bluuebunny/crossref_metadata_2025 huggingface dataset:
The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences
Authors: Gawałko Monika , Duncker David , Manninger Martin , van der Velden Rachel M.J. , Hermans Astrid N.L. , Verhaert Dominique V.M. , Pison Laurent , Pisters Ron , Hemels Martin , Sultan Arian , Steven Daniel , Gupta Dhiraj , Heidbuchel Hein , Sohaib Afzal , Wijtvliet Petra , Tieleman Robert , Gruwez Henri , Chun Julian , Schmidt Boris , Keaney John J. , Müller Patrick , Lodziński Piotr , Svennberg Emma , Hoekstra Olga , Jansen Ward P.J. , Desteghe Lien , de Potter Tom , Tomlinson David R. , Neubeck Lis , Crijns Harry J.G.M. , Pluymaekers Nikki A.H.A. , Hendriks Jeroen M. , Linz Dominik ,   the TeleCheck-AF investigators
Published: February 2021

Aims

TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients.

Methods and results

Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55–71), 62% male] agreed that the FibriCheck® app was easy to use (94%).

Conclusion

Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.
Neoclassical Realist Theories, Intervening Variables, and Paradigmatic Boundaries
Authors: Götz Elias
Published: February 2021

Extant neoclassical realist scholarship has identified a range of real-world factors (e.g., state capacity, interest group pressure, strategic culture, and leadership personality) that serve as intervening variables between systemic imperatives and states’ foreign policy behavior. Despite these elaborations, the intervening variable concept remains underdeveloped. In this article, I show that neoclassical realists have lumped together three different types of causal factors under the label intervening variable: (1) moderating factors, (2) complementary factors, and (3) primary causes. Making these distinctions explicit will enable scholars to increase the analytical precision of neoclassical realist approaches, choose appropriate research designs to test them, and define more clearly the paradigmatic boundaries of neoclassical realism vis-à-vis other perspectives.
The Domestic Sources of Détente: State–Society Relations and Foreign Policy Change during the Cold War
Authors: Chryssogelos Angelos , Martill Benjamin
Published: February 2021

Research on foreign policy change claims leaders seek to restructure their country's foreign relations when internal and external opportunity structures are permissive. However, a number of prominent efforts at achieving change have occurred during times of considerable domestic upheaval and rigid international constraints. To understand why, this article examines three well-known cases of Cold War foreign policy change, focusing on the external relations of Charles de Gaulle in France, John G. Diefenbaker in Canada, and Willy Brandt in West Germany. These cases suggest that domestic upheaval and foreign policy change were inextricably interwoven and that efforts to effect strategic change on a grand scale were motivated by a desire to respond to the demands of marginalized domestic constituencies without incurring the costs of domestic reform. Our analysis suggests key moments of international change are best understood as domestic incorporation strategies rather than instances of significant and principled foreign policy change.
Hydrogen Sulfide Upregulates Acid-sensing Ion Channels via the MAPK-Erk1/2 Signaling Pathway
Authors: Peng Zhong , Kellenberger Stephan
Published: February 2021

Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation, and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a, and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of the extracellular signal-regulated kinase (pErk1/2), which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as for example facilitation of learning and memory, protection during seizure activity, and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.
Application of the differential effective medium theory to determine fluid saturation and crack density from measured P- and S-wave velocities
Authors: Zillmer M , Kashtan B M , Doukoure F , Marthelot J-M
Published: February 2021

The differential effective medium (DEM) theory studied in this paper describes elastic moduli of a fractured medium with help of differential equations, where crack density is the independent variable and fluid saturation is a parameter. The effective medium is isotropic for randomly oriented flat ellipsoidal cracks and thus fully characterized by two elastic constants. In this article we derive an analytical solution of the equation for Poisson’s ratio and we transform the differential equation for Young’s modulus into a non-linear algebraic equation. Fluid saturation and crack density can then be determined from measured wave propagation velocities by a simple algorithm. We also derive approximate solutions for elastic moduli as a function of crack density and saturation, which allows to quantify the uncertainty of the result due to measurement errors. The DEM theory leads to higher crack densities than the self-consistent method and to lower crack densities than the non-interacting theory for measured elastic moduli, while all three methods give similar fluid saturation fractions. As an example of application of our theoretical results, we study weathered granite in the Strengbach water catchment in the Vosges mountains in France. We have performed full waveform sonic logging measurements in an 86-m-deep borehole located at an altitude of 1130 m above sea level, which is used for hydrogeophysical and geochemical studies of a granitic aquifer. The logging data allows us to investigate P and S waves in the depth range between 40 and 80 m. The P- and S-wave propagation velocities take average values of 5.0 and 2.7 km s–1, respectively, with the highest values of 5.8 and 3.2 km s–1 at 75–80 m depth. From these velocities we obtain a water saturation of 75 ± 25 per cent. The crack density describes the degree of weathering of the granite, which generally decreases with depth, but takes high values near layers of strongly weathered granite. Crack density is on average 0.5, with the highest value of 1.0 at 65 m and the lowest value of 0.2 at 75 m depth. The analysis of the full waveform logging data by the DEM method supports results from previous geochemical and hydrological studies in the Strengbach catchment which concluded that water is stored in deeper layers of the granitic aquifer.
A Comparative Study Between Two Combat Injury Severity Scores
Authors: García Cañas Rafael , Navarro Suay Ricardo , Rodríguez Moro Carlos , Crego Vita Diana M , Arias Díaz Javier , Areta Jiménez Fco. Javier
Published: February 2021

