Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Vitamin D Supplementation, Food Fortification, or Bolus Injection on Vitamin D Status in Children Aged 2-18 Years: A Meta-Analysis.

Meta-analyses on the effect of vitamin D intake on status in children are lacking, especially those focused on vitamin D-fortified foods. The objective of this meta-analysis was to investigate the effect of vitamin D interventions (fortified foods, supplements, bolus injections) on vitamin D status in children 2-18 y of age. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, literature searches were conducted up to December 2016. Randomized placebo-controlled vitamin D interventions in healthy children aged 2-18 y were included. A random-effects model was used with I2 assessing heterogeneity. We included 26 trials (5403 children) with interventions (n = 9 fortified foods, n = 15 supplements, n = 2 bolus injections) from 100-4000 IU vitamin D/d over 4 wk to 2 y. The serum 25-hydroxyvitamin D [25(OH)D] weighted mean difference for all 26 trials (23.5 nmol/L; 95% CI: 20.7, 26.3 nmol/L; I2 = 99.9%) resulted in a mean increase of 1.0 nmol/L (95% CI: 0.3, 1.7 nmol/L) for each increase of 100 IU vitamin D/d (per 1 µg/d : 0.4 nmol/L; 95% CI: 0.1, 0.7 nmol/L). The response per 100 IU vitamin D/d was greater in trials with a mean baseline serum 25(OH)D <30 nmol/L, with the use of fortified foods and with baseline vitamin D intakes <100 IU/d. In conclusion, the serum 25(OH)D response to vitamin D intake differs on the basis of baseline status, intakes, and delivery mode, but not age, sex, or latitude.
Validation of the European Society of Cardiology and European Society of Anaesthesiology non-cardiac surgery risk score in patients treated with coronary drug-eluting stent implantation

Aims The current guidelines from the European Society of Cardiology and European Society of Anaesthesiology on non-cardiac surgery (ESC/ESA-NCS) divide surgical procedures into those associated with low risk (<1%), intermediate risk (1-5%), and high risk (>5%) of major adverse cardiac events (MACE). Evaluating surgical risk might be particularly appropriate in patients with recent stent implantation, and thus we validated the ESC/ESA-NCS classification in patients undergoing NCS within 1 year after coronary drug-eluting stent (DES) implantation. Methods and results By record-linking the Western Denmark Heart Registry and the Danish National Patient Registry, we identified 4046 patients, who underwent NCS between 1 and 12 months after DES implantation. Primary outcomes were MACE [cardiac death and myocardial infarction (MI)] and a combined endpoint of mortality and MI within 30 days after surgery. Both MACE (low risk 0.6%, intermediate risk 1.2%, and high risk 3.4%) and the combined endpoint of mortality and MI (1.5%, 4.6%, and 14.9%) were associated with the ESC/ESA-NCS classification. As compared with low-risk surgery, the odds ratios (OR) for MACE were 1.9 [95% confidence interval (CI) 0.9-4.1] for intermediate-risk surgery and 5.8 (95% CI 1.7-20.1) for high-risk surgery. For the combined endpoint of mortality and MI, the OR's were 3.1 (95% CI 2.1-4.7) for intermediate-risk surgery and 11.3 (95% CI 5.9-21.9) for high-risk surgery. Conclusion The ESC/ESA-NCS classification is a valid tool to predict the risk of both MACE and the combined endpoint of mortality and MI for patients undergoing NCS.
A potential Rho GEF and Rac GAP for coupled Rac and Rho cycles during mesenchymal-to-epithelial-like transitions

ABSTRACT The leading edge-to-cadherin contact transitions that occur during metazoan developmental processes and disease states require fine coordination of Rac and Rho pathways. Recently the elmo-mbc complex, a Rac GEF and RhoGAP19D, a Rho GAP were identified as key, conserved regulators that link Rac and Rho during these transitions. The corresponding Rho GEF and Rac GAP remain hidden amongst the large family of GEF and GAP proteins. Identification of these regulators is essential to understand GTPase coordination during these transitions. Here we find two candidates based on the mammalian literature and use RNAi to explore the fly ortholog effects on the dorsal closure epidermis. RhoGEF64C and RhoGAP92B are strong contenders to couple Rac and Rho during mesenchymal-to-epithelial-like transitions.
ALARM NMR for HTS Triage and Chemical Probe Validation

