bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of impurity seeding on the electron energy distribution function in the COMPASS divertor region
Authors: Dimitrova M , Popov Tsv K , Kovacic J , Dejarnac R , Gunn J P , Ivanova P , Imrisek M , Stöckel J , Vondracek P , Hron M , Panek R
Published: October 2020

In the COMPASS tokamak, series of experiments were performed aimed at studying the impact of nitrogen, neon, and argon impurity seeding on the electron energy distribution function (EEDF) in the divertor region. The experiments were conducted in D-shaped, L-mode, deuterium plasmas. In order to obtain the radial distribution of the floating potential, ion saturation current, electron temperatures, and densities, the current-voltage characteristics were measured by Langmuir probes embedded in the COMPASS tokamak divertor. The properties of the plasma in the divertor region were measured before and during impurity seeding. Before the N2 seeding, the EEDF was bi-Maxwellian with a low-energy electron fraction with temperatures 3.5–5 eV, and a higher-energy one with temperatures in the range of 10 eV to 23 eV. During seeding with an increasing number of molecules per second, the EEDF changed from bi-Maxwellian to Maxwellian and the electron temperature decreased. The time-evolution was studied of the change in the EEDF during N2 seeding. When the seeding was carried out by a valve in the private flux region, the duration of the transition from a bi-Maxwellian to a Maxwellian EEDF was about 10–15 ms. When the N2 seeding took place through a low-field side valve, the transition from a bi-Maxwellian to a Maxwellian EEDF took longer −25–45 ms. The temporal evolution was also analyzed of the plasma parameters’ radial profiles when neon and argon were puffed using a valve in the divertor low-field side. The application is discussed of the probe measurements’ results to calculating the parallel heat-flux densities in the divertor region of the COMPASS tokamak.
Spherical accretion flow onto general parameterized spherically symmetric black hole spacetimes *
Authors: Yang Sen , Liu Cheng , Zhu Tao , Zhao Li , Wu Qiang , Yang Ke , Jamil Mubasher
Published: October 2020

The transonic phenomenon of black hole accretion and the existence of the photon sphere characterize strong gravitational fields near a black hole horizon. Here, we study the spherical accretion flow onto general parametrized spherically symmetric black hole spacetimes. We analyze the accretion process for various perfect fluids, such as the isothermal fluids of ultra-stiff, ultra-relativistic, and sub-relativistic types, and the polytropic fluid. The influences of additional parameters, beyond the Schwarzschild black hole in the framework of general parameterized spherically symmetric black holes, on the flow behavior of the above-mentioned test fluids are studied in detail. In addition, by studying the accretion of the ideal photon gas, we further discuss the correspondence between the sonic radius of the accreting photon gas and the photon sphere for general parameterized spherically symmetric black holes. Possible extensions of our analysis are also discussed.
Relic density of asymmetric Dark Matter with Sommerfeld enhancement *
Authors: Abudurusuli Aihemaitijiang , Iminniyaz Hoernisa
Published: October 2020

We investigate the evolution of abundance of the asymmetric thermal Dark Matter when its annihilation rate at chemical decoupling is boosted by the Sommerfeld enhancement. Next, we discuss the effect of kinetic decoupling on the relic abundance of asymmetric Dark Matter when the interaction rate depends on velocity. Usually, the relic density of asymmetric Dark Matter is analyzed in the frame of chemical decoupling. Indeed, after decoupling from chemical equilibrium, asymmetric Dark Matter particles and anti-particles are still in kinetic equilibrium for a while. This has no effect for the case of s-wave annihilation since there is no temperature dependence in this case. However, kinetic decoupling has impacts for the case of p-wave annihilation and Sommerfeld enhanced s- and p-wave annihilations. We investigate in detail the extent to which kinetic decoupling affects the relic abundance of asymmetric Dark Matter particles and anti-particles. We find the constraints on the cross section and asymmetry factor using observational data of the relic density of Dark Matter.
The reversed field pinch
Authors: Marrelli L. , Martin P. , Puiatti M.E. , Sarff J.S. , Chapman B.E. , Drake J.R. , Escande D.F. , Masamune S.
Published: October 2020

This paper reviews the research on the reversed field pinch (RFP) in the last three decades. Substantial experimental and theoretical progress and transformational changes have been achieved since the last review (Bodin 1990 Nucl. Fusion
30 1717–37). The experiments have been performed in devices with different sizes and capabilities. The largest are RFX-mod in Padova (Italy) and MST in Madison (USA). The experimental community includes also EXTRAP-T2R in Sweden, RELAX in Japan and KTX in China. Impressive improvements in the performance are the result of exploration of two lines: the high current operation (up to 2 MA) with the spontaneous occurrence of helical equilibria with good magnetic flux surfaces and the active control of the current profile. A crucial ingredient for the advancements obtained in the experiments has been the development of state-of-art active feedback control systems allowing the control of MHD instabilities in presence of a thin shell. The balance between achievements and still open issues leads us to the conclusion that the RFP can be a valuable and diverse contributor in the quest for fusion electricity.
Adsorption kinetics feature extraction from breathprint obtained by graphene based sensors for diabetes diagnosis
Authors: Kalidoss Ramji , Umapathy Snekhalatha , Kothalam Radhakrishnan , Sakthivelu Uthvag
Published: October 2020

