bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-selectin inhibitors as potential therapeutics for COVID-19 treatment: in silico screening study
Authors: Šmak Pavel , Chandrabose Selvaraj , Tvaroška Igor , Koča Jaroslav
Published: March 2021

Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the globe. The spectrum of disease is broad but among hospitalized patients with COVID-19, respiratory failure from acute respiratory distress syndrome is the leading cause of mortality. There is an urgent need for an effective treatment. The current focus has been developing novel therapeutics, including antivirals, protease inhibitors, vaccines and targeting the overactive cytokine response with anti-cytokine therapy. The overproduction of early response proinflammatory cytokines results in what has been described as a “cytokine storm” is leading eventually to death when the cells fail to terminate the inflammatory response. Accumulating evidence shows that inflammatory cytokines induce selectin ligands that play a crucial role in the pathogenesis of inflammatory diseases by mediating leukocyte migration from the blood into the tissue. Thus, the selectins and selectin ligands represent a promising therapeutic target for the treatment of COVID-19. In this paper, potential pan-selectin inhibitors were identified employing a virtual screening using a docking procedure. For this purpose, the Asinex and ZINC databases of ligands, including approved drugs, biogenic compounds and glycomimetics, altogether 923,602 compounds, were screened against the P-, L- and E-selectin. At first, the experimentally confirmed inhibitors were docked into all three selectins’ carbohydrate recognition domains to assess the suitability of the screening procedure. Finally, based on the evaluation of ligands binding, we propose 10 purchasable pan-selectin inhibitors to develop COVID-19 therapeutics.
Advancing foreign policy analysis by studying leaders from the global South
Authors: Brummer Klaus
Published: March 2021

Using the concept of ‘context sensitivity’ as organizing theme, this article explores different avenues of advancing foreign policy analysis (FPA) scholarship based on insights from the global South. Since foreign policy decision-makers in the global South operate in (at times very) different political environments than their western counterparts, the applicability of FPA approaches cannot be taken as a given, which is why their context sensitivity (i.e., the extent to which core concepts and indicators contained in those approaches travel to non-western settings) needs to be explored. This article suggests that our understanding of the motives and behaviours of individual decision-makers can be advanced in three distinct ways based on insights from the global South. First, several of the FPA constructs that focus on individual decision makers have seen hardly any applications to non-western cases, which is why the latter contributes to ascertaining the analytical scope of those constructs. Second, taking more fully into account the differences in decision-making environments within which leaders from the global South operate can advance leader-oriented FPA approaches by helping to specify certain theoretical assumptions proposed by them. Finally, the aspiration to analyse leaders from the global South can advance FPA in terms of method by, for instance, developing non-English language coding schemes for profiling leaders based on speech acts that are cognizant of the specificities of individual languages, while at the same time allowing for measurement equivalence across different languages.
Political leadership and gendered multilevel games in foreign policy
Authors: Aggestam Karin , True Jacqui
Published: March 2021

Gender intersects as a major fault-line in increasingly polarized, contemporary global politics. Many democratic states in the global North and South have adopted pro-gender norms in their foreign policies, while other states and populist regimes have resisted the promotion of gender equality and women's rights. This article analyses how political leaders harness gender dynamics to further their power, status and authority to act in foreign policy. While scholarship on foreign policy analysis has emphasized the role of individuals, political leaders and their followers, and of two-level games balancing domestic and international pressures, we advance a novel theoretical concept: ‘gendered multilevel games’. This new concept highlights the gendered dynamics of the problem of agency and structure in foreign policy, which are generated from the interactions between the domestic, international and transnational levels, and reach within and across states. To illustrate the utility of this concept, we analyse foreign policy leadership and the variation in gendered multilevel games in four vignettes: (1) hyper-masculinity and revisionist leadership; (2) normative leadership and gendered nation-branding; (3) compassionate leadership and gendered transnational symbolism; and (4) contested leadership on pro- and anti-gender norms in foreign policy. Importantly, these empirical illustrations show how adept political leaders navigate pro- and anti-gender norms to achieve core and often divergent foreign policy goals.
Automation, digitalization, and changes in occupational structures in the automobile industry in Germany, Japan, and the United States: a brief history from the early 1990s until 2018
Authors: Krzywdzinski Martin
Published: March 2021

A major concern in the current public discussion is rapidly accelerating automation and in particular the use of robots. Many experts and researchers see it as a driver of employment losses hitting in particular so called routine jobs. The present study challenges this perspective. It examines two central questions: First, what approaches to automation and digitalization have been pursued in the automotive industry in Germany, Japan, and the United States? Second, how have employment and its occupational composition in the automotive industry developed in the three countries? The first part of the study focuses on the evolution of automation and digitalization approaches in the automotive industry from the early 1990s until today. It combines a qualitative analysis of press articles and a quantitative evaluation of the development of the stock of industrial robots from 1993 to 2018 based on the statistics of the International Federation of Robotics. The second part of the study focuses on the change in employment structures using occupational statistics from the Bureau of Labor Statistics (US), the Federal Employment Agency (Germany), and the Statistics Bureau of Japan. The results of the study question the perception of an automation-related threat to employment and especially to production employment. At the same time, they highlight differences between automation and digitalization approaches in Germany, Japan, and the United States as well as different paths of change in employment structures.
Interactivity of biochemical and physical stimuli during epigenetic conditioning and cardiomyocytic differentiation of stem and progenitor cells derived from adult hearts
Authors: Zeng Wendy R , Doran Pauline M
Published: March 2021