Nonspecific target engagement by test compounds and purported chemical probes is a significant source of assay interference and promiscuous bioactivity in high‐throughput screening (HTS) and chemical biology. Most counter‐screens for thiol‐reactive compounds utilize mass spectrometry or fluorescence detection, as well as nonproteinaceous reporters like glutathione that may not always approximate the reactivity of protein side chains. By contrast, a La assay to detect reactive molecules by nuclear magnetic resonance (ALARM NMR) is an industry‐developed protein‐based [1H‐13C]‐heteronuclear multiple quantum coherence NMR counter‐screen to identify nonspecific protein interactions by test compounds by reporting their tendencies to modulate the human La antigen conformation. This article is a user's guide to the production of the 13C‐labeled La antigen reporter protein and reaction of test compounds with this reporter protein, as well as the collection and analysis of characteristic NMR spectra. Combined with other assay interference counter‐screens, this assay will enhance chemical biology by helping researchers better prioritize chemical matter, which will increase the number of tractable HTS screening actives and aid in the development of better chemical probes. © 2018 by John Wiley & Sons, Inc.
National survey in elderly care on the process of adopting a new regulation aiming to prevent and treat malnutrition in Sweden

Guided by the i-PARIHS framework, this study investigates perceived facilitators in the process of adopting a new regulation launched in 2015 which aims to prevent and treat malnutrition. In May 2016, a national web-based questionnaire was emailed to chief medical nurses in elderly care in all Swedish municipalities (n = 290). The response rate in this cross-sectional study was 75% (n = 217). Fifty per cent of the municipalities had adopted new routines, 42% had started and 8% had not. One third of the respondents considered malnutrition to be a major problem in elderly care and about half considered the new national regulation to have strengthened local work. A logistic regression showed that the odds for having adopted new routines were higher for CMNs with long experience in elderly care and who had previously worked to prevent malnutrition, and for those who considered the new national regulation helpful. To extract underlying factors in the adoption process, two principal component analyses were performed for key actors and support. For key actors, the analysis yielded four factors, explaining 67% of the total variance; (a) first line team, (b) expert team, (c) management team and (d) surrounding resources. For support, the analysis yielded three factors, which explained 65% of the total variance; (a) agile teamwork, (b) management and leadership and (c) acceptance. The slow adoption rate of the regulation raises questions about its impact; this might be an effect of the general trend of decentralisation in the Swedish welfare sector, and in elderly care in particular, making it hard to attain change that is steered centrally. However, malnutrition is a pronounced problem in elderly care and the mandatory nature of the new regulation therefore warrants further investigation of whether its launch has contributed to a reduction of malnutrition by investigating outcomes and preventive actions carried out in practice.
Human β3-Adrenoreceptor is Resistant to Agonist-Induced Desensitization in Renal Epithelial Cells

Background/Aims: We recently showed that the β3-adrenoreceptor (β3AR) is expressed in mouse kidney collecting ducts (CD) cells along with the type-2 vasopressin receptor (AVPR2). Interestingly, a single injection of a β3AR selective agonist promotes a potent antidiuretic effect in mice. Before considering the feasibility of chronic β3AR agonism to induce antidiuresis in vivo, we aimed to evaluate in vitro the signaling and desensitization profiles of human β3AR. Methods: Human β3AR desensitization was compared with that of human AVPR2 in cultured renal cells. Video imaging and FRET experiments were performed to dissect β3AR signaling under acute and chronic stimulation. Plasma membrane localization of β3AR, AVPR2 and AQP2 after agonist stimulation was studied by confocal microscopy. Receptors degradation was evaluated by Western blotting. Results: In renal cells acute stimulation with the selective β3AR agonist mirabegron, induced a dose-dependent increase in cAMP. Interestingly, chronic exposure to mirabegron promoted a significant increase of intracellular cAMP up to 12 hours. In addition, a slow and slight agonist-induced internalization and a delayed downregulation of β3AR was observed under chronic stimulation. Furthermore, chronic exposure to mirabegron promoted apical expression of AQP2 also up to 12 hours. Conversely, long-term stimulation of AVPR2 with dDAVP showed short-lasting receptor signaling, rapid internalization and downregulation and apical AQP2 expression for no longer than 3 h. Conclusions: Overall, we conclude that β3AR is less prone than AVPR2 to agonist-induced desensitization in renal collecting duct epithelial cells, showing sustained cAMP production, preserved membrane localization and delayed degradation after 12 hours agonist exposure. These results may be important for the potential use of chronic pharmacological stimulation of β3AR to promote antidiuresis overcoming in vivo renal concentrating defects caused by inactivating mutations of the AVPR2.
Cognitive decline and alcohol consumption adjusting for functional status over a 3-year period in French speaking community living older adults.

