Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-sectional multicentre study on the cohort of all the French junior lecturers in general practice

Abstract Background: General practice became an academic discipline quite recently in many western countries. In France, junior lecturer work is specified in a three-part mandate: medical work in general practice, teaching in the university, and research. Since 2007, 130 junior lecturers have been appointed in general practice. The aim of the creation of junior lecturer status was to align general practice with other specialties and to develop research and education in primary care. Objectives: To describe the healthcare, teaching and research undertaken by junior lecturers in general practice, practising in October 2014. Methods: A cross-sectional multicentre study using an online self-administered questionnaire on the cohort composed of all the junior lecturers in general practice with open questions and the qualitative analysis of written verbatim accounts. Results: Of the 95 junior lecturers practising at the date of the study, 75 (79%) responded; average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three half-days per week respectively in healthcare, teaching and research. The healthcare activity was predominantly carried out in the community (73%). Thirty-nine per cent worked as part of a multi-professional team taking on 50 consultations per week. Most of the educational work involved lecturing and mentoring students specializing in general practice (median 86 hours per year). Research output increased during the fellowship. Research topics were varied and relevant to the disciplinary field. Conclusion: During the fellowship, the balancing, and even the reinforcement, of healthcare and research contributions were accompanied by a significant investment in educational provision.
Choosing important health outcomes for comparative effectiveness research: An updated systematic review and involvement of low and middle income countries

Background Core outcome sets (COS) comprise a minimum set of outcomes that should be measured and reported in all trials for a specific health condition. The COMET (Core Outcome Measures in Effectiveness Trials) Initiative maintains an up to date, publicly accessible online database of published and ongoing COS. An annual systematic review update is an important part of this process. Methods This review employed the same, multifaceted approach that was used in the original review and the previous two updates. This approach has identified studies that sought to determine which outcomes/domains to measure in clinical trials of a specific condition. This update includes an analysis of the inclusion of participants from low and middle income countries (LMICs) as identified by the OECD, in these COS. Results Eighteen publications, relating to 15 new studies describing the development of 15 COS, were eligible for inclusion in the review. Results show an increase in the use of mixed methods, including Delphi surveys. Clinical experts remain the most common stakeholder group involved. Overall, only 16% of the 259 COS studies published up to the end of 2016 have included participants from LMICs. Conclusion This review highlights opportunities for greater public participation in COS development and the involvement of stakeholders from a wider range of geographical settings, in particular LMICs.
Age‐related changes in the social behavior of tufted capuchin monkeys

The effects of aging on the social behavior of nonhuman primates is little understood, especially in New World monkeys. We studied the members of a colony of tufted capuchin monkeys (Sapajus sp.) in order to evaluate age related changes in their social behavior. We conducted observations on 25 subjects aged 4–36 years, living in captive social groups. We found that affiliative interactions (grooming and proximity) decreased with age, and that grooming was increasingly directed to a single preferred partner. Manipulation of objects in the environment also decreased with age, while locomotion and aggression showed no change. Overall, these results concur with previous findings on both human and nonhuman primates, and cast doubts on interpretations of age associated changes in human social behavior that rely of uniquely human advanced cognitive capacities.
On the internal pollution mechanisms in the globular cluster NGC 6121 (M4): heavy-element abundances and AGB models ⋆

Globular clusters display significant variations in their l ight-element content, pointing to the existence of a second stellar generation formed from t he ejecta of an earlier generation. The nature of these internal polluters is still a matte r of debate: the two most popular scenarios indicate intermediate-mass AGB stars and fast rotating massive stars. Abundances determination for some key elements can help distinguish between these competitor candidates. We present in this paper Y abundances for a sample of 103 red giant branch stars in NGC 6121. Within measurement errors, we find that the [Y/Fe] is constant in this cluster contrary to a recent suggestion. For a subsample of six stars we a lso find [Rb/Fe] to be constant, consistent with previous studies showing no variation in ot her s-process elements. We also present a new set of stellar yields for intermediate-mass AG B stellar models of 5 and 6 solar masses, including heavy element s-process abundances. The uncertainties on the mass-loss rate, the mixing-length parameter, and the nuclear reactio n rates have a major impact on the stellar abundances. Within the IM-AGB pollution scenario, the constant abundance of heavy elements inside the cluster requires a marginal s-process effi ciency in IM-AGB stars. Such a constrain could still be satisfied by the present models assu ming a stronger mass-loss rate. The uncertainties mentioned above are limiting the predictive power of intermediate-mass AGB models. For these reasons, at the moment we are not able to clearly rule out their role as main polluters of the second population stars in globular cluste rs.
Learning to Adapt Structured Output Space for Semantic Segmentation