The correlation between blood glucose and breath acetone suggested by several studies has spurred the research community to develop an electronic (e-nose) for diabetes diagnosis. Herein, we have validated the in-house graphene based sensors with known acetone concentration. The sensor performances such as sensitivity, selectivity and stability (SSS) suggested their potential use in acquiring breath print. The 10% higher mean saturation voltage for 30 diabetic subjects ensured a discrimination accuracy of 65% with a positive correlation (r= 0.88) between biochemically measured and non-invasively estimated (glycated haemoglobin) HbA1c. For the improvement of classification rate, thirteen features associated with the adsorption kinetics were extracted from the breathprint from each of the three sensors. The features given as an input to the Naïve Bayes classification model fetched an accuracy of 68.33%. Elimination of redundant features by distinction index and one-R feature ranking algorithm results in Naïve Bayes algorithm with improved performances. The success rate has improved to 70% using the subset of features ranked by one-R algorithm. These results indicated the use of feature ranking algorithms and prediction models for the improvement in accuracy of our in-house fabricated graphene based sensors.
Terahertz surface plasmon propagation in a near field coupled asymmetric resonators based planar waveguide
Authors: Dhriti K M , Islam Maidul , Kumar Gagan
Published: October 2020

In this article, we investigate terahertz surface plasmons propagation in a planar waveguide comprising asymmetric resonators placed in close proximity. The waveguide is designed to support surface plasmon polaritons at two distinct terahertz frequencies, ω
1 and ω
2, which are near to each other. This is accomplished by carefully designing the unit cell comprising of two resonators with slightly different sizes. The resonators in the form of rectangular apertures are placed along the transverse direction in the near field regime. We observe an absorption window surrounded by two transmission resonances which are coupled to each other. As the resonators are moved apart, we observe a switching from the coupled to an uncoupled resonance state. The absorption window can be tuned by changing the resonance frequency of the resonators, which depends upon its structural parameters. We have employed a theoretical model to understand the coupling mechanism between the resonators and the dispersive behavior resulting in the absorption window. The proposed study is significant in the construction of planar terahertz components such as slow lights systems, buffers, etc, where strongly dispersive mediums play a vital role.
A method of depth extension in 3D shape measurement by geometric constraints
Authors: Lv Shenzhen , Zhang Yuyuan , Wang Jian , Sun Qiang
Published: October 2020

In this paper a new method to extend the measurement depth limited by geometric constraints for objects with large depth variances is presented. This method mainly includes the following steps: (1) using the watershed image segmentation algorithm to extract the correct part of the discontinuous absolute phase distribution obtained by geometric constraints, and making a binary mask of the correspondent region; (2) using the window Fourier filter-quality guided phase unwrapping algorithm to obtain the relative phase distribution of the tested object; (3) using the binary mask to get the difference between the relative and the absolute phases; (4) converting the relative phase distribution to absolute phase distribution by referring to their phase difference in the mask region. The experimental results prove the effectiveness and correctness of the proposed method.
Thermal stability of titanium hydride modified by the electrochemical deposition of titanium metal
Authors: Yastrebinsky R N , Pavlenko V I , Karnauhov A A , Cherkashina N I , Yastrebinskaya A V
Published: October 2020

This study aims to address the poor thermal stability of titanium hydride. Surface microstructural observations, differential thermal analysis, and electron-probe analysis of the thermal stability and phase composition measurements of a titanium hydride fraction that was modified by the electrochemical deposition of titanium metal are presented. It is demonstrated that the metallic titanium deposited on the surface of the fraction acts as an effective trap for hydrogen diffusion into the surface layers upon thermal heating. Modification of the surface of the titanium hydride fraction by electrochemical deposition of titanium metal increased its initial temperature of dehydrogenation by 231.8 °C. The concentration of the hydride phase at the surface layer at 500 °C increased to 87.2% due to the structural redistribution of atomic hydrogen and the hydrogenation of metallic titanium at the surface layer.
Joint Modeling of Individual Trajectories, Within-Individual Variability, and a Later Outcome: Systolic Blood Pressure Through Childhood and Left Ventricular Mass in Early Adulthood
Authors: Parker Richard M A , Leckie George , Goldstein Harvey , Howe Laura D , Heron Jon , Hughes Alun D , Phillippo David M , Tilling Kate
Published: October 2020

Within-individual variability of repeatedly measured exposures might predict later outcomes (e.g., blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP). Because 2-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modeling approach, examining associations of mean BP and BPV across childhood with left ventricular mass (indexed to height; LVMI) in early adulthood with data (collected 1990–2011) from the UK Avon Longitudinal Study of Parents and Children cohort. Using multilevel models, we allowed BPV to vary between individuals (a “random effect”) as well as to depend on covariates (allowing for heteroskedasticity). We further distinguished within-clinic variability (“measurement error”) from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher body weights, and in female participants and was positively correlated with mean BP. BPV had a weak positive association with LVMI (10% increase in within-individual BP variance was predicted to increase LVMI by 0.21%, 95% credible interval: −0.23, 0.69), but this association became negative (−0.78%, 95% credible interval: −2.54, 0.22) once the effect of mean BP on LVMI was adjusted for. This joint modeling approach offers a flexible method of relating repeatedly measured exposures to later outcomes.
The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid
Authors: de Sonnaville Sophia F A M , van Strien Miriam E , Middeldorp Jinte , Sluijs Jacqueline A , van den Berge Simone A , Moeton Martina , Donega Vanessa , van Berkel Annemiek , Deering Tasmin , De Filippis Lidia , Vescovi Angelo L , Aronica Eleonora , Glass Rainer , van de Berg Wilma D J , Swaab Dick F , Robe Pierre A , Hol Elly M
Published: October 2020

Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification. Cerebrospinal fluid (CSF) is an integral part of the neurogenic niche in development as it is in direct contact with radial glial cells, and it is important in regulating proliferation and migration. Yet, the effect of CSF on neural stem cells in the subventricular zone of the adult human brain is unknown. We hypothesized a persistent stimulating effect of ventricular CSF on neural stem cells in adulthood, based on the literature, describing bulging accumulations of subventricular cells where CSF is in direct contact with the subventricular zone. Here, we show by immunohistochemistry on post-mortem adult human subventricular zone sections that neural stem cells are in close contact with CSF via protrusions through both intact and incomplete ependymal layers. We are the first to systematically quantify subventricular glial nodules denuded of ependyma and consisting of proliferating neural stem and progenitor cells, and showed that they are present from foetal age until adulthood. Neurosphere, cell motility and differentiation assays as well as analyses of RNA expression were used to assess the effects of CSF of adult humans on primary neural stem cells and a human immortalized neural stem cell line. We show that human ventricular CSF increases proliferation and decreases motility of neural stem cells. Our results also indicate that adult CSF pushes neural stem cells from a relative quiescent to a more active state and promotes neuronal over astrocytic lineage differentiation. Thus, CSF continues to stimulate neural stem cells throughout aging.
Temporally Distinct Roles for the Zinc Finger Transcription Factor Sp8 in the Generation and Migration of Dorsal Lateral Ganglionic Eminence (dLGE)-Derived Neuronal Subtypes in the Mouse
Authors: Kuerbitz J , Madhavan M , Ehrman L A , Kohli V , Waclaw R R , Campbell K
Published: October 2020

Progenitors in the dorsal lateral ganglionic eminence (dLGE) are known to give rise to olfactory bulb (OB) interneurons and intercalated cells (ITCs) of the amygdala. The dLGE enriched transcription factor Sp8 is required for the normal generation of ITCs as well as OB interneurons, particularly the calretinin (CR)-expressing subtype. In this study, we used a genetic gain-of-function approach in mice to examine the roles Sp8 plays in controlling the development of dLGE-derived neuronal subtypes. Misexpression of Sp8 throughout the ventral telencephalic subventricular zone (SVZ) from early embryonic stages, led to an increased generation of ITCs which was dependent on Tshz1 gene dosage. Additionally, Sp8 misexpression impaired rostral migration of OB interneurons with clusters of CR interneurons seen in the SVZ along with decreased differentiation of calbindin OB interneurons. Sp8 misexpression throughout the ventral telencephalon also reduced ventral LGE neuronal subtypes including striatal projection neurons. Delaying Sp8 misexpression until E14–15 rescued the striatal and amygdala phenotypes but only partially rescued OB interneuron reductions, consistent with an early window of striatal and amygdala neurogenesis and ongoing OB interneuron generation at this late stage. Our results demonstrate critical roles for the timing and neuronal cell-type specificity of Sp8 expression in mouse LGE neurogenesis.
Black–White Disparities in Social and Behavioral Determinants of Health Index and Their Associations with Self-rated Health and Functional Limitations in Older Adults
Authors: Rhee Taeho Greg , Lee Kathy , Schensul Jean J
Published: October 2020

Background

To characterize cumulative risk scores of social and behavioral determinants of health (SDoH) and examine their association with self-rated general health and functional limitations between non-Hispanic black and white older adults in the United States.

Method

We used data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), with a nationally representative sample of black and white adults aged 65 or older (n = 954 unweighted). We quantified the cumulative risk scores of SDoH (eg, food insecurity, education and poverty), ranging from 0 (no risk at all) to 8 (highest risk), and used multivariable-adjusted logistic and Poisson regression analyses to assess the association of SDoH by racial group with self-rated health and functional limitations, adjusting for other covariates.

Results

Black older adults had a higher mean cumulative risk score than white counterparts (2.3 ± 2.1 vs 1.5 ± 1.0; p < .001). Black older adults were more likely to report lower self-rated health than white older adults in each of SDoH domains (p < .01 for each). In multivariable-adjusted analyses, black older adults were more likely to report lower self-rated health than white older adults (p < .01 for all) regardless of SDoH risk factors. However, those with high SDoH risk factors (ie, ≥3 risk factors) were more likely to report functional limitations than those in the low-risk group (ie, <3 risk factors) in both racial groups (p < .01 for all).