Mixed populations of cardiosphere-derived stem and progenitor cells containing proliferative and cardiomyogenically committed cells were obtained from adult rat hearts. The cells were cultured in either static 2D monolayers or dynamic 3D scaffold systems with fluid flow. Cardiomyocyte lineage commitment in terms of GATA4 and Nkx2.5 expression was significantly enhanced in the dynamic 3D cultures compared with static 2D conditions. Treatment of the cells with 5-azacytidine (5-aza) produced different responses in the two culture systems, as activity of this chemical epigenetic conditioning agent depended on the cell attachment and hydrodynamic conditions provided during culture. Cell growth was unaffected by 5-aza in the static 2D cultures but was significantly reduced under dynamic 3D conditions relative to untreated controls. Myogenic differentiation measured as Mef2c expression was markedly upregulated by 5-aza in the dynamic 3D cultures but downregulated in the static 2D cultures. The ability of the physical environment to modulate the cellular cardiomyogenic response to 5-aza underscores the interactivity of biochemical and physical stimuli applied for cell differentiation. Accordingly, observations about the efficacy of 5-aza as a cardiomyocyte induction agent may not be applicable across different culture systems. Overall, use of dynamic 3D rather than static 2D culture was more beneficial for cardio-specific myogenesis than 5-aza treatment, which generated a more ambiguous differentiation response.
Evaluating the Effect of a Modified Sample Preparation on SARS-CoV-2 Detection in a Cartridge-Based Platform
Authors: Zhen Wei , Whitfield Natalie N , Smith Elizabeth , Shaw Christine , Ivy Cristina , Douglas Caylee , Bickford Stephanie , Berry Gregory J
Published: March 2021

Introduction

The ePlex® SARS-CoV-2 emergency use authorization (EUA) test is a cartridge-based assay for the detection of SARS-CoV-2 in nasopharyngeal specimens. Since performance data has been previously published on this platform, the manufacturer has modified the workflow design in order to improve assay performance. Evaluation of the new workflow, which eliminated the sample delivery device (SDD), led to a dramatic improvement of assay performance while saving time and making cartridge loading more convenient.

Methods

145 confirmed positive nasopharyngeal swab specimens were used to evaluate the assay analytical sensitivity, accuracy, and overall time-saving for the 2 workflows that is with and without the use of SDD on the ePlex SARS-CoV-2 test.

Results

Elimination of the SDD step led to a dramatic increase in accuracy and the overall limit of detection when using 145 previously defined and valid SARS-CoV-2 positive specimens with relatively low, medium, and high cycle thresholds (CT). This simple workflow change led to an overall detection from 94/145 (64.8%) to 131/145 (90.3%), with an additional 37 specimens being detected. CT value ranges revealed that 90% of the specimens in the 33 ≤ CT < 35.3 CT range were detected, whereas with the SDD workflow, only 30% of positive specimens were detected in this same range. Hands-on time for each specimen also improved and showed overall time savings.

Conclusion

The simple workflow modification eliminating the SDD led to an overall improvement in the detection of positive specimens and also simplified workflow and reduced hands-on time.
Adaptations of Breast Imaging Centers to the COVID-19 Pandemic: A Survey of California and Texas
Authors: Chalfant James S , Cohen Ethan O , Leung Jessica W T , Pittman Sarah M , Kothari Pranay D , Downey John R , Sohlich Rita E , Chong Alice , Grimm Lars J , Hoyt Anne C , Ojeda-Fournier Haydee , Joe Bonnie N , Trinh Long , Rosen Eric L , Feig Stephen A , Aminololama-Shakeri Shadi , Ikeda Debra M
Published: March 2021

Objective

To determine the early impact of the COVID-19 pandemic on breast imaging centers in California and Texas and compare regional differences.

Methods

An 11-item survey was emailed to American College of Radiology accredited breast imaging facilities in California and Texas in August 2020. A question subset addressed March–April government restrictions on elective services (“during the shutdown” and “after reopening”). Comparisons were made between states with chi-square and Fisher’s tests, and timeframes with McNemar’s and paired t-tests.

Results

There were 54 respondents (54/240, 23%, 26 California, 28 Texas). Imaging volumes fell during the shutdown and remained below pre-pandemic levels after reopening, with reduction in screening greatest (ultrasound 12% of baseline, mammography 13%, MRI 23%), followed by diagnostic MRI (43%), procedures (44%), and diagnostics (45%). California reported higher volumes during the shutdown (procedures, MRI) and after reopening (diagnostics, procedures, MRI) versus Texas (P = 0.001–0.02). Most screened patients (52/54, 96% symptoms and 42/54, 78% temperatures), and 100% (53/53) modified check-in and check-out. Reading rooms or physician work were altered for social distancing (31/54, 57%). Physician mask (45/48, 94%), gown (15/48, 31%), eyewear (22/48, 46%), and face shield (22/48, 46%) use during procedures increased after reopening versus pre-pandemic (P < 0.001–0.03). Physician (47/54, 87%) and staff (45/53, 85%) financial impacts were common, but none reported terminations.

