Miracle-dz/UniFAR-FTUs huggingface dataset:
α-Glucosidase Inhibitors: Diphenyl Ethers and Phenolic Bisabolane Sesquiterpenoids from the Mangrove Endophytic Fungus Aspergillus flavus QQSG-3

Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane sesquiterpenoids (3–6), together with five known related derivatives, were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 obtained from a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, China. The structures of compounds 1–6 were determined by analyzing NMR and HRESIMS data. The absolute configurations of 5 and 6 were assigned by comparing their experimental ECD spectra with those reported for similar compounds in the literature. All isolates were evaluated for their α-glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11 showed strong inhibitory effects with IC50 values in the range of 1.5–4.5 μM.
Estimating divergence times and ancestral breeding systems in Ficus and Moraceae

Background and Aims Although dioecy, which characterizes only 6 % of angiosperm species, has been considered an evolutionary dead end, recent studies have demonstrated that this is not necessarily the case. Moraceae (40 genera, 1100 spp., including Ficus, 750 spp.) are particularly diverse in breeding systems (including monoecy, gynodioecy, androdioecy and dioecy) and thus represent a model clade to study macroevolution of dioecy. Methods Ancestral breeding systems of Ficus and Moraceae were inferred. To do so, a new dated phylogenetic tree of Ficus and Moraceae was first reconstructed by combining a revised 12-fossil calibration set and a densely sampled molecular data set of eight markers and 320 species. Breeding system evolution was then reconstructed using both parsimony and model-based (maximum likelihood and Bayesian) approaches with this new time scale. Key Results The crown group ages of Ficus and Moraceae were estimated in the Eocene (40.6-55.9 Ma) and Late Cretaceous (73.2-84.7 Ma), respectively. Strong support was found for ancestral dioecy in Moraceae. Although the ancestral state of Ficus remained particularly sensitive to model selection, the results show that monoecy and gynodioecy evolved from dioecy in Moraceae, and suggest that gynodioecy probably evolved from monoecy in Ficus. Conclusions Dioecy was found not to be an evolutionary dead end in Moraceae. This study provides a new time scale for the phylogeny and a new framework of breeding system evolution in Ficus and Moraceae.
Telephone-based Dementia Screening I: Automated Semantic Verbal Fluency Assessment

Dementia has a large economic impact on our society as cost-effective population-wide screening for early signs of dementia is still an unsolved medical supply resource problem. A solution should be fast, require a minimum of external material, and automatically indicate potential persons at risk of cognitive decline. Despite encouraging results, leveraging pervasive sensing technologies for automatic dementia screening, there are still two main issues: significant hardware costs or installation efforts and the challenge of effective pattern recognition. Conversely, automatic speech recognition (ASR) and speech analysis have reached sufficient maturity and allow for low-tech remote telephone-based screening scenarios. Therefore, we examine the technologic feasibility of automatically assessing a neuropsychological test---Semantic Verbal Fluency (SVF)--via a telephone-based solution. We investigate its suitability for inclusion into an automated dementia frontline screening and global risk assessment, based on concise telephone-sampled speech, ASR and machine learning classification. Results are encouraging showing an area under the curve (AUC) of 0.85. We observe a relatively low word error rate of 33% despite phone-quality speech samples and a mean age of 77 years of the participants. The automated classification pipeline performs equally well compared to the classifier trained on manual transcriptions of the same speech data. Our results indicate SVF as a prime candidate for inclusion into an automated telephone-screening system.
The Obesities

The study of obesity lends itself to difficulties not only due to our imprecise ability to measure body composition, food consumption, and physical activity but also, even more important, due to complexities involved in defining and conceptualizing obesity. For centuries, obesity has been considered a disease, although researchers and clinicians cannot agree on definitions of “disease” or, if it is one, whether obesity is a disease of metabolism, inflammation, brown fat, chronobiology, the blood-brain barrier, the right brain, or even of infectious origin. The concept of “obesity” as a disease remains controversial to some because not everyone who has excess adipose tissue has any evidence of disease. Obesity, though, has also been considered a sin, a crime against society, an aesthetic crime, a self-inflicted disability, an example of body diversity, a failure in the regulation of energy balance, an appropriate or even inappropriate adaptation to our increasingly obesogenic environment, a genetic disorder, and a psychological/behavioral disorder of overeating involving self-regulation or even addiction. Five major paradigms—medical, sociocultural, evolutionary, environmental, and psychological/behavioral, all with their own subcategorical models—have been identified. All 5 paradigms are required because we are dealing not with “obesity” but with a plurality, the “obesities. ”
Which School Community Agents Influence Adolescents’ Motivational Outcomes and Physical Activity? Are More Autonomy-Supportive Relationships Necessarily Better?

