation and intensive analysis of the method.

Later, he found that the original basic equation was already proposed in the old (1943) treatise [1] and so many related research works have been done and available as materials on the web [2], although many of those seem to be based on qualitative or intuitive analysis. In that sense, some of the analysis here seems to be already known in the field, but some results might be novel, such as boundary conditions, derivation of limit values, estimation of infection rate and adaptive optimization scheme of pool test, strict extension to multi-stage pool test, and explicit derivation of asymptotic approximate solutions of optimal pooling number and achieved efficiency measure, etc.

In any case, he decided to put it together here as a material rather than a formal treatise, hoping that the results here would be useful for deeper mathematical insights into and better understanding of the pool inspection, and also in its actual practice.