Conclusion

Breast imaging volumes during the early pandemic fell more severely in Texas than in California. Safety measures and financial impacts on physicians and staff were similar in both states.
NEM6, KBTBD13-Related Congenital Myopathy: Myopathological Analysis in 18 Dutch Patients Reveals Ring Rods Fibers, Cores, Nuclear Clumps, and Granulo-Filamentous Protein Material
Authors: Bouman Karlijn , Küsters Benno , De Winter Josine M , Gillet Cynthia , Van Kleef Esmee S B , Eshuis Lilian , Brochier Guy , Madelaine Angeline , Labasse Clémence , Boulogne Claire , Van Engelen Baziel G M , Ottenheijm Coen A C , Romero Norma B , Voermans Nicol C , Malfatti Edoardo
Published: March 2021

Nemaline myopathy type 6 (NEM6), KBTBD13-related congenital myopathy is caused by mutated KBTBD13 protein that interacts improperly with thin filaments/actin, provoking impaired muscle-relaxation kinetics. We describe muscle morphology in 18 Dutch NEM6 patients and correlate it with clinical phenotype and pathophysiological mechanisms. Rods were found in in 85% of biopsies by light microscopy, and 89% by electron microscopy. A peculiar ring disposition of rods resulting in ring-rods fiber was observed. Cores were found in 79% of NEM6 biopsies by light microscopy, and 83% by electron microscopy. Electron microscopy also disclosed granulofilamentous protein material in 9 biopsies. Fiber type 1 predominance and prominent nuclear internalization were found. Rods were immunoreactive for α-actinin and myotilin. Areas surrounding the rods showed titin overexpression suggesting derangement of the surrounding sarcomeres. NEM6 myopathology hallmarks are prominent cores, rods including ring-rods fibers, nuclear clumps, and granulofilamentous protein material. This material might represent the histopathologic epiphenomenon of altered interaction between mutated KBTBD13 protein and thin filaments. We claim to classify KBTBD13-related congenital myopathy as rod-core myopathy.
Poplar MYB117 promotes anthocyanin synthesis and enhances flavonoid B-ring hydroxylation by up-regulating the flavonoid 3′,5′-hydroxylase gene
Authors: Ma Dawei , Tang Hao , Reichelt Michael , Piirtola Eerik-Mikael , Salminen Juha-Pekka , Gershenzon Jonathan , Constabel C Peter
Published: March 2021

Flavonoids, such as anthocyanins, proanthocyanidins, and flavonols, are widespread plant secondary metabolites and important for plant adaptation to diverse abiotic and biotic stresses. Flavonoids can be variously hydroxylated and decorated; their biological activity is partly dependent on the degree of hydroxylation of the B-ring. Flavonoid biosynthesis is regulated by MYB transcription factors, which have been identified and characterized in a diversity of plants. Here we characterize a new MYB activator, MYB117, in hybrid poplar (Populus tremula×tremuloides). When overexpressed in transgenic poplar plants, MYB117 enhanced anthocyanin accumulation in all tissues. Transcriptome analysis of MYB117-overexpressing poplars confirmed the up-regulation of flavonoid and anthocyanin biosynthesis genes, as well as two flavonoid 3′,5′-hydroxylase (F3′5′H) genes. We also identified up-regulated cytochrome b5 genes, required for full activity of F3′5′H . Phytochemical analysis demonstrated a corresponding increase in B-ring hydroxylation of anthocyanins, proanthocyanidins, and flavonols in these transgenics. Similarly, overexpression of F3′5′H1 directly in hybrid poplar also resulted in increased B-ring hydroxylation, but without affecting overall flavonoid content. However, the overexpression of the cytochrome b5 gene in F3′5′H1-overexpressing plants did not further increase B-ring hydroxylation. Our data indicate that MYB117 regulates the biosynthesis of anthocyanins in poplar, but also enhances B-ring hydroxylation by up-regulating F3′5′H1.
Seasonal and long-term consequences of esca grapevine disease on stem xylem integrity
Authors: Bortolami Giovanni , Farolfi Elena , Badel Eric , Burlett Regis , Cochard Herve , Ferrer Nathalie , King Andrew , Lamarque Laurent J , Lecomte Pascal , Marchesseau-Marchal Marie , Pouzoulet Jerome , Torres-Ruiz Jose M , Trueba Santiago , Delzon Sylvain , Gambetta Gregory A , Delmas Chloe E L
Published: March 2021

Hydraulic failure has been extensively studied during drought-induced plant dieback, but its role in plant-pathogen interactions is under debate. During esca, a grapevine (Vitis vinifera) disease, symptomatic leaves are prone to irreversible hydraulic dysfunctions but little is known about the hydraulic integrity of perennial organs over the short- and long-term. We investigated the effects of esca on stem hydraulic integrity in naturally infected plants within a single season and across season(s). We coupled direct (ks) and indirect (kth) hydraulic conductivity measurements, and tylose and vascular pathogen detection with in vivo X-ray microtomography visualizations. Xylem occlusions (tyloses) and subsequent loss of stem hydraulic conductivity (ks) occurred in all shoots with severe symptoms (apoplexy) and in more than 60% of shoots with moderate symptoms (tiger-stripe), with no tyloses in asymptomatic shoots. In vivo stem observations demonstrated that tyloses occurred only when leaf symptoms appeared, and resulted in more than 50% loss of hydraulic conductance in 40% of symptomatic stems, unrelated to symptom age. The impact of esca on xylem integrity was only seasonal, with no long-term impact of disease history. Our study demonstrated how and to what extent a vascular disease such as esca, affecting xylem integrity, could amplify plant mortality through hydraulic failure.
A Galactic survey of radio jets from massive protostars
Authors: Purser S J D , Lumsden S L , Hoare M G , Kurtz S
Published: March 2021

In conjunction with a previous southern-hemisphere work, we present the largest radio survey of jets from massive protostars to date with high-resolution (∼0.04 arcsec) Jansky Very Large Array observations towards two subsamples of massive star-forming regions of different evolutionary statuses: 48 infrared-bright, massive, young, stellar objects (MYSOs) and 8 infrared dark clouds (IRDCs) containing 16 luminous ($\hbox{$\, L_{\rm {bol}}$}\gt 10^3\hbox{${\rm \, L_{\odot }}$}$) cores. For 94 per cent of the MYSO sample, we detect thermal radio (α ≥ −0.1 whereby Sν ∝ να) sources coincident with the protostar, of which 84 per cent (13 jets and 25 candidates) are jet like. Radio luminosity is found to scale with $\hbox{$\, L_{\rm {bol}}$}$ similarly to the low-mass case supporting a common mechanism for jet production across all masses. Associated radio lobes tracing shocks are seen towards 52 per cent of jet-like objects and are preferentially detected towards jets of higher radio and bolometric luminosities, resulting from our sensitivity limitations. We find jet mass-loss rate scales with bolometric luminosity as $\hbox{$\dot{m}_{\rm jet}$}\propto \hbox{$\, L_{\rm {bol}}$}^{0.9\pm 0.2}$, thereby discarding radiative, line-driving mechanisms as the dominant jet-launching process. Calculated momenta show that the majority of jets are mechanically capable of driving the massive, molecular outflow phenomena since pjet > poutflow. Finally, from their physical extent we show that the radio emission cannot originate from small, optically thick H ii regions. Towards the IRDC cores, we observe increasing incidence rates/radio fluxes with age using the proxy of increasing luminosity-to-mass (L/M) and decreasing infrared flux ratios $({S_{70{\rm \, \mu m}}}/{S_{24{\rm \, \mu m}}})$. Cores with $({L}/{M})\,\lt \,40\, \hbox{${\rm \, L_{\odot }}$}\hbox{${\rm \, M_{\odot }}$}^{-1}$ are not detected above ($5.8{\rm \, GHz}$) radio luminosities of ${\sim}1{\rm \, mJy}{\rm \, kpc}^2$.
Particle-in-cell simulations of the Cassini spacecraft’s interaction with Saturn’s ionosphere during the Grand Finale
Authors: Zhang Zeqi , Desai Ravindra T , Miyake Yohei , Usui Hideyuki , Shebanits Oleg
Published: March 2021

A surprising and unexpected phenomenon observed during Cassini’s Grand Finale was the spacecraft charging to positive potentials in Saturn’s ionosphere. Here, the ionospheric plasma was depleted of free electrons with negatively charged ions and dust accumulating up to over 95 per cent of the negative charge density. To further understand the spacecraft–plasma interaction, we perform a three-dimensional Particle-In-Cell study of a model Cassini spacecraft immersed in plasma representative of Saturn’s ionosphere. The simulations reveal complex interaction features such as electron wings and a highly structured wake containing spacecraft-scale vortices. The results show how a large negative ion concentration combined with a large negative to positive ion mass ratio is able to drive the spacecraft to the observed positive potentials. Despite the high electron depletions, the electron properties are found as a significant controlling factor for the spacecraft potential together with the magnetic field orientation which induces a potential gradient directed across Cassini’s asymmetric body. This study reveals the global spacecraft interaction experienced by Cassini during the Grand Finale and how this is influenced by the unexpected negative ion and dust populations.
Towards a volumetric census of close white dwarf binaries – I. Reference samples
Authors: Inight K , Gänsicke Boris T , Breedt E , Marsh T R , Pala A F , Raddi R
Published: March 2021

