Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy

The pathogenesis of diabetic neuropathy remains enigmatic. Damage to the vasa nervorum may be responsible for this disorder. Recently, we showed that secretoneurin (SN) induces angiogenesis in hindlimb and myocardial ischemia. Moreover, beneficial effects were observed in wound healing. We therefore hypothesized that SN therapy may ameliorate diabetic neuropathy. We used db/db mice as animal model for neuropathy. Gene therapy was accomplished by intramuscular injection of SN plasmid along the sciatic nerve. Sciatic nerve motor and sensory conduction velocities were then measured for 9 wk. Nerve conduction velocities showed normal values in heterozygous mice for the observational period, but were severely reduced in homozygous mice in which velocities were significantly improved by SN, but not by control plasmid gene therapy. The reaction time in the tail‐flick test improved significantly in SN‐treated animals. The induction of growth of vasa nervorum seems to be part of the underlying mechanism. In addition, SN positively affected Schwann cell function in vitro and induced activation of important signaling pathways. Our observations suggest that SN exerts beneficial effects on nerve function in vivo and on Schwann cells in vitro. It therefore may be a promising treatment option for diabetic neuropathy. —Theurl, M. , Lener, D. , Albrecht‐Schgoer, K. , Beer, A. , Schgoer, W. , Liu, Y. , Stanzl, U. , Fischer‐Colbrie, R. , Kirchmair, R. Gene therapy with the angiogenic neuropeptide secretoneurin ameliorates experimental diabetic neuropathy. FASEB J. 32, 4815–4823 (2018). www.fasebj. org
Quality Teaching Quality Learning

Quality Teaching What do we wish to Achieve? How will we do this? When do we wish to achieve this by? How will we know we are successful? Who is responsible for this element? Compliance with the National Quality Framework and Early Years Learning Framework (K-2) Through regular staff training and information sessions and self assessment and external audits. Beginning Term 3, 2014 and fully implemented 2015/16. Achievement of ‘Proficient’ status at Registration and subsequent audits. KN and JV
Pharmacokinetics of a Pediatric Tribendimidine Dose-Finding Study To Treat Hookworm Infection in African Children

Tribendimidine is a broad-spectrum anthelminthic available in China, which is currently being pursued for U.S. Food and Drug Administration approval for soil-transmitted helminth infections. ABSTRACT Tribendimidine is a broad-spectrum anthelminthic available in China, which is currently being pursued for U.S. Food and Drug Administration approval for soil-transmitted helminth infections. Pharmacokinetic (PK) studies with tribendimidine in children, the main target group for treatment programs, have not been conducted to date. In the framework of a dose-ranging study in hookworm-infected school-aged children in Côte d'Ivoire, children were treated with either 100, 200, or 400 mg tribendimidine. Dried blood spot samples were collected up to 22 h after treatment. The active metabolite, deacetylated amidantel (dADT) and its metabolite acylated dADT (adADT) were quantified using liquid chromatography tandem mass spectrometry. PK parameters were calculated using a noncompartmental model, and univariate logistic regression was applied using maximal blood concentrations (Cmax) and area under the blood concentration-time curve for 0 to 22 h (AUC0–22) as predictors of drug efficacy. Dried blood spot samples of 101 children were analyzed. We observed a less than proportional and proportional exposure in dADT's median Cmax and AUC0–22, respectively, following administration of 100 mg (Cmax = 853 ng/ml; AUC0–22 = 3,019 h · ng/ml) and 400 mg (Cmax = 2,275 ng/ml; AUC0–22 = 12,530 h · ng/ml) tribendimidine. There were large, dose-independent variations in the time to Cmax (Tmax) and ratios of dADT to adADT. We did not detect an influence of Cmax or AUC0–22 of dADT or adADT on drug efficacy or adverse events. Since our study population was bearing hookworm infection of mainly low intensity, additional studies with heavy intensity infections might be required to confirm this observation.
The Limits of Post-Selection Generalization