The first aim of this work was to examine the independent influence of students’ perceived autonomy support for leisure-time physical activity (LTPA), from different school community agents, on motivational outcomes in a LTPA context and objective PA levels. Using both a variable- and person-centered approach, the second aim was to examine how different combinations of autonomy-support were associated with students’ motivational outcomes in a LTPA context and PA levels. A sample of 178 secondary students (M = 13.26 ± 0.64) participated in the study. Autonomy support for LTPA from the PE teacher, mother, father, and peers were the only agents that significantly and positively predicted motivational outcomes in a LTPA context and PA levels. While the two- and three-way interactions of some of these four significant sources significantly increased the explained variance of some motivational outcomes, the plots revealed that the lowest values of motivational outcomes were associated with low values of perceived autonomy support. A cluster analysis revealed five profiles. The “high autonomy support” group reported the most optimal outcomes, whereas the “low autonomy support” group showed the opposite pattern. However, mixed autonomy support profiles did not differ in any of the outcomes. The adoption of a whole-of-school approach seems decisive to empower adolescents to be active in and out of school.
Unity: A General Platform for Intelligent Agents

Recent advances in artificial intelligence have been driven by the presence of increasingly realistic and complex simulated environments. However, many of the existing environments provide either unrealistic visuals, inaccurate physics, low task complexity, restricted agent perspective, or a limited capacity for interaction among artificial agents. Furthermore, many platforms lack the ability to flexibly configure the simulation, making the simulated environment a black-box from the perspective of the learning system. In this work, we propose a novel taxonomy of existing simulation platforms and discuss the highest level class of general platforms which enable the development of learning environments that are rich in visual, physical, task, and social complexity. We argue that modern game engines are uniquely suited to act as general platforms and as a case study examine the Unity engine and open source Unity ML-Agents Toolkit. We then survey the research enabled by Unity and the Unity ML-Agents Toolkit, discussing the kinds of research a flexible, interactive and easily configurable general platform can facilitate.
Nutritional and Physical Activity Interventions to Improve Immunity

Physical activity and nutrition are important in a healthy lifestyle with potential benefits to immunity often overlooked. Infection of the upper respiratory tract, and the associated symptoms, are the most frequent presentations to general practitioners and may have significant economic and social impact. In this review, we consider the role of physical activity and nutrition in improving immunity. Evidence suggests that regular moderate activity is particularly beneficial for immune enhancement and reducing the risk of infection. We also discuss some nutritional strategies. Unfortunately, the evidence for many is weak. Avoiding nutritional deficiencies seems the most pragmatic recommendation. This can be achieved with a balanced diet. Including a variety of fruits and vegetables may help ensure adequate intake of essential nutrients with little risk of excess intake of any single nutrient. Supplementation with individual nutrients is generally not recommended. Multinutrients may be beneficial for those with a preexisting deficiency but not if normal dietary intake is sufficient. Further benefit may be gained from some supplements including probiotics, bovine colostrum, and some plant-derived products (Echinacea, black elderberry, and some polyphenols) but only in specific situations/contexts. Individuals should consider their personal needs, use caution, and avoid the indiscriminate use of supplements.
Deep Single-View 3D Object Reconstruction with Visual Hull Embedding

3D object reconstruction is a fundamental task of many robotics and AI problems. With the aid of deep convolutional neural networks (CNNs), 3D object reconstruction has witnessed a significant progress in recent years. However, possibly due to the prohibitively high dimension of the 3D object space, the results from deep CNNs are often prone to missing some shape details. In this paper, we present an approach which aims to preserve more shape details and improve the reconstruction quality. The key idea of our method is to leverage object mask and pose estimation from CNNs to assist the 3D shape learning by constructing a probabilistic singleview visual hull inside of the network. Our method works by first predicting a coarse shape as well as the object pose and silhouette using CNNs, followed by a novel 3D refinement CNN which refines the coarse shapes using the constructed probabilistic visual hulls. Experiment on both synthetic data and real images show that embedding a single-view visual hull for shape refinement can significantly improve the reconstruction quality by recovering more shapes details and improving shape consistency with the input image.
MANTIS: Model-Augmented Neural neTwork with Incoherent k-space Sampling for efficient MR T2 mapping

