Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis

Background A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures. Methodology/Principal Findings Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31–175) at week 0 to 380 nmol/L (151–535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P = 0.035). Conclusion/Significance Twelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials. Trial Registration Clinicaltrials.gov NCT00940719
Bond strength of aged lingual retainers

Introduction: The purpose of this study was to examine the tensile bond strength (TBS) of two different lingual retainer (LR) composite systems and three LR wires after they were aged by loadcycling and thermocycling. Materials and Methods: A 15 mm length of wire was bonded to the lingual surfaces of pairs of human incisors using two bonding techniques. Seventy-two pairs of incisors were placed into six groups, and loadcycling (50,000 times) and thermocycling (10,000 times) were performed. The failure characteristics examined included the maximum force for debonding and the site of failure. The adhesive remnant index scores were calculated. Data were compared by two-way analysis of variance and Tukey highly significant difference analysis. Results: All groups generally showed statistically significant differences in TBS score (P < 0.05). For each group, the highest average TBS score (P < 0.05) was obtained from a Transbond LR + Remalloy LR combination. The main failure type was a mixed failure. Conclusions: Retainer wire and composite combinations had significant differences. One of the best selection criteria for LRs is the determination of the bond strength needs of a case.
Using Human Reinforcement Learning Models to Improve Robots as Teachers

Robotic teaching has not received nearly as much research attention as robotic learning. In this research, we used the humanoid robot Baxter to provide feedback and positive reinforcement to human participants attempting to achieve a complex task. Our robot autonomously casts the teaching problem as one that invokes the exploration/exploitation tradeoff to understand the cognitive strategy of its human partner and develop an effective motivational approach. We compare our learned reinforcement model with a baseline non-reinforcement approach and with a random reinforcer.
Named Entity Recognition in Chinese Clinical Text Using Deep Neural Network

Rapid growth in electronic health records (EHRs) use has led to an unprecedented expansion of available clinical data in electronic formats. However, much of the important healthcare information is locked in the narrative documents. Therefore Natural Language Processing (NLP) technologies, e.g., Named Entity Recognition that identifies boundaries and types of entities, has been extensively studied to unlock important clinical information in free text. In this study, we investigated a novel deep learning method to recognize clinical entities in Chinese clinical documents using the minimal feature engineering approach. We developed a deep neural network (DNN) to generate word embeddings from a large unlabeled corpus through unsupervised learning and another DNN for the NER task. The experiment results showed that the DNN with word embeddings trained from the large unlabeled corpus outperformed the state-of-the-art CRF's model in the minimal feature engineering setting, achieving the highest F1-score of 0.9280. Further analysis showed that word embeddings derived through unsupervised learning from large unlabeled corpus remarkably improved the DNN with randomized embedding, denoting the usefulness of unsupervised feature learning.
Predicting protein‐DNA binding free energy change upon missense mutations using modified MM/PBSA approach: SAMPDI webserver

Motivation Protein‐DNA interactions are essential for regulating many cellular processes, such as transcription, replication, recombination and translation. Amino acid mutations occurring in DNA‐binding proteins have profound effects on protein‐DNA binding and are linked with many diseases. Hence, accurate and fast predictions of the effects of mutations on protein‐DNA binding affinity are essential for understanding disease‐causing mechanisms and guiding plausible treatments. Results Here we report a new method Single Amino acid Mutation binding free energy change of Protein‐DNA Interaction (SAMPDI). The method utilizes modified Molecular Mechanics Poisson‐Boltzmann Surface Area (MM/PBSA) approach along with an additional set of knowledge‐based terms delivered from investigations of the physicochemical properties of protein‐DNA complexes. The method is benchmarked against experimentally determined binding free energy changes caused by 105 mutations in 13 proteins (compiled ProNIT database and data from recent references), and results in correlation coefficient of 0.72. Availability and implementation http://compbio.clemson.edu/SAMPDI Contact ealexov@clemson.edu Supplementary information Supplementary data are available at Bioinformatics online.
Diffusion Imaging Findings in US Service Members With Mild Traumatic Brain Injury and Posttraumatic Stress Disorder

Objective: Use diffusion tensor imaging to investigate white matter microstructure attributable to mild TBI (mTBI) and/or posttraumatic stress disorder (PTSD). Participants: Twenty-seven individuals with mTBI only, 16 with PTSD only, 42 with mTBI + PTSD, and 43 service members who sustained orthopedic injury. Design: Descriptive cross-sectional study. Main Measures: Clinical diffusion tensor imaging sequence to assess fractional anisotropy, mean, axial, and radial diffusivity within selected regions of interest. Results: Corrected analyses revealed a pattern of lower white matter integrity in the PTSD group for several scalar metrics. Regions affected included primarily right hemisphere areas of the internal capsule. These differences associated with the PTSD only cohort were observed in relation to all 3 comparison groups, while the mTBI + PTSD group did not exhibit any notable pattern of white matter abnormalities. Conclusion: Results suggest that lower resolution scan sequences are sensitive to post–acute abnormalities associated with PTSD, particularly in the right hemisphere. In addition, these findings suggest that ongoing PTSD symptoms are associated with differences in white matter diffusion that are more readily detected in a clinical scan sequence than mTBI abnormalities. Future studies are needed to prospectively assess service members prior to onset of injury to verify this pattern of results.
Evidence for Variation in the Effective Population Size of Animal Mitochondrial DNA

Background It has recently been shown that levels of diversity in mitochondrial DNA are remarkably constant across animals of diverse census population sizes and ecologies, which has led to the suggestion that the effective population of mitochondrial DNA may be relatively constant. Results Here we present several lines of evidence that suggest, to the contrary, that the effective population size of mtDNA does vary, and that the variation can be substantial. First, we show that levels of mitochondrial and nuclear diversity are correlated within all groups of animals we surveyed. Second, we show that the effectiveness of selection on non-synonymous mutations, as measured by the ratio of the numbers of non-synonymous and synonymous polymorphisms, is negatively correlated to levels of mitochondrial diversity. Finally, we estimate the effective population size of mitochondrial DNA in selected mammalian groups and show that it varies by at least an order of magnitude. Conclusions We conclude that there is variation in the effective population size of mitochondria. Furthermore we suggest that the relative constancy of DNA diversity may be due to a negative correlation between the effective population size and the mutation rate per generation.
Influence of combined pesticide and parasite exposure on bumblebee colony traits in the laboratory

Summary 1. Pollinating insects provide vital ecosystem services of enormous importance for economies and biodiversity. Yet, there is a concerning global trend of pollinator declines. Parasites and pesticides are among the suspected principle drivers of these declines. However, especially in the case of key wild pollinators, there are insufficient data on the relative impact of these individual environmental stressors and whether they interact to increase detrimental effects. 2. Using a fully crossed factorial design, we investigated how laboratory exposure to neonicotinoid insecticides, thiamethoxam and clothianidin, over a 9-week period and a prevalent trypanosome gut parasite Crithidia bombi affects various crucial colony traits of the bumblebee Bombus terrestris. 3. We show that chronic dietary exposure from an early stage of colony development to doses of thiamethoxam and clothianidin that could be encountered in the field truncated worker production, reduced worker longevity and decreased overall colony reproductive success. Further, we demonstrate a significant interaction between neonicotinoid exposure and parasite infection on mother queen survival. The fate of the mother queen is intrinsically linked to colony success, and under combined pressure of parasite infection and neonicotinoid exposure, mother queen survival was lowest. This indicates increased detrimental effects of combined exposure on this crucial colony trait. Combined effects may be exacerbated in stressful natural environments where more pronounced parasite virulence is expected. 4. Synthesis and applications. Our findings reiterate that dietary exposure to neonicotinoids can impact on bumblebee colony performance and fitness. The indication of combined negative effects of ecologically relevant pressures suggests additional adverse consequences for long-term population dynamics under complex field conditions. To help safeguard pollinator health, whole life-cycle fitness assessments, particularly for non-Apis bees, stringently incorporating chronic and sublethal side effects of pesticides, as well as interactions with common natural stressors, such as prevalent parasites, should be considered in the corresponding test guidelines.
Atrial ectopy and N-terminal pro-B-type natriuretic peptide as predictors of atrial fibrillation: a population-based cohort study

Aims The risk of incident atrial fibrillation (AF) can be estimated by clinical parameters in the Framingham AF risk model. Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and increased rate of premature atrial contractions (PACs) have been shown to be associated with AF, but the additive value of both of these biomarkers in the Framingham AF risk model has not been fully examined. Methods and results A total of 646 subjects from the Copenhagen Holter Study (mean age 64.4 ± 6.8 years, 41.6% women) with no history of prior AF, stroke or cardiovascular disease were followed for the diagnosis of incident AF or death (median follow-up time 14.4 years). Median NT-proBNP was 6.7 pmol/L (IQR: 3.6-13.5), median PAC count was 1.4 beats/h (IQR: 0.6-4.5), 71 (11.0%) subjects developed AF, and 244 (37.8%) died. Multiple Cox regression including Framingham AF risk score, log-transformed NT-proBNP, and log-transformed PAC showed a significant increase in AF hazard risk [hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.14-1.85, P = 0.002; HR 1.23, 95% CI 1.09-1.39, P = 0.001]. The addition of PAC to the Framingham AF risk model significantly improved the time-dependent area under the receiver operating characteristic curve (AUC 65.6 vs. 72.6; P = 0.008), while the addition of NT-proBNP did not. Conclusion Atrial fibrillation risk discrimination was significantly improved by the addition of PAC to the Framingham AF risk model, but not by the addition of NT-proBNP.
Exploring the impact of visual and movement based priming on a motor intervention in the acute phase post-stroke in persons with severe hemiparesis of the upper extremity

Abstract Purpose: Explore the potential benefits of using priming methods prior to an active hand task in the acute phase post-stroke in persons with severe upper extremity hemiparesis. Methods: Five individuals were trained using priming techniques including virtual reality (VR) based visual mirror feedback and contralaterally controlled passive movement strategies prior to training with an active pinch force modulation task. Clinical, kinetic, and neurophysiological measurements were taken pre and post the training period. Clinical measures were taken at six months post training. Results: The two priming simulations and active training were well tolerated early after stroke. Priming effects were suggested by increased maximal pinch force immediately after visual and movement based priming. Despite having no clinically observable movement distally, the subjects were able to volitionally coordinate isometric force and muscle activity (EMG) in a pinch tracing task. The Root Mean Square Error (RMSE) of force during the pinch trace task gradually decreased over the training period suggesting learning may have occurred. Changes in motor cortical neurophysiology were seen in the unaffected hemisphere using Transcranial Magnetic Stimulation (TMS) mapping. Significant improvements in motor recovery as measured by the Action Research Arm Test (ARAT) and the Upper Extremity Fugl Meyer Assessment (UEFMA) were demonstrated at six months post training by three of the five subjects. Conclusion: This study suggests that an early hand-based intervention using visual and movement based priming activities and a scaled motor task allows participation by persons without the motor control required for traditionally presented rehabilitation and testing. Implications for Rehabilitation Rehabilitation of individuals with severely paretic upper extremities after stroke is challenging due to limited movement capacity and few options for therapeutic training. Long-term functional recovery of the arm after stroke depends on early return of active hand control, establishing a need for acute training methods focused distally. This study demonstrates the feasibility of an early hand-based intervention using virtual reality based priming and scaled motor activities which can allow for participation by persons without the motor control required for traditionally presented rehabilitation and testing.
Use of Substrate-Induced Gene Expression in Metagenomic Analysis of an Aromatic Hydrocarbon-Contaminated Soil

ABSTRACT Metagenomics allows the study of genes related to xenobiotic degradation in a culture-independent manner, but many of these studies are limited by the lack of genomic context for metagenomic sequences. This study combined a phenotypic screen known as substrate-induced gene expression (SIGEX) with whole-metagenome shotgun sequencing. SIGEX is a high-throughput promoter-trap method that relies on transcriptional activation of a green fluorescent protein (GFP) reporter gene in response to an inducing compound and subsequent fluorescence-activated cell sorting to isolate individual inducible clones from a metagenomic DNA library. We describe a SIGEX procedure with improved library construction from fragmented metagenomic DNA and improved flow cytometry sorting procedures. We used SIGEX to interrogate an aromatic hydrocarbon (AH)-contaminated soil metagenome. The recovered clones contained sequences with various degrees of similarity to genes (or partial genes) involved in aromatic metabolism, for example, nahG (salicylate oxygenase) family genes and their respective upstream nahR regulators. To obtain a broader context for the recovered fragments, clones were mapped to contigs derived from de novo assembly of shotgun-sequenced metagenomic DNA which, in most cases, contained complete operons involved in aromatic metabolism, providing greater insight into the origin of the metagenomic fragments. A comparable set of contigs was generated using a significantly less computationally intensive procedure in which assembly of shotgun-sequenced metagenomic DNA was directed by the SIGEX-recovered sequences. This methodology may have broad applicability in identifying biologically relevant subsets of metagenomes (including both novel and known sequences) that can be targeted computationally by in silico assembly and prediction tools.
Nonlinear behavioural model of charge pump PLLs

Despite the nonlinear nature of even the simplest versions of phase locked loops (PLLs), linear models are still used during the first phases of the design of modern PLLs. Even though the linear model may represent a crude approach, its use is justified by the fact that accurate numerical simulations often require a too large amount of CPU time, being PLLs by construction stiff circuits, characterised by very different time scales. This aspect has triggered the need for compact models that allow fast and accurate numerical simulations. The scientific literature numbers several models that have been developed with different approaches and tailored to different simulation environments. In this context, we propose a nonlinear model of a type‐II PLL, which (1) considers both the switching behaviour of the phase/frequency detector and charge pump and the complex dynamics (including the presence of amplitude and phase noise) of the voltage controlled oscillator, (2) is compact and can be easily implemented in modern mixed analog/digital simulators as a behavioural block, and (3) allows the simulation of spurs owing to the nonlinearities of both the charge pump and the fractional frequency divider. Copyright © 2012 John Wiley & Sons, Ltd.
MicroRNA Regulation of Oxidative Stress-Induced Cellular Senescence

Aging is a time-related process of functional deterioration at cellular, tissue, organelle, and organismal level that ultimately brings life to end. Cellular senescence, a state of permanent cell growth arrest in response to cellular stress, is believed to be the driver of the aging process and age-related disorders. The free radical theory of aging, referred to as oxidative stress (OS) theory below, is one of the most studied aging promoting mechanisms. In addition, genetics and epigenetics also play large roles in accelerating and/or delaying the onset of aging and aging-related diseases. Among various epigenetic events, microRNAs (miRNAs) turned out to be important players in controlling OS, aging, and cellular senescence. miRNAs can generate rapid and reversible responses and, therefore, are ideal players for mediating an adaptive response against stress through their capacity to fine-tune gene expression. However, the importance of miRNAs in regulating OS in the context of aging and cellular senescence is largely unknown. The purpose of our article is to highlight recent advancements in the regulatory role of miRNAs in OS-induced cellular senescence.
Sex Differences in Attaining Cigarette Smoking and Nicotine Dependence Milestones Among Novice Smokers

There may be sex differences in the response to nicotine, according to findings of studies in animals; however, sex differences in the natural course of cigarette smoking and nicotine dependence are documented in few studies. Prevalent (n = 240 girls; n = 184 boys) and incident (n = 231 girls; n = 184 boys) cigarette smokers from the Nicotine Dependence in Teens Study were followed up to 5 years after first puff, from age 12 to 18 years (1999-2005). We used Cox proportional hazards models to compare time to development of 3 cigarette-use (i.e., whole cigarette; 100 cigarettes lifetime; regular smoking), and 3 nicotine-dependence symptom (i.e., "really need a cigarette"; mentally addicted; physically addicted) milestones across sex. Girls were at higher risk than boys of attaining all milestones; hazard ratios (95% confidence intervals) ranged from 1.35 (1.06, 1.72) for 100 cigarettes lifetime to 1.74 (1.44, 2.10) for "really need a cigarette. " Among nonregular smokers, 26% (8%; 43%) and 25% (6%; 44%) more girls than boys reported "really need a cigarette" 1 and 2 years, respectively, after first puff. Preventive interventions may need adjustment to incorporate these findings. Additional research should clarify the relative contribution of biological and social underpinnings of these sex differences.
Natural polyphenolic inhibitors against the antiapoptotic BCL-2

Abstract The apoptotic mechanism is regulated by the BCL-2 family of proteins, such as BCL-2 or Bcl-xL, which block apoptosis while Bad, Bak, Bax, Bid, Bim or Hrk induce apoptosis. The overexpression of BCL-2 was found to be related to the progression of cancer and also providing resistance towards chemotherapeutic treatments. In the present study, we found that all polyphenols (apigenin, fisetin, galangin and luteolin) bind to the hydrophobic groove of BCL-2 and the interaction is stable throughout MD simulation run. Luteolin was found to bind with highest negative binding energy and thus, claimed highest potency towards BCL-2 inhibition followed by fisetin. The hydrophobic interactions were found to be critical for stable complex formation as revealed by the vdW energy and ligplot analysis. Finally, on the basis of data obtained during the study, it can be concluded that these polyphenols have the potential to be used as lead molecules for BCL-2 inhibition.
New constructions and practical applications for private stream searching

A system for private stream searching allows a client to retrieve documents matching some search criteria from a remote server while the server evaluating the request remains provably oblivious to the search criteria. In this extended abstract, we give a high level outline of a new scheme for this problem and an experimental analysis of its scalability. The new scheme is highly efficient in practice. We demonstrate the practical applicability of the scheme by considering its performance in the demanding scenario of providing a privacy preserving version of the Google News Alerts service