Introduction

In recent years, specific trauma scoring systems have been developed for military casualties. The objective of this study was to examine the discrepancies in severity scores of combat casualties between the Abbreviated Injury Scale 2005-Military (mAIS) and the Military Combat Injury Scale (MCIS) and a review of the current literature on the application of trauma scoring systems in the military setting.

Methods

A cross-sectional, descriptive, and retrospective study was conducted between May 1, 2005, and December 31, 2014. The study population consisted of all combat casualties attended in the Spanish Role 2 deployed in Herat (Afghanistan). We used the New Injury Severity Score (NISS) as reference score. Severity of each injury was calculated according to mAIS and MCIS, respectively. The severity of each casualty was calculated according to the NISS based on the mAIS (Military New Injury Severity Score—mNISS) and MCIS (Military Combat Injury Scale-New Injury Severity Score—MCIS-NISS). Casualty severity were grouped by severity levels (mild—scores: 1-8, moderate—scores: 9-15, severe—scores: 16-24, and critical—scores: 25-75).

Results

Nine hundred and eleven casualties were analyzed. Most were male (96.37%) with a median age of 27 years. Afghan patients comprised 71.13%. Air medevac was the main casualty transportation method (80.13). Explosion (64.76%) and gunshot wound (34.68%) mechanisms predominated. Overall mortality was 3.51%. Median mNISS and MCIS-NISS were similar in nonsurvivors (36 [IQR, 25-49] vs. [IQR, 25-48], respectively) but different in survivors, 9 (IQR, 4-17) vs. 5 (IQR, 2-13), respectively (P < .0001). The mNISS and MCIS-NISS were discordant in 34.35% (n = 313). Among cases with discordant severity scores, the median difference between mNISS and MCIS-NISS was 9 (IQR, 4-16); range, 1 to 57.

Conclusion

Our study findings suggest that discrepancies in injury severity levels may be observed in one in three of the casualties when using mNISS and MCIS-NISS.
The effects of ΛCDM dark matter substructure on the orbital evolution of star clusters
Authors: Pavanel Nicholas , Webb Jeremy J
Published: February 2021

We present a comprehensive study on how perturbations due to a distribution of Lambda cold dark matter (ΛCDM) dark matter subhalos can lead to star clusters deviating from their orbits. Through a large suite of massless test particle simulations, we find that (i) subhalos with masses less than 108 M⊙ negligibly affect test particle orbits, (ii) perturbations lead to orbital deviations only in environments with substructure fractions $f_{\mathrm{ sub}} \ge 1{{\ \rm per\ cent}}$, (iii) perturbations from denser subhalos produce larger orbital deviations, and (iv) subhalo perturbations that are strong relative to the background tidal field lead to larger orbital deviations. To predict how the variation in test particle orbital energy σe(t) increases with time, we test the applicability of theory derived from single-mass subhalo populations to populations where subhalos have a mass spectrum. We find σe(t) can be predicted for test particle evolution within a mass spectrum of subhalos by assuming subhalos all have masses equal to the mean subhalo mass and by using the local mean subhalo separation to estimate the change in test particle velocities due to subhalo interactions. Furthermore, the orbital distance variation at an orbital distance r can be calculated via $\sigma _r=2.98 \times 10^{-5} \pm 8 \times 10^{-8} (\rm kpc^{-1} km^{-2} s^{2}) \times r \times \sigma _e$ with a dispersion about the line of best-fitting equalling 0.08 kpc. Finally, we conclude that clusters that orbit within 100 kpc of Milky Way-like galaxies experience a change no greater than $2{{\ \rm per\ cent}}$ in their dissolution times.
Supermassive black holes in cosmological simulations I: MBH − M⋆ relation and black hole mass function
Authors: Habouzit Mélanie , Li Yuan , Somerville Rachel S , Genel Shy , Pillepich Annalisa , Volonteri Marta , Davé Romeel , Rosas-Guevara Yetli , McAlpine Stuart , Peirani Sébastien , Hernquist Lars , Anglés-Alcázar Daniel , Reines Amy , Bower Richard , Dubois Yohan , Nelson Dylan , Pichon Christophe , Vogelsberger Mark
Published: February 2021

