Miracle-dz/UniFAR-FTUs huggingface dataset:
Eigenvector centrality for characterization of protein allosteric pathways

Significance Allosteric processes are ubiquitous in macromolecules and regulate biochemical information transfer between spatially distant sites. Despite decades of study, allosteric processes remain generally poorly understood at the molecular level. Here, we introduce the eigenvector centrality measure of mutual information to disentangle the complex interplay of amino acid interactions giving rise to allosteric signaling. The analysis of eigenvector centrality is tested in imidazole glycerol phosphate synthase (IGPS), a prototypical V-type allosteric enzyme. The resulting insights allow us to pinpoint key amino acids in terms of their relevance in the allosteric process, suggesting protein-engineering strategies for control of enzymatic activity. Determining the principal energy-transfer pathways responsible for allosteric communication in biomolecules remains challenging, partially due to the intrinsic complexity of the systems and the lack of effective characterization methods. In this work, we introduce the eigenvector centrality metric based on mutual information to elucidate allosteric mechanisms that regulate enzymatic activity. Moreover, we propose a strategy to characterize the range of correlations that underlie the allosteric processes. We use the V-type allosteric enzyme imidazole glycerol phosphate synthase (IGPS) to test the proposed methodology. The eigenvector centrality method identifies key amino acid residues of IGPS with high susceptibility to effector binding. The findings are validated by solution NMR measurements yielding important biological insights, including direct experimental evidence for interdomain motion, the central role played by helix hα1, and the short-range nature of correlations responsible for the allosteric mechanism. Beyond insights on IGPS allosteric pathways and the nature of residues that could be targeted by therapeutic drugs or site-directed mutagenesis, the reported findings demonstrate the eigenvector centrality analysis as a general cost-effective methodology to gain fundamental understanding of allosteric mechanisms at the molecular level.
Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight

Genetic variation of the fat mass and obesity associated gene (FTO) has been identified as a risk factor for obesity and obesity traits. Distribution of FTO single nutleotide polymorphisms (SNPs) rs1421085T>C, rs9939609T>A, rs8057044G>A and copy number variation (CNV) was evaluated in association with childhood obesity or overweight status in children with Mayan ethnicity.
Mycobacterial glycolipid Di-O-acyl trehalose promotes a tolerogenic profile in dendritic cells

Due to prolonged coevolution with the human being, Mycobacterium tuberculosis has acquired a sophisticated capacity to evade host immunity and persist in a latent state in the infected individual. As part of this evolutive process, mycobacteria have developed a highly complex cell wall that acts as a protective barrier. Herein we studied the effects of Di-O-acyl trehalose, a cell-wall glycolipid of virulent mycobacteria on murine bone marrow-derived dendritic cells. We have demonstrated that Di-O-Acyl-trehalose promotes a tolerogenic phenotype in bone marrow-derived murine DCs activated with mycobacterial antigens and Toll-like receptor agonists. This phenotype included low expression of antigen presentation and costimulatory molecules and altered cytokine production with downregulation of IL-12 and upregulation of IL-10, an anti-inflammatory cytokine. Additional markers of tolerogenicity were the expression of Indoleamine 2,3-dioxygenase and CD25. Furthermore, Di-O-Acyl-Trehalose promoted the expansion of FoxP3+ regulatory T lymphocytes. A better understanding of mycobacterial cell-wall components involved in the evasion of immunity is a prerequisite to designing better strategies to fight tuberculosis.
Functional connection between the stereotyped behavior and the motor front area in children with autism