Background The effect of alcohol consumption on cognitive decline is not clear. We aimed to study the association between alcohol consumption and cognitive functioning controlling for functional heath status. Methods A total of 1610 older adults with a score ≥26 on the Mini-Mental State Examination (MMSE) were followed to assess the change in scores at the 3-year follow-up. Information on alcohol consumption as well as socio-demographic, lifestyle, psychosocial and clinical factors, as well as health service use were assessed at baseline and 3-year follow-up interviews. Linear mixed models with repeated measures were used stratifying by functional status. Results Close to 73% reported consuming alcohol in the past 6 months, of which 11% were heavy drinkers (≥11 and ≥16 drinks for women and men). A significant decrease in MMSE scores was observed in low functioning non-drinkers (-1.48; 95% CI: -2.06, -0.89) and light to moderate drinkers (-0.99; 95% CI: -1.54, -0.44) and high functioning non-drinkers (-0.51; 95% CI: -0.91, -0.10). Conclusions Alcohol consumption did not contribute to cognitive decline. Cognitive decline was greater in individuals reporting low functional status. Research should focus on the interaction between changing patterns of alcohol consumption and social participation in individuals with low and high functioning status.
A density functional theory-based analysis of the structural, topological and electronic properties of gemcitabine drug adsorption on the pyrrolidine functionalized single-walled carbon nanotube

Abstract The stability of gemcitabine anticancer drug on the functionalized (8,0) zigzag carbon nanotube as a drug delivery vehicle is studied within the formalism of the density functional theory calculations to understand the role of the pyrrolidine functional group in binding the adsorbed molecule to the drug delivery system as well as improving water solubility. The binding energies, natural bond orbital calculations, and the quantum theory of atoms in molecules results are obtained to provide more evidences related to the intermolecular interaction between gemcitabine drug and the functionalized nanotube. The negative binding energy corresponds to favorable binding of gemcitabine drug to the functionalized nanotube and presence of the active sites available for hydrogen bond formation facilitates better drug binding to the nanotube sidewall. The results presented in this article indicate that pyrrolidine functionalized carbon nanotube seems to be a novel material for drug delivery applications. Communicated by Heidar Moradnia
Molecular dynamics and free energy studies on the Drosophila melanogaster and Leptinotarsa decemlineata ecdysone receptor complexed with agonists: Mechanism for binding and selectivity

Abstract The ecdysone receptor is a nuclear hormone receptor that plays a pivotal role in the insect metamorphosis and development. To address the molecular mechanisms of binding and selectivity, the interactions of two typical agonists Ponasterone A and 20-Hydroxyecdysone with Drosophila melanogaster (DME) and Leptinotarsa decemlineata ecdysone (LDE) receptors were investigated by homology modeling, molecular docking, molecular dynamic simulation, and thermodynamic analysis. We discover that 1) the L5-loop, L11-loop, and H12 helix for DME, L7-loop, and L11-loop for LDE are more flexible, which affect the global dynamics of the ligand-binding pocket, thus facilitating the ligand recognition of ecdysone receptor; 2) several key residues (Thr55/Thr37, Phe109/Phe91, Arg95/Arg77, Arg99/Arg81, Phe108/Leu90, and Ala110/Val92) are responsible for the binding of the proteins; 3) the binding-free energy is mainly contributed by the van der Waals forces as well as the electrostatic interactions of ligand and receptor; 4) the computed binding-free energy difference between DME-C1 and LDE-C1 is –4.65 kcal/mol, explains that C1 can form many more interactions with the DME; 5) residues Phe108/Leu90 and Ala110/Val92 have relatively position and orientation difference in the two receptors, accounting most likely for the ligand selectivity of ecdysone receptor from different orders of insects. This study underscores the expectation that different insect pests should be able to discriminate among compounds from different as yet undiscovered compounds, and the results firstly show a structural and functional relay between the agonists and receptors (DME and LDE), which can provide an avenue for the development of target-specific insecticides. Communicated by Ramaswamy H. Sarma
High quality whole genome sequence of an abundant Holarctic odontocete, the harbour porpoise (Phocoena phocoena)