Convolutional neural network-based approaches for semantic segmentation rely on supervision with pixel-level ground truth, but may not generalize well to unseen image domains. As the labeling process is tedious and labor intensive, developing algorithms that can adapt source ground truth labels to the target domain is of great interest. In this paper, we propose an adversarial learning method for domain adaptation in the context of semantic segmentation. Considering semantic segmentations as structured outputs that contain spatial similarities between the source and target domains, we adopt adversarial learning in the output space. To further enhance the adapted model, we construct a multi-level adversarial network to effectively perform output space domain adaptation at different feature levels. Extensive experiments and ablation study are conducted under various domain adaptation settings, including synthetic-to-real and cross-city scenarios. We show that the proposed method performs favorably against the state-of-the-art methods in terms of accuracy and visual quality.
A unified approach for quantifying and interpreting DNA shape readout by transcription factors

Transcription factors (TFs) interpret DNA sequence by probing the chemical and structural properties of the nucleotide polymer. DNA shape is thought to enable a parsimonious representation of dependencies between nucleotide positions. Here, we propose a unified mathematical representation of the DNA sequence dependence of shape and TF binding, respectively, which simplifies and enhances analysis of shape readout. First, we demonstrate that linear models based on mononucleotide features alone account for 60–70% of the variance in minor groove width, roll, helix twist, and propeller twist. This explains why simple scoring matrices that ignore all dependencies between nucleotide positions can partially account for DNA shape readout by a TF. Adding dinucleotide features as sequence‐to‐shape predictors to our model, we can almost perfectly explain the shape parameters. Building on this observation, we developed a post hoc analysis method that can be used to analyze any mechanism‐agnostic protein–DNA binding model in terms of shape readout. Our insights provide an alternative strategy for using DNA shape information to enhance our understanding of how cis‐regulatory codes are interpreted by the cellular machinery.
Sensitivity analysis for missing data in regulatory submissions

The National Research Council Panel on Handling Missing Data in Clinical Trials recommended that sensitivity analyses have to be part of the primary reporting of findings from clinical trials. Their specific recommendations, however, seem not to have been taken up rapidly by sponsors of regulatory submissions. The NRC report's detailed suggestions are along rather different lines than what has been called sensitivity analysis in the regulatory setting up to now. Furthermore, the role of sensitivity analysis in regulatory decision‐making, although discussed briefly in the NRC report, remains unclear. This paper will examine previous ideas of sensitivity analysis with a view to explaining how the NRC panel's recommendations are different and possibly better suited to coping with present problems of missing data in the regulatory setting. It will also discuss, in more detail than the NRC report, the relevance of sensitivity analysis to decision‐making, both for applicants and for regulators. Published 2015. This article is a U.S. Government work and is in the public domain in the USA
Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase: suppressed accumulation into tumor cells by target gene knockdown

ObjectivesWe have developed a radiolabeled uracil derivative, 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) as a novel single photon emission computed tomography probe for thymidine phosphorylase (TP). This radioiodinated IIMU has a high affinity for TP and highly accumulates in the TP-expressing tumor cell line A431 (human epidermoid carcinoma). To evaluate the specificity of the cellular uptake of IIMU to TP expression, we examined the effects of TP knockdown on the uptake of 125I-labeled IIMU (125I-IIMU) in the tumor cells. MethodsTP-specific small interfering RNA (siRNA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-specific siRNA (positive control), and negative control siRNA were transfected into A431 cells, respectively. Target-mRNA and protein expression levels of TP and GAPDH were examined 48 and 72 h after transfection, respectively. The cellular uptake level of 125I-IIMU was also evaluated 72 h after transfection. The results were compared after normalization with the corresponding negative controls. ResultsAfter TP-specific and GAPDH-specific siRNA transfection, the expression levels of TP and GAPDH mRNA decreased significantly to 41 and 29%, respectively, compared with the negative control (P<0.001 for both). The expression levels of TP and GAPDH protein also significantly decreased to 34 and 30%, respectively (P<0.001 for both). After TP-specific siRNA transfection, the cellular uptake level of 125I-IIMU decreased significantly to 66% (P<0.001). In contrast, GAPDH siRNA transfection did not significantly affect the cellular uptake level of 125I-IIMU. ConclusionsiRNA-mediated TP knockdown significantly decreased the cellular uptake level of 125I-IIMU. This finding indicates that the uptake of IIMU in tumor cells is TP specific and directly corresponds to TP expression levels.
Macropinocytosis: A Metabolic Adaptation to Nutrient Stress in Cancer

Oncogenic mutations, such as Ras mutations, drive not only enhanced proliferation but also the metabolic adaptations that confer to cancer cells the ability to sustain cell growth in a harsh tumor microenvironment. These adaptations might represent metabolic vulnerabilities that can be exploited to develop novel and more efficient cancer therapies. Macropinocytosis is an evolutionarily conserved endocytic pathway that permits the internalization of extracellular fluid via large endocytic vesicles known as macropinosomes. Recently, macropinocytosis has been determined to function as a nutrient-scavenging pathway in Ras-driven cancer cells. Macropinocytic uptake of extracellular proteins, and their further degradation within endolysosomes, provides the much-needed amino acids that fuel cancer cell metabolism and tumor growth. Here, we review the molecular mechanisms that govern the process of macropinocytosis, as well as discuss recent work that provides evidence of the important role of macropinocytosis as a nutrient supply pathway in cancer cells.
Tar level of cigarettes smoked and risk of smoking-related diseases

Abstract Background: Opinions differ on the relationship between tar level and risk of smoking-related disease. However, except for lung cancer, few reviews have evaluated the epidemiological evidence. Here the relationship of tar level to risk of the four main smoking-related diseases is considered. Methods: Papers comparing risk of lung cancer, COPD, heart disease or stroke in smokers of lower and higher tar yield cigarettes were identified from reviews and searches, relative risk estimates being extracted comparing the lowest and highest tar groups. Meta-analyses investigated heterogeneity by various study characteristics. Results: Twenty-six studies were identified, nine of prospective design and 17 case–control. Two studies grouped cigarettes by nicotine rather than tar. Seventeen studies gave results for lung cancer, 16 for heart disease, five for stroke and four for COPD. Preferring relative risks adjusted for daily amount smoked, where adjusted and unadjusted estimates were available, combined estimates for lowest versus highest tar (or nicotine) groups were 0.78 (95% confidence interval 0.70–0.88) for lung cancer, 0.86 (0.81–0.91) for heart disease, 0.77 (0.62–0.95) for stroke and 0.81 (0.65–1.02) for COPD. Lower risks were generally evident in subgroups by publication period, gender, study design, location and extent of confounder adjustment. Estimates were similar preferring data unadjusted for amount smoked or excluding nicotine-based estimates. Conclusions: Despite evidence that smokers substantially compensate for reduced cigarette yields, the results clearly show lower risks in lower tar smokers. Limitations of the evidence are discussed, but seem unlikely to affect this conclusion.
Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells

The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins. From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process. However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition. The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
A time‐varying effect model for examining group differences in trajectories of zero‐inflated count outcomes with applications in substance abuse research

This study proposes a time‐varying effect model for examining group differences in trajectories of zero‐inflated count outcomes. The motivating example demonstrates that this zero‐inflated Poisson model allows investigators to study group differences in different aspects of substance use (e.g., the probability of abstinence and the quantity of alcohol use) simultaneously. The simulation study shows that the accuracy of estimation of trajectory functions improves as the sample size increases; the accuracy under equal group sizes is only higher when the sample size is small (100). In terms of the performance of the hypothesis testing, the type I error rates are close to their corresponding significance levels under all settings. Furthermore, the power increases as the alternative hypothesis deviates more from the null hypothesis, and the rate of this increasing trend is higher when the sample size is larger. Moreover, the hypothesis test for the group difference in the zero component tends to be less powerful than the test for the group difference in the Poisson component. Copyright © 2016 John Wiley & Sons, Ltd.
Control of Hierarchical Structure of Crystalline Nanofibers Based on the Cooperative Phenomena of Functional Molecular Group as the Target of Expression of New Physical Properties: Creation of Molecular Conductors and Enhancement of Thixotropic Ability