While statistics and machine learning offers numerous methods for ensuring generalization, these methods often fail in the presence of *post selection*---the common practice in which the choice of analysis depends on previous interactions with the same dataset. A recent line of work has introduced powerful, general purpose algorithms that ensure a property called *post hoc generalization* (Cummings et al., COLT'16), which says that no person when given the output of the algorithm should be able to find any statistic for which the data differs significantly from the population it came from. In this work we show several limitations on the power of algorithms satisfying post hoc generalization. First, we show a tight lower bound on the error of any algorithm that satisfies post hoc generalization and answers adaptively chosen statistical queries, showing a strong barrier to progress in post selection data analysis. Second, we show that post hoc generalization is not closed under composition, despite many examples of such algorithms exhibiting strong composition properties.
Global Distribution of Human Protoparvoviruses

Development of next-generation sequencing and metagenomics has revolutionized detection of novel viruses. Among these viruses are 3 human protoparvoviruses: bufavirus, tusavirus, and cutavirus. These viruses have been detected in feces of children with diarrhea. In addition, cutavirus has been detected in skin biopsy specimens of cutaneous T-cell lymphoma patients in France and in 1 melanoma patient in Denmark. We studied seroprevalences of IgG against bufavirus, tusavirus, and cutavirus in various populations (n = 840), and found a striking geographic difference in prevalence of bufavirus IgG. Although prevalence was low in adult populations in Finland (1.9%) and the United States (3.6%), bufavirus IgG was highly prevalent in populations in Iraq (84.8%), Iran (56.1%), and Kenya (72.3%). Conversely, cutavirus IgG showed evenly low prevalences (0%–5.6%) in all cohorts, and tusavirus IgG was not detected. These results provide new insights on the global distribution and endemic areas of protoparvoviruses.
Where to Go Next: A Spatio-temporal LSTM model for Next POI Recommendation

Next Point-of-Interest (POI) recommendation is of great value for both location-based service providers and users. Recently Recurrent Neural Networks (RNNs) have been proved to be effective on sequential recommendation tasks. However, existing RNN solutions rarely consider the spatio-temporal intervals between neighbor check-ins, which are essential for modeling user check-in behaviors in next POI recommendation. In this paper, we propose a new variant of LSTM, named STLSTM, which implements time gates and distance gates into LSTM to capture the spatio-temporal relation between successive check-ins. Specifically, one-time gate and one distance gate are designed to control short-term interest update, and another time gate and distance gate are designed to control long-term interest update. Furthermore, to reduce the number of parameters and improve efficiency, we further integrate coupled input and forget gates with our proposed model. Finally, we evaluate the proposed model using four real-world datasets from various location-based social networks. Our experimental results show that our model significantly outperforms the state-of-the-art approaches for next POI recommendation.
Stochastic and deterministic modelling of cell migration

Mathematical models are vital interpretive and predictive tools used to assist in the understanding of cell migration. There are typically two approaches to modelling cell migration: either micro-scale, discrete or macro-scale, continuum. The discrete approach, using agent-based models (ABMs), is typically stochastic and accounts for properties at the cell-scale. Conversely, the continuum approach, in which cell density is often modelled as a system of deterministic partial differential equations (PDEs), provides a global description of the migration at the population level. Deterministic models have the advantage that they are generally more amenable to mathematical analysis. They can lead to significant insights for situations in which the system comprises a large number of cells, at which point simulating a stochastic ABM becomes computationally expensive. However, finding an appropriate continuum model to describe the collective behaviour of a system of individual cells can be a difficult task. Deterministic models are often specified on a phenomenological basis, which reduces their predictive power. Stochastic ABMs have advantages over their deterministic continuum counterparts. In particular, ABMs can represent individual-level behaviours (such as cell proliferation and cell-cell interaction) appropriately and are amenable to direct parameterisation using experimental data. It is essential, therefore, to establish direct connections between stochastic micro-scale behaviours and deterministic macro-scale dynamics. In this Chapter we describe how, in some situations, these two distinct modelling approaches can be unified into a discrete-continuum equivalence framework. We provide an overview of some of the more recent advances in this field and we point out some of the relevant questions that remain unanswered.
Lateral Sinus Floor Elevation Performed with Trapezoidal and Modified Triangular Flap Designs: A Randomized Pilot Study of Post-Operative Pain Using Thermal Infrared Imaging