Conclusion

SDoH-related black–white disparities remain persistent in older age. In particular, SDoH index scores for black and white older adults were differentially associated with functional limitations. Addressing SDoH should be an important consideration in reducing gaps in black–white disparities of functioning.
Exploring lectin–glycan interactions to combat COVID-19: Lessons acquired from other enveloped viruses
Authors: Nascimento da Silva Luís Cláudio , Mendonça Juliana Silva Pereira , de Oliveira Weslley Felix , Batista Karla Lílian Rodrigues , Zagmignan Adrielle , Viana Isabelle Freire Tabosa , dos Santos Correia Maria Tereza
Published: October 2020

The emergence of a new human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed great pressure on the health system worldwide. The presence of glycoproteins on the viral envelope opens a wide range of possibilities for the application of lectins to address some urgent problems involved in this pandemic. In this work, we discuss the potential contributions of lectins from nonmammalian sources in the development of several fields associated with viral infections, most notably COVID-19. We review the literature on the use of nonmammalian lectins as a therapeutic approach against members of the Coronaviridae family, including recent advances in strategies of protein engineering to improve their efficacy. The applications of lectins as adjuvants for antiviral vaccines are also discussed. Finally, we present some emerging strategies employing lectins for the development of biosensors, microarrays, immunoassays and tools for purification of viruses from whole blood. Altogether, the data compiled in this review highlight the importance of structural studies aiming to improve our knowledge about the basis of glycan recognition by lectins and its repercussions in several fields, providing potential solutions for complex aspects that are emerging from different health challenges.
Whole exome sequencing reveals pathogenic variants inMYO3A,MYO15AandCOL9A3and differential frequencies in ancestral alleles in hearing impairment genes among individuals from Cameroon
Authors: Wonkam Ambroise , Manyisa Noluthando , Bope Christian D , Dandara Collet , Chimusa Emile R
Published: October 2020

There is scarcity of known gene variants of hearing impairment (HI) in African populations. This knowledge deficit is ultimately affecting the development of genetic diagnoses. We used whole exome sequencing to investigate gene variants, pathways of interactive genes and the fractions of ancestral overderived alleles for 159 HI genes among 18 Cameroonian patients with non-syndromic HI (NSHI) and 129 ethnically matched controls. Pathogenic and likely pathogenic (PLP) variants were found in MYO3A, MYO15A and COL9A3, with a resolution rate of 50% (9/18 patients). The study identified significant genetic differentiation in novel population-specific gene variants at FOXD4L2, DHRS2L6, RPL3L and VTN between HI patients and controls. These gene variants are found in functional/co-expressed interactive networks with other known HI-associated genes and in the same pathways with VTN being a hub protein, that is, focal adhesion pathway and regulation of the actin cytoskeleton (P-values <0.05). The results suggest that these novel population-specific gene variants are possible modifiers of the HI phenotypes. We found a high proportion of ancestral allele versus derived at low HI patients-specific minor allele frequency in the range of 0.0–0.1. The results showed a relatively low pickup rate of PLP variants in known genes in this group of Cameroonian patients with NSHI. In addition, findings may signal an evolutionary enrichment of some variants of HI genes in patients, as the result of polygenic adaptation, and suggest the possibility of multigenic influence on the phenotype of congenital HI, which deserves further investigations.
Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye
Authors: Sun Wesley R , Ramirez Sara , Spiller Kelly E , Zhao Yan , Fuhrmann Sabine
Published: October 2020

Uveal coloboma represents one of the most common congenital ocular malformations accounting for up to 10% of childhood blindness (~1 in 5000 live birth). Coloboma originates from defective fusion of the optic fissure (OF), a transient gap that forms during eye morphogenesis by asymmetric, ventral invagination. Genetic heterogeneity combined with the activity of developmentally regulated genes suggests multiple mechanisms regulating OF closure. The tumor suppressor and FERM domain protein Neurofibromin 2 (NF2) controls diverse processes in cancer, development and regeneration, via Hippo pathway and cytoskeleton regulation. In humans, NF2 mutations can cause ocular abnormalities, including coloboma, however, its actual role in OF closure is unknown. Using conditional inactivation in the embryonic mouse eye, our data indicate that loss of Nf2 function results in a novel underlying cause for coloboma. In particular, mutant eyes show substantially increased retinal pigmented epithelium (RPE) proliferation in the fissure region with concomitant acquisition of RPE cell fate. Cells lining the OF margin can maintain RPE fate ectopically and fail to transition from neuroepithelial to cuboidal shape. In the dorsal RPE of the optic cup, Nf2 inactivation leads to a robust increase in cell number, with local disorganization of the cytoskeleton components F-actin and pMLC2. We propose that RPE hyperproliferation is the primary cause for the observed defects causing insufficient alignment of the OF margins in Nf2 mutants and failure to fuse properly, resulting in persistent coloboma. Our findings indicate that limiting proliferation particularly in the RPE layer is a critical mechanism during OF closure.
R&D collaborations along the industry life cycle: the case of German photovoltaics manufacturer
Authors: Hipp Ann
Published: October 2020

