Miracle-dz/UniFAR-FTUs huggingface dataset:
A Long-Term Study of Acotiamide in Patients with Functional Dyspepsia: Results from an Open-Label Phase III Trial in Japan on Efficacy, Safety and Pattern of Administration

Background: This long-term 48-week study of acotiamide was carried out to investigate the efficacy, safety and administration pattern in patients with functional dyspepsia (FD). Methods: This was a multicenter, open-label, single-arm, long-term phase III study in which patients with FD were given acotiamide, 100 mg t.i. d. , for 48 weeks. The two major efficacy endpoints were global overall treatment efficacy (OTE) and the elimination rate of three cardinal symptoms (i.e. postprandial fullness, early satiation and upper abdominal bloating), which were evaluated weekly and daily by the patients, respectively. The long-term administration patterns were investigated by following the patients based on cessation and readministration criteria. Results: Efficacy was analyzed in 405 patients. The OTE improvement rate was 26.1% at week 1 and increased with time. It was 60.6% at week 8 and subsequently maintained. Similarly, the symptom elimination rate increased up to week 8. Many patients who met the cessation criterion achieved remission of FD symptoms after experiencing dose interruption and readministration. The incidence rate of adverse drug reactions was 11.5% and most of the adverse drug reactions were mild in severity except increased ALT in 1 patient. Conclusion: FD symptoms were controlled by intermittent administration of acotiamide even in patients with relapsing FD.
WAVE BREAKING OVER LOCAL TOPOGRAPHY DURING THE MAP IOP 15 MISTRAL EVENT: OBSERVATIONS AND HIGH-RESOLUTION NUMERICAL SIMULATIONS

This study investigates the fundamental processes involved in the severe Mistral’s windstorm occurring during the MAP IOP 15 (from 06 to 09 November 1999). It is based on numerical high-resolution simulations performed with the RAMS non-hydrostatic model at 3 km resolution. The simulation is found able to capture the flow complexity both upstream of the Alps and in coastal regions affected by the Mistral. The simulations accurately reproduce dynamical and thermodynamical fields observed by the observational network consisting of two UHF wind profilers set up near Marseille and Toulon and two radiosoundings at Lyon and Nimes. The model indicates that the Mistral is mainly governed by flow splitting and downslope accelerations occurring at different scales. Wave breaking are triggered above local topography resulting in hydraulic jumps that in turn induce two mountain wakes trailing from the Alps and the Massif Central. The flow is accelerated by channelling effects between these two wakes. The simulations therefore evidence that channelling effects by the Rhone valley do not explain the Mistral’s dynamics, which are fundamentally three-dimensional, multi-scaled and formed by a multitude of orographic processes.
Rapamycin ameliorates the CTLA4‐Ig–mediated defect in CD8+ T cell immunity during gammaherpesvirus infection

Latent viral infections are a major concern among immunosuppressed transplant patients. During clinical trials with belatacept, a CTLA4‐Ig fusion protein, patients showed an increased risk of Epstein–Barr virus‐associated posttransplant lymphoproliferative disorder, thought to be due to a deficient primary CD8+ T cell response to the virus. Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus‐specific CD8+ T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4‐Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen‐specific CD8+ T cells. However, the addition of rapamycin to the CTLA4‐Ig regimen was able to quantitatively and qualitatively restore the antigen‐specific CD8+ T cell response to the virus. This improvement was physiologically relevant, in that CTLA4‐Ig treated animals exhibited a greater viral burden following infection that was reduced to levels observed in untreated immunocompetent animals by the addition of rapamycin. These results reveal that modulation of T cell differentiation though inhibition of mTOR signaling can restore virus‐specific immune competence even in the absence of CD28 costimulation, and have implications for improving protective immunity in transplant recipients.
Essential Oils and Their Components as Modulators of Antibiotic Activity against Gram-Negative Bacteria

Gram-negative bacteria cause infections that are difficult to treat due to the emergence of multidrug resistance. This review summarizes the current status of the studies investigating the capacity of essential oils and their components to modulate antibiotic activity against Gram-negative bacteria. Synergistic interactions are particularly discussed with reference to possible mechanisms by which essential oil constituents interact with antibiotics. Special emphasis is given to essential oils and volatile compounds that inhibit efflux pumps, thus reversing drug resistance in Gram-negative bacteria. In addition, indifference and antagonism between essential oils/volatile compounds and conventional antibiotics have also been reported. Overall, this literature review reveals that essential oils and their purified components enhance the efficacy of antibiotics against Gram-negative bacteria, being promising candidates for the development of new effective formulations against Gram-negative bacteria.
Complete nucleotide sequence of a milk-transmitted mouse mammary tumor virus: two frameshift suppression events are required for translation of gag and pol