The past decade has seen significant progress in understanding galaxy formation and evolution using large-scale cosmological simulations. While these simulations produce galaxies in overall good agreement with observations, they employ different sub-grid models for galaxies and supermassive black holes (BHs). We investigate the impact of the sub-grid models on the BH mass properties of the Illustris, TNG100, TNG300, Horizon-AGN, EAGLE, and SIMBA simulations, focusing on the MBH − M⋆ relation and the BH mass function. All simulations predict tight MBH − M⋆ relations, and struggle to produce BHs of $M_{\rm BH}\leqslant 10^{7.5}\, \rm M_{\odot }$ in galaxies of $M_{\star }\sim 10^{10.5}\!-\!10^{11.5}\, \rm M_{\odot }$. While the time evolution of the mean MBH − M⋆ relation is mild ($\rm \Delta M_{\rm BH}\leqslant 1\, dex$ for 0 $\leqslant z \leqslant$ 5) for all the simulations, its linearity (shape) and normalization varies from simulation to simulation. The strength of SN feedback has a large impact on the linearity and time evolution for $M_{\star }\leqslant 10^{10.5}\, \rm M_{\odot }$. We find that the low-mass end is a good discriminant of the simulation models, and highlights the need for new observational constraints. At the high-mass end, strong AGN feedback can suppress the time evolution of the relation normalization. Compared with observations of the local Universe, we find an excess of BHs with $M_{\rm BH}\geqslant 10^{9}\, \rm M_{\odot }$ in most of the simulations. The BH mass function is dominated by efficiently accreting BHs ($\log _{10}\, f_{\rm Edd}\geqslant -2$) at high redshifts, and transitions progressively from the high-mass to the low-mass end to be governed by inactive BHs. The transition time and the contribution of active BHs are different among the simulations, and can be used to evaluate models against observations.
Segmentation of spectroscopic images of the low solar atmosphere by the self-organizing map technique
Authors: Schilliro F , Romano P
Published: February 2021

We describe the application of semantic segmentation by using the self-organizing map technique to an high spatial and spectral resolution data set acquired along the H α line at 656.28 nm by the Interferometric Bi-dimensional Spectrometer installed at the focus plane of the Dunn solar telescope. This machine learning approach allowed us to identify several features corresponding to the main structures of the solar photosphere and chromosphere. The obtained results show the capability and flexibility of this method to identifying and analysing the fine structures which characterize the solar activity in the low atmosphere. This is a first successful application of the SOM technique to astrophysical data sets.
Light-curve calculations for triple microlensing systems
Authors: Kuang Renkun , Mao Shude , Wang Tianshu , Zang Weicheng , Long Richard J
Published: February 2021

We present a method to compute the magnification of a finite source star lensed by a triple lens system based on the image boundary (contour integration) method. We describe a new procedure to obtain continuous image boundaries from solutions of the tenth-order polynomial obtained from the lens equation. Contour integration is then applied to calculate the image areas within the image boundaries, which yields the magnification of a source with uniform brightness. We extend the magnification calculation to limb-darkened stars approximated with a linear profile. In principle, this method works for all multiple lens systems, not just triple lenses. We also include an adaptive sampling and interpolation method for calculating densely covered light curves. The C++ source code and a corresponding python interface are publicly available.
The global significance of biodiversity science in China: an overview
Authors: Mi Xiangcheng , Feng Gang , Hu Yibo , Zhang Jian , Chen Lei , Corlett Richard T , Hughes Alice C , Pimm Stuart , Schmid Bernhard , Shi Suhua , Svenning Jens-Christian , Ma Keping
Published: February 2021

Biodiversity science in China has seen rapid growth over recent decades, ranging from baseline biodiversity studies to understanding the processes behind evolution across dynamic regions such as the Qinghai-Tibetan Plateau. We review research, including species catalogues, biodiversity monitoring, the origins, distributions, maintenance, and threats to biodiversity, biodiversity-related ecosystem function and services, and species and ecosystems' responses to global change. Next, we identify priority topics, offer suggestions and priorities for future biodiversity research in China. These priorities include 1) the ecology and biogeography of the Qinghai-Tibetan Plateau and surrounding mountains, and that of subtropical and tropical forests across China; 2) marine and inland aquatic biodiversity, and 3) effective conservation and management to identify and maintain synergies between biodiversity and socio-economic development to fulfil China's vision for becoming an ecological civilization. In addition, we propose three future strategies: 1) translate advanced biodiversity science into practice for biodiversity conservation; 2) strengthen capacity building and application of advanced technology, including high-throughput sequencing, genomics, and remote sensing; 3) strengthen and expand international collaborations. Based on the recent rapid progress of biodiversity research, China is well-positioned to become a global leader in biodiversity research in the near future.
Guilt, Innocence, and Remaining Doubts: Some Considerations on the Congregation for the Doctrine of the Faith’s Three-Verdict System of Deciding Cases of Sexual Abuse
Authors: Hahn Judith
Published: February 2021