The harbour porpoise (Phocoena phocoena) is a highly mobile cetacean found in waters across the Northern hemisphere. It occurs in coastal water and inhabits water basins that vary broadly in salinity, temperature, and food availability. These diverse habitats could drive differentiation among populations. Here we report the first harbour porpoise genome, assembled de novo from a Swedish Kattegat individual. The genome is one of the most complete cetacean genomes currently available, with a total size of 2.7 Gb and 50% of the total length found in just 34 scaffolds. Using the largest 122 scaffolds, we were able to validate a high level of homology to the chromosome-level genome assembly of the closest related species for which such resource was available, the domestic cattle (Bos taurus). The draft annotation comprises 22,154 predicted gene models, which we further annotated through matches to the NCBI nucleotide database, GO categorization, and motif prediction. To infer the adaptive abilities of this species, as well as their population history, we performed a Bayesian skyline analysis, and produced results that are concordant with the demographic history of this species, including expansion and fragmentation events. Overall, this genome assembly, together with the draft annotation, represents a crucial addition to the limited genetic markers currently available for the study of porpoises and Phocoenidae conservation, phylogeny, and evolution.
Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy

Abstract The aim of this study was to optimize the cationic PEGylated niosome-containing anti-cancer drugs and siRNA to enhance the therapeutic response. Therefore, various surfactant-based (tween-60) vesicles of doxorubicin (DOX; a chemotherapeutic drug) and quercetin (QC; a chemosensitizer) were prepared. To load siRNA on niosomes, 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) was used as a cationic lipid. The optimum formulation containing tween-60:cholesterol:DPPC:DOTAP:DSPE-PEG2000 at 49.5:5.5:15:25:5 demonstrated that the vesicle size and zeta potential were 52.8 ± 2.7 nm and +27.4 ± 2.3 mV, respectively. Entrapment efficiency (EE%) for DOX and QC was 86.4 ± 2.1% and 94.9 ± 3.9%, respectively. Moreover, the drug release during 6 h was 32.1 ± 1.6% and 30.5 ± 1.3% for DOX and QC, respectively denoted on the controlled release. The gel retardation assay demonstrated that siRNA could be successfully loaded into a cationic niosome:siRNA in a weight ratio 40:1. Additionally, noisome-encapsulated drugs had a higher toxicity against cancer cells when compared with un-encapsulated forms and the synergistic effects of co-delivery of siRNA and DOX with QC on gastric, prostate, breast cancer cells as well as human foreskin fibroblast as a normal cell line was shown. The results showed that the co-delivery of drugs and siRNA using cationic PEGylated niosomes exhibited an increased anti-cancer activity against the tumor cell death. It seems that cationic PEGylated niosomes have opened up a new avenue to enrich the armamentarium of therapeutic agents to fight cancer. Graphical Abstract
Structure of the bifunctional cryptochrome aCRY from Chlamydomonas reinhardtii

Abstract Photolyases and cryptochromes form an almost ubiquitous family of blue light photoreceptors involved in the repair and maintenance of DNA integrity or regulatory control. We found that one cryptochrome from the green alga Chlamydomonas reinhardtii (CraCRY) is capable of both, control of transcript levels and the sexual cycle of the alga in a positive (germination) and negative manner (mating ability), as well as catalyzing the repair of UV-DNA lesions. Its 1.6 Å crystal structure shows besides the FAD chromophore an aromatic tetrad that is indispensable in animal-like type I cryptochromes for light-driven change of their signaling-active redox state and formation of a stable radical pair. Given CraCRY’s catalytic activity as (6-4) photolyase in vivo and in vitro, we present the first co-crystal structure of a cryptochrome with duplex DNA comprising a (6-4) pyrimidine–pyrimidone lesion. This 2.9 Å structure reveals a distinct conformation for the catalytic histidine His1, H357, that challenges previous models of a single-photon driven (6-4) photolyase mechanism.
A group mental health randomized controlled trial for female refugees in Malaysia.

Forcibly displaced persons confront multiple stressors while awaiting permanent asylum or resettlement and often experience high levels of emotional distress. This study assessed an 8-week somatic-focused culturally adapted cognitive-behavioral therapy (CBT) group intervention with 39 female refugees from Afghanistan living in Kuala Lumpur, Malaysia. Twenty-nine participants were randomly assigned to treatment conditions, resulting in 20 participants in two separate treatment groups and 9 in a waitlist control group. An additional 10 participants were not randomly assigned and therefore were treated as an additional treatment group and analyzed separately. A three-group piecewise linear growth model was specified in Mplus using Bayesian estimation. Dependent variables included emotional distress, anxiety, depression, posttraumatic stress, and social support. From baseline to posttreatment assessments, initial intervention participants experienced significant declines in emotional distress (b = -16.90, p < .001), anxiety (b = -.80, p < .001), depression (b = -.59, p < .001), and posttraumatic stress (b = -.24, p < .05). Gains were maintained three months posttreatment, with similar trends observed among nonrandomized participants. Subsequent to receiving treatment, the waitlist control participants also showed significant declines in emotional distress (b = -20.88, p < .001), anxiety (b = -1.10, p < .001), depression (b = -.79, p < .001), and posttraumatic stress scores (b = -.82, p < .001). Comparing the treatment groups to the waitlist control group revealed large effect sizes: Cohen's d was 2.14 for emotional distress, 2.31 for anxiety, 2.42 for depression, and 2.07 for posttraumatic stress. Relevant public health findings include low drop out, group format, and facilitation by a trained community member. (PsycINFO Database Record
The Snowden Phone: A Comparative Survey of Secure Instant Messaging Mobile Applications (authors' version)

In recent years, it has come to attention that governments have been doing mass surveillance of personal communications without the consent of the citizens. As a consequence of these revelations, developers have begun releasing new protocols for end-to-end encrypted conversations, extending and making popular the old Off-the-Record protocol. New implementations of such end-to-end encrypted messaging protocols have appeared, and several popular chat applications have been updated to use such protocols. In this survey, we compare six existing applications for end-to-end encrypted instant messaging, namely, Signal, WhatsApp, Wire, Viber, Riot, and Telegram, most of them implementing one of the recent and popular protocols called Signal. We conduct five types of experiments on each of the six applications using the same hardware setup. During these experiments, we test 21 security and usability properties specially relevant for applications (not protocols). The results of our experiments demonstrate that the applications vary in terms of the usability and security properties they provide, and none of them are perfect. In consequence, we make 12 recommendations for improvement of either security, privacy, or usability, suitable for one or more of the tested applications.
Immunohistochemical visualization of the signature of activated Hedgehog signaling pathway in cutaneous epithelial tumors

Activation of the Hedgehog (HH) signaling pathway plays a critical role in the development of basal cell carcinoma (BCC). HH signaling activity is produced by nuclear translocation of transcription factors, glioma‐associated oncogene homolog (GLI). Among three GLI subfamilies, GLI1 is the only full‐length transcriptional activator, and its nuclear localization is recognized as a signature event in HH signaling activation. However, limited published work has investigated the nuclear staining of GLI1 protein in human tumor tissue samples by immunohistochemical analysis. In this study, we performed immunohistochemical staining of GLI1 in 382 cases of cutaneous epithelial tumors, including 196 BCC cases, using rabbit monoclonal antihuman GLI1 antibody (C68H3). As a result, 98.2% cases of BCC showed a diffuse and strong nuclear staining pattern regardless of the histological subtype. Positive staining was mainly restricted to the tumor nests, while the overlying epidermis was negative suggesting specificity of the antibody. In further analysis of other cutaneous epithelial tumors, 100% (4/4) cases of trichoblastoma, 15.1% (5/33) Bowen's disease, 3.5% (1/28) actinic keratosis and 12.5% (4/32) squamous cell carcinoma showed the nuclear staining pattern of GLI1. This suggested that HH signaling is also dysregulated in some other cutaneous malignant tumors. In conclusion, the C68H3 antibody is a useful tool for revealing activation of HH signaling in immunohistochemical analysis.