Miracle-dz/UniFAR-FTUs huggingface dataset:
Testing for genetic interactions in complex disease with distance correlation

Understanding epistasis (genetic interaction) may shed some light on the genomic basis of common diseases, including disorders of maximum interest due to their high socioeconomic burden, like schizophrenia. Distance correlation is an association measure that characterises general statistical independence between random variables, not only the linear one. Here, we propose distance correlation as a novel tool for the detection of epistasis from case-control data of single-nucleotide polymorphisms (SNPs). On the methodological side, we highlight the derivation of the explicit asymptotic distribution of the test statistic. We show that this is the only way to obtain enough computational speed for the method to be used in practice, in a scenario where the resampling techniques found in the literature are impractical. Our simulations show satisfactory calibration of significance, as well as comparable or better power than existing methodology. We conclude with the application of our technique to a schizophrenia genetics dataset, obtaining biologically sound insights.
Influence of Linear Model Under Ellipsoidal Restriction

We deal with the data deleted model and the mean shift model under ellipsoidal restriction and obtain the equivalence of the diagonal statistic between the two models.We show not only the relationship of the estimators before and after deletion in the data deleted model,but also the relationship of the hap matrix.At last,we give the influence function under the given conditions,and give an example to illustrate our method.
Serum Levels of 8-Iso-Prostaglandin F2aα and Raftlin in Patients with Generalized Anxiety Disorder

Objective Although there are neurobiological studies of patients with generalized anxiety disorder (GAD), the topic is still open to research. Lipid peroxidation can generate new molecular signal sequences by altering protein amounts and activity. 8-Iso-Prostaglandin F2aα (8-iso-PGF2α) is known to be an important lipid peroxidation marker. Raftlin, which is defined as a major lipid raft protein, is important for the regulation of signal transduction and inflammatory processes. Methods Our aim in this study was to compare the 8-iso-PGF2α and Raftlin levels of forty patients diagnosed with GAD and 40 healthy controls (age-sex and body mass index-matched). Results In the present study, increased serum 8-iso-PGF2α and Raftlin levels were found in patients with GAD compared to healthy controls. Conclusion To our knowledge, this is the first study to examine 8-iso-PGF2α and Raftlin levels in patients with GAD. These results expand our knowledge of oxidative stress and inflammatory processes in patients with GAD. Our study should be considered preliminary and further studies should be performed with larger sample groups comparing values before and after treatment.
Measuring hair cortisol concentration, insomnia symptoms and quality of life in preschool children with severe early childhood caries – a case-control pilot study

Abstract Objective This study aimed to 1) investigate the relationships between hair cortisol concentration (HCC), insomnia symptoms, Health-Related Quality of Life (HRQoL) and Oral Health-Related Quality of Life (OHRQoL) in preschool children with severe early childhood caries, 2) compare HCC, insomnia symptoms, HRQoL and OHRQoL in preschool children with severe early childhood caries with these factors in children without clinical signs of dental caries, and 3) explore correlations between caries scores and HCC, insomnia symptoms, HRQoL and OHRQoL. Material and Methods A case-control pilot study, including 12 children with severe early childhood caries and 28 controls, aged 3-5 years. Dental examination was performed and hair samples for cortisol were taken. Parents filled out questionnaires about their child’s insomnia symptoms, HRQoL and OHRQoL. Interpreters were used in families with language difficulties. Results The key findings in this pilot study were tendencies that children with severe early childhood caries had more insomnia symptoms, and poorer OHRQoL than the controls. Caries scores was correlated with insomnia symptoms and OHRQoL. Conclusions Dentists should include questions about the child’s sleep when they see the child, as insomnia related to dental caries may lead to several physical, mental, and social problems.
A model for Janus and Epimetheus

In this work we present a model that tries to fit the behaviour of Janus and Epimetheus, two co-orbital moons of Saturn. This has been done before using the model for the two-dimensional restricted three-body problem, and although suitable orbits where found, there was a problem: their low stability. We improve this model by taking Saturn's oblateness into consideration, and study it to see if it fits the orbits of Janus and Epimetheus and improves the stability of such orbits.
How to Procrastinate Productively With ADHD: A Study of Smartphone Use, Depression, and Other Academic Variables Among University Students With ADHD Symptoms

