bluuebunny/crossref_metadata_2025 huggingface dataset:
A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality
Authors: Smart Lucinda , Fawkes Neil , Goggin Paul , Pennick Graham , Rainsford K. D. , Charlesworth Bruce , Shah Neil
Published: August 2020

The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19.
Embodied Cognition, affects and language comprehension
Authors: Odendahl Johannes
Published: August 2020

Our main considerations take as a starting point the educational policy demand for a model of competence of text comprehension, which should make it possible to measure and systematically increase comprehension accomplishments and competences. The approach of classical cognitive psychology appears particularly suitable for this purpose, which determines comprehension as a rule-guided transfer of a sign complex into a mental representation. However, such representationalism tends to be aporetic in character. A way out of this problem is offered by recent concepts of understanding from the area ofEmbodied Cognition, according to which all mental operations are embedded in physical interaction processes. Comprehension means, in this sense, letting physical primary experiences be reproduced in a trial-action fashion. This approach is, in this paper, reconsidered in relation to the role of subjectivity and affect: Physical experiences are meaning-generating because they exhibit a subjectively perceived affective valence between pleasure and suffering. The beginning of all understanding therefore is to be located within the emotional sphere.

Such a conception of understanding is supposed to have a considerable impact upon language- and literature teaching in schools. For example, training of reading skills should always be embedded in body-bound experiences. Moreover, learning and understanding both mean cultivating an alert ear for affective undertones, needs and irritations, which might even lead to drawing the curricular benchmarks and competency targets into question. Finally, as art and literature establish areas of freedom and play, literature teaching, especially, needs to be founded on affective awareness, discursive openness and proceeding voluntariness.
MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation
Authors: Guarino Maria Luisa , Massimi Isabella , Alemanno Laura , Conti Laura , Angiolillo Dominick J. , Pulcinelli Fabio M.
Published: August 2020

The impact of inhibition of multidrug resistance protein 4 (MRP4) on nitric oxide (NO) resistance and on ADP-induced platelet aggregation is unknown. The aim of this investigation was to verify whether platelet NO resistance correlates with MRP4 expression and evaluate whether this can be reduced by in vitro MRP4 inhibition mediated by cilostazol. Moreover, we assessed if inhibition of MRP4-mediated transport reduces ADP-induced platelet reactivity. The inhibitory effect of sodium nitroprusside (SNP), a NO-donor that enhances cyclic guanosine monophosphate (cGMP) cytosolic concentration, was assessed in platelets obtained from aspirin treated patients and in a control population. The inhibitory effect of SNP was evaluated by ADP-induced aggregation in SNP-treated platelets. The impact of MRP4 on ADP-induced platelet aggregation was performed in high on aspirin residual platelet reactivity (HARPR) patients and compared to healthy volunteers (HV), and a control cohort (CTR). In aspirin-treated patients with high levels of MRP4, reduced SNP inhibition was found compared to those with low levels of MRP4. MRP4 inhibition by cilostazol significantly reduced ADP-induced platelet aggregation in HARPR population, and to a lesser extent in HV and CTR populations. In conclusion, cilostazol can mitigate the hyper-reactive platelet phenotype of HARPR patients by reducing residual ADP-induced platelet aggregation and increasing NO-dependent endothelial antiplatelet effects.
Triboelectrochemistry: Influence of Applied Electrical Potentials on Friction and Wear of Lubricated Contacts
Authors: Spikes Hugh A.
Published: August 2020

Research on the effects of applied electrical potential on friction and wear, a topic sometimes termed “Triboelectrochemistry”, has been reviewed. Historically, most such research has focussed on aqueous lubricants, whose relatively high electrical conductivities enable use of three-electrode electrochemical kinetic techniques, in which the electrode potential at a single electrode|fluid interface is controlled relative to a suitable reference electrode. This has led to identification of several different mechanisms by which applied electrode potentials can influence friction and wear. Of these, the most practically important are: (i) promotion of adsorption/desorption of polar additives on tribological surfaces by controlling the latters’ surface charges; (ii) stimulation or suppression of redox reactions involving either oxygen or lubricant additives at tribological surfaces. In recent years, there has been growing interest in the effects of applied electrical potentials on rubbing contacts lubricated by non-aqueous lubricants, such as ester- and hydrocarbon-based oils. Two different approaches have been used to study this. In one, a DC potential difference in the mV to V range is applied directly across a thin film, lubricated contact to form a pair of electrode|fluid interfaces. This has been found to promote some additive reactions and to influence friction and wear. However, little systematic exploration has been reported of the underlying processes and generally the electrode potentials at the interfaces have not been well defined. The second approach is to increase the conductivity of non-aqueous lubricants by adding secondary electrolytes and/or using micro/nanoscale electrodes, to enable the use of three-electrode electrochemical methods at single metal|fluid interfaces, with reference and counter electrodes. A recent development has been the introduction of ionic liquids as both base fluids and lubricant additives. These have relatively high electrical conductivities, allowing control of applied electrode potentials of individual metal|fluid interfaces, again with reference and counter electrodes. The broadening use of “green”, aqueous-based lubricants also enlarges the possible future scope of applied electrode potentials in tribology. From research to date, there would appear to be considerable opportunities for using applied electrical potentials both to promote desirable and to supress unwanted lubricant interactions with rubbing surfaces, thereby improving the tribological performance of lubricated machine components.