Abstract Object: Autism spectrum disorders (ASD) is characterized by stereotyped behavior, attention deficit and/or impaired sensory perception to external stimuli. Its neurobiological mechanisms remain unclear. In this study we examined the resting-state functional connectivity of the premotor area and investigated its correlation with behavioral variables to determine whether connectivity alterations can distinguish ASD from healthy controls. Methods: 39 children with ASD and 42 healthy children with matched age, sex and intelligence were recruited. All the 81 subjects had behavioral index evaluation and underwent resting-state functional magnetic resonance imaging (fMRI) scans. After MRI data preprocessing, the left and right premotor areas were selected as region of interest (ROI) seeds to perform functional connectivity. Groups were compared, and the correlation between functional connectivity and behavioral indicators was analyzed. Results: Compared with healthy controls, ASD children showed significantly increased functional connectivity between the left premotor area and the posterior cingulate gyrus or anterior lobe of wedge, but functional connectivity between the left premotor area and the left insular lobe was decreased (p < 0.05, FDR correction). In addition, the connectivity between the left premotor area and the left insular lobe was negatively correlated with the behavioral scores (p < 0.05). Conclusion: Imbalanced premotor functional connectivity may be one possible mechanism of stereotyped behavior in ASD.
MorpheuS: Generating Structured Music with Constrained Patterns and Tension

Automatic music generation systems have gained in popularity and sophistication as advances in cloud computing have enabled large-scale complex computations such as deep models and optimization algorithms on personal devices. Yet, they still face an important challenge, that of long-term structure, which is key to conveying a sense of musical coherence. We present the MorpheuS music generation system designed to tackle this problem. MorpheuS’ novel framework has the ability to generate polyphonic pieces with a given tension profile and long- and short-term repeated pattern structures. A mathematical model for tonal tension quantifies the tension profile and state-of-the-art pattern detection algorithms extract repeated patterns in a template piece. An efficient optimization metaheuristic, variable neighborhood search, generates music by assigning pitches that best fit the prescribed tension profile to the template rhythm while hard constraining long-term structure through the detected patterns. This ability to generate affective music with specific tension profile and long-term structure is particularly useful in a game or film music context. Music generated by the MorpheuS system has been performed live in concerts.
Individual cognitive stimulation therapy for people with intellectual disability and dementia: protocol of a feasibility randomised controlled trial

Introduction Cognitive stimulation therapy (CST) is a psychosocial intervention for dementia. Group CST is effective in reducing cognitive decline and improving quality of life in patients with dementia. There is some evidence that individual CST (iCST) may be beneficial in reducing cognitive decline. People with intellectual disability (ID) have an increased risk of dementia. However, there are no published studies of CST in people with ID and dementia. This protocol describes the feasibility and acceptability of a randomised controlled trial of iCST delivered by carers to people with ID and dementia, compared with treatment as usual (TAU). The results of this study will inform the design of a future definitive randomised controlled trial. Methods and analysis The iCST intervention has been adapted for this trial. Forty dyads (individuals with ID and their carer) will be randomised to either iCST or TAU. The manualised intervention comprises 40 iCST sessions delivered by a carer for 30 min, twice a week, over 20 weeks. The primary outcome will be process measures assessing the feasibility and acceptability of the intervention and trial procedures. The secondary outcome will be changes in the scores of outcome measures (cognition, functional ability and quality of life in individuals with ID, and caregiver burden, competence in managing dementia, and anxiety and depression in carers). Data will be collected at baseline, 11 weeks and at 21 weeks. A process evaluation will examine adherence to iCST and will include qualitative interviews with participants to identify aspects of the intervention that were or were not successful. Ethics and dissemination The study has received ethical approval. The results of the study will be presented at conferences and submitted to a peer reviewed journal. Trial registration number ISRCTN18312288; Pre-results.
Functional Characterization of Abicipar-Pegol, an Anti-VEGF DARPin Therapeutic That Potently Inhibits Angiogenesis and Vascular Permeability.

Purpose DARPin molecules are a novel class of small proteins that contain engineered ankyrin repeat domain(s) and bind to target proteins with high specificity and affinity. Abicipar-pegol (abicipar), a DARPin molecule targeting vascular endothelial growth factor-A (VEGF-A), is currently under evaluation in patients with age-related macular degeneration. The pharmacodynamic properties of abicipar were characterized using in vivo and in vitro assays. Methods The binding affinity of abicipar was assessed using a kinetic exclusion assay (KinExA). In vitro assays evaluated abicipar effects on VEGF-A165-induced calcium mobilization and tube formation in human umbilical vein endothelial cells. Abicipar was tested in vivo in a mouse model of corneal neovascularization and a rabbit model of chronic retinal neovascularization. The efficacies of abicipar and ranibizumab were compared in a rabbit model of VEGF-A165-induced retinal vasculopathy. Results Abicipar has a high affinity for the soluble isoforms of VEGF-A; binding affinities for human VEGF-A165 are approximately 100-fold greater than those of ranibizumab and bevacizumab and are similar for rat VEGF-A164 but approximately 20-fold lower for rabbit VEGF-A165. Abicipar was effective in cell-based and in vivo models of angiogenesis and vascular leak, blocking neovascularization in a mouse model of corneal neovascularization and vascular permeability in a rabbit model of chronic neovascularization. In a rabbit model of VEGF-A165-induced vasculopathy, the duration of effect of abicipar was longer than ranibizumab when the two compounds were administered at molar-equivalent doses. Conclusions These data support the testing of abicipar as a treatment for retinal diseases characterized by neovascularization and vascular leak.
Sustainable diets and food-based dietary guidelines.

Abstract Food-based dietary guidelines (FBDGs) have been developed by countries around the world as simple policy instruments to promote better diets for individuals and populations. The guidance historically has been based on country-specific, diet-related morbidity and mortality. As the environmental impacts of food consumption and production push planetary boundaries, the case for inclusion of elements of environmental sustainability into FBDGs becomes compelling. Issues addressed include biodiversity, plant-based diets, meat and dairy consumption and production, sustainable fish consumption, processed foods, local, seasonal and organic production, standards of ethical treatment for livestock, waste and lifestyle behaviours. Examples from official FBDGs are presented, along with examples of quasi-official guidelines. Challenges and failures are also discussed, related to lack of political support and vested interests. With consideration given to all the international agreements signed by nations related to both nutrition and environmental sustainability, the logical integration should yield country-specific sustainable FBDGs.
Vancomycin trough level and loading dose

php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Infection and Drug Resistance 2018:11 2393–2396 Infection and Drug Resistance Dovepress
Ultra-Low-Dose 18F-Florbetaben Amyloid PET Imaging Using Deep Learning with Multi-Contrast MRI Inputs.

Forty data sets from 39 patients (mean age 6 standard deviation [SD], 67 years 6 8), including 16 male patients and 23 female patients (mean age, 66 years 6 6 and 68 years 6 9, respectively), who underwent simultaneous amyloid (fluorine 18 [ 18 F]–florbetaben) PET/MRI examinations were acquired from March 2016 through October 2017 and retrospectively analyzed. One hundredth of the raw list-mode PET data were randomly chosen to simulate a low-dose (1%) acquisition. Convolutional neural networks were implemented with low-dose PET and multiple MR images (PET-plus-MR model) or with low-dose PET alone (PET-only) as inputs to predict full-dose PET images. Quality of the synthesized images was evaluated while Bland-Altman plots assessed the agreement of regional standard uptake value ratios (SUVRs) between image types. Two readers scored image quality on a five-point scale (5 = excellent) and determined amyloid status (positive or negative). Statistical analyses were carried out to assess the difference of image quality metrics and reader agreement and to determine confidence intervals (CIs) for reading results. Results: The synthesized images (especially from the PET-plus-MR model) showed marked improvement on all quality metrics compared with the low-dose image. All PET-plus-MR images scored 3 or higher, with proportions of images rated greater than 3 similar to those for the full-dose images ( 2 10% difference [eight of 80 readings], 95% CI: 2 15%, 2 5%). Accuracy for amyloid status was high (71 of 80 readings [89%]) and similar to intrareader reproducibility of full-dose images (73 of 80 [91%]). The PET-plus-MR model also had the smallest mean and variance for SUVR difference to full-dose images. Conclusion
Ferromagnetism in graphene traced to antisymmetric orbital combination of involved electronic states

Based on first principles calculations, we reveal that the origin of ferromagnetism caused by electrons in graphene with vacancies can be traced to electrons partially filling -antibonding and -nonbonding states, which are induced by the vacancies and appear near the Fermi level. Because the spatial wavefunctions of both states are composed of atomic orbitals in an antisymmetric configuration, their spin wavefunctions should be symmetric according to the electron exchange antisymmetric principle, leading to electrons partially filling these states in spin polarization. Since this state originates not from interactions between the atoms but from the unpaired orbitals due to the removal of orbitals on the minority sublattice, the state is constrained, distributed on the atoms of the majority sublattice, and decays gradually from the vacancy as ∼. According to these characteristics, we concluded that the state plays a critical role in magnetic ordering in graphene with vacancies. If the vacancy concentration in graphene is large enough to cause the decay-length regions to overlap, constraining the orbital components as little as possible on the minority sublattice atoms in the overlap regions results in the vacancy-induced states being coherent. The coherent process in the overlap region leads to the wavefunctions in all the involved regions antisymmetrized, consequently causing ferromagnetism according to the electron exchange antisymmetric principle. This unusual mechanism concerned with the origin of -electron magnetism and magnetic ordering has never before been reported and is distinctly different from conventional mechanisms. Consequently, we can explain how such a weak magnetization with such a high critical temperature can be experimentally observed in proton-irradiated graphene.
High-sensitivity C reactive protein and risk of cardiovascular disease in China-CVD study

Background This study aimed to assess the association of high sensitivity C-reactive protein (hs-CRP) with cardiovascular disease (CVD) in middle-aged Chinese population. Methods The baseline was collected 2009–2010, and follow-up was conducted in 2016–2017. Data of hs-CRP were from baseline examination and re-examination in 2016–2017 using transmission turbidimetry with a measurement range of 0–42 000. The primary outcome was CVD including coronary heart disease events and stroke events. Results Among 8688 participants free from CVD (at baseline, mean age, 50.1 years, 3897 were males), there were 189 CVD events, occurred during a median follow-up of 6.34 years (54 685 person-years at risk). From the Kaplan-Meier curve, we found that there was a progressive increase in CVD event rates by hs-CRP tertiles (log-rank test, p<0.001). Baseline hs-CRP was linearly associated with CVD (p for trend=0.015) even after adjusting for known CVD risk factors. Furthermore, the net reclassification improvement when hs-CRP was added to a model based on traditional factors was 7.85% for CVD (p=0.003). In addition, the correlation between change of hs-CRP and CVD was conducted in a subgroup (n=4778). However, we did not find the correlation between hs-CRP change and CVD (correlation coefficient: −0.003, p=0.846). Conclusions In the middle-aged Chinese population, hs-CRP was associated with increased risk of developing CVD. Although there was no correlation between hs-CRP change and CVD, the level of hs-CRP was higher at follow-up than baseline even among those with CVD. More attention should be given to those with higher level of hs-CRP for CVD prevention.
ADHD Comorbid With Major Depression on Parents and Teachers Perceptions

Objective: Examine the Strengths and Difficulties Questionnaire (SDQ) responses of parents and teachers for children with ADHD comorbid with major depressive disorder (MDD), with an emphasis on determining how well the respondent groups’ responses correlate, and how well the results obtained perform as predictors of clinical diagnosis. Method: The SDQ was completed by parents and teachers of (n = 215 participants, 7-12 years old) in ADHD, MDD, ADHD + MDD, and healthy control groups. Agreement between parent and teacher SDQs and their concordance with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnoses were assessed. Receiver operating characteristic (ROC) and Kappa concordance analyses were used to compare the groups with the health control group. Results: The comorbid group presented greater impairments than the ADHD, MDD, and control groups (p < .001). Conclusion: The presence of psychiatric comorbidity causes greater impairment for school children with ADHD. The SDQ has good sensitivity for detecting these children and correlates well with DSM diagnosis.
An Unusual Presentation of Lupus Vulgaris and the Practical Usefulness of Dermatoscopy