Objective: The association between chemical dependency and Attention-Deficit Hyperactivity Disorder is widely recognized, but there is less data regarding modern behavioral addictions among young adults. Method: In this cross-sectional study, a sample of 408 Hungarian college students (67.2% female, mean age 23.37 years [SD = 3.87]) responded to an online survey including the Adult ADHD Self-Report Scale, the Center for Epidemiologic Studies-Depression Scale (CES-D), the Procrastination Scale, the Short College Boredom Scale, and the Smartphone Addiction Scale (SAS-SV). Results: Regression analyses showed that passive procrastination (ß = .31, p < .001), depression (ß = .20, p < .001), academic boredom (ß = .18, p < .001), active procrastination (ß = −.12, p < .001), and smartphone addiction (ß = .13, p < .001) were significantly related to ADHD symptoms, accounting for 41% of the variance. Conclusion: Findings provide important additions to knowledge of mental health challenges among young adults with ADHD.
Stratospheric gravity waves revealed in NWP model forecasts

Current operational numerical weather prediction models potentially have sufficient spatial and temporal resolution to resolve much of the inertia‐gravity wave spectrum (e.g. horizontal wavelengths in the region of 100–1000 km typically, and even longer zonal wavelengths in the Tropics). The effects of gravity wave dynamics are usually considered to be subgrid‐scale and parametrizable, either as stationary, mountain waves or travelling, non‐orographic waves. Simple techniques for isolating these waves in both the Met Office and ECMWF forecast models are presented and their associated wave fluxes (including three‐dimensional Eliassen–Palm fluxes) are computed for August 2006. In addition, a limited‐area configuration of the Met Office Unified model with 4 km horizontal resolution is run over a region that includes the southern half of the Andes mountain range. Spectral decompositions of the wave energy and momentum fluxes show a distinct peak in power at horizontal wavelengths of about 400 km, irrespective of whether a 4 or 40 km grid is used, although about one half of the power resides in wavelengths shorter than 200 km. The computed Eliassen–Palm fluxes are shown to be similar to the net parametrized gravity wave drag, although the latter are too widespread and uniform over the oceans, reflecting the absence of geographical source variation. Comparison of the time mean temperature amplitude of the waves in the mid‐stratosphere with estimates derived from limb‐sounder satellite measurements from the HIRDLS project suggests that forecast models are capable of capturing the correct overall strength and distribution of gravity wave activity. Copyright © 2011 British Crown copyright, the Met Office. Published by John Wiley & Sons Ltd.
Regenerative Therapy in Sexual Medicine: The Hard Facts

ERECTILE dysfunction (ED) is a complex medical condition defined as the inability to achieve and maintain an erection satisfactory for intercourse. In addition to lifestyle changes, some commonly used treatment options have been phosphodiesterase type 5 inhibitors (PDE5is), intracavernosal injections, intraurethral pellets/gel, vacuum devices, and penile prostheses. However, none of these traditional treatment options offer a permanent cure for ED. This necessitates the continuous development of regenerative therapies. Modalities that are currently being developed and analyzed include low-intensity shock wave therapy (LI-SWT), stem cell therapy (SCT), and platelet-rich plasma therapy (PRPT). These therapies have emerged as promising minimally invasive treatment options for ED that may be utilized as first-line treatments or in men who did not tolerate or improve with standard therapies. We aim to summarize the evidence supporting these therapies and current recommendations regarding their use.
Assessment of a novel variation in DHODH gene causing Miller syndrome: The first report in Chinese population

Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup‐shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits.
Active Materials for Functional Origami.

In recent decades, origami has been explored to aid in the design of engineering structures. These structures span multiple scales and have been demonstrated to be used towards various areas such as aerospace, metamaterial, biomedical, robotics, and architectural applications. Conventionally, origami or deployable structures have been actuated by hands, motors, or pneumatic actuators, which can result in heavy or bulky structures. On the other hand, active materials, which reconfigure in response to external stimulus, eliminate the need for external mechanical loads and bulky actuation systems. Thus, in recent years, active materials incorporated with deployable structures have shown promise for remote actuation of light weight, programmable origami. In this review, active materials such as shape memory polymers and alloys, hydrogels, liquid crystal elastomers, magnetic soft materials, and covalent adaptable network polymers, their actuation mechanisms, as well as how they have been utilized for active origami and where these structures are applicable is discussed. Additionally, the state-of-the-art fabrication methods to construct active origami are highlighted. The existing structural modeling strategies for origami, the constitutive models used to describe active materials, and the largest challenges and future directions for active origami research are summarized. This article is protected by copyright. All rights reserved.
Cardiomyocyte electrophysiology and its modulation: current views and future prospects