We sequenced two recombinant DNA clones constituting a single provirus of the milk-transmitted mouse mammary tumor virus characteristic of BR6 mice. The complete provirus is 9,901 base pairs long, flanked by 6 base-pair duplications of cellular DNA at the site of integration. Five extensive blocks of open reading frame corresponding to the gag gene, the presumed protease, the pol and env genes, and the open reading frame orf within the long terminal repeat of the provirus were readily discernible. Translation of gag, protease, and pol involved three different translational reading frames to produce the three overlapping polyprotein precursors Pr77, Pr110, and Pr160 found in virus-infected cells. Synthesis of the reverse transcriptase and endonuclease therefore required two separate frameshifts to suppress the termination codons at the ends of the Pr77 and Pr110 domains. Direct evidence is presented for translational readthrough of both stop codons in an in vitro protein synthesis system.
Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China

Sputum culture plays an important role in monitoring treatment response in patients with multidrug-resistant tuberculosis (MDR-TB), and sputum culture conversion is a clinical tool used to predict therapeutic efficacy [1]. Monthly culture monitoring is essential for earlier detection of treatment failure in patients with MDR-TB. More sensitive signals of nonresponse would further avoid adverse outcomes [2]. The timing of testing for culture conversion has potential as a marker of MDR-TB treatment success http://ow.ly/borO308pPXg
A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis

Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty‐five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large‐scale trials to validate these findings in patients with RA and other arthritic conditions. Copyright © 2012 John Wiley & Sons, Ltd.
Stability and change in older adults' social contact and social support: the Cardiovascular Health Study.

OBJECTIVES The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life. METHODS Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time. RESULTS Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time. DISCUSSION The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.
Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity

Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD+-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic.
What can be learned from brain‐death models?

Brain death of the donor is an important risk factor influencing graft outcome. In addition to its nonspecific effects, it potentiates graft immunogenicity and increases host alloresponsiveness. Thus brain death in addition to other unspecific injuries such as organ procurement, preservation and consequences of ischemia/reperfusion injury, contributes towards the change of an inert organ to an immunological altered graft. Prior to engraftment, brain death initiates a cascade of molecular and cellular events including the release of proinflammatory mediators leading to cellular infiltrates. Those events may affect the incidence of both acute and chronic changes, developing and contributing to reduced graft survival. Consequently, strategies to reduce the immunogenicity or the pro‐inflammatory status of the graft are becoming more attractive and might even help to improve organ quality and graft function.
Variance estimation in the analysis of microarray data

Summary. Microarrays are one of the most widely used high throughput technologies. One of the main problems in the area is that conventional estimates of the variances that are required in the t‐statistic and other statistics are unreliable owing to the small number of replications. Various methods have been proposed in the literature to overcome this lack of degrees of freedom problem. In this context, it is commonly observed that the variance increases proportionally with the intensity level, which has led many researchers to assume that the variance is a function of the mean. Here we concentrate on estimation of the variance as a function of an unknown mean in two models: the constant coefficient of variation model and the quadratic variance–mean model. Because the means are unknown and estimated with few degrees of freedom, naive methods that use the sample mean in place of the true mean are generally biased because of the errors‐in‐variables phenomenon. We propose three methods for overcoming this bias. The first two are variations on the theme of the so‐called heteroscedastic simulation–extrapolation estimator, modified to estimate the variance function consistently. The third class of estimators is entirely different, being based on semiparametric information calculations. Simulations show the power of our methods and their lack of bias compared with the naive method that ignores the measurement error. The methodology is illustrated by using microarray data from leukaemia patients.
Time‐Course Analysis of Flow Mediated Dilation for the Evaluation of Endothelial Function After a High‐Fat Meal in African Americans

Background Flow‐mediated dilation (FMD) is used to assess endothelial function through changes in vascular diameter after hyperemia. High‐fat meal (HFM) has been shown to induce endothelial dysfunction; recent studies, however, reported conflicting results in obese African American women (AAW). Differences in the method used to analyze FMD may explain these discrepancies. Methods and Results In protocol 1, we assessed the time course of FMD and compared the repeatability of FMD using the individual maximum peak dilation (FMD peak) and the dilation at 60 seconds (FMD 60). Sixteen AAW (age, 42±10.4 years; body mass index [BMI], 39±5.8 kg/m2) were studied on 2 occasions, 4 weeks apart, under fasting conditions (study 1 and study 2). In protocol 2, we used the most repeatable measurement from protocol 1 to assess changes in endothelial function after an HFM in 17 AAW (agen 42±11.1 years; BMIn 38±5.6 kg/m2). We found that FMD peak was the most repeatable measurement (N=16; study 1, 5.31±3.12% and study 2, 5.80±2.91%; r=0.94). After an HFM, the baseline brachial artery diameter significantly increased at 2 hours (0.10 mm; 95% confidence interval [CI], 0.01–0.18; P=0.03) and at 4 hours (0.17 mm; 95% CI, 0.09–0.25; P<0.001). At 2 hours, the FMD peak decreased compared with pre‐HFM (−1.76; 95% CI, −3.55–0.02; P≤0.05). Conclusions The individual's maximum peak dilation after hyperemia is the most consistent measure to assess the effect of an HFM on endothelial function. Endothelial dysfunction occurred at 2 hours after an HFM in AAW. Clinical Trial Registration URL: https://clinicaltrials.gov/ Unique identifiers: NCT01334554 and NCT02126735.
Fractional anisotropy distributions in 2- to 6-year-old children with autism.