Industrial evolution prompts firms to enter into R&D collaborations to ensure competitiveness and substantial growth. This study expands the industry life cycle concept to include the extent and types of R&D collaborations. I analyze 6581 R&D collaborations by 60 manufacturers in the German photovoltaics (PV) industry from 1980 to 2016 using a negative binomial regression model. The results indicate that the number of R&D collaborations is higher in the post-shakeout than in the pre-shakeout period of an industry. While this is particularly true for science-based R&D collaborations with universities and public research organizations, market-based R&D collaborations evolve from predominantly competitors before an industry’s shakeout to suppliers and customers after a shakeout has occurred.
Optimal shape of the harvest control rule for different fishery management objectives
Authors: Yagi Tatsunori , Yamakawa Takashi
Published: October 2020

To determine the optimal shape of the harvest control rule (HCR) achieving common fisheries management objectives (maximizing the average catch, reducing the deviation of yields, and avoiding stock collapse) and ensure robustness to observation errors, we estimate the optimal values of biological reference points (BRPs) composing the HCR. While traditional HCRs usually consist of three BRPs based on the fishing mortality coefficient (F3-HCR), we introduce an alternative HCR defined by 21 BRPs based on the catch levels (C21-HCR) to cover various possible shapes of HCR including smooth ones. We compare the shape and the performance between the optimal C21-HCR and the optimal F3-HCR and conclude that the optimal HCR can be composed of the gradual combination of the basic strategies: the constant escapement strategy, the constant harvest rate (CHR) strategy, and the constant catch strategy. However, the current F3-HCR does not necessarily allow this combination and generally returns lower performance levels than the optimal C21-HCR (since the basic strategy is confined to CHR) excluding the range of low biomass. This result will provide a clear perspective to improve HCR according to the magnitude of assessment errors and to compromise multiple fisheries management objectives when various stakeholders are involved.
Convective and absolute instability of falling viscoelastic liquid jets surrounded by a gas
Authors: Alhushaybari A , Uddin J
Published: October 2020

We examine the convective and absolute instability of a 2D axisymmetric viscoelastic liquid jet falling vertically in a medium of an inviscid gas under the influence of gravity. We use the upper-convected Maxwell model to describe the viscoelastic liquid jet and together with an asymptotic approach, based on the slenderness of the jet, we obtain steady-state solutions. By considering travelling wave modes, and using linear instability analysis, the dispersion relation, relating the frequency to wavenumber of disturbances, is derived. We solve this dispersion relation numerically using the Newton–Raphson method and explore regions of instability in parameter space. In particular, we investigate the influence of gravity, the effect of changing the gas-to-liquid density ratio, the Weber number and the Deborah number on convective and absolute instability. In this paper, we utilize a mapping technique developed by Afzaal (2014, Breakup and instability analysis of compound liquid jets. Doctoral Dissertation, University of Birmingham) to find the cusp point in the complex frequency plane and its corresponding first-order saddle point (the pinch point) in the complex wavenumber plane for absolute instability. The convective/absolute instability boundary is identified for various parameter regimes along the axial length of the jet.
Analytic Sensitivity of 3 Nucleic Acid Detection Assays in Diagnosis of SARS-CoV-2 Infection
Authors: Sieker Jakob T , Horowitz Coby , Hu Cheng-Tsung K , Lacombe-Daphnis Meriane , Chirokas Bernadette , Pina Coteia , Heger Nicholas E , Rabson Arthur R , Zhou Ming , Bogen Steven A , Horowitz Gary L
Published: October 2020

Background

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription PCR is the primary method to diagnose coronavirus disease 2019 (COVID-19). However, the analytic sensitivity required is not well defined and it is unclear how available assays compare.

Methods

For the Abbott RealTime SARS-CoV-2 assay (m2000; Abbott Molecular), we determined that it could detect viral concentrations as low as 26 copies/mL, we defined the relationship between cycle number and viral concentrations, and we tested naso- and oropharyngeal swab specimens from 8538 consecutive individuals. Using the m2000 as a reference assay method, we described the distribution of viral concentrations in these patients. We then used selected clinical specimens to determine the positive percent agreement of 2 other assays with more rapid turnaround times [Cepheid Xpert Xpress (GeneXpert; Cepheid); n = 27] and a laboratory developed test on the Luminex ARIES system [ARIES LDT (Luminex); n = 50] as a function of virus concentrations, from which we projected their false-negative rates in our patient population.

Results

SARS-CoV-2 was detected in 27% (95% CI: 26%–28%) of all specimens. Estimated viral concentrations were widely distributed, and 17% (95% CI: 16%–19%) of positive individuals had viral concentrations <845 copies/mL. Positive percent agreement was strongly related to viral concentration, and reliable detection (i.e., ≥95%) was observed at concentrations >100 copies/mL for the GeneXpert but not the ARIES LDT, corresponding to projected false-negative rates of 4% (95% CI: 0%–21%) and 27% (95% CI: 11%–46%), respectively.