The Congregation for the Doctrine of the Faith recently published a Vademecum to guide the ecclesiastical investigation and adjudication of cases of sexual abuse of minors committed by Catholic clergy. By collecting existing regulations, the Vademecum provides some remarkable insights into how the congregation operates its penal trials. The document inter alia discloses that the congregation operates with three verdicts in penal trials, ‘constat’, ‘non constat’, and ‘constat de non’, which roughly correlate with the verdicts ‘guilty’, ‘not proven’, and ‘not guilty’ of Scottish law. It is particularly this differentiation of two acquittals, with the same legal effects but different implications, which fundamentally impacts how the congregation decides penal cases. I will shed more light on this issue by introducing the regular canonical verdict system and the congregation’s innovation, by comparing it with secular two- and three-verdict systems, and by discussing my findings to discover the merits and demerits of three verdicts.
When it is Wrong to Hold On
Authors: Katz Larissa
Published: February 2021

Private law as a rule presumes we hold on to what we have. A principle of non-derogation from the grant seems to be at odds with this: far from presuming that grantors part with the least they could on making a grant, the principle generates the presumption that a grantor conveys all she has to give. In this paper I explain the principle of non-derogation from the grant in terms of an appointment of a successor to a position of authority, and so the ideal of a grant as a conveyance of the full authority associated with that position. Voluntarist as to whether a legal power is exercised, the law’s approach is rationalist as to the effects of its exercise, making sense of particular grants in terms of the ideal of a grant. This explains both why there is a strong presumption against change in our relations with others (and the demand for juridical reasons to explain any change) and at the same time, once rebutted, a presumption that the grant conveys what is reasonably necessary for it to operate as the appointment of another fully to that position of authority.
Positive Side Effects? The Impact of Populist Radical Right Parties in Government on the Media Visibility of the Austrian Parliament
Authors: Miklin Eric , Dolezal Martin
Published: February 2021

This article takes up the scholarly debate on the relationship between populism and democracy and analyses the effect populist radical right parties (PRRPs) in government have had on the representative function of the Austrian parliament. Building on insights from theories of newsworthiness, we expect these parties to positively affect the visibility of parliament due to the increased conflict between governing and mainstream opposition parties, thereby increasing parliamentary accountability. Our analysis covers the period from 1994 to 2020, with PRRPs in government from 2000 to 2007 and again from 2017 to 2019. Empirical inference is based on the weekly coverage of the Austrian parliament’s first chamber (Nationalrat) in a sample of four daily newspapers. The findings show that the first term in government did indeed have a positive and significant effect on media coverage. However, that this effect is not found for the second term suggests that its existence and size depend on the concrete political circumstances under which governments and media outlets operate.
Classification of three-generation models by orbifolding magnetized T2 × T2
Authors: Hoshiya Kouki , Kikuchi Shota , Kobayashi Tatsuo , Ogawa Yuya , Uchida Hikaru
Published: February 2021

We study orbifolding by the $\mathbb{Z}_2^{\rm (per)}$ permutaion of $T^2_1 \times T^2_2$ with magnetic fluxes and its twisted orbifolds. We classify the possible three-generation models which lead to non-vanishing Yukawa couplings on the magnetized $T^2_1 \times T^2_2$ and orbifolds including the $\mathbb{Z}_2^{\rm (per)}$ permutation and $\mathbb{Z}_2^{\rm (t)}$ twist. We also study the modular symmetry on such orbifold models. As an illustrating model, we examine the realization of quark masses and mixing angles.
Association between In-hospital Mortality and Low Cardiac Output Syndrome with Morning versus Afternoon Cardiac Surgery
Authors: Hijazi Ryan M. , Sessler Daniel I. , Liang Chen , Rodriguez-Patarroyo Fabio A. , Soltesz Edward G. , Duncan Andra E.
Published: February 2021

Background

Recent work suggests that having aortic valve surgery in the morning increases risk for cardiac-related complications. This study therefore explored whether mortality and cardiac complications, specifically low cardiac output syndrome, differ for morning and afternoon cardiac surgeries.

Methods

The study included adults who had aortic and/or mitral valve repair/replacement and/or coronary artery bypass grafting from 2011 to 2018. The components of the in-hospital composite outcome were in-hospital mortality and low cardiac output syndrome, defined by requirement for at least two inotropic agents at 24 to 48 h postoperatively or need for mechanical circulatory support. Patients who had aortic cross-clamping between 8 and 11 am (morning surgery) versus between 2 and 5 pm (afternoon surgery) were compared on the incidence of the composite outcome.

Results

Among 9,734 qualifying operations, 0.4% (29 of 6,859) died after morning, and 0.7% (20 of 2,875) died after afternoon surgery. The composite of in-hospital mortality and low cardiac output syndrome occurred in 2.8% (195 of 6,859) of morning patients and 3.4% (97 of 2,875) of afternoon patients: morning versus afternoon confounder-adjusted odds ratio, 0.96 (95% CI, 0.75 to 1.24; P = 0.770). There was no evidence of interaction between morning versus afternoon and surgery type (P = 0.965), and operation time was statistically nonsignificant for surgery subgroups.

Conclusions

Patients having aortic valve surgery, mitral valve surgery, and/or coronary artery bypass grafting with aortic cross-clamping in the morning and afternoon did not have significantly different outcomes. No evidence was found to suggest that morning or afternoon surgical timing alters postoperative risk.

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Managing intergroup silos to improve patient flow
Authors: Kreindler Sara A. , Hastings Stephanie , Mallinson Sara , Brierley Meaghan , Birney Arden , Tarraf Rima , Winters Shannon , Johnson Keir
Published: February 2021

Background

Health care managers face the critical challenge of overcoming divisions among the many groups involved in patient care, a problem intensified when patients must flow across multiple settings. Surprisingly, however, the patient flow literature rarely engages with its intergroup dimension.

Purpose

This study explored how managers with responsibility for patient flow understand and approach intergroup divisions and “silo-ing” in health care.

Methodology/Approach

We conducted in-depth interviews with 300 purposively sampled senior, middle, and frontline managers across 10 Canadian health jurisdictions. We undertook thematic analysis using sensitizing concepts drawn from the social identity approach.

Results

Silos, at multiple levels, were reported in every jurisdiction. The main strategies for ameliorating silos were provision of formal opportunities for staff collaboration, persuasive messages stressing shared values or responsibilities, and structural reorganization to redraw group boundaries. Participants emphasized the benefits of the first two but described structural change as neither necessary nor sufficient for improved collaboration.

Conclusion

Silos, though an unavoidable feature of organizational life, can be managed and mitigated. However, a key challenge in redefining groups is that the easiest place to draw boundaries from a social identity perspective may not be the best place from one of system design. Narrowly defined groups forge strong identities more easily, but broader groups facilitate coordination of care by minimizing the number of boundaries patients must traverse.

Practice Implications

A thoughtfully designed combination of strategies may help to improve intergroup relations and their impact on flow. It may be ideal to foster a “mosaic” identity that affirms group allegiances at multiple levels.
Longitudinal Changes of Cognitive Deficits and Treatment Outcome of Cognitive Behavioral Therapy for Major Depression
Authors: Bernhardt Maren , Schwert Christine , Aschenbrenner Steffen , Weisbrod Matthias , Schröder Annette
Published: February 2021

The current study examined neuropsychological changes over the course of cognitive behavioral therapy (CBT) in outpatients with major depressive disorder and the influence of cognitive deficits as predictors of clinical outcome in depression. A neuropsychological test battery was carried out on depressed outpatients (N = 54) at the beginning and at the end of CBT. Small improvements were found in divided attention, figural memory, and processing speed from pre- to posttreatment. Cognitive deficits in executive functions before treatment predicted the clinical outcome at the end of CBT. The present study reveals that attention and memory deficits are most likely to improve over the course of treatment, whereas executive functions remain stable in the long term. Depressed patients with worse executive functions at the beginning of treatment seem to benefit more from long-term CBT therapy.
Lockdown and non-COVID-19 deaths: Cause-specific mortality during the first wave of the 2020 pandemic in Norway. A population-based register study
Authors: Raknes Guttorm , Strøm Marianne Sørlie , Sulo Gerhard , Øverland Simon , Roelants Mathieu , Juliusson Petur Benedikt
Published: February 2021

Objective

To explore the potential impact of the first wave of COVID-19 pandemic on all cause and cause-specific mortality in Norway.

Design

Population based register study.

Setting

The Norwegian cause of Death Registry and the National Population Register of Norway.

Participants

All recorded deaths in Norway during March to May from 2010 to 2020.

Main outcome measures

Rate (per 100 000) of all-cause mortality and causes of death in the EU Shortlist for Causes of Death March to May 2020. The rates were age-standardised and adjusted to a 100% register coverage and compared with a 95% prediction interval (PI) based on corresponding rates for 2010-2019.

Results

113 710 deaths were included, of which 10 226 from 2020. We did not observe any deviation from predicted total mortality. There were fewer than predicted deaths from chronic lower respiratory diseases excluding asthma (11.4, 95% PI 11.8 to 15.2) and from other non-ischemic, non-rheumatic heart diseases (13.9, 95% PI 14.5 to 20.2). The death rates were higher than predicted for Alzheimer’s disease (7.3, 95% PI 5.5 to 7.3) and diabetes mellitus (4.1, 95% PI 2.1 to 3.4).

