julilili42/papers huggingface dataset:
Comparison of gut-directed hypnotherapy and unspecific hypnotherapy as self-help format in children and adolescents with functional abdominal pain or irritable bowel syndrome: a randomized pilot study
2017-10-11

Objective Psychosocial treatments for chronic abdominal pain in childhood or adolescence are effective, but time consuming and hardly available. In the present study, gut-directed hypnotherapy (GDHT) and unspecific hypnotherapy (UHT) were compared to evaluate the feasibility and efficacy of a hypnotherapeutic self-help intervention. Participants and methods Children/adolescents between 6 and 17 years of age with chronic abdominal pain were randomized to GDHT or UHT. The treatment period was 12 weeks each. Measurements were performed before and after treatment. The primary outcome was a pain diary. Analysis was carried out as per protocol. Results Of 45 participants included, 13 were lost to follow-up. Thirty-two participants (14 GHDT, 18 UHT) were analyzed. Dropouts had higher pain severity. Completers in both conditions showed good adherence and a similar decrease in days with pain and pain duration. Pain intensity decreased only in the UHT condition. Eleven participants (two GDHT, nine UHT) achieved clinical remission (&gt;80% improvement) and 13 participants (seven GDHT, six UHT) improved significantly (30–80%). Conclusion Results suggest a high efficacy of standardized home-based hypnotherapy for children/adolescents with abdominal pain. Children/adolescents with high pain severity are at risk of dropping out. The UHT condition showed slight evidence of superiority, but conditions were equivalent on most outcomes. Taken together, self-help approaches based on hypnotherapy could close a treatment gap and prevent chronification.
Echoes of Affective Stimulation in Brain connectivity Networks
2017-10-11

Affective experience has effects on subjective feelings, physiological indices, entails immediate activity changes in the brain, and even influences brain networks in a protracted manner. However, it is still unclear, how the functional connectivity (FC) interplay between major intrinsic connectivity networks upon affective stimulation depends on affective valence, and whether this is specific for affective experience, i.e., can be distinguished from cognitive task execution. Our study included fMRI scans during and after affective stimulation with sad and neutral movies and a working memory task complemented with measures of cardiovascular activity and mood. Via parcellation of the brain into default mode network (DMN), central executive network (CEN), and dorsal attention network, and application of network-based statistics, we identified subnetworks associated with changing psychological contexts. Specific effects for affective stimulation with negative valence were both reduced heart rate variability and mood, and upregulated FC of inter-CEN-DMN connections while intra-DMN connections were downregulated. Furthermore, results demonstrated a valence-specific dynamic carry-over effect in nodes of the CEN, which temporarily increased their FC strength after affective stimulation with negative valence and exhibited distinct temporal profiles. The reported effects were clearly distinguishable from those of a cognitive task and further elucidate the trajectory of affective experience.
Excessive burden of lysosomal storage disorder gene variants in Parkinson’s disease
2017-10-12

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility.
Ecological plant epigenetics: Evidence from model and non‐model species, and the way forward
2017-10-12

Abstract Growing evidence shows that epigenetic mechanisms contribute to complex traits, with implications across many fields of biology. In plant ecology, recent studies have attempted to merge ecological experiments with epigenetic analyses to elucidate the contribution of epigenetics to plant phenotypes, stress responses, adaptation to habitat, and range distributions. While there has been some progress in revealing the role of epigenetics in ecological processes, studies with non‐model species have so far been limited to describing broad patterns based on anonymous markers of DNA methylation. In contrast, studies with model species have benefited from powerful genomic resources , which contribute to a more mechanistic understanding but have limited ecological realism. Understanding the significance of epigenetics for plant ecology requires increased transfer of knowledge and methods from model species research to genomes of evolutionarily divergent species, and examination of responses to complex natural environments at a more mechanistic level. This requires transforming genomics tools specifically for studying non‐model species, which is challenging given the large and often polyploid genomes of plants. Collaboration among molecular geneticists, ecologists and bioinformaticians promises to enhance our understanding of the mutual links between genome function and ecological processes.
GABA—from Inhibition to Cognition: Emerging Concepts
2017-10-12

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.
Effekt: extensible algebraic effects in Scala (short paper)
2017-10-12