Purpose: Post-operative pain and swelling are frequently observed after sinus lift procedures. The aim of the present study was the clinical evaluation of swelling and pain of two different sinus flap lift techniques using a visual analogue scale (VAS), verbal rating scale (VRS), and infrared thermal imaging (i.e., thermography). Materials Methods: A randomized controlled trial was conducted with 15 patients (30 sinuses in total) randomly allocated into two groups. For the sinuses of Group I a trapezoidal flap was used, while for Group II a modified triangular flap without anterior release was utilized. Postoperative pain was scored by means of a 100-mm VAS ranging from 0 (no pain) to 100 (worst pain imaginable), and was recorded at 2, 4, 6 and 14 days after surgery. Swelling was recorded by a verbal rating scale (VRS) and was classified into four categories: a score of 1 referred the absence of swelling, patients with intra-oral swelling in the surgical zone scored 2, any extra-oral swelling in the surgical zone scored 3, and intense swelling exhibited by extra-oral swelling extending beyond the surgical zone scored 4. The facial temperature was recorded before and after sinus augmentation, and at 2, 4, 6, and 14 days post-surgery to check the course of healing. Results: In Group I pain intensity was recorded at 2 days after surgery with a mean score of 38.67 ± 6.4 mm. Swelling was greater at 2 and 4 days, and was absent at day 6. The facial temperature difference before and after the procedure was 4.737 °C ± 0.37. In Group II the pain score were lower than in Group I (p < 0.05). The score for swelling was 2 on the first and second days, and was reduced on day 4. After the second day the difference in temperature was significantly reduced as compared to the day of surgery (0.77 °C); at 2 and 4 days no difference was registered. Conclusions: The results of this clinical study show the significant effectiveness of the modified triangular flap in the sinus lift procedure for reducing pain and swelling.
Rsd balances (p)ppGpp level by stimulating the hydrolase activity of SpoT during carbon source downshift in Escherichia coli

Significance Most bacteria accumulate the molecular alarmone (p)ppGpp to divert resources away from growth and division toward biosynthesis under various nutrient limitations. Despite its crucial role, uncontrolled accumulation of this alarmone causes severe growth inhibition and cell death. Thus, fine-tuning the cellular (p)ppGpp level is required to ensure survival and adaptation under harsh nutritional conditions. Here, we identify Rsd as a stimulator of the (p)ppGpp-degrading activity of SpoT during carbon source downshift in Escherichia coli, and this regulation is controlled by the phosphorylation state of HPr, a general component of the PEP-dependent sugar transport system. This study establishes a direct link between sugar signaling and the bacterial stringent response. Bacteria respond to nutritional stresses by changing the cellular concentration of the alarmone (p)ppGpp. This control mechanism, called the stringent response, depends on two enzymes, the (p)ppGpp synthetase RelA and the bifunctional (p)ppGpp synthetase/hydrolase SpoT in Escherichia coli and related bacteria. Because SpoT is the only enzyme responsible for (p)ppGpp hydrolysis in these bacteria, SpoT activity needs to be tightly regulated to prevent the uncontrolled accumulation of (p)ppGpp, which is lethal. To date, however, no such regulation of SpoT (p)ppGpp hydrolase activity has been documented in E. coli. In this study, we show that Rsd directly interacts with SpoT and stimulates its (p)ppGpp hydrolase activity. Dephosphorylated HPr, but not phosphorylated HPr, of the phosphoenolpyruvate-dependent sugar phosphotransferase system could antagonize the stimulatory effect of Rsd on SpoT (p)ppGpp hydrolase activity. Thus, we suggest that Rsd is a carbon source-dependent regulator of the stringent response in E. coli.
Gender is not simply a matter of black and white, or is it?

Based on research in physical anthropology, we argue that brightness marks the abstract category of gender, with light colours marking the female gender and dark colours marking the male gender. In a set of three experiments, we examine this hypothesis, first in a speeded gender classification experiment with male and female names presented in black and white. As expected, male names in black and female names in white are classified faster than the reverse gender-colour combinations. The second experiment relies on a gender classification task involving the disambiguation of very briefly appearing non-descript stimuli in the form of black and white ‘blobs’. The former are classified predominantly as male and the latter as female names. Finally, the processes driving light and dark object choices for males and females are examined by tracking the number of fixations and their duration in an eye-tracking experiment. The results reveal that when choosing for a male target, participants look longer and make more fixations on dark objects, and the same for light objects when choosing for a female target. The implications of these findings, which repeatedly reveal the same data patterns across experiments with Dutch, Portuguese and Turkish samples for the abstract category of gender, are discussed. The discussion attempts to enlarge the subject beyond mainstream models of embodied grounding. This article is part of the theme issue ‘Varieties of abstract concepts: development, use and representation in the brain’.
Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease

Abstract Context Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed. Objective The aim of this review was to systematically assess the effects of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric patients with NAFLD. Data Sources The online information service ProQuest Dialog was used to search 8 literature databases. Study Selection Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could be isolated were eligible for inclusion. Data Extraction The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and data transcriptions and study quality assessments were conducted in duplicate. Each effect size was expressed as the weighted mean difference and 95%CI, using a random-effects model and the inverse of the variance as a weighting factor. Results Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy), and in steatosis score (assessed via ultrasonography). Histological measures of disease [which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were unaffected by n-3 LC-PUFA supplementation. Conclusions Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD. Additional trials are needed to better understand the effects of n-3 LC-PUFAs on histological outcomes in patients with NASH. Systematic Review Registration PROSPERO CRD42017055951.
Emergence of Quantum Phase-Slip Behaviour in Superconducting NbN Nanowires: DC Electrical Transport and Fabrication Technologies

Superconducting nanowires undergoing quantum phase-slips have potential for impact in electronic devices, with a high-accuracy quantum current standard among a possible toolbox of novel components. A key element of developing such technologies is to understand the requirements for, and control the production of, superconducting nanowires that undergo coherent quantum phase-slips. We present three fabrication technologies, based on using electron-beam lithography or neon focussed ion-beam lithography, for defining narrow superconducting nanowires, and have used these to create nanowires in niobium nitride with widths in the range of 20–250 nm. We present characterisation of the nanowires using DC electrical transport at temperatures down to 300 mK. We demonstrate that a range of different behaviours may be obtained in different nanowires, including bulk-like superconducting properties with critical-current features, the observation of phase-slip centres and the observation of zero conductance below a critical voltage, characteristic of coherent quantum phase-slips. We observe critical voltages up to 5 mV, an order of magnitude larger than other reports to date. The different prominence of quantum phase-slip effects in the various nanowires may be understood as arising from the differing importance of quantum fluctuations. Control of the nanowire properties will pave the way for routine fabrication of coherent quantum phase-slip nanowire devices for technology applications.
The effect of educational package on sexual function in cold temperament women of reproductive age

INTRODUCTION: Sexual health is one of the key factors to sustain marital life and having a good sexual function. On the other hand, temperament affects sexual function. Training is also one of the basic foundations for promoting sexual health. Therefore, the researcher has designed and implemented a study (2017) aimed “determining the study of educational package on sexual function in cold temperament women of reproductive age. ” METHODS: This randomized clinical trial study was performed on 80 women in two groups (40 in each group). This study was done, in available method, on no pregnant women aged 20–40 years old that referred to health centers in Mashhad. DASS 21 sexual function and determining temperament questionnaires were completed in two groups before intervention. At first, the sexual function training package was held by the researcher at 6 sessions (twice a week for 3 weeks) that was based on nutrition, sport, and lifestyle axes. The control group also received routine care. A week after intervention finished, all the units completed a sexual function questionnaire. The results were analyzed by these techniques as SPSS software (version 16) and statistical tests such as Independent t-test, T-pair, Mann–Whitney, Chi-square, and Fisher's exact test. RESULTS: At the beginning of the study, there was no statistically significant difference between the personal characteristics and the mean score of sexual function and all its dimensions in the two groups. The mean sexual performance score and all its dimensions after intervention were significantly different in intervention and control groups P < 0.001. Sexual function and all its dimensions were improved after intervention in the intervention group. CONCLUSION: Giving sexual function package has improved the sexual function of cold temperament women. So, for routine caring of cold temperament women, it is better that health center employees consider this training package as an effective, easy, available, nonpharmacological, and economic intervention.
Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction

Abstract Objective To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials. Methods A search of the literature was conducted using Medline, PubMed, MeSH and ScienceDirect. Combinations of the search terms “preeclampsia,” “screening,” “prediction,” “Doppler,” “Doppler velocimetry,” “fetal growth restriction,” “small for gestational age” and “uterine artery” were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included. Results Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ∼ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants. Conclusion The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR.