Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of a specific training programme on the neuromodulation of pain in female patient with fibromyalgia (DouFiSport): a 24-month, controlled, randomised, double-blind protocol

Introduction The main symptom of fibromyalgia (FM) is diffuse pain. There is currently no aetiological treatment for FM. However, all pain associations and best practice guidelines strongly advocate the practice of aerobic physical activity to improve the symptoms of FM subjects. The mechanisms of dysfunctional pain are mostly central and related to stress axis dysfunction (autonomic nervous system and corticotropic axis). Our main objective is to assess the efficacy of a specific training programme on endogenous pain control mechanisms in female patients with FM. Further aims include rebalancing the autonomic neurovegetative system, improving quality of life and sleep quality, and reintegrating patients into society and work. Methods and analysis 110 female patients with FM diagnosed on American College of Rheumatology 2010 criteria, aged 18–65 years and meeting inclusion conditions will be recruited and randomised into two groups (active and semiactive). The training programme will consist of three 45 min sessions per week of supervised, individualised physical activity over 2 years. Only the intensity of the exercises will differ between the two groups (moderate intensity vs low intensity). All outcome measures will be conducted at baseline (T0), after 6–9 months of training (T6–9) and after 24 months of training (T24). The primary endpoint will be an improvement of pain modulation (activation of diffuse noxious inhibitory control) evaluated by the stimulation test. The secondary endpoint will be relief of pain, anxiety, depression, stress, sleep disorders, pain impact on life quality, and improved heart rate, blood pressure and salivary cortisol. Ethics and dissemination This study is approved by the Committee for the Protection of Persons West VI. The results will be published in specialised scientific journals and will be presented at scientific meetings on pain and/or physical activity. Trial registration number NCT02486965; Pre-results.
Long-term follow-up for Psychological stRess in Intensive CarE (PRICE) survivors: study protocol for a multicentre, prospective observational cohort study in Australian intensive care units

Introduction There are little published data on the long-term psychological outcomes in intensive care unit (ICU) survivors and their family members in Australian ICUs. In addition, there is scant literature evaluating the effects of psychological morbidity in intensive care survivors on their family members. The aims of this study are to describe and compare the long-term psychological outcomes of intubated and non-intubated ICU survivors and their family members in an Australian ICU setting. Methods and analysis This will be a prospective observational cohort study across four ICUs in Australia. The study aims to recruit 150 (75 intubated and 75 non-intubated) adult ICU survivors and 150 family members of the survivors from 2015 to 2018. Long-term psychological outcomes and effects on health-related quality of life (HRQoL) will be evaluated at 3 and 12 months follow-up using validated and published screening tools. The primary objective is to compare the prevalence of affective symptoms in intubated and non-intubated survivors of intensive care and their families and its effects on HRQoL. The secondary objective is to explore dyadic relations of psychological outcomes in patients and their family members. Ethics and dissemination The study has been approved by the relevant human research ethics committees (HREC) of Australian Capital Territory (ACT) Health (ETH.11.14.315), New South Wales (HREC/16/HNE/64), South Australia (HREC/15/RAH/346). The results of this study will be published in a peer-reviewed medical journal and presented to the local intensive care community and other stakeholders. Trial registration number ACTRN12615000880549; Pre-results.
Do baby boomers feel healthier than earlier cohorts after retirement age? The Lausanne cohort Lc65+ study