Conclusions

There was no significant difference in the frequency of the major causes of death in the first wave of the 2020 COVID-19 pandemic in Norway. An increase in diabetes mellitus deaths and reduced mortality due to some heart and lung conditions may be linked to infection control measures.
Accuracy of Samsung Smartphone Integrated Pulse Oximetry Meets Full FDA Clearance Standards for Clinical Use
Authors: Browne Sara H. , Bernstein Mike , Bickler Philip E.
Published: February 2021

Background

Pulse oximetry is used as an assessment tool to gauge the severity of COVID-19 infection and identify patients at risk of poor outcomes. 1,2,3,4 The pandemic highlights the need for accurate pulse oximetry, particularly at home, as infection rates increase in multiple global regions including the UK, USA and South Africa 5. Over 100 million Samsung smartphones containing dedicated biosensors (Maxim Integrated Inc, San Jose, CA) and preloaded Apps to perform pulse oximetry, are in use globally. We performed detailed in human hypoxia testing on the Samsung S9 smartphone to determine if this integrated hardware meets full FDA/ISO requirements for clinical pulse oximetry.

Methods

The accuracy of integrated pulse oximetry in the Samsung 9 smartphone during stable arterial oxygen saturations (SaO2) between 70% and 100% was evaluated in 12 healthy subjects. Inspired oxygen, nitrogen, and carbon dioxide partial pressures were monitored and adjusted via a partial rebreathing circuit to achieve stable target SaO2 plateaus between 70% and 100%. Arterial blood samples were taken at each plateau and saturation measured on each blood sample using ABL-90FLEX blood gas analyzer. Bias, calculated from smartphone readings minus the corresponding arterial blood sample, was reported as root mean square deviation (RMSD).

Findings

The RMSD of the over 257 data points based on blood sample analysis obtained from 12 human volunteers tested was 2.6%.

Interpretation

Evaluation of the smartphone pulse oximeter performance is within requirements of <3.5% RMSD blood oxygen saturation (SpO2) value for FDA/ISO clearance for clinical pulse oximetry. This is the first report of smartphone derived pulse oximetry measurements that meet full FDA/ISO accuracy certification requirements. Both Samsung S9 and S10 contain the same integrated pulse oximeter, thus over 100 million smartphones in current global circulation could be used to obtain clinically accurate spot SpO2 measurements to support at home assessment of COVID-19 patients.
Experiences of supported isolation in returning travellers during the early COVID-19 response: an interview study
Authors: Carter H. , Weston D. , Greenberg N. , Oliver I. , Robin C. , Rubin G. J. , Wessely S. , Amlôt R.
Published: February 2021

Objectives

To understand the experiences of those who underwent supported isolation as part of the response to the COVID-19 pandemic, after returning to the UK from Wuhan, China.

Design

We used semi-structured interviews to capture participants’ experiences and perceptions of supported isolation.

Setting

Telephone interviews carried out within approximately one month of an individual leaving supported isolation.

Participants

26 people who underwent supported isolation at either Arrowe Park Hospital (n = 18) or Kents Hill Park Conference Centre (n = 8) after being repatriated from Wuhan in January – February 2020.

Results

Participants were willing to undergo supported isolation because they understood that it would protect themselves and others. Positive treatment by staff was fundamental to participants’ willingness to comply with isolation procedures. Despite the high level of compliance, participants expressed some uncertainty about what the process would involve.

Conclusions

As hotel quarantine is introduced across the UK for international arrivals, our findings suggest that those in charge should: communicate effectively before, during and after quarantine, emphasising why quarantine is important and how it will protect others; avoid enforcement and focus on supporting and promoting voluntary compliance; facilitate shared social experiences for those in quarantine; and ensure all necessary supplies are provided. Doing so will increase adherence and reduce any negative effects on wellbeing.
Clinical evaluation of the Abbott Alinity SARS-CoV-2 spike-specific quantitative IgG and IgM assays in infected, recovered, and vaccinated groups
Authors: Narasimhan Madhusudhanan , Mahimainathan Lenin , Araj Ellen , Clark Andrew E. , Markantonis John , Green Allen , Xu Jing , SoRelle Jeffrey A. , Alexis Charles , Fankhauser Kimberly , Parikh Hiren , Wilkinson Kathleen , Reczek Annika , Kopplin Noa , Yekkaluri Sruthi , Balani Jyoti , Thomas Abey , Singal Amit , Sarode Ravi , Muthukumar Alagarraju
Published: February 2021