Close white dwarf binaries play an important role across a range of astrophysics, including thermonuclear supernovae, the Galactic low-frequency gravitational wave signal, and the chemical evolution of the Galaxy. Progress in developing a detailed understanding of the complex, multithreaded evolutionary pathways of these systems is limited by the lack of statistically sound observational constraints on the relative fractions of various sub-populations and their physical properties. The available samples are small, heterogeneous, and subject to a multitude of observational biases. Our overarching goal is to establish a volume-limited sample of all types of white dwarf binaries that is representative of the underlying population as well as sufficiently large to serve as a benchmark for future binary population models. In this first paper, we provide an overview of the project, and assemble reference samples within a distance limit of 300 pc of known white dwarf binaries spanning the most common sub-classes: post-common envelope binaries containing a white dwarf plus a main-sequence star, cataclysmic variables, and double-degenerate binaries. We carefully vet the members of these “Gold” samples, which span most of the evolutionary parameter space of close white dwarf binary evolution. We also explore the differences between magnitude and volume limited close white dwarf binary samples, and discuss how these systems evolve in their observational properties across the Gaia Hertzsprung–Russell diagram.
The EDGE-CALIFA survey: self-regulation of star formation at kpc scales
Authors: Barrera-Ballesteros J K , Sánchez S F , Heckman T , Wong T , Bolatto A , Ostriker E , Rosolowsky E , Carigi L , Vogel S , Levy R C , Colombo D , Luo Yufeng , Cao Yixian
Published: March 2021

The processes that regulate star formation are essential to understand how galaxies evolve. We present the relation between star formation rate density, ΣSFR , and hydrostatic mid-plane pressure,Ph, for 4260 star-forming regions of kpc size located in 96 galaxies included in the EDGE-CALIFA survey covering a wide range of stellar masses and morphologies. We find that these two parameters are tightly correlated, showing a smaller scatter in comparison to other star-forming relations. A power law, with a slightly sublinear index, is a good representation of this relation. Its residuals show a significant anticorrelation with both stellar age and metallicity whereas the total stellar mass may also play a secondary role in shaping the ΣSFR–Ph relation. For actively star-forming regions, we find that the effective feedback momentum per unit stellar mass (p*/m*), measured from thePh/ΣSFR  ratio increases withPh. The median value of this ratio for all the sampled regions is larger than the expected momentum just from supernovae explosions. Morphology of the galaxies, including bars, does not seem to have a significant impact in the ΣSFR–Ph relation. Our analysis indicates that local ΣSFR self-regulation comes mainly from momentum injection to the interstellar medium from supernovae explosions. However, other mechanisms in disc galaxies may also play a significant role in shaping the ΣSFR at kpc scales. Our results also suggest thatPh is the main parameter that modulates star formation at kpc scales, rather than individual components of the baryonic mass.
On the impact of batch effect correction in TCGA isomiR expression data
Authors: Ibing Susanne , Michels Birgitta E , Mosdzien Moritz , Meyer Helen R , Feuerbach Lars , Körner Cindy
Published: March 2021

MicroRNAs (miRNAs) are small non-coding RNAs with diverse functions in post-transcriptional regulation of gene expression. Sequence and length variants of miRNAs are called isomiRs and can exert different functions compared to their canonical counterparts. The Cancer Genome Atlas (TCGA) provides isomiR-level expression data for patients of various cancer entities collected in a multi-center approach over several years. However, the impact of batch effects within individual cohorts has not been systematically investigated and corrected for before. Therefore, the aim of this study was to identify relevant cohort-specific batch variables and generate batch-corrected isomiR expression data for 16 TCGA cohorts. The main batch variables included sequencing platform, plate, sample purity and sequencing depth. Platform bias was related to certain length and sequence features of individual recurrently affected isomiRs. Furthermore, significant downregulation of reported tumor suppressive isomiRs in lung tumor tissue compared to normal samples was only observed after batch correction, highlighting the importance of working with corrected data. Batch-corrected datasets for all cohorts including quality control are provided as supplement. In summary, this study reveals that batch effects present in the TCGA dataset might mask biologically relevant effects and provides a valuable resource for research on isomiRs in cancer (accessible through GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE164767).
A Novel Framework for Network-Targeted Neuropsychiatric Deep Brain Stimulation
Authors: Allawala Anusha , Bijanki Kelly R , Goodman Wayne , Cohn Jeffrey F , Viswanathan Ashwin , Yoshor Daniel , Borton David A , Pouratian Nader , Sheth Sameer A
Published: March 2021