Conclusions

Substantial proportions of clinical specimens have low to moderate viral concentrations and may be missed by methods with less analytic sensitivity.
Orofacial dyskinesia post resection of pineal gland tumor
Authors: Yazbeck Mohamad , Dabboucy Baraa , Comair Youssef
Published: October 2020

We reported a case of a 33-year-old lady who was diagnosed with a Pineal tumor and underwent craniotomy and gross total surgical resection of the mass through a right occipital transtentorial approach. Immediately upon extubation, the patient started to have persistent chewing-like movements typical of orofacial dyskinesia that resulted later in buccal mucosal injury and swelling of the lips. The movements spontaneously resolved after 3 days. The patient was not taking any medications that were known to induce such movements. Literature review showed that one of the possible mechanisms could be that the suddenly reduced melatonin level in the acute postoperative period leads to dysregulation of dopamine secretion in the nigrostriatal and limbic system causing these abnormal movements. To the best of our knowledge, this is the first such reported complication of orofacial dyskinesia post craniotomy for resection of the pineal tumor in humans.
Samurai and Southern Belles: Interracial Romance, Southern Morality, and the 1860 Japanese Embassy
Authors: Doan Natalia
Published: October 2020

The 1860 Japanese Embassy to the United States was the first diplomatic encounter between Japanese and American people on American soil, and sparked a whirlwind of national optimism and cultural fantasy that challenged the linked conceptions of race, masculinity, and power. In a time when interracial relationships were prohibited in much of the United States, seventeen-year-old samurai Tateishi Onojirō, nicknamed “Tommy,” and his rising count of love letters made headlines across America. This article argues that, in 1860, representations of the 1860 Japanese Embassy and Tateishi in daily Southern newspapers were used to further complicate the concept of Japanese masculinity and dramatize the differences between the American North and South. The perceived desirability of American women became a source of pride at the same time interracial encounters between American women and the Japanese embassy threatened American racial hierarchies. Examining how interactions between samurai diplomats and transnational actors challenged antebellum hierarchies of race, masculinity, and power expands the significance of the 1860 embassy to the study of gender and interracial romantic relations, the production of regional identity, and the influence of Tokugawa Japan on antebellum American identity formation.
Coordinated homeostasis of essential mineral nutrients: a focus on iron
Authors: Hanikenne Marc , Esteves Sara M , Fanara Steven , Rouached Hatem
Published: October 2020

In plants, iron (Fe) transport and homeostasis are highly regulated processes. Fe deficiency or excess dramatically limits plant and algal productivity. Interestingly, complex and unexpected interconnections between Fe and various macro- and micronutrient homeostatic networks, supposedly maintaining general ionic equilibrium and balanced nutrition, are currently being uncovered. Although these interactions have profound consequences for our understanding of Fe homeostasis and its regulation, their molecular bases and biological significance remain poorly understood. Here, we review recent knowledge gained on how Fe interacts with micronutrient (e.g. zinc, manganese) and macronutrient (e.g. sulfur, phosphate) homeostasis, and on how these interactions affect Fe uptake and trafficking. Finally, we highlight the importance of developing an improved model of how Fe signaling pathways are integrated into functional networks to control plant growth and development in response to fluctuating environments.
Low-Dose Activated Protein C Suppresses the Development of Cerebral Infarction and Neurological Deficits in Mice
Authors: Yamato Keiko , Nakajo Yukako , Yamamoto-Imoto Hitomi , Kokame Koichi , Miyata Toshiyuki , Takahashi Jun C , Kataoka Hiroharu , Yanamoto Hiroji
Published: October 2020

BACKGROUND

A large prospective study previously reported that a higher plasma level of protein C (PC) was associated with a lower incidence of ischemic stroke.

OBJECTIVE

To investigate the neuroprotective properties of activated PC (APC) against acute ischemic stroke using the 3-vessel occlusion model.

METHODS

Male C57BL/6J mice received APC (human APC) at 0.25, 0.5, or 1.0 (low dose) or 2.0, 4.0, or 8.0 mg/kg (high dose). Edaravone (Eda) (1.0, 3.0, or 10 mg/kg, a neuroprotectant approved for use in Japan), albumin (2.0 mg/kg), heparin (100 or 600 U/kg), or saline was used as the control. The drug or control was administered intravenously twice in the initial 24 h or 5 times in 3 d, starting 5 min after the induction of ischemia.

RESULTS

Low-dose APC significantly reduced lesion volumes, not affecting the depth of ischemia. High-dose APC did not significantly reduce lesion volumes, causing hemorrhagic transformation in some cases. In the chronic phase, lesion volumes were significantly suppressed in the APC or Eda group, and only the APC group showed a significant attenuation of neurological deficits. The protease-activated receptor (PAR)-1 antagonist SCH79797, administered during preischemia, completely abolished APC-induced neuroprotection. The overshoot-like abrupt recovery in regional cerebral blood flow observed in the control in the initial reperfusion phase was significantly suppressed by the APC treatment, indicating that the cerebral autoregulation system, consisting of endothelial cells and blood-brain barrier functions, was preserved.

CONCLUSION

Low-dose APC, potentially via the PAR-1-dependent anti-inflammatory cascade, protects the brain against ischemic stroke without increasing the risk of hemorrhagic transformation or death.
Optimizing Hepatitis C Virus (HCV) Treatment in a US Colocated HCV/Opioid Agonist Therapy Program
Authors: Habchi Jackie , Thomas Aurielle M , Sprecht-Walsh Sophie , Arias Elenita , Bratberg Jeffrey , Hurley Linda , Hart Susan , Taylor Lynn E
Published: October 2020

Background

A minority of patients with opioid use disorder are treated for hepatitis C virus infection (HCV). While colocated HCV and opioid agonist therapy (OAT) along with harm reduction can facilitate prevention and cascade to cure, there are few real-world examples of such embedded care models in the United States in the direct-acting antiviral (DAA) era.