Objective Despite the popular belief that baby boomers are ageing in better health than previous generations, limited scientific evidence is available since baby boomers have turned retirement age only recently. This study aimed to compare self-reported health status at ages 65–70 years among three cohorts of older people born before, during and at the end (baby boomers) of the Second World War. Design Repeated cross-sectional population-based study. Setting Community in a region of French-speaking Switzerland. Participants Community-dwelling older adults who enrolled in the Lausanne cohort 65+ study at ages 65–70 years in 2004 (n=1561), 2009 (n=1489) or 2014 (n=1678). Outcomes Number of self-reported chronic conditions (from a list of 11) and chronic symptoms (from a list of 11); depressive symptoms; self-rated health (very good, good, average, poor or very poor); fear of disease (not afraid at all, barely afraid, a bit afraid, quite afraid or very afraid); self-perception of ageing; disability in basic and instrumental activities of daily living. Results There was no significant difference between cohorts in the number of self-reported chronic conditions and chronic symptoms as well as the presence of difficulty in basic activities of daily living, depressive symptoms, fear of disease and negative self-perception of ageing. In women only, significant differences between cohorts were observed in self-rated health (p=0.005) and disability in instrumental activities of daily living (p=0.003), but these associations did not remain significant in logistic regression models adjusted for sociodemographic characteristics and unhealthy behaviours. Conclusions Despite important sociodemographic differences between older baby boomers and earlier cohorts, most health indicators did not suggest any trend towards a compression of morbidity. Future studies comparing these three cohorts at more advanced age are required to further investigate whether differences emerge later in life.
The Impact of Transient Ischemic Attack (TIA) on Brain and Behavior

Transient ischemic attack (TIA) was originally defined as self-resolving focal cerebral ischemia with symptoms lasting <24 h. The newer definition also added the limitation that there should be no evidence of acute brain tissue infarction, to recognize that acute injury to the brain can result from ischemia of <24-h duration. However, several recent findings suggest that having a TIA correlates with deficits that can persist far beyond the resolution of clinical symptoms, even in the absence of imaging evidence of ischemic tissue injury. These deficits may be the result of subtle perturbations to brain structure and/or function that are not easily appreciated using the standard clinical and imaging tools that are currently employed in practice. Here, we will discuss evidence that suggests that TIA may lead to lasting changes to the structure and function of the brain.
Transcriptional Analysis of the Human IgE-Expressing Plasma Cell Differentiation Pathway

IgE is secreted by plasma cells (PCs) and is central to allergic disease. Using an ex vivo tonsil B cell culture system, which mimics the Th2 responses in vivo, we have recently characterized the development pathway of human IgE-expressing PCs. In this system, as in mice, we reported the predisposition of IgE-expressing B cells to differentiate into PCs. To gain a comprehensive understanding of the molecular events involved in the differentiation of human IgE+ B cells into PCs we have used the Illumina HumanHT-12 v4 Expression BeadChip array to analyse the gene expression profile of ex vivo generated human IgE+ B cells at various stages of their differentiation into PCs. We also compared the transcription profiles of IgE+ and IgG1+ cells to discover isotype-specific patterns. Comparisons of IgE+ and IgG1+ cell transcriptional profiles revealed molecular signatures specific for IgE+ cells, which diverge from their IgG1+ cell counterparts upon differentiation into PCs. At the germinal center (GC) stage of development, unlike in some mouse studies of IgE biology, we observed similar rates of apoptosis and no significant differences in the expression of apoptosis-associated genes between the IgE+ and IgG1+ B cells. We identified a gene interaction network associated with early growth response 1 (EGR1) that, together with the up-regulated IRF4, may account for the predisposition of IgE+ B cells to differentiate into PCs. However, despite their swifter rates of PC differentiation, the transcription profile of IgE+ PCs is more closely related to IgE+ and IgG1+ plasmablasts (PBs) than to IgG1+ PCs, suggesting that the terminal differentiation of IgE+ cells is impeded. We also show that IgE+ PCs have increased levels of apoptosis suggesting that the IgE+ PCs generated in our in vitro tonsil B cell cultures, as in mice, are short-lived. We identified gene regulatory networks as well as cell cycle and apoptosis signatures that may explain the diverging PC differentiation programme of these cells. Overall, our study provides a detailed analysis of the transcriptional pathways underlying the differentiation of human IgE-expressing B cells and points to molecular signatures that regulate IgE+ PC differentiation and function.
Construction of the First SNP-Based Linkage Map Using Genotyping-by-Sequencing and Mapping of the Male-Sterility Gene in Leaf Chicory

We report the first high-density linkage map construction through genotyping-by-sequencing (GBS) in leaf chicory (Cichorium intybus subsp. intybus var. foliosum, 2n = 2x = 18) and the SNP-based fine mapping of the linkage group region carrying a recessive gene responsible for male-sterility (ms1). An experimental BC1 population, segregating for the male sterility trait, was specifically generated and 198 progeny plants were preliminary screened through a multiplexed SSR genotyping analysis for the identification of microsatellite markers linked to the ms1 locus. Two backbone SSR markers belonging to linkage group 4 of the available Cichorium consensus map were found genetically associated to the ms1 gene at 5.8 and 12.1 cM apart. A GBS strategy was then used to produce a high-density SNP-based linkage map, containing 727 genomic loci organized into 9 linkage groups and spanning a total length of 1,413 cM. 13 SNPs proved to be tightly linked to the ms1 locus based on a subset of 44 progeny plants analyzed. The map position of these markers was further validated by sequence-specific PCR experiments using an additional set of 64 progeny plants, enabling to verify that four of them fully co-segregated with male-sterility. A mesosynteny analysis revealed that 10 genomic DNA sequences encompassing the 13 selected SNPs of chicory mapped in a peripheral region of chromosome 5 of lettuce (Lactuca sativa L.) spanning about 18 Mbp. Since a MYB103-like gene, encoding for a transcription factor involved in callose dissolution of tetrads and exine development of microspores, was found located in the same chromosomal region, this orthologous was chosen as candidate for male-sterility. The amplification and sequencing of its CDS using accessions with contrasting phenotypes/genotypes (i.e., 4 male sterile mutants, ms1ms1, and 4 male fertile inbreds, Ms1Ms1) enabled to detect an INDEL of 4 nucleotides in its second exon, responsible for an anticipated stop codon in the male sterile mutants. This polymorphism was subsequently validated through allele-specific PCR assays and found to fully co-segregate with male-sterility, using 64 progeny plants of the same mapping BC1 population. Overall, our molecular data could be practically exploited for genotyping plant materials and for marker-assisted breeding schemes in leaf chicory.
Personality Traits and Attitudes Toward Traffic Safety Predict Risky Behavior Across Young, Adult, and Older Drivers

In the last few decades, several studies have investigated the role of personality traits and attitudes toward traffic safety in predicting driving behaviors in diverse types of drivers across several countries. However, to the best of our knowledge, no studies so far have investigated the possible moderating role played by age in relation to predictors of accident risk. Answering this open question would provide information about the generalizability of the model across different subpopulations and would make possible the tailoring of the interventions to specific target groups. The study involved 1,286 drivers from three different age groups (young: n = 435; adult: n = 412; old: n = 439) which completed a questionnaire measuring drivers’ personality traits (i.e., anxiety, hostility, excitement seeking, altruism, normlessness), positive attitudes toward traffic safety, risky driving behaviors (i.e., errors, lapses, and traffic violations), accident involvement and number of traffic fines issued in the last 12 months. Multi-group Variance Based Structural Equation Modeling (VB-SEM) across the three age groups showed that the hypothesized model had a good fit with the data in all the three age groups. However, some pattern of relationships between the variables varied across the three groups, for example, if considering the direct effects of personality traits on risky driving behaviors, anxiety, altruism, and normlessness predicted violations only in young and adult drivers, whereas excitement seeking was associated with lapses only in young drivers; anxiety was a positive predictor of drivers’ errors, both in adult and older drivers, whereas excitement seeking predicted errors in adult and young drivers. On the other hand, attitudes significantly and negatively predicted violations and errors in all the three age groups, whereas they significantly and negatively predicted lapses only in young and older drivers. The results of the present study provided empirical basis to develop evidence-based road safety interventions differently tailored to the specific life’s stage of the drivers.
Interspecific Variation in Seasonal Migration and Brumation Behavior in Two Closely Related Species of Treefrogs