Algebraic effects are an interesting way to structure effectful programs and offer new modularity properties. We present the Scala library Effekt, which is implemented in terms of a monad for multi-prompt delimited continuations and centered around capability passing. This makes the newly proposed feature of implicit function types a perfect fit for the syntax of our library. Basing the library design on capability passing and a polymorphic embedding of effect handlers furthermore opens up interesting dimensions of extensibility. Preliminary benchmarks comparing Effekt with an established library suggest significant speedups.
Genomics of Immunotherapy-Associated Hyperprogressors—Letter
2017-10-12

Kato and colleagues ([1][1]) reported 4 cancer patients with metastatic disease, hyperprogression under treatment with anti-PD-1/PD-L1 monotherapy, and a cooccurring MDM2/4 amplification in the cancer cells. They defined hyperprogression as time-to-treatment failure 50% increase in tumor
Stage 1 Registered Report: Effect of deficient phagocytosis on neuronal survival and neurological outcome after temporary middle cerebral artery occlusion (tMCAo)
2017-10-12

<ns4:p>Stroke is a major cause of death and disability worldwide. In addition to neuronal death resulting directly from energy depletion due to lack of blood supply, inflammation and microglial activation following ischemic brain injury has been increasingly recognized to be a key contributor to the pathophysiology of cerebrovascular disease. However, our understanding of the cross talk between the ischemic brain and the immune system is limited. Recently, we demonstrated that following focal ischemia, death of mature viable neurons can be executed through phagocytosis by microglial cells or recruited macrophages, i.e. through phagoptosis. It was shown that inhibition of phagocytic signaling pathways following endothelin-1 induced focal cerebral ischemia leads to increased neuronal survival and neurological recovery. This suggests that inhibition of specific phagocytic pathways may prevent neuronal death during cerebral ischemia. To further explore this potential therapeutic target, we propose to assess the role of phagocytosis in an established model of temporary (45min) middle cerebral artery occlusion, and to evaluate neuronal survival and neurological recovery in mice with deficient phagocytosis.</ns4:p>
Surface characteristics of dental implants: A review
2017-10-13

There is clear relevance for the influence of topographical and wetting characteristics on a macromolecular and cellular level at endosseous implant/biosystem interfaces. However, we are still far away from designing sophisticated implant surfaces with the best possible, selective functionality for each specific tissue or cavity interface. Firstly, because our knowledge of the respective surface related reactions is at best fragmentary. Secondly, because manufacturing of multi-scaled complex surfaces including distinct nanotopographies, wetting properties, and stable cleanliness is still a technical challenge and far away from being reproducibly transferred to implant surfaces.
Immunogenic stress and death of cancer cells: Contribution of antigenicity vs adjuvanticity to immunosurveillance
2017-10-13

Summary Cancer cells are subjected to constant selection by the immune system, meaning that tumors that become clinically manifest have managed to subvert or hide from immunosurveillance. Immune control can be facilitated by induction of autophagy, as well as by polyploidization of cancer cells. While autophagy causes the release of ATP , a chemotactic signal for myeloid cells, polyploidization can trigger endoplasmic reticulum stress with consequent exposure of the “eat‐me” signal calreticulin on the cell surface, thereby facilitating the transfer of tumor antigens into dendritic cells. Hence, both autophagy and polyploidization cause the emission of adjuvant signals that ultimately elicit immune control by CD 8 + T lymphocytes. We investigated the possibility that autophagy and polyploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. Mass spectrometry led to the identification of peptides that were presented on major histocompatibility complex (MHC) class I molecules in an autophagy‐dependent fashion or that were specifically exposed on the surface of polyploid cells, yet lost upon passage of such cells through immunocompetent (but not immunodeficient) mice. However, the preferential recognition of autophagy‐competent and polyploid cells by the innate and cellular immune systems did not correlate with the preferential recognition of such peptides in vivo. Moreover, vaccination with such peptides was unable to elicit tumor growth‐inhibitory responses in vivo. We conclude that autophagy and polyploidy increase the immunogenicity of cancer cells mostly by affecting their adjuvanticity rather than their antigenicity.
Subgrain Rotation Recrystallization During Shearing: Insights From Full‐Field Numerical Simulations of Halite Polycrystals
2017-10-13