Methods

We conducted a retrospective chart review to determine sustained virologic response (SVR) and reinfection rates during the first 5-year period of DAA availability among individuals tested and treated on-site at Rhode Island’s only nonprofit methadone maintenance program.

Results

Of 275 who initiated DAAs, the mean age (range) was 43 (22–71) years, 34.5% were female, 57.5% had genotype 1a, 23.3% had cirrhosis, and 92% were Medicaid recipients. SVR was 85.0% (232/273), while modified intent-to-treat SVR was 93.2% (232/249); 17 patients did not achieve SVR, 2 awaited SVR 12 weeks post-end-of-treatment, and 24 were lost to follow-up. Thirty reinfections were identified over 375.5 person-years of follow-up (rate, 7.99/100 person-years). The median time to first reinfection (interquartile range) was 128 (85.25–202.5) days. Before July 1, 2018, 72 patients accessed DAAs over 3.7 years; after Medicaid DAA restrictions were lifted, 109 patients accessed DAAs over 1.3 years. The Prior Authorization (PA) process requires many steps, differing across 11 RI insurers, taking 45–120 minutes per patient.

Conclusions

DAA treatment was effective among a marginalized population in an urban colocated OAT/HCV program. Removing DAA restrictions facilitates treatment initiation. The PA process remains a modifiable barrier to expanding capacity in the United States.
Remdesivir Use in Patients Requiring Mechanical Ventilation due to COVID-19
Authors: Lapadula Giuseppe , Bernasconi Davide Paolo , Bellani Giacomo , Soria Alessandro , Rona Roberto , Bombino Michela , Avalli Leonello , Rondelli Egle , Cortinovis Barbara , Colombo Enrico , Valsecchi Maria Grazia , Migliorino Guglielmo Marco , Bonfanti Paolo , Foti Giuseppe ,   Remdesivir-Ria Study Group, Gambaro Alessandra , Spolti Anna , Beretta Ilaria , Bisi Luca , Cappelletti Anna , Chiesa Elisabetta , Cogliandro Viola , Columpsi Paola , Foresti Sergio , Gustinetti Giulia , Iannuzzi Francesca , Pollastri Ester , Rossi Marianna , Sabbatini Francesca , Squillace Nicola , Ferlicca Daniela , Mauri Fabrizia , Giani Marco , Pozzi Matteo , Russotto Vincenzo , Gambaro Alessandra , Spolti Anna , Beretta Ilaria , Bisi Luca , Cappelletti Anna , Chiesa Elisabetta , Cogliandro Viola , Columpsi Paola , Foresti Sergio , Gustinetti Giulia , Iannuzzi Francesca , Pollastri Ester , Rossi Marianna , Sabbatini Francesca , Squillace Nicola , Ferlicca Daniela , Mauri Fabrizia , Giani Marco , Pozzi Matteo , Russotto Vincenzo
Published: October 2020

Background

Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain.

Methods

All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups.

Results

One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0–16] vs 5 [0–14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27–3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26–2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19–3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model.

Conclusions

In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.
Demographic and occupational determinants of anti-SARS-CoV-2 IgG seropositivity in hospital staff
Authors: Martin Christopher A , Patel Prashanth , Goss Charles , Jenkins David R , Price Arthur , Barton Linda , Gupta Pankaj , Zaccardi Francesco , Jerina Helen , Duraisingham Sai , Brunskill Nigel J , Khunti Kamlesh , Pareek Manish
Published: October 2020

Background

Although evidence suggests that demographic characteristics including minority ethnicity increase the risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is unclear whether these characteristics, together with occupational factors, influence anti-SARS-CoV-2 IgG seroprevalence in hospital staff.

Methods

We conducted cross-sectional surveillance examining seroprevalence of anti-SARS-CoV-2 IgG amongst staff at University Hospitals of Leicester (UHL) NHS Trust. We quantified seroprevalence stratified by ethnicity, occupation and seniority of practitioner and used logistic regression to examine demographic and occupational factors associated with seropositivity.

Results

A total of 1148/10662 (10.8%) hospital staff members were seropositive. Compared to White staff (seroprevalence 9.1%), seroprevalence was higher in South Asian (12.3%) and Black (21.2%) staff. The occupations and department with the highest seroprevalence were nurses/healthcare assistants (13.7%) and the Emergency Department (ED)/Acute Medicine (17.5%), respectively. Seroprevalence decreased with seniority in medical/nursing practitioners. Minority ethnicity was associated with seropositivity on an adjusted analysis (South Asian: aOR 1.26; 95%CI: 1.07–1.49 and Black: 2.42; 1.90–3.09). Anaesthetics/ICU staff members were less likely to be seropositive than ED/Acute medicine staff (0.41; 0.27–0.61).