Quantitative mapping of magnetic resonance (MR) parameters have been shown as valuable methods for improved assessment of a range of diseases. Due to the need to image an anatomic structure multiple times, parameter mapping usually requires long scan times compared to conventional static imaging. Therefore, accelerated parameter mapping is highly-desirable and remains a topic of great interest in the MR research community. While many recent deep learning methods have focused on highly efficient image reconstruction for conventional static MR imaging, applications of deep learning for dynamic imaging and in particular accelerated parameter mapping have been limited. The purpose of this work was to develop and evaluate a novel deep learning-based reconstruction framework called Model-Augmented Neural neTwork with Incoherent k-space Sampling (MANTIS) for efficient MR parameter mapping. Our approach combines end-to-end CNN mapping with k-space consistency using the concept of cyclic loss to further enforce data and model fidelity. Incoherent k-space sampling is used to improve reconstruction performance. A physical model is incorporated into the proposed framework, so that the parameter maps can be efficiently estimated directly from undersampled images. The performance of MANTIS was demonstrated for the spin-spin relaxation time (T2) mapping of the knee joint. Compared to conventional reconstruction approaches that exploited image sparsity, MANTIS yielded lower errors and higher similarity with respect to the reference in the T2 estimation. Our study demonstrated that the proposed MANTIS framework, with a combination of end-to-end CNN mapping, signal model-augmented data consistency, and incoherent k-space sampling, represents a promising approach for efficient MR parameter mapping. MANTIS can potentially be extended to other types of parameter mapping with appropriate models.
The Effectiveness and Cost-Effectiveness of Screening for and Vaccination Against Hepatitis B Virus among Migrants in the EU/EEA: A Systematic Review

Migrants from hepatitis B virus (HBV) endemic countries to the European Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA population but account for 25% of total chronic Hepatitis B (CHB) infection. Migrants from high HBV prevalence regions are at the highest risk for CHB morbidity. These migrants are at risk of late detection of CHB complications; mortality and onwards transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of CHB screening and vaccination programs among migrants to the EU/EEA. We found no RCTs or direct evidence evaluating the effectiveness of CHB screening on morbidity and mortality of migrants. We therefore used a systematic evidence chain approach to identify studies relevant to screening and prevention programs; testing, treatment, and vaccination. We identified four systematic reviews and five additional studies and guidelines that reported on screening and vaccination effectiveness. Studies reported that vaccination programs were highly effective at reducing the prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following vaccination. Two meta-analyses of therapy for chronic HBV infection found improvement in clinical outcomes and intermediate markers of disease. We identified nine studies examining the cost-effectiveness of screening for CHB: a strategy of screening and treating CHB compared to no screening. The median acceptance of HB screening was 87.4% (range 32.3–100%). Multiple studies highlighted barriers to and the absence of effective strategies to ensure linkage of treatment and care for migrants with CHB. In conclusion, screening of high-risk children and adults and vaccination of susceptible children, combined with treatment of CHB infection in migrants, are promising and cost-effective interventions, but linkage to treatment requires more attention.
The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy

Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the art about the study of the interactions between CTCs and the immune system. We intend to analyze the impact that the cells of the immune system have in limiting or promoting the metastatic capability of CTCs. To this purpose, we will examine studies that correlate CTCs, immune cells, and patient prognosis, and we will also discuss relevant animal models that have contributed to the understanding of the mechanisms of immune-mediated metastasis. We will then consider some studies in which CTCs seem to play a promising role in monitoring cancer patients during immunotherapy regimens. We believe that, from an accurate and profound knowledge of the interactions between CTCs and the immune system, new immunotherapeutic strategies against cancer might emerge in the future.
Decreased blood CD4+PD-1+ and CD8+PD-1+ T cells in psoriatic patients with and without arthritis