Normal and abnormal cardiac rhythms are of key physiological and clinical interest. This introductory article begins from Sylvio Weidmann's key historic 1950s microelectrode measurements of cardiac electrophysiological activity and Singh & Vaughan Williams's classification of cardiotropic targets. It then proceeds to introduce the insights into cardiomyocyte function and its regulation that subsequently emerged and their therapeutic implications. We recapitulate the resulting view that surface membrane electrophysiological events underlying cardiac excitation and its initiation, conduction and recovery constitute the final common path for the cellular mechanisms that impinge upon this normal or abnormal cardiac electrophysiological activity. We then consider progress in the more recently characterized successive regulatory hierarchies involving Ca2+ homeostasis, excitation–contraction coupling and autonomic G-protein signalling and their often reciprocal interactions with the surface membrane events, and their circadian rhythms. Then follow accounts of longer-term upstream modulation processes involving altered channel expression, cardiomyocyte energetics and hypertrophic and fibrotic cardiac remodelling. Consideration of these developments introduces each of the articles in this Phil. Trans. B theme issue. The findings contained in these articles translate naturally into recent classifications of cardiac electrophysiological targets and drug actions, thereby encouraging future iterations of experimental cardiac electrophysiological discovery, and testing directed towards clinical management. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal Ca2+

Rhythms of electrical activity in all regions of the heart can be influenced by a variety of intracellular membrane bound organelles. This is true both for normal pacemaker activity and for abnormal rhythms including those caused by early and delayed afterdepolarizations under pathological conditions. The influence of the sarcoplasmic reticulum (SR) on cardiac electrical activity is widely recognized, but other intracellular organelles including lysosomes and mitochondria also contribute. Intracellular organelles can provide a timing mechanism (such as an SR clock driven by cyclic uptake and release of Ca2+, with an important influence of intraluminal Ca2+), and/or can act as a Ca2+ store involved in signalling mechanisms. Ca2+ plays many diverse roles including carrying electric current, driving electrogenic sodium–calcium exchange (NCX) particularly when Ca2+ is extruded across the surface membrane causing depolarization, and activation of enzymes which target organelles and surface membrane proteins. Heart function is also influenced by Ca2+ mobilizing agents (cADP-ribose, nicotinic acid adenine dinucleotide phosphate and inositol trisphosphate) acting on intracellular organelles. Lysosomal Ca2+ release exerts its effects via calcium/calmodulin-dependent protein kinase II to promote SR Ca2+ uptake, and contributes to arrhythmias resulting from excessive beta-adrenoceptor stimulation. A separate arrhythmogenic mechanism involves lysosomes, mitochondria and SR. Interacting intracellular organelles, therefore, have profound effects on heart rhythms and NCX plays a central role. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Human atrial fibrillation and genetic defects in transient outward currents: mechanistic insights from multi-scale computational models

Previous studies have linked dysfunctional Ito arising from mutations to KCND3-encoded Kv4.3 and KCND2-encoded Kv4.2 to atrial fibrillation. Using computational models, this study aimed to investigate the mechanisms underlying pro-arrhythmic effects of the gain-of-function Kv4.3 (T361S, A545P) and Kv4.2 (S447R) mutations. Wild-type and mutant Ito formulations were developed from and validated against experimental data and incorporated into the Colman et al. model of human atrial cells. Single-cell models were incorporated into one- (1D) and two-dimensional (2D) models of atrial tissue, and a three-dimensional (3D) realistic model of the human atria. The three gain-of-function mutations had similar, albeit quantitatively different, effects: shortening of the action potential duration; lowering the plateau membrane potential, abbreviating the effective refractory period (ERP) and the wavelength (WL) of atrial excitation at the tissue level. Restitution curves for the WL, the ERP and the conduction velocity were leftward shifted, facilitating the conduction of atrial excitation waves at high excitation rates. The mutations also increased lifespan and stationarity of re-entry in both 2D and 3D simulations, which further highlighted a mutation-induced increase in spatial dispersion of repolarization. Collectively, these changes account for pro-arrhythmic effects of these Kv4.3 and Kv4.2 mutations in facilitating AF. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
COMPUTATION METHOD OF CHEMICAL EQUILIBRIUM OF COMPLEX SYSTEM

The chaos-Monte Carlo algorithm(CMCA) was proposed for solving chemical equilibrium of complex system.By introducing random well-distributed points into the Monte Carlo algorithm, this new approach showed good convergent probability and high-speed.Equilibrium composition of some complex systems,such as methanol synthesis, ammonia oxidation, and Claus process were calculated.The results showed good agreement with Liu Xiaodi’s and Xu Jinhuo’s calculations.Compared with the gradient method, the genetic algorithm and the modified genetic algorithm,the CMCA is simple, general and insensitive to initial value.It is an efficient algorithm based on the theory of minimization of Gibbs free energy to solve chemical equilibrium of complex system.
Cross-lingual Text Reuse Detection at Document Level for English-Urdu Language Pair