BACKGROUND Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. METHODS A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating δ, the estimated mean and standard deviation of the approximating F for each distribution. RESULTS The estimated δ parameter, , was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of was the driving force behind these results. CONCLUSIONS While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition.
The role of the avian hippocampus in spatial memory

Avian hippocampal function is surveyed, using data drawn from three areas: conventional laboratory paradigms, pigeon navigation, and food-storing. Damage to the avian hippocampus disrupts performance in laboratory tasks that tap spatial learning and memory, and also disrupts both pigeon homing and cache recovery by food-storing birds. Further evidence of hippocampal involvement in food-storing is provided by the fact that the hippocampus of food-storing birds is selectively enlarged. These findings lend support to the notion that the hippocampus plays a critical role in spatial learning and memory. However, avian hippocampal lesions (like mammalian hippocampal lesions) also disrupt certain laboratory tasks that do not have an overt spatial component. Moreover, analysis of the effects of hippocampal lesions on navigation find, first, that basic navigational processes are left intact, and second, that at least some of the disruption of homing may be caused by disruption of the associability of information derived from the sun compass - a non-spatial deficit. Finally, attempts to demonstrate that the enlarged hippocampus of food-storing birds is associated with enhanced spatial memory have failed to deliver conclusive support. The extensive parallels between effects of hippocampal lesions in birds and mammals suggest that both the spatial and the non-spatial deficits form part of a single syndrome, one that cannot readily be explained in terms of disruption of specifically spatial processes.
MSO definable string transductions and two-way finite-state transducers

We extend a classic result of Büchi, Elgot, and Trakhtenbrot: MSO definable string transductions i.e., string-to-string functions that are definable by an interpretation using monadic second-order (MSO) logic, are exactly those realized by deterministic two-way finite-state transducers, i.e., finite-state automata with a two-way input tape and a one-way output tape. Consequently, the equivalence of two mso definable string transductions is decidable. In the nondeterministic case however, MSO definable string tranductions, i.e., binary relations on strings that are mso definable by an interpretation with parameters, are incomparable to those realized by nondeterministic two-way finite-state transducers. This is a motivation to look for another machine model, and we show that both classes of MSO definable string transductions are characterized in terms of Hennie machines, i.e., two-way finite-state transducers that are allowed to rewrite their input tape, but may visit each position of their input only a bounded number of times.
Communities of co-commenting in the Russian LiveJournal and their topical coherence

– The paper addresses the problem of what drives the formation of latent discussion communities, if any, in the blogosphere: topical composition of posts or their authorship? The purpose of this paper is to contribute to the knowledge about structure of co-commenting. , – The research is based on a dataset of 17,386 full text posts written by top 2,000 LiveJournal bloggers and over 520,000 comments that result in about 4.5 million edges in the network of co-commenting, where posts are vertices. The Louvain algorithm is used to detect communities of co-commenting. Cosine similarity and topic modeling based on latent Dirichlet allocation are applied to study topical coherence within these communities. , – Bloggers unite into moderately manifest communities by commenting roughly the same sets of posts. The graph of co-commenting is sparse and connected by a minority of active non-top commenters. Communities are centered mainly around blog authors as opinion leaders and, to a lesser extent, around a shared topic or topics. , – The research has to be replicated on other datasets with more thorough hand coding to ensure the reliability of results and to reveal average proportions of topic-centered communities. , – Knowledge about factors around which co-commenting communities emerge, in particular clustered opinion leaders that often attract such communities, can be used by policy makers in marketing and/or political campaigning when individual leadership is not enough or not applicable. , – The research contributes to the social studies of online communities. It is the first study of communities based on co-commenting that combines examination of the content of commented posts and their topics.
Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca2+ Cycling

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca2+. A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca2+ pump and the ryanodine receptor 2, leading to increased Ca2+ uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca2+-release channels and accelerates Ca2+ reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca2+ transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca2+ cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure.