julilili42/papers huggingface dataset:
Functional connectivity changes following interpersonal reactivity
2017-11-21

Abstract Attachment experiences substantially influence emotional and cognitive development. Narratives comprising attachment‐dependent content were proposed to modulate activation of cognitive‐emotional schemata in listeners. We studied the effects after listening to prototypical attachment narratives on wellbeing and countertransference‐reactions in 149 healthy participants. Neural correlates of these cognitive‐emotional schema activations were investigated in a 7 Tesla rest‐task‐rest fMRI‐study (23 healthy males) using functional connectivity (FC) analysis of the social approach network (seed regions: left and right Caudate Nucleus, CN). Reduced FC between left CN and bilateral dorsolateral prefrontal cortex (DLPFC) represented a general effect of prior auditory stimulation. After presentation of the insecure‐dismissing narrative, FC between left CN and bilateral temporo‐parietal junction, and right dorsal posterior Cingulum was reduced, compared to baseline. Post‐narrative FC‐patterns of insecure‐dismissing and insecure‐preoccupied narratives differed in strength between left CN and right DLPFC. Neural correlates of the moderating effect of individual attachment anxiety were represented in a reduced CN‐DLPFC FC as a function of individual neediness‐levels. These findings suggest specific neural processing of prolonged mood‐changes and schema activation induced by attachment‐specific speech patterns. Individual desire for interpersonal proximity was predicted by attachment anxiety and furthermore modulated FC of the social approach network in those exposed to such narratives.
Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection
2017-11-22

Antibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP–reactive B cells in PfSPZ-CVac–induced protective immunity. These two antibodies showed poor sporozoite binding and weak inhibition of parasite traversal and development, and did not protect mice from infection with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses demonstrated that one antibody interacts with a polymorphic region overlapping two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite escape from humoral and cellular immunity. Our data identify important features underlying C-PfCSP shortcomings as a vaccine target.
Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation
2017-11-22

Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain.
TeV Gamma-Ray Observations of the Binary Neutron Star Merger GW170817 with H.E.S.S.
2017-11-22

Abstract We search for high-energy gamma-ray emission from the binary neutron star merger GW170817 with the H.E.S.S. Imaging Air Cherenkov Telescopes. The observations presented here have been obtained starting only 5.3 hr after GW170817. The H.E.S.S. target selection identified regions of high probability to find a counterpart of the gravitational-wave event. The first of these regions contained the counterpart SSS17a that has been identified in the optical range several hours after our observations. We can therefore present the first data obtained by a ground-based pointing instrument on this object. A subsequent monitoring campaign with the H.E.S.S. telescopes extended over several days, covering timescales from 0.22 to 5.2 days and energy ranges between to . No significant gamma-ray emission has been found. The derived upper limits on the very-high-energy gamma-ray flux for the first time constrain non-thermal, high-energy emission following the merger of a confirmed binary neutron star system.
Identification and Functional Characterization of Phosphorylation Sites of the Human Papillomavirus 31 E8^E2 Protein
2017-11-22

ABSTRACT The papillomavirus E2 protein regulates transcription, replication, and nuclear retention of viral genomes. Phosphorylation of E2 in the hinge region has been suggested to modulate protein stability, DNA-binding activity, and chromosomal attachment. The papillomavirus E8^E2 protein shares the hinge domain with E2 and acts as a repressor of viral replication. Mass spectrometry analyses of human papillomavirus 31 (HPV31) E8^E2 and E2 proteins identify phosphorylated S78, S81, and S100 in E8^E2 and S266 and S269 in E2 in their hinge regions. Phos-tag analyses of wild-type and mutant proteins indicate that S78 is a major phosphorylation site in E8^E2, but the corresponding S266 in E2 is not. Phosphorylation at S78 regulates E8^E2's repression activity of reporter constructs, whereas the corresponding E2 mutants do not display a phenotype. Phosphorylation at S78 does not alter E8^E2's protein stability, nuclear localization, or binding to DNA or to cellular NCoR/SMRT complexes. Surprisingly, in the context of HPV31 genomes, mutation of E8^E2 S78 does not modulate viral replication or transcription in undifferentiated or differentiated cells. However, comparative transcriptome analyses of differentiated HPV31 E8^E2 S78A and S78E cell lines reveal that the expression of a small number of cellular genes is changed. Validation experiments suggest that the transcription of the cellular LYPD2 gene is altered in a phospho-S78 E8^E2-dependent manner. In summary, our data suggest that phosphorylation of S78 in E8^E2 regulates its repression activity by a novel mechanism, and this seems to be important for the modulation of host cell gene expression but not viral replication. IMPORTANCE Posttranslational modification of viral proteins is a common feature to modulate their activities. Phosphorylation of serine residues S298 and S301 in the hinge region of the bovine papillomavirus type 1 E2 protein has been shown to restrict viral replication. The papillomavirus E8^E2 protein shares the hinge domain with E2 and acts as a repressor of viral replication. A large fraction of HPV31 E8^E2 is phosphorylated at S78 in the hinge region, and this is important for E8^E2's repression activity. Surprisingly, phosphorylation at S78 in E8^E2 has no impact on viral replication in tissue culture but rather seems to modulate the expression of a small number of cellular genes. This may indicate that phosphorylation of viral transcription factors serves to broaden their target gene specificity.
Immune correlates of clinical outcome in melanoma
2017-11-22