In recent years, the problem of Cross-Lingual Text Reuse Detection (CLTRD) has gained the interest of the research community due to the availability of large digital repositories and automatic Machine Translation (MT) systems. These systems are readily available and openly accessible, which makes it easier to reuse text across languages but hard to detect. In previous studies, different corpora and methods have been developed for CLTRD at the sentence/passage level for the English-Urdu language pair. However, there is a lack of large standard corpora and methods for CLTRD for the English-Urdu language pair at the document level. To overcome this limitation, the significant contribution of this study is the development of a large benchmark cross-lingual (English-Urdu) text reuse corpus, called the TREU (Text Reuse for English-Urdu) corpus. It contains English to Urdu real cases of text reuse at the document level. The corpus is manually labelled into three categories (Wholly Derived = 672, Partially Derived = 888, and Non Derived = 697) with the source text in English and the derived text in the Urdu language. Another contribution of this study is the evaluation of the TREU corpus using a diversified range of methods to show its usefulness and how it can be utilized in the development of automatic methods for measuring cross-lingual (English-Urdu) text reuse at the document level. The best evaluation results, for both binary (F1 = 0.78) and ternary (F1 = 0.66) classification tasks, are obtained using a combination of all Translation plus Mono-lingual Analysis (T+MA) based methods. The TREU corpus is publicly available to promote CLTRD research in an under-resourced language, i.e., Urdu.
Effect of Communicative and Critical Health Literacy on Trust in Physicians Among Patients With Systemic Lupus Erythematosus (SLE): The TRUMP2-SLE Project

Objective Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE). Methods This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one’s physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit. Results A total of 362 patients with SLE were included. Trust in one’s physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference −6.88, 95% CI −11.72 to −2.04, respectively). Longer internet use was associated with both higher communicative and critical HL. Conclusion The findings suggest that rheumatologists need to improve their communication to match each patient’s HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.
Interferon regulatory factor 3 mediates effective antiviral responses to human coronavirus 229E and OC43 infection

Interferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate the transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). While the sensitivity of human coronaviruses to IFNs has been characterized, antiviral roles of IRFs during human coronavirus infection are not fully understood. Type I or II IFN treatment protected MRC5 cells from human coronavirus 229E infection, but not OC43. Cells infected with 229E or OC43 upregulated ISGs, indicating that antiviral transcription is not suppressed. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of IRFs demonstrated that IRF1 and IRF3 have antiviral properties against OC43, while IRF3 and IRF7 are effective in restricting 229E infection. IRF3 activation effectively promotes transcription of antiviral genes during OC43 or 229E infection. Our study suggests that IRFs may be effective antiviral regulators against human coronavirus infection.
Sources and pathways of halomethoxybenzenes in northern Baltic estuaries

Introduction Thousands of halogenated natural products (HNPs) are generated in the ocean and on land. A subset of these, halomethoxybenzenes (HMBs), are released from both natural and anthropogenic sources. Here we consider: 1. Brominated anisoles (BAs), transformation products of bromophenols. 2. Drosophilin A methyl ether (DAME: 1,2,4,5-tetrachloro-3,6-dimethoxybenzene), a secondary metabolite of terrestrial fungi. 3. Tetrachloroveratrole (TeCV: 1,2,3,4-tetrachloro-5,6-dimethoxybenzene), a lignin byproduct found in bleached kraft mill effluent. 4. Pentachloroanisole (PeCA), a metabolite of the wood preservative pentachlorophenol. Methods We examined several ecosystem compartments to determine sources and exchange processes for these HMBs: air, precipitation, rivers, forest fungi and litter, and water from northern Baltic estuaries and offshore. Samples were analyzed for HMBs by capillary gas chromatography – quadrupole mass spectrometry. Results and discussion All four types of HMBs were found in air, and BAs, DAME and TeCV were also present in precipitation. BAs and DAME were common in rivers and estuaries, whereas TeCV was low and PeCA was below detection. DAME was identified in several species of fungi and in forest litter; TeCV was occasionally present, but BAs and PeCA were below detection. Concentrations of BAs were higher in estuaries than in rivers or offshore waters, showing that estuaries are hot spots for production. BAs were negatively or not correlated with chlorophyll-a, suggesting contribution by heterotrophic bacteria as well as known production by phytoplankton and macroalgae. DAME was negatively or not correlated with BAs and did not appear to be produced in the estuaries; fungi and forest litter containing fungal mycelia are suggested as sources. HMBs volatilize from sea and land, disperse through the atmosphere, and return via precipitation and rivers. Production and biogeochemical cycles are influenced by climate change and we suggest BAs and DAME for following partitioning and exchange processes. Graphical abstract