The COVID-19 pandemic continues to impose a significant burden on global health infrastructure. While identification and containment of new cases remains important, laboratories must now pivot and consider assessment of SARS-CoV-2 immunity in the setting of the recent availability of multiple COVID-19 vaccines. Here we have utilized the latest Abbott Alinity semi-quantitative IgM and quantitative IgG spike protein (SP) serology assays (IgMSP and IgGSP) in combination with Abbott Alinity IgG nucleocapsid (NC) antibody test (IgGNC) to assess antibody responses in a cohort of 1236 unique participants comprised of naïve, SARS-CoV-2 infected, and vaccinated (including both naïve and recovered) individuals. The IgMSP and IgGSP assays were highly specific (100%) with no cross-reactivity to archived samples recovered prior to the emergence of SARS-CoV-2, including those from individuals with seasonal coronavirus infections. Clinical sensitivity was 96% after 15 days for both IgMSP and IgGSP assays individually. When considered together, the sensitivity was 100%. A combination of NC- and SP-specific serologic assays clearly differentiated naïve, SARS-CoV-2-infected, and vaccine-related immune responses. Vaccination resulted in a significant increase in IgGSP and IgMSP titers, with a major rise in IgGSP following the booster (second) dose in the naïve group. In contrast, SARS-CoV-2 recovered individuals had several fold higher IgGSP responses than naïve following the primary dose, with a comparatively dampened response following the booster. This work illustrates the strong clinical performance of these new serological assays and their utility in evaluating and distinguishing serological responses to infection and vaccination.
Systematic Phenotyping and Characterization of the 5xFAD mouse model of Alzheimer’s Disease
Authors: Forner Stefania , Kawauchi Shimako , Balderrama-Gutierrez Gabriela , Kramár Enikö A. , Matheos Dina P. , Phan Jimmy , Javonillo Dominic I. , Tran Kristine Minh , Hingco Edna , da Cunha Celia , Rezaie Narges , Alcantara Joshua Andrei , Baglietto-Vargas David , Jansen Camden , Neumann Jonathan , Wood Marcelo A. , MacGregor Grant R. , Mortazavi Ali , Tenner Andrea J. , LaFerla Frank M. , Green Kim N.
Published: February 2021

Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer’s disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6J strain background, across its lifespan – including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. This comprehensive analysis included quantification of plaque burden, Aβ biochemical levels, and neuropathology, neurophysiological measurements and behavioral and cognitive assessments, and evaluation of microglia, astrocytes, and neurons. Analysis of transcriptional changes was conducted using bulk-tissue generated RNA-seq data from microdissected cortices and hippocampi as a function of aging, which can be explored at the UCI Mouse Explorer and AD Knowledge Portal. This deep-phenotyping pipeline identified novel aspects of age-related pathology in the 5xFAD model.
PEAK3 pseudokinase represents a pro-migratory and -invasive signalling scaffold
Authors: Hou Jianmei , Nguyen Elizabeth V , Surudoi Minglyanna , Roy Michael J , Patel Onisha , Lucet Isabelle S , Ma Xiuquan , Daly Roger J
Published: February 2021

The PEAK family of pseudokinases comprises PEAK1 and PEAK2 as well as the recently-identified PEAK3. PEAK1/2 play fundamental roles in regulating tyrosine kinase signal output and oncogenesis, while PEAK3 remains poorly-characterized. Here, we demonstrate that PEAK3 undergoes homotypic association as well as heterotypic interaction with PEAK1/2. PEAK3 also recruits ASAP1/2, Cbl and PYK2 and the adaptors Grb2 and CrkII, with binding dependent on PEAK3 dimerization. PEAK3 tyrosine phosphorylation on Y24 is also dependent on dimerization as well as Src family kinase activity, and interestingly, is decreased via PTPN12 in response to EGF treatment. Y24 phosphorylation is required for binding of Grb2 and ASAP1. Overexpression of PEAK3 in MDA-MB-231 breast cancer cells enhanced cell elongation and cell motility, while knockdown of endogenous PEAK3 decreased cell migration. In addition, overexpression of PEAK3 in PEAK1/2 compound knock-out MCF-10A breast epithelial cells enhanced acinar growth and invasion in 3D culture, with the latter phenotype dependent on PEAK3 tyrosine phosphorylation and binding of Grb2 and ASAP1. These findings characterize PEAK3 as an integral member of the PEAK family with scaffolding roles that promote cell proliferation, migration and invasion.
SARS-CoV-2 nucleocapsid protein dually regulates innate immune responses
Authors: Zhao Yinghua , Sui Liyan , Wu Ping , Wang Wenfang , Tan Guangyun , Wang Zedong , Yu Yang , Hou Zhijun , Wang Guoqing , Liu Quan
Published: February 2021

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein interacted with the tripartite motif protein 25 (TRIM25), thereby dually regulating the phosphorylation and nuclear translocation of IRF3, STAT1 and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress retinoic acid-inducible gene I (RIG-I) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.
Mechanical Mapping of Bioprinted Hydrogel Models by Brillouin Microscopy
Authors: Mahmodi Hadi , Piloni Alberto , Utama Robert , Kabakova Irina
Published: February 2021