Summary Melanoma has long been recognized as a potentially immunogenic tumour, but only recently has it become clear that the reason for this resides in its many ultraviolet (UV)‐induced mutations and expression of multiple autoantigens which can be targeted by the immune system. The first successful applications of immune‐based treatments included passive immunotherapy using high‐dose interleukin (IL)‐2 and/or adoptive transfer of natural killer (NK)‐cells, as well as active immunotherapy using whole cell‐derived or peptide vaccines. In the intervening decades, it has become clear that these approaches can lead to durable responses in stage III/IV melanoma, and even to functional cures – but only in a vanishingly small fraction of patients. With the advent of immune checkpoint blockade first with anti‐cytotoxic T‐lymphocyte 4 (CTLA‐4), then with anti‐programmed cell death 1 (PD‐1) antibodies, and combinations thereof, the small percentage of responding patients may be increased to half, a major accomplishment in this refractory disease. Improved techniques for identifying mutation‐derived neoantigens and thus more sophisticated active immunotherapies, probably combined with checkpoint blockade, currently hold great promise for further increasing the fraction of responding patients. As additional immunomodulatory antibodies and therapies become available, it will be increasingly important to develop diagnostic tools to determine which particular therapy is likely to elicit the best response for the individual patient. Practically speaking, therapy selection and efficacy monitoring on the basis of the results of a blood test would be most desirable. The purpose of this review is to consider the feasibility of identifying ‘immune signatures’ for predicting responses and determining mechanisms responsible for success or failure of these immunotherapies.
Stereo‐Consistent Contours in Object Space
2017-11-22

Abstract Notebook scribbles, art or technical illustrations—line drawings are a simplistic method to visually communicate information. Automated line drawings often originate from virtual 3D models, but one cannot trivially experience their three‐dimensionality. This paper introduces a novel concept to produce stereo‐consistent line drawings of virtual 3D objects. Some contour lines do not only depend on an objects geometry, but also on the position of the observer. To accomplish consistency between multiple view positions, our approach exploits geometrical characteristics of 3D surfaces in object space. Established techniques for stereo‐consistent line drawings operate on rendered pixel images. In contrast, our pipeline operates in object space using vector geometry, which yields many advantages: The position of the final viewpoint(s) is flexible within a certain window even after the contour generation, e.g. a stereoscopic image pair is only one possible application. Such windows can be concatenated to simulate contours observed from an arbitrary camera path. Various types of popular contour generators can be handled equivalently, occlusions are natively supported and stylization based on geometry characteristics is also easily possible.
Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium
2017-11-23

BACKGROUND: Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors. METHODS: Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status. RESULTS: The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction = 0.009), adult height (P-interaction = 0.025) and current use of combined MHT (P-interaction = 0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P = 0.013 for global and 0.18 for tail-based tests). CONCLUSIONS: The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.
Switching between Multiple Codes of SNARC-Like Associations: Two Conceptual Replication Attempts with Anodal tDCS in Sham-Controlled Cross-Over Design
2017-11-23

In societies with left-to-right reading direction, left-side vs. right-side behavioral decisions are faster for relatively small vs. large number magnitudes, and vice versa, a phenomenon termed Spatial-Numerical Associations of Response Codes (SNARC) effect. But also for non-numerical sequential items, SNARC-like effects were observed, suggesting a common neurocognitive mechanism based on the ordinal structures of both numbers and sequences. Modulation of prefrontal networks that are involved in providing spatial associations during cognitive behavior can contribute to elaborate their neuropsychological theoretical foundations. With transcranial direct current stimulation (tDCS) directed to the left prefrontal cortex, we recently showed that (i) cathodal tDCS can block the emergence of spatial-numerical associations and that (ii) anodal tDCS can reverse spatial associations of sequential order, most likely based on markedness correspondence. Two conceptual replication attempts of the latter reversal of space-order associations are presented in the current sham-controlled experiment, using either weekdays (Monday-Friday) or month names (January-December) as stimuli in the temporal order classification task. In addition, to control for possible influences of notation, number stimuli were presented as written German names (One-Five). We report on a successful modulation of spatial-numerical associations of response codes (SNARC) effects with month stimuli induced by anodal tDCS, but failed to observe the same reversal of SNARC effects for weekday stimuli. The former stimulation effect was orthogonal to the small anodal tDCS effect on written number words, which replicates the dissociation of SNARC effects for numbers vs. non-numerical sequences. Moreover, this result reinforces the hypothesis that the ordinal item and task structure was the source of dissociation (as opposed to verbal presentation). We suggest that the diverging results can be explained by the markedness correspondence account of spatial associations in a multiple coding framework. Left-hemispheric prefrontal excitation from anodal tDCS renders verbal markedness relatively more dominant, but this effect is not absolute. We discuss task contagion, study design, and individual differences in performance measures or tDCS response as possible contributors to systematic variation of the weights of multiple coding parameters for spatial-numerical associations.
Age-related changes in microglial physiology: the role for healthy brain ageing and neurodegenerative disorders
2017-11-23