In this chapter, a study on two kinds of examples of functional nanofibers has been introduced. In the first section, the formation of nanofiber morphology at a mesoscopic scale and molecular level stacking of a tetrathiafulvalene (TTF) derivative with a chiral group were investigated by the one-dimensional growth method in interfacial molecu‐ lar films. Monomolecular films of a TTF derivative with a chiral borneol group display a two-dimensional phase transition at the air/water interface. The formation of nanonet‐ work domains is attributed to the organized aggregation of the TTF derivatives, which is a result of strong intermolecular interactions. In the second section, the formation of nanofiber morphology at a mesoscopic scale and molecular level packing of an amphi‐ philic diamide derivative with two hydrocarbons were investigated by the in interfacial molecular films. It has found that the growth of this nanofiber morphology is encour‐ aged by the application of the epitaxial growth in the spin-cast film with 1 wt% layered silicate having long hydrocarbons. As mention above, it is found that mesoscopic morphological formation of super-hierarchical structure of the nanofibers having a crystalline arrangement at A level can be induced conductivity and the thixotropy at macroscopic level.
Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma

Abstract The combination of intermediate-dose cyclophosphamide (ID-CTX) and granulocyte colony-stimulating factor (G-CSF) fails to mobilize peripheral blood stem cells (PBSCs) in approximately 20% of treated patients with multiple myeloma (MM). In this cohort study, patients with MM underwent PBSC mobilization with either an ID-CTX plus G-CSF plus recombinant human thrombopoietin (rhTPO) regimen (72 patients; TPO group), or an ID-CTX plus G-CSF regimen (70 patients; non-TPO group). In the TPO group, the median CD34+ harvest was 5.36 × 106 per kg of body weight (0.50–22.39 × 106 per kg of body weight), with a harvest success rate of 91.7% (66/72), and an excellence rate of 55.6% (40/72). In the non-TPO group, the median CD34+ harvest was 3.30 × 106 per kg of body weight (0.20–21.14 × 106 per kg of body weight), with a harvest success rate of 75.7% (53/70), and an excellence rate of 25.7% (18/70). The median count of the CD34+ cells collected, success rate of collection, and excellence rate of collection were significantly higher in the TPO group than in the non-TPO group (P=.0001, P=.01, and P = .0001, respectively). Time to granulocyte and platelet engraftment was faster among patients in the TPO group than that in those from the non-TPO group. No platelet engraftment delay (>21 days) was observed among patients in the TPO group, while 3 patients in the non-TPO group displayed delayed platelet engraftment. Adding rhTPO to the ID-CTX chemotherapy plus G-CSF regimen improved treatment efficacy in mobilizing PBSCs for autologous hematopoietic stem cell transplantation.
Regulation of a nonholonomic autonomous underwater vehicle with parametric modeling uncertainty using Lyapunov functions

Addresses the problem of regulating the dynamic model of a nonholonomic underactuated autonomous underwater vehicle (AUV) to a point with a desired orientation. A time-invariant discontinuous controller is proposed that yields convergence of the trajectories of the closed-loop system in the presence of parametric modeling uncertainty. Controller design relies on a non-smooth coordinate transformation in the original state space followed by the derivation of a Lyapunov-based, adaptive, smooth control law in the new coordinates. Convergence of the regulation system is analyzed and simulation results are presented.
Design and Implementation of iMacros-based Data Crawler for Behavioral Analysis of Facebook Users

Obtaining the desired dataset is still a prime challenge faced by researchers while analysing Online Social Network (OSN) sites. Application Programming Interfaces (APIs) provided by OSN service providers for retrieving data impose several unavoidable restrictions which make it difficult to get a desirable dataset. In this paper, we present an iMacros technology-based data crawler called IMcrawler,capable of collecting every piece of information which is accessible through a browser from the Facebook website within the legal framework reauthorized by Facebook.The proposed crawler addresses most of the challenges allied with web data extraction approaches and most of the APIs provided by OSN service providers. Two broad sections have been extracted from Facebook user profiles, namely, Personal Information and Wall Activities. The collected data is pre-processed into two datasets and each data set is statistically analysed to draw semantic knowledge and understand the several behavioral aspects of Facebook users such as kind of information mostly disclosed by users, gender differences in the pattern of revealed information, highly posted content on the network, highly performed activities on the network, the relationships among personal and post attributes, etc. To the best of our knowledge, the present work is the first attempt towards providing the detailed description of crawler design and gender-based information revealing behaviour of Facebook users.