Graphical Abstract
Bioaugmentation of Soil Contaminated with Zinc
Authors: Strachel Rafał , Wyszkowska Jadwiga , Baćmaga Małgorzata
Published: August 2020

An experiment described in this work aimed to establish the role of bioaugmentation in minimizing adverse outcomes of loamy sand contamination with zinc. The bioaugmentation was conducted with the use of microbial strains being most resistant to the action of zinc, which were isolated from the soil contaminated with 1250 mg Zn2+ kg−1 dry matter (DM) of soil after 12-month incubation. The soil was inoculated with 4 strains of bacteria (Bacillus licheniformis KT986159.1, Bacillus sp. KF956639.1, Gordonia amicalis KM113029.1, Leifsonia sp. KJ191763.1) and 4 strains of fungi (Penicillium raperi KC797647.1, Penicillium janthinellum AY373921.1, Penicillium glabrum LT558918.1, Trichoderma harzianum LN714612.1). In the case of the non-contaminated soil, a metal dose of 250 mg Zn2+ kg−1 DM of soil contributed to enhanced proliferation and microorganisms and enzymatic activity. In turn, zinc in its highest dose (1250 mg Zn2+ kg−1 DM of soil) evoked adverse effects, which were manifested in reduced numbers and diversity of microorganisms and suppressed activity of soil enzymes. This contamination rate stimulated only the proliferation of fungi, but their ecophysiological diversity was reduced either. The bioaugmentation treatment minimized adverse effects of zinc. Unfortunately, the use of autochthonous microorganisms failed to reduce zinc bioavailability in the soil.
Ion-Implanted Epitaxially Grown Gd2O3 on Silicon with Improved Electrical Properties
Authors: Joseph A. , Lilienkamp G. , Wietler T. F. , Osten H. J.
Published: August 2020

The effects of nitrogen incorporation by high-dose ion implantation in epitaxial gadolinium oxide (Gd2O3) films on Si (111) followed by annealing have been investigated. The nitrogen content in the oxide layer was changed by altering the implantation dose. The presence of nitrogen incorporation on the Gd2O3 layer was studied using Auger electron spectroscopy. Nitrogen incorporation is believed to occur by filling the oxygen vacancies or by removing hydroxyl group ions in Gd2O3. A maximum concentration of 11% was obtained for nitrogen in the interface between the silicon dioxide and Gd2O3 layer and the implanted areas of the Gd2O3 oxide layer after sputter depth profiling. The nitrogen distribution in the layer was found to be non-uniform. Nitrogen incorporation sharply reduced the leakage current and effectively suppressed the hysteresis. Leakage current was two orders lower compared with the pure Gd2O3.
The future of combination therapies in advanced melanoma
Authors: Hoeller Christoph
Published: August 2020

The combination of Cytotoxic T-Lymphozyte Antigen-4 (CTLA‑4) and Programmed death-1 (PD‑1) antibodies and the combination of BRAF and MEK inhibitors are the current clinical standards for combination immune and targeted therapy for melanoma, respectively. The success of these therapies has stimulated research into novel drug combinations for melanoma, of which a large majority are based on combination with PD‑1 or PD-Ligand 1 (PD-L1) blocking drugs. Thus, the aim is to provide an overview of the most important combination strategies in late stage clinical development and an outlook on drug combinations in early development that might enter larger clinical trials within the next few years.
Household Composition and Gender Differences in Parental Time Investments
Authors: Bibler Andrew J.
Published: August 2020

Recent research has documented the relatively poor performance of boys, especially those from single-mother households, on a number of outcomes. Differences in noncognitive skills are often cited as a main contributing factor. However, we still know little about the underlying mechanisms driving differences in noncognitive skills and other outcomes. This article provides empirical evidence that parental time investments, defined as the amount of time that parents spend participating in activities with their child, change differentially by child gender following a transition from a two-parent to single-mother household. Boys experience larger investment reductions following the change in household structure, which may help facilitate previously documented gender gaps in noncognitive skills for those in single-mother households. Boys lose an estimated additional 3.8 hours per week in fathers’ time investments, nearly 30% of average weekly paternal investments across the sample. The difference is increasing with age, concentrated in leisure and entertainment activities, with little to no evidence that mothers increase investments in boys relative to girls after such transitions.
Flexible Ethikgremien. Impulse zur Institutionalisierung ethisch verantwortlicher Feldforschung in der Konflikt- und Fluchtforschung
Authors: Krause Ulrike , Williams Timothy
Published: August 2020

Forschungsvorhaben in der Konflikt- und Fluchtforschung finden häufig in schwierigen Kontexten statt und erfordern forschungsethische Reflexionen. Welche Bedeutungen kommen Ethikkommissionen und -prüfungen zur Förderung und Sicherstellung von ethisch verantwortlicher Forschung in diesen Bereichen zu? Mit dieser Ausgangsfrage setzen wir uns in dem Beitrag auseinander und kontrastieren Argumente für und gegen standardisierte Kommissionen und Prüfungen. Da sich Kritiken häufig auf zu starke Kontrollen solcher Kommissionen richten, Forschende aber den Austausch als relevant erachten, schlagen wir die Einrichtung und Nutzung von flexiblen interdisziplinären Ethikgremien vor. Diese Gremien würden nicht die Prüfungen, sondern vielmehr den Austausch über forschungsethische Fragen in den Mittelpunkt rücken. Mithilfe empirischer Beispiele zum Thema Sicherheit, konkret zur Forschung über genderbasierte Gewalt und zum Umgang mit sexueller Orientierung von Forschenden und Teilnehmenden reflektieren wir die Notwendigkeit ethisch verantwortlicher Forschung sowie den möglichen Mehrwert flexibler Ethikgremien.
VALUATION OF HYBRID FINANCIAL AND ACTUARIAL PRODUCTS IN LIFE INSURANCE BY A NOVEL THREE-STEP METHOD
Authors: Deelstra Griselda , Devolder Pierre , Gnameho Kossi , Hieber Peter
Published: August 2020

Financial products are priced using risk-neutral expectations justified by hedging portfolios that (as accurate as possible) match the product’s payoff. In insurance, premium calculations are based on a real-world best-estimate value plus a risk premium. The insurance risk premium is typically reduced by pooling of (in the best case) independent contracts. As hybrid life insurance contracts depend on both financial and insurance risks, their valuation requires a hybrid valuation principle that combines the two concepts of financial and actuarial valuation. The aim of this paper is to present a novel three-step projection algorithm to valuate hybrid contracts by decomposing their payoff in three parts: a financial, hedgeable part, a diversifiable actuarial part, and a residual part that is neither hedgeable nor diversifiable. The first two parts of the resulting premium are directly linked to their corresponding hedging and diversification strategies, respectively. The method allows for a separate treatment of unsystematic, diversifiable mortality risk and systematic, aggregate mortality risk related to, for example, epidemics or population-wide improvements in life expectancy. We illustrate our method in the case of CAT bonds and a pure endowment insurance contract with profit and compare the three-step method to alternative valuation operators suggested in the literature.
The thick skin bias in judgments about people in poverty
Authors: CHEEK NATHAN N. , SHAFIR ELDAR
Published: August 2020

We present a series of studies documenting what we call a ‘thick skin bias’ in people's perceptions of those living in poverty. Across a wide range of life events, from major to minor, people of lower socioeconomic status (SES) are systematically perceived as being less harmed by negative experiences than higher-SES people, even when this is patently false. In 18 studies, including a pre-registered survey of a nationally representative sample, we find that laypeople and professionals show the thick skin bias. We distinguish the bias from a tendency to dehumanize those in poverty and argue it cannot be attributed to the belief that the mere expectation that bad things will happen buffers people in poverty from suffering. The thick skin bias has potentially profound implications for the institutional and interpersonal neglect of those most in need of greater care and resources.
Fluid Permeation Through A Membrane With Infinitesimal Permeability Under Reynolds Lubrication
Authors: Tazaki Asahi , Takeuchi Shintaro , Miyauchi Suguru , Zhang Lucy T. , Onishi Ryo , Kajishima Takeo
Published: August 2020

To understand the lubrication-dominated permeation through a membrane, numerical simulations of permeation through a moving corrugated permeable membrane is carried out with a fully validated numerical method. Through comparisons between the numerical results and the results of an asymptotic analysis of permeate flux (under an infinitesimal permeability condition) using Reynolds lubrication equation, the effect of permeation on lubrication and its inverse effect (i.e., the dependence of permeation on lubrication) are discussed. The linear and non-linear dependences of the relaxation of the lubrication pressure due to membrane permeation are identified. The effect of the tangential component of the permeate flux is evaluated by a linear analysis, and the limitation of Reynolds-type lubrication is discussed.
Bounded solutions for an ordinary differential system from the Ginzburg–Landau theory
Authors: Beaulieu Anne
Published: August 2020

In this paper, we look at a linear system of ordinary differential equations as derived from the two-dimensional Ginzburg–Landau equation. In two cases, it is known that this system admits bounded solutions coming from the invariance of the Ginzburg–Landau equation by translations and rotations. The specific contribution of our work is to prove that in the other cases, the system does not admit any bounded solutions. We show that this bounded solution problem is related to an eigenvalue problem.
Maternal supplementation with uridine influences fatty acid and amino acid constituents of offspring in a sow–piglet model
Authors: Gao Lu-min , Liu Yi-lin , Zhou Xihong , Zhang Yan , Wu Xin , Yin Yu-long
Published: August 2020

To investigate the cumulative effects of maternal supplementation with nucleotides in the form of uridine (UR) on fatty acid and amino acid constituents of neonatal piglets, fifty-two sows in late gestation were assigned randomly into the control (CON) group (fed a basal diet) or UR group (fed a basal diet with 150 g/t UR). Samples of neonates were collected during farrowing. Results showed that supplementing with UR in sows’ diet significantly decreased the birth mortality of pigs (P = 0·05), and increased serum total cholesterol, HDL and LDL of neonatal piglets (P < 0·05). Moreover, the amino acid profile of serum and liver of neonatal piglets was affected by the addition of UR in sows’ diets (P < 0·05). Furthermore, an up-regulation of mRNA expression of energy metabolism-related genes, including fatty acid elongase 5, fatty acid desaturase 1, hormone-sensitive lipase and cholesterol-7a-hydroxylase, was observed in the liver of neonates from the UR group. Additionally, a decrease in placental gene expression of excitatory amino acid transporters 2, excitatory amino acid transporter 3 and neutral AA transporter 1 in the UR group was concurrently observed (P < 0·05), and higher protein expression of phosphorylated protein kinase B, raptor, PPARα and PPARγ in placenta from the UR group was also observed (P < 0·05). Together, these results showed that maternal UR supplementation could regulate placental nutrient transport, largely in response to an alteration of mTORC1–PPAR signalling, thus regulating the nutrition metabolism of neonatal piglets and improving reproductive performance.
‘A field of divine activity’: Divine aseity and holy scripture in dialogue with John Webster and Karl Barth
Authors: Rempel Brent A.
Published: August 2020

In dialogue with John Webster and Karl Barth, this essay considers the intersection of divine aseity and holy scripture. I argue that the doctrine of holy scripture is constituted by a backward reference, namely, the plentiful life of the triune God. The doctrine of divine aseity denotes God's self-existent triune life, which anchors God's bestowal of life. Construed negatively, aseity establishes the incommensurability of God and creatures by distinguishing, without sundering, scripture and God's self-communicative presence. Construed positively, aseity constitutes scripture as ‘a field of divine activity’, the sphere of the life-giving missions of the Word and Spirit. The triune God who livesa se, elects the texts of scripture to serve as intermediaries of God's vivifying address.
Seed nutrient content rather than size influences seed dispersal by scatterhoarding rodents in a West African montane forest
Authors: Yadok Biplang G. , Forget Pierre-Michel , Gerhard Daniel , Aliyu Babale , Chapman Hazel
Published: August 2020

Rodents can be important in seed dispersal through their scatterhoarding behaviour, yet, the seed traits that are most influential in seed removal by Afrotropical scatterhoarding rodents remains unclear. Here, we investigated the effect of seed size and nutrient content of four seed species on the scatterhoarding behaviour of rodents in an Afromontane forest, Ngel Nyaki forest, Nigeria. To do this we marked with thread-tags the seeds of Santiria trimera, Beilschmedia mannii, Carapa oreophila and Anthonotha noldeae and observed their fate. We predicted that (1) caching frequency would be higher for larger than smaller seed species; (2) caching frequency would be higher for nutrient-rich than nutrient-poor seeds; (3) larger seeds would be taken across farther distances; and (4) survival of cached seeds would be higher for nutrient-rich seeds. In contrast to studies elsewhere we found no difference in caching probabilities based on seed size, although nutrient-rich (high fat content) seeds had a higher probability of being predated than seeds with lower fat content. Larger and smaller seeds were dispersed over the same distances and nutrient-poor (high fibre content) seeds survived longer in seed caches. Overall, our findings suggest that large, nutrient-rich seed species are less likely to be dispersed by rodents.
ḤUNAYN IBN ISḤĀQ'S CONCEPTION OF HIS READING PUBLIC ACCORDING TO A PREVIOUSLY UNPUBLISHED LETTER
Authors: Connelly Coleman
Published: August 2020

This article presents an edition, translation, and analysis of a prefatory letter addressed by the Galen translator Ḥunayn ibn Isḥāq (d. 873) to one of his East-Syrian Christian patrons, the physician Salmawayh ibn Bunān (d. 840). Ḥunayn composed this Letter to Salmawayh ibn Bunān in Syriac, but it survives only in his nephew's Arabic translation. Since its discovery over eighty years ago, the text has received little attention and has never before been published in its entirety. The Letter provides new insight into Ḥunayn's early career and the Christian milieu in which he moved, demonstrating his indebtedness to the Syriac literary past exemplified by the prefaces of the earlier Galen translator Sergius of Rēšʿaynā (d. 536). At the same time, the Letter indicates part of what made ʿAbbāsid-era translators like Ḥunayn different from their late ancient predecessors. This study argues that increased demand from patrons and Ḥunayn's close reading of Galen's Hippocratic commentaries yielded the Letter’s novel claim that readers of all abilities can and should have access to ancient Greek scientific texts. In this way, the Letter hints tantalizingly at Ḥunayn's understanding of his own literary and scientific project and its relationship with the ancient Greek tradition.
Monochromatic cycle partitions in random graphs
Authors: Lang Richard , Lo Allan
Published: August 2020

Erdős, Gyárfás and Pyber showed that every r-edge-coloured complete graph Kn can be covered by 25 r2 log r vertex-disjoint monochromatic cycles (independent of n). Here we extend their result to the setting of binomial random graphs. That is, we show that if
$p = p(n) = \Omega(n^{-1/(2r)})$
, then with high probability any r-edge-coloured G(n, p) can be covered by at most 1000r4 log r vertex-disjoint monochromatic cycles. This answers a question of Korándi, Mousset, Nenadov, Škorić and Sudakov.
THE EFFECTS OF FISCAL POLICY AT THE EFFECTIVE LOWER BOUND
Authors: Bonam Dennis , De Haan Jakob , Soederhuizen Beau
Published: August 2020

We estimate the effects of government spending shocks during prolonged episodes of low interest rates, which we consider as proxy for the effective lower bound (ELB). Using a panel VAR model for 17 advanced countries, we find that both the government consumption and investment multipliers are significantly higher, and exceed unity, when interest rates are persistently low. Distinguishing between construction- and equipment-related government investments, we find that only the former raises output by significantly more when the ELB binds. This result can be explained by existing New Keynesian models featuring time-to-build constraints on government investment.
Availability and placement of healthy and discretionary food in Australian supermarkets by chain and level of socio-economic disadvantage
Authors: Schultz Sally , Cameron Adrian J , Grigsby-Duffy Lily , Robinson Ella , Marshall Josephine , Orellana Liliana , Sacks Gary
Published: August 2020

Objective:

The current study aimed to investigate availability and placement of healthy and discretionary (less healthy) food in supermarkets in Victoria, Australia, and examine variation by supermarket chain and area-level socio-economic disadvantage.

Design:

Cross-sectional supermarket audit. Measures included: (i) proportion of shelf space (in square metres) allocated to selected healthy and discretionary food and beverages; (ii) proportion of end-of-aisle, checkout and island bin displays containing discretionary food and beverages and (iii) proportion of space within end-of-aisle, checkout and island bin displays devoted to discretionary food and beverages.

Setting:

Metropolitan areas of Melbourne and Geelong, Australia. Assessment: June–July 2019.

Participants:

Random sample of 104 stores, with equal numbers from each supermarket group (Coles, Woolworths, Aldi and Independent stores) within strata of area-level socio-economic position.

Results:

Proportion of shelf space devoted to selected discretionary foods was greater for Independent stores (72·7 %) compared with Woolworths (65·7 %), Coles (64·8 %) and Aldi (63·2 %) (all P < 0·001). Proportion of shelf space devoted to selected discretionary food for all Coles, Woolworths and Aldi stores was 9·7 % higher in the most compared with the least disadvantaged areas (P = 0·002). Across all stores, 90 % of staff-assisted checkout displays and 50 % of end-of-aisle displays included discretionary food. Aldi was less likely to feature discretionary food in end-of-aisle and checkout displays compared with other supermarket groups.

Conclusions:

Extensive marketing of discretionary food in all Australian supermarket chains was observed, which is likely to strongly influence purchasing patterns and population diets. Findings should be used to inform private and public sector policies to reduce marketing of discretionary food in supermarkets.
Multifactorial disorders and polygenic risk scores: predicting common diseases and the possibility of adverse selection in life and protection insurance
Authors: Maxwell Jessye M. , Russell Richard A. , Wu Hei Man , Sharapova Natasha , Banthorpe Peter , O’Reilly Paul F , Lewis Cathryn M
Published: August 2020

During the past decade, genetics research has allowed scientists and clinicians to explore the human genome in detail and reveal many thousands of common genetic variants associated with disease. Genetic risk scores, known as polygenic risk scores (PRSs), aggregate risk information from the most important genetic variants into a single score that describes an individual’s genetic predisposition to a given disease. This article reviews recent developments in the predictive utility of PRSs in relation to a person’s susceptibility to breast cancer and coronary artery disease. Prognostic models for these disorders are built using data from the UK Biobank, controlling for typical clinical and underwriting risk factors. Furthermore, we explore the possibility of adverse selection where genetic information about multifactorial disorders is available for insurance purchasers but not for underwriters. We demonstrate that prediction of multifactorial diseases, using PRSs, provides population risk information additional to that captured by normal underwriting risk factors. This research using the UK Biobank is in the public interest as it contributes to our understanding of predicting risk of disease in the population. Further research is imperative to understand how PRSs could cause adverse selection if consumers use this information to alter their insurance purchasing behaviour.
International Theory Book Symposium on Peter J. Katzenstein and Lucia A. Seybert, eds, Protean Power: Exploring the Uncertain and Unexpected in World Politics
Authors: Hymans Jacques E. C.
Published: August 2020

Katzenstein and Seybert's Protean Power offers a fresh perspective on the concept of power in international relations (IR) theory. Standard IR theory defines power as control power, which exists in the world of calculable risk. But IR must also grapple with protean power, which exists in the world of incalculable uncertainty. In this symposium, scholars representing a variety of theoretical perspectives evaluate the concept of protean power as it stands now and as it should develop in the future.
Optimism and risk of incident hypertension: a target for primordial prevention
Authors: Kubzansky Laura D. , Boehm Julia K. , Allen Andrew R. , Vie Loryana L. , Ho Tiffany E. , Trudel-Fitzgerald Claudia , Koga Hayami K. , Scheier Lawrence M. , Seligman Martin E. P.
Published: August 2020

Aims

Optimism is associated with reduced cardiovascular disease risk; however, few prospective studies have considered optimism in relation to hypertension risk specifically. We investigated whether optimism was associated with a lower risk of developing hypertension in U.S. service members, who are more likely to develop high blood pressure early in life. We also evaluated race/ethnicity, sex and age as potential effect modifiers of these associations.

Methods

Participants were 103 486 hypertension-free U.S. Army active-duty soldiers (mean age 28.96 years, 61.76% White, 20.04% Black, 11.01% Hispanic, 4.09% Asian, and 3.10% others). We assessed optimism, sociodemographic characteristics, health conditions, health behaviours and depression status at baseline (2009–2010) via self-report and administrative records, and ascertained incident hypertension over follow-up (2010–2014) from electronic health records and health assessments. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and adjusted models for a broad range of relevant covariates.

Results

Over a mean follow-up of 3.51 years, 15 052 incident hypertension cases occurred. The highest v. lowest optimism levels were associated with a 22% reduced risk of developing hypertension, after adjusting for all covariates including baseline blood pressure (HR = 0.78; 95% CI = 0.74–0.83). The difference in hypertension risk between the highest v. lowest optimism was also maintained when we excluded soldiers with hypertension in the first two years of follow-up and, separately, when we excluded soldiers with prehypertension at baseline. A dose–response relationship was evident with higher optimism associated with a lower relative risk (p < 0.001). Higher optimism was consistently associated with a lower risk of developing hypertension across sex, age and most race/ethnicity categories.

Conclusions

In a diverse cohort of initially healthy male and female service members particularly vulnerable to developing hypertension, higher optimism levels were associated with reduced hypertension risk independently of sociodemographic and health factors, a particularly notable finding given the young and healthy population. Results suggest optimism is a health asset and a potential target for public health interventions.
Undiagnosed depression, persistent depressive symptoms and seeking mental health care: analysis of immigrant and non-immigrant participants of the Canadian Longitudinal Study of Aging
Authors: Farid D. , Li P. , Da Costa D. , Afif W. , Szabo J. , Dasgupta K. , Rahme E.
Published: August 2020

Aims

Early diagnosis and treatment of depression are associated with better prognosis. We used baseline data of the Canadian Longitudinal Study on Aging (2012–2015; ages 45–85 years) to examine differences in prevalence and predictors of undiagnosed depression (UD) between immigrants and non-immigrants at baseline and persistent and/or emerging depressive symptoms (DS) 18 months later. At this second time point, we also examined if a mental health care professional (MHCP) had been consulted.

Methods

We excluded individuals with any prior mood disorder and/or current anti-depressive medication use at baseline. UD was defined as the Center for Epidemiological Studies Depression 10 score ⩾10. DS at 18 months were defined as Kessler 10 score ⩾19. The associations of interest were examined in multivariate logistic regression models.

Results

Our study included 4382 immigrants and 18 620 non-immigrants. The mean age (standard deviation) in immigrants was 63 (10.3) yearsv.65 (10.7) years in non-immigrants and 52.1%v.57.1% were male. Among immigrants, 12.2% had UD at baseline of whom 34.2% had persistent DS 18 months laterv.10.6% and 31.4%, respectively, among non-immigrants. Female immigrants were more likely to have UD than female non-immigrants (odds ratio 1.50, 95% confidence interval 1.25–1.80) but no difference observed for men. The risk of persistent DS and consulting an MHCP at 18 months did not differ between immigrants and non-immigrants.

Conclusions

Female immigrants may particularly benefit from depression screening. Seeking mental health care in the context of DS should be encouraged.
The Ups and Downs of Tides
Authors: Green J. A. , Haigh Ivan , Pickering Mark
Published: August 2020

The size of tides has changed in the past and will continue to change in the future due to natural and anthropogenic influences on estuaries, coastlines, and near shore regions.
Childhood maltreatment and cognitive functioning: the role of depression, parental education, and polygenic predisposition
Authors: Goltermann Janik , Redlich Ronny , Grotegerd Dominik , Dohm Katharina , Leehr Elisabeth J. , Böhnlein Joscha , Förster Katharina , Meinert Susanne , Enneking Verena , Richter Maike , Repple Jonathan , DeVillers Immanuel , Kloecker Marine , Jansen Andreas , Krug Axel , Nenadić Igor , Brosch Katharina , Meller Tina , Stein Frederike , Schmitt Simon , Rietschel Marcella , Streit Fabian , Witt Stephanie H. , Forstner Andreas J. , Nöthen Markus M. , Baune Bernhard T. , Andlauer Till F. M. , Kircher Tilo , Opel Nils , Dannlowski Udo
Published: August 2020

Childhood maltreatment is associated with cognitive deficits that in turn have been predictive for therapeutic outcome in psychiatric patients. However, previous studies have either investigated maltreatment associations with single cognitive domains or failed to adequately control for confounders such as depression, socioeconomic environment, and genetic predisposition. We aimed to isolate the relationship between childhood maltreatment and dysfunction in diverse cognitive domains, while estimating the contribution of potential confounders to this relationship, and to investigate gene–environment interactions. We included 547 depressive disorder and 670 healthy control participants (mean age: 34.7 years, SD = 13.2). Cognitive functioning was assessed for the domains of working memory, executive functioning, processing speed, attention, memory, and verbal intelligence using neuropsychological tests. Childhood maltreatment and parental education were assessed using self-reports, and psychiatric diagnosis was based on DSM-IV criteria. Polygenic scores for depression and for educational attainment were calculated. Multivariate analysis of cognitive domains yielded significant associations with childhood maltreatment (η²p = 0.083,P < 0.001), depression (η²p = 0.097,P < 0.001), parental education (η²p = 0.085,P < 0.001), and polygenic scores for depression (η²p = 0.021,P = 0.005) and educational attainment (η²p = 0.031,P < 0.001). Each of these associations remained significant when including all of the predictors in one model. Univariate tests revealed that maltreatment was associated with poorer performance in all cognitive domains. Thus, environmental, psychopathological, and genetic risk factors each independently affect cognition. The insights of the current study may aid in estimating the potential impact of different loci of interventions for cognitive dysfunction. Future research should investigate if customized interventions, informed by individual risk profiles and related cognitive preconditions, might enhance response to therapeutic treatments.
Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals
Authors: Zhang Fan , Gan Rui , Zhen Ziqi , Hu Xiaoli , Li Xiang , Zhou Fengxia , Liu Ying , Chen Chuangeng , Xie Shuangyu , Zhang Bailing , Wu Xiaoke , Huang Zhiwei
Published: August 2020

The global Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has affected more than eight million people. There is an urgent need to investigate how the adaptive immunity is established in COVID-19 patients. In this study, we profiled adaptive immune cells of PBMCs from recovered COVID-19 patients with varying disease severity using single-cell RNA and TCR/BCR V(D)J sequencing. The sequencing data revealed SARS-CoV-2-specific shuffling of adaptive immune repertories and COVID-19-induced remodeling of peripheral lymphocytes. Characterization of variations in the peripheral T and B cells from the COVID-19 patients revealed a positive correlation of humoral immune response and T-cell immune memory with disease severity. Sequencing and functional data revealed SARS-CoV-2-specific T-cell immune memory in the convalescent COVID-19 patients. Furthermore, we also identified novel antigens that are responsive in the convalescent patients. Altogether, our study reveals adaptive immune repertories underlying pathogenesis and recovery in severe versus mild COVID-19 patients, providing valuable information for potential vaccine and therapeutic development against SARS-CoV-2 infection.
Membranous NOX5-derived ROS oxidizes and activates local Src to promote malignancy of tumor cells
Authors: Chen Jie , Wang Yan , Zhang Weimin , Zhao Di , Zhang Lingyuan , Fan Jiawen , Li Jinting , Zhan Qimin
Published: August 2020

Reactive oxygen species (ROS) localized at the precise subcellular compartments are essential for regulating the activity of signaling proteins. Furthermore, ROS are master regulators of tumor malignant progression that respond to a diverse set of environmental stress, especially hypoxia. NADPH oxidases (NOXs) appear to be activated within discrete subcellular compartments to facilitate local ROS production. However, the subcellular function of NOXs in hypoxic tumor is still unclear. In this study, we demonstrated that NOX5 was greatly upregulated in clinical esophageal squamous cell carcinoma (ESCC) tumors, ESCC cell lines or primary ESCC cells, and elevated NOX5 was correlated to malignancy of ESCC tumors and poor prognosis. NOX5 induced the malignant progression of ESCC by activating Src, especially under hypoxic condition. Mechanistically, we showed that hypoxia promoted the interaction between NOX5 and Pyk2 on cell membrane via facilitating Ca2+-mediated Pyk2 Tyr402 site phosphorylation. Subsequently, Pyk2 acted as a scaffold for c-Abl phosphorylating the catalytic domain of NOX5 Tyr476/478 sites, which in turn upregulated hydrogen peroxide (H2O2) inside the Pyk2/NOX5 complex to oxidize and activate local Src. These findings provide insights into the biological significance of NOX5 in the development of ESCC.
Oxidized-LDL inhibits testosterone biosynthesis by affecting mitochondrial function and the p38 MAPK/COX-2 signaling pathway in Leydig cells
Authors: Jing Jun , Ding Ning , Wang Dandan , Ge Xie , Ma Jinzhao , Ma Rujun , Huang Xuan , Jueraitetibaike Kadiliya , Liang Kuan , Wang Shuxian , Cao Siyuan , Zhao Allan Zijian , Yao Bing
Published: August 2020

Abnormal lipid/lipoprotein metabolism induced by obesity may affect spermatogenesis by inhibiting testosterone synthesis in Leydig cells. It is crucial to determine which components of lipoproteins inhibit testosterone synthesis. Circulating oxidized low-density lipoprotein (oxLDL), the oxidized form of LDL, has been reported to be an independent risk factor for decreased serum testosterone levels. However, whether oxLDL has a damaging effect on Leydig cell function and the detailed mechanisms have been rarely studied. This study first showed the specific localization of oxLDL and mitochondrial structural damage in testicular Leydig cells of high-fat diet-fed mice in vivo. We also found that oxLDL reduced the mitochondrial membrane potential (MMP) by disrupting electron transport chain and inhibited testosterone synthesis-related proteins and enzymes (StAR, P450scc, and 3β‑HSD), which ultimately led to mitochondrial dysfunction and decreased testosterone synthesis in Leydig cells. Further experiments demonstrated that oxLDL promoted lipid uptake and mitochondrial dysfunction by inducing CD36 transcription. Meanwhile, oxLDL facilitated COX2 expression through the p38 MAPK signaling pathway in Leydig cells. Blockade of COX-2 attenuated the oxLDL-induced decrease in StAR and P450scc. Our clinical results clarified that the increased serum oxLDL level was associated with a decline in circulating testosterone levels. Our findings amplify the damaging effects of oxLDL and provide the first evidence that oxLDL is a novel metabolic biomarker of male-acquired hypogonadism caused by abnormal lipid metabolism.
Antifungal drug miconazole ameliorated memory deficits in a mouse model of LPS-induced memory loss through targeting iNOS
Authors: Yeo In Jun , Yun Jaesuk , Son Dong Ju , Han Sang-Bae , Hong Jin Tae
Published: August 2020

Alzheimer’s disease (AD) is closely related to neuroinflammation, and the increase in inflammatory cytokine generation and inducible nitric oxide synthase (iNOS) expression in the brain of a patient with AD is well known. Excessive cytokines can stimulate iNOS in microglia and astroglia and overproduce nitric oxide, which can be toxic to neurons. The disease–gene–drug network analysis based on the GWAS/OMIM/DEG records showed that miconazole (MCZ) affected AD through interactions with NOS. Inhibiting iNOS can reduce neuroinflammation, thus preventing AD progression. To investigate the prophylactic role of antifungal agent in the AD development, a lipopolysaccharide-induced memory disorder mouse model was used, and cognitive function was assessed by Morris water maze test and passive avoidance test. MCZ treatment significantly attenuated cognitive impairment, suppressed iNOS and cyclooxygenase-2 expression, and activation of astrocyte and microglial BV2 cells, as well as reduced cytokine levels in the brains and lipopolysaccharide-treated astrocytes and microglia BV2 cells. In further mechanism studies, Pull-down assay and iNOS luciferase activity data showed that MCZ binds to iNOS and inhibited transcriptional activity. Our results suggest that MCZ is useful for ameliorating the neuroinflammation-mediated AD progression by blocking iNOS expression.
Mechanism of ribosome rescue by alternative ribosome-rescue factor B
Authors: Chan Kai-Hsin , Petrychenko Valentyn , Mueller Claudia , Maracci Cristina , Holtkamp Wolf , Wilson Daniel N. , Fischer Niels , Rodnina Marina V.
Published: August 2020

Alternative ribosome-rescue factor B (ArfB) rescues ribosomes stalled on non-stop mRNAs by releasing the nascent polypeptide from the peptidyl-tRNA. By rapid kinetics we show that ArfB selects ribosomes stalled on short truncated mRNAs, rather than on longer mRNAs mimicking pausing on rare codon clusters. In combination with cryo-electron microscopy we dissect the multistep rescue pathway of ArfB, which first binds to ribosomes very rapidly regardless of the mRNA length. The selectivity for shorter mRNAs arises from the subsequent slow engagement step, as it requires longer mRNA to shift to enable ArfB binding. Engagement results in specific interactions of the ArfB C-terminal domain with the mRNA entry channel, which activates peptidyl-tRNA hydrolysis by the N-terminal domain. These data reveal how protein dynamics translate into specificity of substrate recognition and provide insights into the action of a putative rescue factor in mitochondria.
Single cell electron collectors for highly efficient wiring-up electronic abiotic/biotic interfaces
Authors: Yu Yang-Yang , Wang Yan-Zhai , Fang Zhen , Shi Yu-Tong , Cheng Qian-Wen , Chen Yu-Xuan , Shi Weidong , Yong Yang-Chun
Published: August 2020

By electronically wiring-up living cells with abiotic conductive surfaces, bioelectrochemical systems (BES) harvest energy and synthesize electric-/solar-chemicals with unmatched thermodynamic efficiency. However, the establishment of an efficient electronic interface between living cells and abiotic surfaces is hindered due to the requirement of extremely close contact and high interfacial area, which is quite challenging for cell and material engineering. Herein, we propose a new concept of a single cell electron collector, which isin-situbuilt with an interconnected intact conductive layer on and cross the individual cell membrane. The single cell electron collector forms intimate contact with the cellular electron transfer machinery and maximizes the interfacial area, achieving record-high interfacial electron transfer efficiency and BES performance. Thus, this single cell electron collector provides a superior tool to wire living cells with abiotic surfaces at the single-cell level and adds new dimensions for abiotic/biotic interface engineering.
Life histories determine divergent population trends for fishes under climate warming
Authors: Wang Hui-Yu , Shen Sheng-Feng , Chen Ying-Shiuan , Kiang Yun-Kae , Heino Mikko
Published: August 2020

Most marine fish species express life-history changes across temperature gradients, such as faster growth, earlier maturation, and higher mortality at higher temperature. However, such climate-driven effects on life histories and population dynamics remain unassessed for most fishes. For 332 Indo-Pacific fishes, we show positive effects of temperature on body growth (but with decreasing asymptotic length), reproductive rates (including earlier age-at-maturation), and natural mortality for all species, with the effect strength varying among habitat-related species groups. Reef and demersal fishes are more sensitive to temperature changes than pelagic and bathydemersal fishes. Using a life table, we show that the combined changes of life histories upon increasing temperature tend to facilitate population growth for slow life-history populations, but reduce it for fast life-history ones. Within our data, lower proportions (25–30%) of slow life-history fishes but greater proportions of fast life-history fishes (42–60%) show declined population growth rates under 1 °C warming. Together, these findings suggest prioritizing sustainable management for fast life-history species.