We report a case report of lupus vulgaris (LV) presented on the extremities of an 80-year-old man. He was misdiagnosed as having psoriasis and referred to our department for a second-opinion evaluation. The discrepancy between the clinical manifestation which was misleading and the dermatoscopic findings raised the suspicion of an underlying granulomatous disease and we proceeded to skin biopsy. The histopathologic examination set the diagnosis of LV.
Visibility of MRI prostate lesions on B-mode transrectal ultrasound.

AIM Prostate biopsies are usually done with transrectal ultrasound (TRUS) in B-mode (B TRUS) but multiparametric MRI (mpMRI) is the gold imaging standard for the visualization of clinically significant prostate cancer (PCa), since a lowPCa detection rate is reported for B TRUS. The aim of this study was to assess the visibility of MRI lesions on B TRUS and to determine which factors may influence the visibility on B TRUS. MATERIAL AND METHODS 142 men with 148 lesions reported on mpMRI underwent a B TRUS/mpMRI fusion targeted biopsy of the prostate and were included in this retrospective study. During the biopsy, images were obtained and stored in the institution's PACS. These images were reviewed by two radiologists to determine, whether an mpMRI lesion was or was not visible on B TRUS. RESULTS Overall 92 from 148 mpMRI lesions (62.2%) were visible on B TRUS. The location of the lesion in the prostate, the PIRADS classification of the lesions and the size of the lesion had no significant influence on the visibility on B TRUS. Only the prostate volume had a significant influence on visibility: in smaller prostates significantly more lesions were visible on B TRUS than in large glands (p+0.041; 45.1 ml vs 54 ml). CONCLUSION The use of newer high-end ultrasound units as well as experience gained from fusion biopsies enables us to see 62.2 % of all suspicious mpMRI lesions on B TRUS. B TRUS images merit a thorough examination during a conventional biopsy setting.
Polydatin Alleviates Radiation-Induced Testes Injury by Scavenging ROS and Inhibiting Apoptosis Pathways

Background Exposure to ionizing radiation (IR) induces severe damage in multiple human tissues. The testes are extremely sensitive to IR, and testes irradiation can result in infertility and abnormality. A novel and safe radioprotector for testes injury from IR is needed. Polydatin (PD) has been proved to have anti-oxidant and anti-inflammatory effects, indicating its potential application in radiation protection. Material/Methods Male wild-type C57BL/6 mice (8 weeks old) were exposed to ionizing radiation. At different times after irradiation, testes were isolated and subjected to hematoxylin-eosin (HE) staining and TUNEL staining, as well as related quantification. ELISA assay was used to measure the level of inflammatory cytokines, and apoptosis proteins were detected by Western blot assay. Intracellular ROS was measured by DCFH-DA flow cytometry method. Results In the present study, we demonstrated that polydatin effectively alleviated testes injury and retained sperm viability. PD pretreatment also inhibited cell apoptosis caused by irradiation. Radiation-induced decrease of FSH and testosterone was also inhibited by PD treatment. Finally, we showed that PD obviously reduced the ROS level, using DCFH-DA method. We also found that PD reduced the concentration of the oxidative products MDA and 8-OHdG. PD also inhibited apoptosis-related proteins such as Bax and caspase 3. Conclusions Our data proved that polydatin effectively alleviated testes injury after irradiation, mainly through reducing ROS and oxidative stress. Our findings suggest polydatin as a potential radioprotector for testes radiation damage.