Deep brain stimulation (DBS) has emerged as a promising therapy for neuropsychiatric illnesses, including depression and obsessive-compulsive disorder, but has shown inconsistent results in prior clinical trials. We propose a shift away from the empirical paradigm for developing new DBS applications, traditionally based on testing brain targets with conventional stimulation paradigms. Instead, we propose a multimodal approach centered on an individualized intracranial investigation adapted from the epilepsy monitoring experience, which integrates comprehensive behavioral assessment, such as the Research Domain Criteria proposed by the National Institutes of Mental Health. In this paradigm-shifting approach, we combine readouts obtained from neurophysiology, behavioral assessments, and self-report during broad exploration of stimulation parameters and behavioral tasks to inform the selection of ideal DBS parameters. Such an approach not only provides a foundational understanding of dysfunctional circuits underlying symptom domains in neuropsychiatric conditions but also aims to identify generalizable principles that can ultimately enable individualization and optimization of therapy without intracranial monitoring.
Impact of race on care, readmissions, and survival for patients with glioblastoma: an analysis of the National Cancer Database
Authors: Hodges Tiffany R , Labak Collin M , Mahajan Uma V , Wright Christina Huang , Wright James , Cioffi Gino , Gittleman Haley , Herring Eric Z , Zhou Xiaofei , Duncan Kelsey , Kruchko Carol , Sloan Andrew E , Barnholtz-Sloan Jill S
Published: March 2021

Background

The objective of this study was to explore racial/ethnic factors that may be associated with survival in patients with glioblastoma by querying the National Cancer Database (NCDB).

Methods

The NCDB was queried for patients diagnosed with glioblastoma between 2004 and 2014. Patient demographic variables included age at diagnosis, sex, race, ethnicity, Charlson–Deyo score, insurance status, and rural/urban/metropolitan location of zip code. Treatment variables included surgical treatment, extent of resection, chemotherapy, radiation therapy, type of radiation, and treatment facility type. Outcomes included 30-day readmission, 30- and 90-day mortality, and overall survival. Multivariable Cox regression analyses were performed to evaluate variables associated with race and overall survival.

Results

A total of 103 652 glioblastoma patients were identified. There was a difference in the proportion of patients for whom surgery was performed, as well as the proportion receiving radiation, when stratified by race (P < .001). Black non-Hispanics had the highest rates of unplanned readmission (7.6%) within 30 days (odds ratio [OR]: 1.39 compared to White non-Hispanics, P < .001). Asian non-Hispanics had the lowest 30- (3.2%) and 90-day mortality (9.8%) when compared to other races (OR: 0.52 compared to White non-Hispanics, P = .031). Compared to White non-Hispanics, we found Black non-Hispanics (hazard ratio [HR]: 0.88, P < .001), Asian non-Hispanics (HR: 0.72, P < .001), and Hispanics (HR: 0.69, P < .001) had longer overall survival.

Conclusions

Differences in treatment and outcomes exist between races. Further studies are needed to elucidate the etiology of these race-related disparities and to improve outcomes for all patients.
Clinical Value Evaluation of microRNA-324-3p and Other Available Biomarkers in Patients With HBV Infection–Related Hepatocellular Carcinoma
Authors: Zhao Li , Yang Qian , Liu Jianbo
Published: March 2021

Background

Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC.

Methods

Expression of miR-324-3p in HBV infection–related cells and patients was estimated using quantitative real-time polymerase chain reaction (PCR). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, alpha-fetoprotein (AFP), and protein induced by vitamin K absence/antagonist II (PIVKA-II) in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B patients (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using the chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC.

Results

HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC cases with HBV infection, and the combination of miR-324-3p, AFP, and PIVKA-II showed improved diagnostic performance. Additionally, high-serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage, and poor overall survival prognosis.

Conclusions

High-serum miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.
(Mis)Attributing the Causes of American Job Loss
Authors: Mutz Diana C
Published: March 2021

What difference does it make if people attribute the loss of manufacturing jobs to trade as opposed to automation? Attributions of responsibility for social problems help shape mass opinion. In this study I use two experiments, including one nationally representative probability survey-experiment, to examine the consequences of attributing job loss to trade versus automation. Findings suggest that as of 2018, public discourse attributes manufacturing job loss in America primarily to trade. When I experimentally manipulate attributions of responsibility for job loss, I find important consequences for levels of mass support for international trade, the extent of negative emotions arising from job loss, and beliefs that trade restrictions and tariffs can bring back manufacturing jobs. Finally, job loss that is attributed to trade—even when it is a single job loss—also serves as a threat to the national ingroup, which triggers a heightened sense of national superiority among white Americans.
COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries
Authors: Tan Eng Hooi , Sena Anthony G , Prats-Uribe Albert , You Seng Chan , Ahmed Waheed-Ul-Rahman , Kostka Kristin , Reich Christian , Duvall Scott L , Lynch Kristine E , Matheny Michael E , Duarte-Salles Talita , Bertolin Sergio Fernandez , Hripcsak George , Natarajan Karthik , Falconer Thomas , Spotnitz Matthew , Ostropolets Anna , Blacketer Clair , Alshammari Thamir M , Alghoul Heba , Alser Osaid , Lane Jennifer C E , Dawoud Dalia M , Shah Karishma , Yang Yue , Zhang Lin , Areia Carlos , Golozar Asieh , Recalde Martina , Casajust Paula , Jonnagaddala Jitendra , Subbian Vignesh , Vizcaya David , Lai Lana Y H , Nyberg Fredrik , Morales Daniel R , Posada Jose D , Shah Nigam H , Gong Mengchun , Vivekanantham Arani , Abend Aaron , Minty Evan P , Suchard Marc , Rijnbeek Peter , Ryan Patrick B , Prieto-Alhambra Daniel
Published: March 2021

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017–18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5–93.2%), chronic kidney disease (14.0–52.7%) and heart disease (29.0–83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2–4.3% vs 6.32–24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.
Comparing cost-utility of DMARDs in autoantibody-negative rheumatoid arthritis patients
Authors: Nathalie Luurssen-Masurel , Mulligen Van Elise , Maria Weel Angelique Elisabeth Adriana , Wilhelmina Hazes Johanna Maria , Pieter de Jong Pascal Hendrik
Published: March 2021

Objectives

To evaluate the 1-year cost-effectiveness between three different initial treatment strategies in autoantibody-negative RA patients, according to 2010 criteria.