Abstract Microglia are the main immune cells of the brain contributing, however, not only to brain’s immune defense but also to many basic housekeeping functions such as development and maintenance of functional neural networks, provision of trophic support for surrounding neurons, monitoring and modulating the levels of synaptic activity, cleaning of accumulating extracellular debris and repairing microdamages of the brain parenchyma. As a consequence, age-related alterations in microglial function likely have a manifold impact on brain’s physiology. In this review, I discuss the recent data about physiological properties of microglia in the adult mammalian brain; changes observed in the brain innate immune system during healthy aging and the probable biological mechanisms responsible for them as well as changes occurring in humans and mice during age-related neurodegenerative disorders along with underlying cellular/molecular mechanisms. Together these data provide a new conceptual framework for thinking about the role of microglia in the context of age-mediated brain dysfunction.
SPECTRE: a suite of phylogenetic tools for reticulate evolution
2017-11-23

Abstract Summary Split-networks are a generalization of phylogenetic trees that have proven to be a powerful tool in phylogenetics. Various ways have been developed for computing such networks, including split-decomposition, NeighborNet, QNet and FlatNJ. Some of these approaches are implemented in the user-friendly SplitsTree software package. However, to give the user the option to adjust and extend these approaches and to facilitate their integration into analysis pipelines, there is a need for robust, open-source implementations of associated data structures and algorithms. Here, we present SPECTRE, a readily available, open-source library of data structures written in Java, that comes complete with new implementations of several pre-published algorithms and a basic interactive graphical interface for visualizing planar split networks. SPECTRE also supports the use of longer running algorithms by providing command line interfaces, which can be executed on servers or in High Performance Computing environments. Availability and implementation Full source code is available under the GPLv3 license at: https://github.com/maplesond/SPECTRE. SPECTRE’s core library is available from Maven Central at: https://mvnrepository.com/artifact/uk.ac.uea.cmp.spectre/core. Documentation is available at: http://spectre-suite-of-phylogenetic-tools-for-reticulate-evolution.readthedocs.io/en/latest/ Supplementary information Supplementary data are available at Bioinformatics online.
Effects of exposure to water disinfection by-products in a swimming pool: A metabolome-wide association study
2017-11-24

Our study identified numerous molecular changes following a swim in a chlorinated pool. While we could not explicitly evaluate which experiment-related factors induced these associations, molecular characterization highlighted metabolic features associated with exposure changes during swimming.
Effect of orlistat or metformin in overweight and obese polycystic ovary syndrome patients with insulin resistance
2017-11-24

The aim of this study was to evaluate the effect of orlistat or metformin combined with Diane-35 on anthropometric, hormonal and metabolic parameters in overweight and obese polycystic ovary syndrome (PCOS) patients with insulin resistance (fasting insulin > 10 mIU/L). A total of 240 PCOS women were randomly allocated to orlistat plus Diane-35(OD group), metformin plus Diane-35(MD group), orlistat plus metformin plus Diane-35(OMD group) or Diane-35 (D group). Body weight, BMI, waist and hip circumference, blood pressure, endocrine profile, lipid profile and insulin resistance were assessed at baseline and after 3 months. Significant reductions in waist and hip circumference, serum LH, total testosterone and uric acid were observed in all groups compared with baseline. TG and TC significantly decreased in the OD group. Homeostasis model assessment insulin resistance (HOMA-IR) index was reduced in the OD (p = .015), MD (p = .001) and OMD (p = .004) groups. Body weight, BMI, systolic BP and HDL-C significantly changed in the OD and OMD group compared with the D group (p < .05). Side effects were less with orlistat than metformin. This study demonstrated that orlistat is more effective in reducing weight and lipid profile than metformin. Besides, orlistat has mild side-effects and is better tolerated compared with metformin.
Brain-Computer Interfaces for Post-Stroke Motor Rehabilitation: A Meta-Analysis
2017-11-24

ABSTRACT Objective Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Methods Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. Results We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors fulfilling the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinical important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference (SMD) of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a sub-clinical level. Interpretation We found a medium to large effect size of BCI therapy compared to controls. This suggests that BCI technology might be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.
Demands and Needs for Psycho-Oncological eHealth Interventions in Women With Cancer: Cross-Sectional Study
2017-11-24

Psycho-oncological eHealth applications may be very beneficial for women with cancer, especially when they address psycho-oncological content topics like anxiety, ability to cope, depressive feelings, self-esteem, or adjustment to a new life situation. The findings of this study indicate that psycho-oncological eHealth applications are a promising medium to improve the psychosocial care and enhance individual disease management and engagement among women with cancer.