Conclusions

Ethnicity and occupational factors, including specialty and seniority, are associated with seropositivity for anti-SARS-Cov-2 IgG. These findings could be used to inform occupational risk assessments for front-line healthcare workers.
Endotypes of primary osteoarthritis identified by plasma metabolomics analysis
Authors: Werdyani Salem , Liu Ming , Zhang Hongwei , Sun Guang , Furey Andrew , Randell Edward W , Rahman Proton , Zhai Guangju
Published: October 2020

Objective

To identify endotypes of osteoarthritis (OA) by a metabolomics analysis.

Methods

Study participants included hip/knee OA patients and controls. Fasting plasma samples were metabolomically profiled. Common factor analysis and K-means clustering were applied to the metabolomics data to identify the endotypes of OA patients. Logistic regression was utilized to identify the most significant metabolites contributing to the endotypes. Clinical and epidemiological factors were examined in relation to the identified OA endotypes.

Results

Six hundred and fifteen primary OA patients and 237 controls were included. Among the 186 metabolites measured, 162 passed the quality control analysis. The 615 OA patients were classified in three clusters (A, 66; B, 200; and C, 349). Patients in cluster A had a significantly higher concentration of butyrylcarnitine (C4) than other clusters and controls (all P < 0.0002). Elevated C4 is thought to be related to muscle weakness and wasting. Patients in cluster B had a significantly lower arginine concentration than other clusters and controls (all P < 7.98 × 10−11). Cluster C patients had a significantly lower concentration of lysophosphatidylcholine (with palmitic acid), which is a pro-inflammatory bioactive compound, than other clusters and controls (P < 3.79 × 10−6). Further, cluster A had a higher BMI and prevalence of diabetes than other clusters (all P ≤ 0.0009), and also a higher prevalence of coronary heart disease than cluster C (P = 0.04). Cluster B had a higher prevalence of coronary heart disease than cluster C (P = 0.003) whereas cluster C had a higher prevalence of osteoporosis (P = 0.009).

Conclusion

Our data suggest three possible clinically actionable endotypes in primary OA: muscle weakness, arginine deficit and low inflammatory OA.
Mendelian randomization study on vitamin D levels and osteoarthritis risk: a concise report
Authors: Bergink Arjan P , Trajanoska Katerina , Uitterlinden André G , van Meurs Joyce B J
Published: October 2020

Objective

The role of vitamin D in OA is unclear and previous epidemiological studies have provided inconsistent results. We conducted a two-sample Mendelian randomization (MR) study to investigate the causal relationship between genetically determined serum vitamin D levels and hip/knee OA.

Methods

Six single-nucleotide polymorphisms (SNPs) associated with vitamin D levels in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits Consortium were selected as instrumental variables. Summary statistics of the SNPs effects on OA were derived from the Iceland and UK Biobank, comprising 23 877 knee OA cases, 17 151 hip OA cases and >562 000 controls. The control samples match the OA cases in age, sex and county of origin.

Results

The MR analyses showed no causal association between genetically determined vitamin D levels and knee OA [odds ratio (OR) 1.03 (95% CI 0.84, 1.26)] or hip OA [OR 1.06 (95% CI 0.83, 1.35)].

Conclusion

Genetic variations associated with low vitamin D serum levels are not associated with increased risk of hip or knee OA in community-dwelling older adults, suggesting that vitamin D levels are not causally linked to OA. It is therefore unlikely that vitamin D supplementation protects against hip or knee OA.
A Recessively Inherited Risk Locus on Chromosome 13q22-31 Conferring Susceptibility to Schizophrenia
Authors: Mahmood Tariq , El-Asrag Mohammed E , Poulter James A , Cardno Alastair G , Tomlinson Anneka , Ahmed Sophia , Al-Amri Ahmed , Nazari Jamshid , Neill Joanna , Chamali Rifka S , Kiwan Nancy , Ghuloum Suhaila , Alhaj Hamid A , Randerson Moor Juliette , Khan Shabana , Al-Amin Hassen , Johnson Colin A , Woodruff Peter , Wilkinson Iain D , Ali Manir , Clapcote Steven J , Inglehearn Chris F
Published: October 2020

We report a consanguineous family in which schizophrenia segregates in a manner consistent with recessive inheritance of a rare, partial-penetrance susceptibility allele. From 4 marriages between 2 sets of siblings who are half first cousins, 6 offspring have diagnoses of psychotic disorder. Homozygosity mapping revealed a 6.1-Mb homozygous region on chromosome 13q22.2-31.1 shared by all affected individuals, containing 13 protein-coding genes. Microsatellite analysis confirmed homozygosity for the affected haplotype in 12 further apparently unaffected members of the family. Psychiatric reports suggested an endophenotype of milder psychiatric illness in 4 of these individuals. Exome and genome sequencing revealed no potentially pathogenic coding or structural variants within the risk haplotype. Filtering for noncoding variants with a minor allele frequency of <0.05 identified 17 variants predicted to have significant effects, the 2 most significant being within or adjacent to the SCEL gene. RNA sequencing of blood from an affected homozygote showed the upregulation of transcription from NDFIP2 and SCEL. NDFIP2 is highly expressed in brain, unlike SCEL, and is involved in determining T helper (Th) cell type 1 and Th2 phenotypes, which have previously been implicated with schizophrenia.