Methods

For this analysis we selected all RA patients within the intermediate probability stratum of the treatment in the Rotterdam Early Arthritis Cohort (tREACH) trial. The tREACH had a treat-to-target approach, aiming for low DAS <2.4, and treatment adjustments could occur every 3 months. Initial treatment strategies consisted of MTX 25 mg/week (initial MTX, iMTX), iHCQ 400 mg/day or an oral glucocorticoids tapering scheme without DMARDs (iGCs). Data on quality-adjusted life-years, measured with the European Quality of Life 5-Dimensions 3 Levels (EQ-5D-3L), healthcare and productivity costs were used.

Results

Average quality-adjusted life-years (s.d.), for iMTX, iHCQ and iGCs were respectively 0.71 (0.14), 0.73 (0.14) and 0.71 (0.15). The average total costs (s.d.) for iMTX, iHCQ and iGCs were, respectively, €10 832 (14.763), €11 208 (12.801) and €10 502 (11.973). Healthcare costs were mainly determined by biological costs, which were significantly lower in the iHCQ group compared with iGCs (P < 0.05). However, costs due to presenteeism were the highest in the iHCQ group (55%) followed by iMTX (27%) and iGCs (18%). The incremental cost-effectiveness ratios did not differ between treatment strategies. At a willingness-to-pay level of €50 000, the Dutch threshold for reimbursement of medical care, iHCQ had the highest probability (38.7%) of being cost-effective, followed by iGCs (31.1%) and iMTX (30.2%).

Conclusion

iHCQ had the lowest healthcare and highest productivity costs, resulting in a non-significant incremental cost-effectiveness ratio. However, iHCQ had the highest chance of being cost-effective at the Dutch willingness-to-pay threshold for healthcare reimbursement. Therefore, we believe that iHCQ is a good alternative to iMTX in autoantibody-negative RA patients, but validation is needed.

Clinical trial registration number

ISRCTN26791028
Associations between longitudinal trajectories of insomnia symptoms and sleep duration with objective physical function in postmenopausal women: the Study of Women’s Health Across the Nation
Authors: Kline Christopher E , Colvin Alicia B , Pettee Gabriel Kelley , Karvonen-Gutierrez Carrie A , Cauley Jane A , Hall Martica H , Matthews Karen A , Ruppert Kristine M , Neal-Perry Genevieve S , Strotmeyer Elsa S , Sternfeld Barbara
Published: March 2021

Study Objectives

Examine the association between trajectories of self-reported insomnia symptoms and sleep duration over 13 years with objective physical function.

Methods

We utilized data from 1,627 Study of Women’s Health Across the Nation participants, aged 61.9 ± 2.7 years at the end of the 13-year follow-up. Latent class growth models identified trajectories of insomnia symptoms (trouble falling asleep, frequent night-time awakenings, and/or early morning awakening) and sleep duration over 13 years. Physical function tests were performed at the end of the 13-year period: 40-ft walk, 4-m walk, repeated chair stand, grip strength, and balance. Multivariable regression analyses examined each physical function measure according to the insomnia symptom or sleep duration trajectory group.

Results

Five insomnia symptom trajectories and two sleep duration trajectories were identified. Women with a consistently high likelihood of insomnia symptoms and women with a decreased likelihood of insomnia symptoms (i.e. improving) had slower gait speed (3.5% slower 40-ft walk [consistently high], 3.7% slower 4-m walk [improving]; each p ≤ .05) than those with a consistently low likelihood of insomnia symptoms. In contrast, women with a steep increase in the likelihood of insomnia symptoms over time and women with persistent insufficient sleep duration had lower odds of having a balance problem (odds ratio [OR] = 0.36 and OR = 0.61, respectively; each p < .02) compared to those with a consistently low likelihood of insomnia symptoms and those with persistent sufficient sleep duration, respectively.

Conclusion

These results suggest that women’s sleep during midlife has important implications for maintaining physical function during the transition into older adulthood.
Effects of conditioning temperature and pellet mill die speed on pellet quality and relative stabilities of phytase and xylanase
Authors: Evans Caitlin E , Saensukjaroenphon Marut , Gebhardt Jordan T , Stark Charles R , Paulk Chad B
Published: March 2021

The objective of this experiment was to determine the effect of conditioning temperature and die speed on pellet quality and enzyme stability of phytase and xylanase. Treatments were initially arranged as a 2 × 3 factorial of conditioning temperature (74 and 85 °C) and die speed (127, 190, and 254 rpm); however, when conditioning at 85 °C, it was not possible to pellet at 127 rpm. Thus, data were analyzed in two different segments using the GLIMMIX procedure of SAS. First, linear and quadratic contrasts were utilized to test the response to increasing die speed at 74 °C. Second, the data was analyzed as a 2 × 2 factorial of conditioning temperature (74 and 85 °C) and die speed (190 and 254 rpm). Treatments were arranged in a completely randomized design and replicated three times. Diets were conditioned for approximately 30 s and pelleted with a 4.8-mm-diameter × 44.5-mm-effective length die at a rate of 4.5 MT/h. Pellet durability index (PDI) was determined using the tumble box and Holmen NHP 100 methods. Samples of the unconditioned mash (M), conditioned mash (CM), and pellets (P) were collected and analyzed for phytase and xylanase concentration. Relative enzyme stabilities were expressed as CM:M, P:CM, and P:M. Stabilities expressed as P:M were used an indication of enzyme stability through the entire pelleting process. Diets conditioned at 74 °C showed no evidence of difference in phytase or xylanase P:M stability when decreasing die speed from 254 to 127 rpm. However, when conditioning diets at 74 °C, decreasing die speed increased (linear, P < 0.001) PDI. There was no conditioning temperature × die speed interaction for overall xylanase P:M stability or PDI. However, there was a conditioning temperature × die speed interaction (P < 0.01) for phytase P:M stability. When conditioning diets at 85 °C, increasing die speed decreased phytase P:M stability. However, when conditioning at 74 °C, increasing die speed did not influence phytase P:M stability. For main effects of conditioning temperature, increasing temperature improved (P < 0.001) PDI with no evidence of difference for xylanase P:M stability. For the main effects of die speed (254 vs. 190 rpm), decreasing die speed decreased (P < 0.001) the P:M xylanase stability, but there was no evidence of difference for PDI. The results of this trial indicate that die speed should be taken into consideration when evaluating enzyme stability of both phytase and xylanase as pellet mill models may be operating at different speeds. Additionally, increasing conditioning temperature will improve PDI but may result in decreased phytase stability.
Effects of varying sources of Cu, Zn, and Mn on mineral status and preferential intake of salt-based supplements by beef cows and calves and rainfall-induced metal loss
Authors: Arthington John D , Silveira Maria L , Caramalac Luana S , Fernandes Henrique J , Heldt Jeff S , Ranches Juliana
Published: March 2021

Three studies were completed to evaluate the effects of Cu, Zn, and Mn source on preferential intake, trace mineral status, and rainfall-induced metal loss of salt-based mineral supplements. Mineral supplements were formulated to contain 2,500, 5,500, and 4,000 mg/kg of Cu, Zn, and Mn, respectively. Supplements differed only by source of Cu, Zn, and Mn, which were hydroxychloride, organic, or sulfate sources. In Exp. 1, the three formulations were offered simultaneously for 18 wk to preweaned beef calves (four pastures; 17 calves per pasture) within separate containers inside covered cow-exclusion areas. Consumption averaged 21 ± 2.4 g/calf daily (sum of all three sources), with a greater (P < 0.001) percentage of the total intake coming from the hydroxychloride vs. organic or sulfate sources of Cu, Zn, and Mn. In Exp. 2, the same sulfate and hydroxychloride formulations were randomly assigned to pastures (n = 4 pastures per treatment) containing 18 to 20 cow–calf pairs/pasture. Treatments were offered for 20 wk within covered areas designed to assess cow and calf intake separately. At weaning, liver biopsies were collected from four cow–calf pairs/pasture (n = 16 cows and calves per treatment). Source of Cu, Zn, and Mn had no effect on voluntary mineral intake among calves (P = 0.44) and cows (P = 0.14). Calves consuming mineral containing hydroxychloride sources of Cu, Zn, and Mn tended (P = 0.06) to have greater average daily gain over the 20-wk period compared with calves consuming sulfate sources of the same elements (1.09 vs. 1.06 kg/d; SEM = 0.013). Mineral status of cows and calves was not affected (P ≥ 0.17) by source of Cu, Zn, and Mn. In Exp. 3, each of the mineral formulations from Exp. 1 was exposed to a 10.2-cm precipitation event delivered in three equal 3.4-cm applications within a week. To accomplish this, 750 g of mineral was placed into Buchner funnels (177 cm2) on 20- to 25-µm pore filter paper. Deionized water (pH adjusted to 5.6) was poured over the mineral. Total leaching losses of Cu, Zn, and Mn were less (P < 0.001) for formulations containing hydroxychloride vs. organic and sulfate sources. These results imply that, when offered a choice, calves preferentially consume mineral supplements formulated with hydroxychloride vs. sulfate or organic sources of Cu, Zn, and Mn. In addition, hydroxychloride sources of Cu, Zn, and Mn are less susceptible to rainfall-induced leaching losses compared with sulfate and organic sources.