Introduction Psoriasis with and without arthritis have common immunological mechanisms which among others involve the interactions between cytokines produced by T cells, including Th1, Th17 and Th22. Although quite a lot is known about psoriasis pathogenesis, the cause of chronic immune activation and response in the disease remains unclear. One of the negative regulators of the immune system is programmed death 1 (PD-1). Aim To assess the expression level of PD-1 in the peripheral T cells of psoriatic patients with and without arthritis. Material and methods The study included 23 psoriatic patients with arthritis, 52 psoriatic patients without arthritis and 52 healthy controls. The percentages of CD3+, CD4+, CD8+, CD4+PD-1+ and CD8+PD-1+ T cells were analyzed using flow cytometry. Results The percentages of CD4+PD-1+ as well as CD8+PD-1+ T cells in the psoriatic patients both with and without arthritis were significantly lower than in the control group. The percentages of CD4+PD-1+ as well as CD8+PD-1+T cells were not significantly different between the psoriatic patients with and without arthritis. A significant positive correlation between PD-1 expression on the CD4+ and CD8+ T cells was found in the psoriatic patients without arthritis. Conclusions Impairment of the negative co-stimulation from PD-1 may be another common characteristic of psoriasis both with and without arthritis.
Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study and Review of the Literature

Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.
In silico screening of deleterious single nucleotide polymorphisms (SNPs) and molecular dynamics simulation of disease associated mutations in gene responsible for oculocutaneous albinism type 6 (OCA 6) disorder

Abstract Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with oculocutaneous albinism type 6 (OCA6) disorder and is involved in skin and hair pigmentation. It is involved in the maturation of melanosomes and melanin synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The present study involves the use of computational techniques in order to obtain a detailed picture of the most probable mutations that are associated with SLC24A5. From the observed result it was found that the mutation S145F is most deleterious and disease associated is predicted using several bioinformatics tools. The 3-D structures of native and mutant (S145F) were modeled in order to understand protein functionality using ab initio Robetta server. The modeled structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE Ramachandran plot analysis. The most validated structure undergoes molecular dynamics simulations (MDS) study to understand the structural and functional behaviour of the native and mutant proteins. The MDS result showed the more flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5 protein structure it became more rigid and might disturb the conformational changes and glycosylation function of protein structure and might play role in inducing the OCA6. This study provides a significant insight into the underlying molecular mechanism involved in albinism associated with OCA6. It further helps scientists to develop a drug therapy against OCA 6 disease. Communicated by Ramaswamy H. Sarma
Subconcussive impacts and imaging findings over a season of contact sports

The effect of repeated subconcussive head impacts in youth and high school sports on the developing brain is poorly understood. Emerging neuroimaging data correlated with biomechanical exposure metrics are beginning to demonstrate relationships across a variety of modalities. The long-term consequences of these changes are unknown. A review of the currently available literature on the effect of subconcussive head impacts on youth and high school-age male football players provides compelling evidence for more focused studies of these effects in these vulnerable populations.
NAD+-dependent synthesis of a 5′-phospho-ADP-ribosylated RNA/DNA cap by RNA 2′-phosphotransferase Tpt1

Abstract RNA 2′-phosphotransferase Tpt1 converts an internal RNA 2′-monophosphate to a 2′-OH via a two-step NAD+-dependent mechanism in which: (i) the 2′-phosphate attacks the C1″ of NAD+ to expel nicotinamide and form a 2′-phospho-ADP-ribosylated RNA intermediate; and (ii) the ADP-ribose O2″ attacks the phosphate of the RNA 2′-phospho-ADPR intermediate to expel the RNA 2′-OH and generate ADP-ribose 1″–2″ cyclic phosphate. Tpt1 is an essential component of the fungal tRNA splicing pathway that generates a unique 2′-PO4, 3′-5′ phosphodiester splice junction during tRNA ligation. The wide distribution of Tpt1 enzymes in taxa that have no fungal-type RNA ligase raises the prospect that Tpt1 might catalyze reactions other than RNA 2′-phosphate removal. A survey of Tpt1 enzymes from diverse sources reveals that whereas all of the Tpt1 enzymes are capable of NAD+-dependent conversion of an internal RNA 2′-PO4 to a 2′-OH (the canonical Tpt1 reaction), a subset of Tpt1 enzymes also catalyzed NAD+-dependent ADP-ribosylation of an RNA or DNA 5′-monophosphate terminus. Aeropyrum pernix Tpt1 (ApeTpt1) is particularly adept in this respect. One-step synthesis of a 5′-phospho-ADP-ribosylated cap structure by ApeTpt1 (with no subsequent 5′-phosphotransferase step) extends the repertoire of the Tpt1 enzyme family and the catalogue of ADP-ribosylation reactions involving nucleic acid acceptors.