Abstract We present, for the first time, results of full‐field numerical simulations of subgrain rotation recrystallization of halite polycrystals during simple shear deformation. The series of simulations show how microstructures are controlled by the competition between (i) grain size reduction by creep by dislocation glide and (ii) intracrystalline recovery encompassing subgrain coarsening by coalescence through rotation and alignment of the lattices of neighboring subgrains. A strong grain size reduction develops in models without intracrystalline recovery, as a result of the formation of high‐angle grain boundaries when local misorientations exceed 15°. The activation of subgrain coarsening associated with recovery decreases the stored strain energy and results in grains with low intracrystalline heterogeneities. However, this type of recrystallization does not significantly modify crystal preferred orientations. Lattice orientation and grain boundary maps reveal that this full‐field modeling approach is able to successfully reproduce the evolution of dry halite microstructures from laboratory deformation experiments, thus opening new opportunities in this field of research. We demonstrate how the mean subgrain boundary misorientations can be used to estimate the strain accommodated by dislocation glide using a universal scaling exponent of about 2/3, as predicted by theoretical models. In addition, this strain gauge can be potentially applied to estimate the intensity of intracrystalline recovery, associated with temperature, using quantitative crystallographic analyses in areas with strain gradients.
Isoscalar single-pion production in the region of Roper and d⁎(2380) resonances
2017-10-13

Exclusive measurements of the quasi-free pn -&amp;gt; pp pi(-) and pp -&amp;gt; pp pi(0) reactions have been performed by means of pd collisions at T-p= 1.2 GeV using the WASA detector setup at COSY. Total and differential cross sections have been obtained covering the energy region T-p= 0.95-1.3 GeV (root s = 2.3-2.46 GeV), which includes the regions of triangle(1232), N*(1440) and d*(2380) resonance excitations. From these measurements the isoscalar single-pion production has been extracted, for which data existed so far only below T-p = 1 GeV. We observe a substantial increase of this cross section around 1 GeV, which can be related to the Roper resonance N*(1440), the strength of which shows up isolated from the triangle resonance in the isoscalar (N pi)(I=0) invariant-mass spectrum. No evidence for a decay of the dibaryon resonance d*(2380) into the isoscalar (NN pi)(I=0) channel is found. An upper limit of 180 mu b (90% CL.) corresponding to a branching ratio of 9% has been deduced.
Discriminating Non-Native Segmental Length Contrasts Under Increased Task Demands
2017-10-13

The present study examines how vulnerable perception of second language prosody is to increased task demands. German learners of Japanese, German non-learners without exposure to Japanese, and Japanese native listeners were tested in their ability to discriminate consonant length contrasts (compared to vowel length contrasts that served as a control condition). Memory load was increased by a longer inter-stimulus interval (2500 ms compared to 300 ms) and the demand on attention control was enhanced through the addition of the acoustic complexity of the stimuli (i.e., through a task-irrelevant pitch fall that occurred simultaneously with a consonant length contrast). The results showed high discrimination abilities, in all groups, when task demands were lowest. With increased task demands, only non-native listeners’ discrimination abilities decreased: non-learners were strongly affected by both increased memory load and higher demand on attention control, while learners were only affected by the latter. The task-irrelevant acoustic complexity of the stimuli had a stronger impact on performance than increased memory load did. The findings suggest that second language learners established novel phonological representations but that the ability to use them could only be applied in the absence of distracting acoustic information. The non-native listeners’ reduced sensitivity under increased task demands explains why even advanced learners still face difficulties in daily listening situations with numerous distractions.
Maximum norm stability and error estimates for the evolving surface finite element method
2017-10-13

We show convergence in the natural and norm for a semidiscretization with linear finite elements of a linear parabolic partial differential equations on evolving surfaces. To prove this, we show error estimates for a Ritz map, error estimates for the material derivative of a Ritz map and a weak discrete maximum principle.
Modified hCFTRmRNA restores normal lung function in a mouse model of cystic fibrosis
2017-10-13

Abstract Being a classic monogenic disease, gene therapy has always been a promising therapeutic approach for Cystic Fibrosis (CF). However, numerous trials using DNA or viral vectors encoding the correct protein resulted in a general low efficacy. In the last years, chemically modified messenger RNA (cmRNA) has been proven to be a highly potent, pulmonary effective drug. We thus explored the expression of human (h)CFTR encoded by h CFTR cmRNA in vitro , analyzed by flow cytometry and Western Blot and its function with a YFP assay. Very similar effects could be observed in vivo when h CFTR cmRNA was assembled with Chitosan-coated PLGA to nanoparticles (NPs) and intratracheally (i.t.) or intravenously (i.v) injected, the latter one as an alternative administration route to circumvent the clogged airways of CF patients. This significantly improved lung function, which suggests that h CFTR cmRNA-NPs are a promising therapeutic option for CF patients independent of their CFTR genotype.
Gestational age modulates neural correlates of intentional, but not automatic number magnitude processing in children born preterm
2017-10-13