Most amphibians migrate between flooded habitats for breeding and dry habitats for non-breeding activities, however, differences in closely related species may highlight divergent evolutionary histories. Through field surveys, Harmonic Direction Finder tracking and laboratory behavioural experiments during the wintering season, we demonstrated differences in seasonal migration and hibernation habitats between Dryophytes suweonensis and D. japonicus. We found that D. japonicus migrated towards forests for overwintering and then back to rice paddies for breeding in spring. By contrast, D. suweonensis was found to hibernate buried in the vicinity of rice paddies, its breeding habitat. We also found that the difference in migrating behaviour matched with variation in microhabitat use during brumation and hibernation between the two species. Our findings highlight different ecological requirements between the two species, which may result from their segregated evolutionary histories, with speciation potentially linked to species use of a new breeding habitat. Additionally, the use of rice paddies for both breeding and hibernation may contribute to the endangered status of D. suweonensis because of the degradation of hibernation sites in winter.
Carbon-Based Nanomaterials for Biomedical Applications: A Recent Study

The study of carbon-based nanomaterials (CBNs) for biomedical applications has attracted great attention due to their unique chemical and physical properties including thermal, mechanical, electrical, optical and structural diversity. With the help of these intrinsic properties, CBNs, including carbon nanotubes (CNT), graphene oxide (GO), and graphene quantum dots (GQDs), have been extensively investigated in biomedical applications. This review summarizes the most recent studies in developing of CBNs for various biomedical applications including bio-sensing, drug delivery and cancer therapy.
Finding k-dominant skylines in high dimensional space

Given a d-dimensional data set, a point p dominates another point q if it is better than or equal to q in all dimensions and better than q in at least one dimension. A point is a skyline point if there does not exists any point that can dominate it. Skyline queries, which return skyline points, are useful in many decision making applications.Unfortunately, as the number of dimensions increases, the chance of one point dominating another point is very low. As such, the number of skyline points become too numerous to offer any interesting insights. To find more important and meaningful skyline points in high dimensional space, we propose a new concept, called k-dominant skyline which relaxes the idea of dominance to k-dominance. A point p is said to k-dominate another point q if there are k ≤ d dimensions in which p is better than or equal to q and is better in at least one of these k dimensions. A point that is not k-dominated by any other points is in the k-dominant skyline.We prove various properties of k-dominant skyline. In particular, because k-dominant skyline points are not transitive, existing skyline algorithms cannot be adapted for k-dominant skyline. We then present several new algorithms for finding k-dominant skyline and its variants. Extensive experiments show that our methods can answer different queries on both synthetic and real data sets efficiently.
Active learning via transductive experimental design

This paper considers the problem of selecting the most informative experiments x to get measurements y for learning a regression model y = f(x). We propose a novel and simple concept for active learning, transductive experimental design, that explores available unmeasured experiments (i.e., unlabeled data) and has a better scalability in comparison with classic experimental design methods. Our in-depth analysis shows that the new method tends to favor experiments that are on the one side hard-to-predict and on the other side representative for the rest of the experiments. Efficient optimization of the new design problem is achieved through alternating optimization and sequential greedy search. Extensive experimental results on synthetic problems and three real-world tasks, including questionnaire design for preference learning, active learning for text categorization, and spatial sensor placement, highlight the advantages of the proposed approaches.
Neural crest migration is driven by a few trailblazer cells with a unique molecular signature narrowly confined to the invasive front

Neural crest (NC) cell migration is crucial to the formation of peripheral tissues during vertebrate development. However, howNCcells respond to different microenvironments to maintain persistence of direction and cohesion in multicellular streams remains unclear. To address this, we profiled eight subregions of a typical cranial NC cell migratory stream. Hierarchical clustering showed significant differences in the expression profilesof the lead threesubregionscomparedwithnewlyemergedcells. Multiplexed imagingofmRNAexpressionusing fluorescenthybridization chain reaction (HCR) quantitatively confirmed the expression profiles of lead cells. Computationalmodeling predicted that a small fraction of lead cells that detect directional information is optimal for successful stream migration. Single-cell profiling then revealed a unique molecular signature that is consistent and stable over time in a subset of lead cells within the most advanced portion of the migratory front, which we term trailblazers.Model simulations that forced a lead cell behavior in the trailing subpopulation predicted cell bunching near themigratory domain entrance. Misexpression of the trailblazer molecular signature by perturbation of two upstream transcription factors agreed with the in silico prediction and showed alterations to NC cell migration distance and stream shape. These data are the first to characterize themolecular diversity within an NC cell migratory stream and offer insights into how molecular patterns are transduced into cell behaviors.
Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development

ABSTRACT Vascular endothelial growth factor A (Vegfa) has important roles in endochondral bone formation. Osteoblast precursors, endothelial cells and osteoclasts migrate from perichondrium into primary ossification centers of cartilage templates of future bones in response to Vegfa secreted by (pre)hypertrophic chondrocytes. Perichondrial osteolineage cells also produce Vegfa, but its function is not well understood. By deleting Vegfa in osteolineage cells in vivo, we demonstrate that progenitor-derived Vegfa is required for blood vessel recruitment in perichondrium and the differentiation of osteoblast precursors in mice. Conditional deletion of Vegfa receptors indicates that Vegfa-dependent effects on osteoblast differentiation are mediated by Vegf receptor 2 (Vegfr2). In addition, Vegfa/Vegfr2 signaling stimulates the expression and activity of Indian hedgehog, increases the expression of β-catenin and inhibits Notch2. Our findings identify Vegfa as a regulator of perichondrial vascularity and osteoblast differentiation at early stages of bone development. Summary: In developing bone, Vegf expressed in osteolineage precursors regulates early osteoblast differentiation and blood vessel recruitment through interactions with other signalling pathways.
Drosophila Vps4 promotes Epidermal growth factor receptor signaling independently of its role in receptor degradation

Endocytic trafficking of signaling receptors is an important mechanism for limiting signal duration. Components of the Endosomal Sorting Complexes Required for Transport (ESCRT), which target ubiquitylated receptors to intra-lumenal vesicles (ILVs) of multivesicular bodies, are thought to terminate signaling by the epidermal growth factor receptor (EGFR) and direct it for lysosomal degradation. In a genetic screen for mutations that affect Drosophila eye development, we identified an allele of Vacuolar protein sorting 4 (Vps4), which encodes an AAA ATPase that interacts with the ESCRT-III complex to drive the final step of ILV formation. Photoreceptors are largely absent from Vps4 mutant clones in the eye disc, and even when cell death is genetically prevented, the mutant R8 photoreceptors that develop fail to recruit surrounding cells to differentiate as R1-R7 photoreceptors. This recruitment requires EGFR signaling, suggesting that loss of Vps4 disrupts the EGFR pathway. In imaginal disc cells mutant for Vps4, EGFR and other receptors accumulate in endosomes and EGFR target genes are not expressed; epistasis experiments place the function of Vps4 at the level of the receptor. Surprisingly, Vps4 is required for EGFR signaling even in the absence of Shibire, the Dynamin that internalizes EGFR from the plasma membrane. In ovarian follicle cells, in contrast, Vps4 does not affect EGFR signaling, although it is still essential for receptor degradation. Taken together, these findings indicate that Vps4 can promote EGFR activity through an endocytosis-independent mechanism. SUMMARY: The AAA ATPase Vps4 is required for and promotes EGFR activity during Drosophila eye development, acting via an endocytosis-independent mechanism.