Three-dimensional (3D) bioprinting has revolutionised the field of biofabrication by delivering precise, cost-effective and a relatively simple way of engineeringin vitroliving systems in high volume for use in tissue regeneration, biological modelling, drug testing and cell-based diagnostics. The complexity of modern bioprinted systems requires quality control assessment to ensure the resulting product meets the desired criteria of structural design, micromechanical performance and long-term durability. Brillouin microscopy could be an excellent solution for micromechanical assessment of the bioprinted models during or post-fabrication since this technology is non-destructive, label-free and is capable of microscale 3D imaging. In this work, we demonstrate the application of Brillouin microscopy to 3D imaging of hydrogel microstructures created through drop-on-demand bioprinting. In addition, we show that this technology can resolve variations between mechanical properties of the gels with slightly different polymer fractions. This work confirms that Brillouin microscopy can be seen as a characterisation technology complementary to bioprinting, and in the future can be combined within the printer design to achieve simultaneous real-time fabrication and micromechanical characterisation ofin vitrobiological systems.
Grasp Aperture Corrections in Reach-to-Grasp Movements Do Not Alter Size Perception
Authors: van Polanen Vonne
Published: February 2021

When grasping an object, the opening between the fingertips (grip aperture) scales with the size of the object. If an object changes in size, the grip aperture has to be corrected. In this study, it was investigated whether such corrections would influence the perceived size of objects. The grasping plan was manipulated with a preview of the object, after which participants initiated their reaching movement without vision. In a minority of the grasps, the object changed in size after the preview and participants had to adjust their grasping movement. Visual feedback was manipulated in two experiments. In experiment 1, vision was restored during reach and both visual and haptic information was available to correct the grasp and lift the object. In experiment 2, no visual information was provided during the movement and grasps could only be corrected using haptic information. Participants made reach-to-grasp movements towards two objects and compared these in size. Results showed that participants adjusted their grasp to a change in object size from preview to grasped object in both experiments. However, a change in object size did not bias the perception of object size or alter discrimination performance. In experiment 2, a small perceptual bias was found when objects changed from large to small. However, this bias was much smaller than the difference that could be discriminated and could not be considered meaningful. Therefore, it can be concluded that the planning and execution of reach-to-grasp movements do not affect the perception of object size.
Engineering the Immune Adaptor Protein STING as a Biologic
Authors: Sun Xin , Ni Yun , He Yanpu , Yang Mengdi , Tani Tetsuo , Kitajima Shunsuke , Barbie David A. , Li Jiahe
Published: February 2021

Activation of the stimulator of interferon genes (STING) pathway through cyclic dinucleotides (CDNs) has been explored extensively as potent vaccine adjuvants against infectious diseases as well as to increase tumor immunogenicity towards cancer immunotherapy in solid tumors. Over the last decade, a myriad of synthetic vehicles, including liposomes, polymers, and other nanoparticle platforms, have been developed to improve the bioavailability and therapeutic efficacy of STING agonists in preclinical mouse models. In comparison to synthetic materials, protein-based carriers represent an attractive delivery platform owing to their biocompatibility, amenability to genetic engineering, and intrinsic capacity to form well-defined structures. In the present work, we have engineered the immune adaptor STING as a protein-based delivery system for efficient encapsulation and intracellular delivery of CDNs. Through genetic fusion with a protein transduction domain, the recombinant STING can spontaneously penetrate cells to markedly enhance the delivery of CDNs in a mouse vaccination model and a syngeneic mouse melanoma model. Moreover, motivated by recent findings that certain tumor cells can evade immune surveillance via loss of STING expression, we further unveiled that our STING platform can serve as a functional vehicle to restore the STING signaling in a panel of lung and melanoma cell lines with impaired STING expression. Taken together, our STING-based protein delivery platform may offer a unique direction towards targeting STING-silenced tumors as well as augmenting the efficacy of STING-based vaccine adjuvants.
Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples
Authors: Biji Abhijith , Khatun Oyahida , Swaraj Shachee , Narayan Rohan , Rajmani Raju , Sardar Rahila , Satish Deepshikha , Mehta Simran , Bindhu Hima , Jeevan Madhumol , Saini Deepak K , Singh Amit , Gupta Dinesh , Tripathi Shashank
Published: February 2021

While our battle with the COVID-19 pandemic continues, a multitude of Omics data has been generated from patient samples in various studies, which remains to be translated. We conducted a meta-analysis of published transcriptome and proteome profiles of nasal swab and bronchioalveolar lavage fluid (BALF) samples of COVID-19 patients, to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swab/BALF samples from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Analysis of these data revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of COVID-19 disease. Furthermore, Thioredoxin gene (TXN) was identified as a significant upregulated host factor in our overlap analysis. An FDA-approved drug Auranofin, which inhibits Thioredoxin reduction, was found to mitigate SARS-CoV-2 replicationin vitroandin vivoin the hamster challenge model. Overall, this study translates COVID-19 host response Big Data into potential clinical interventions.