Abstract Premature birth is a significant risk factor for learning disabilities in general and mathematics learning difficulties in particular. However, the exact reasons for this relation are still unknown. While typical numerical development is associated with a frontal‐to‐parietal shift of brain activation with increasing age, influences of gestational age have hardly been considered so far. Therefore, we investigated the influence of gestational age on the neural correlates of number processing in 6‐ and 7‐year‐old children born prematurely (n = 16). Only the numerical distance effect – as a measure of intentional number magnitude processing – elicited the fronto‐parietal activation pattern typically observed for numerical cognition. On the other hand, the size congruity effect – as a measure of automatic number magnitude processing – was associated with activation of brain areas typically attributed to cognitive control. Most importantly, however, we observed that gestational age reliably predicted the frontal‐to‐parietal shift of activation observed for the numerical distance effect. Our findings seem to indicate that human numerical development may start even before birth and prematurity might hamper neural facilitation of the brain circuitry subserving numerical cognition. In turn, this might contribute to the high risk of premature children to develop mathematical learning difficulties.
Service Offshoring and Firm Employment
2017-10-13

Major technological advances have recently spurred a new wave of offshoring in services, which used to be non-tradable. Should service workers in developed countries worry about their jobs? Trade theory has given a nuanced answer to this question, suggesting that efficiency gains from offshoring may counteract direct job losses, which leaves the predicted net effect ambiguous. This paper investigates the employment effects of service offshoring in a newly combined and exceptionally detailed panel dataset, covering almost the entire universe of German firms’ service imports over the years 2002-2013. It exploits firm-specific export supply shocks by partner countries and service types as an instrumental variable to find that service offshoring has increased firm employment. In line with the canonical trade in tasks model, the employment gains are greater in firms with higher initial levels of service offshoring.
The ethical justification for the use of non-human primates in research: the Weatherall report revisited
2017-10-14

The Weatherall report on the use of non-human primates in research was published in 2006. Its main conclusion was that there is a strong scientific case for the use of non-human primates in some cases, but the report stressed the importance of evaluating each case in the light of the availability of alternatives. In addition to arguing for the scientific necessity of using non-human primates in research, the report also provided an ethical justification. As could be expected, the report was harshly criticised by animal rights groups, but in the academic literature, only two critical replies appeared. In what follows, I will describe the ethical justification for non-human primate research as it is laid out in the Weatherall report and then consider the criticism in the academic literature. I conclude that the report’s ethical justification for the use of non-human primates in research, in particular in basic neuroscientific research, has not been convincingly challenged by its critics. Since the criticism of the report is limited and represents only a small part of the academic discussion about the use of non-human primates in research, and a still smaller part of the ethical discussion about animal research, it is important that the discussion continue both at the academic and social level.
From 2-Alkylsulfanylimidazoles to 2-Alkylimidazoles: An Approach towards Metabolically More Stable p38α MAP Kinase Inhibitors
2017-10-14

In vitro and in vivo metabolism studies revealed that 2-alkylsulfanylimidazole ML3403 (4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2-amine) undergoes rapid oxidation to the sulfoxide. Replacing the sulfur atom present in the two potent p38α mitogen-activated protein (MAP) kinase inhibitors ML3403 and LN950 (2-((5-(4-fluorophenyl)-4-(2-((3-methylbutan-2-yl)amino)pyridin-4-yl)-1H-imidazol-2-yl)thio)ethan-1-ol) by a methylene group resulted in 2-alkylimidazole derivatives 1 and 2, respectively, having a remarkably improved metabolic stability. The 2-alkylimidazole analogs 1 and 2 showed 20% and 10% biotransformation after 4 h of incubation with human liver microsomes, respectively. They display a 4-fold increased binding affinity towards the target kinase as well as similar in vitro potency and ex vivo efficacy relative to their 2-alkylsulfanylimidazole counterparts ML3403 and LN950. For example, 2-alkylimidazole 2, the analog of LN950, inhibits both the p38α MAP kinase as well as the LPS-stimulated tumor necrosis factor-α release from human whole blood in the low double-digit nanomolar range.