julilili42/papers huggingface dataset:
Cerebellar involvement in learning to balance a cart-pole system
2019-03-25

ABSTRACT The role of the cerebellum in error-based motor adaptation is well examined. In contrast, the involvement of the cerebellum in reward-based motor learning is less clear. In this study, we examined cerebellar involvement in a reward-based motor learning task, namely learning to control a virtual cart-pole system, over five consecutive days. Subjects with focal cerebellar lesions were compared to age-matched controls in terms of learning performance and underlying control mechanisms. Based on the overall balancing performance we have identified two subgroups of patients: (1) patients with learning performance comparable to healthy controls and (2) patients with decelerated learning, unsaturated learning progress after five days and decreased inter-manual transfer. Furthermore, we found that online learning is impaired while offline learning is partly preserved in cerebellar subjects. Regarding control mechanisms, decreased control performance was associated with impairments in predictive action timing. Voxel-wise lesion symptom mapping based on the two subgroups revealed strong associations between impairments in controlling the virtual cart-pole system and lesions in intermediate and lateral parts of lobules V and VI. These results together with previous reports suggest that the ability to predict the dynamics of the cart-pole system is an important factor for the reward-based skill acquisition process.
Supplementing Essential Polyunsaturated Fatty Acids—A Matter of Respecting Fetal Development
2019-03-25

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Glial Activation Markers in CSF and Serum From Patients With Primary Progressive Multiple Sclerosis: Potential of Serum GFAP as Disease Severity Marker?
2019-03-26

<b>Background:</b> In progressive multiple sclerosis (MS), glial activation is thought to be a relevant mechanism of disability progression. Therefore, <i>in vivo</i> assessment of the glial cell activity is, in the emerging treatment era of primary progressive MS (PPMS), more important than ever. <b>Objectives:</b> To test the association of cerebrospinal fluid (CSF) and serum markers of glial activation in PPMS patients; including glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (CHI3L1), soluble variant of triggering receptor expressed on myeloid cells 2 (sTREM2), and marker of neuroaxonal damage (Neurofilament light chain, NfL) as well as clinical severity. <b>Methods:</b> CSF and serum samples from PPMS patients were collected in the MS-centers at Universities of Freiburg (<i>n</i> = 49), Ulm (<i>n</i> = 27), Muenster (<i>n</i> = 11), and Rostock (<i>n</i> = 6). sTREM2 and CHI3L1 levels were measured using the previously reported ELISA assays, while NfL and GFAP were measured using SIMOA assays. Clinical data included age, gender, disease duration, treatment status, and Expanded Disability Status Scale (EDSS). <b>Results:</b> 93 CSF samples and 71 matching serum samples were analyzed. The median age of patients was 49 years and disease duration 4.5 years. GFAP<sub>serum</sub> correlated with EDSS after correction for age (β = 0.3, <i>p</i> = 0.001). Furthermore, EDSS was higher in patients with a GFAP<sub>serum</sub> level ≥ 151.7 pg/ml compared to patients with GFAP<sub>serum</sub> below this cut-off (5.5 vs. 4.0, <i>p</i> = 0.009). Other markers did not correlate with the clinical severity. Moreover, we found a correlation between NfL<sub>CSF</sub> and GFAP<sub>CSF</sub>, sTREM2 and CHI3L1 (ρ = 0.4 for GFAP<sub>CSF</sub> and sTREM2, ρ = 0.3 for CHI3L1, <i>p</i> < 0.01 for sTREM2 and CHI3L1 and <0.001 for GFAP<sub>CSF</sub>). CHI3L1 did not correlate with GFAP<sub>CSF</sub> but with sTREM2 (ρ = 0.4, <i>p</i> < 0.01). <b>Discussion:</b> The correlation between the glial activation markers in CSF with the markers of neuroaxonal demise supports the notion of the glial involvement in PPMS. The positive correlation between GFAP<sub>CSF</sub> with disease duration and GFAP<sub>serum</sub> with the clinical severity of the disease may highlight a particular role of the astrocytes in PPMS and mark the potential of GFAP<sub>serum</sub> as a disease severity marker.
Ab initio three-loop calculation of the W-exchange contribution to nonleptonic decays of double charm baryons
2019-03-26

We have made an ab initio three-loop quark model calculation of the -exchange contribution to the nonleptonic two-body decays of the doubly charmed baryons and . The -exchange contributions appear in addition to the factorizable tree graph contributions and are not suppressed in general. We make use of the covariant confined quark model previously developed by us to calculate the tree graph as well as the -exchange contribution. We calculate helicity amplitudes and quantitatively compare the tree graph and -exchange contributions. Finally, we compare the calculated decay widths with those from other theoretical approaches when they are available.
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
2019-03-26

<b>Introduction</b>: Perioperative anesthesia delivers pre-, intra-, and postoperative care to meet the needs of patients undergoing diagnostic and surgical procedures. Major challenges are patients at the extremes of age and individuals with a pre-existing disease burden. Frequent problems are the development of chronic pain and cognitive dysfunction upon surgery. Current perioperative pharmacotherapy utilizes a number of drugs acting at GABA<sub>A</sub> receptors. <b>Area covered</b>: This review evaluates novel formulations and newly designed GABAergic drugs, offering future improvements in perioperative anesthesia, especially for reducing mortality and avoiding cognitive dysfunction and chronic pain as an outcome of surgery. <b>Expert opinion</b>: There are multiple reasons for mounting efforts in the development of novel GABAergic medications. First, requirements in perioperative anesthesia care have substantially changed during the last two decades. In this respect, the dramatic increase in life expectancy is the most important factor. Moreover, research has considerably expanded our knowledge of how drugs in current clinical use act on the molecular level. Almost all ongoing developmental programs choose chemical structures of well-tried agents as a starting point for exploring the properties of structural analogs. This strategy aims to maintain the clinically desired actions of mother compounds while attempting to extinguish adverse side effects.
Studying a Light Sensor with Light: Multiphoton Imaging in the Retina
2019-03-26

Two-photon imaging of light stimulus-evoked neuronal activity has been used to study all neuron classes in the vertebrate retina, from the photoreceptors to the retinal ganglion cells. Clearly, the ability to study retinal circuits down to the level of single synapses or zoomed out at the level of complete populations of neurons, has been a major asset in our understanding of this beautiful circuit. In this chapter, we discuss the possibilities and pitfalls of using an all-optical approach in this highly light-sensitive part of the brain.
Specifying the role of BAK1‐interacting receptor‐like kinase 3 in brassinosteroid signaling
2019-03-26

Abstract Brassinosteroids (BR) are involved in the control of several developmental processes ranging from root elongation to senescence and adaptation to environmental cues. Thus, BR perception and signaling have to be precisely regulated. One regulator is BRI1‐associated kinase 1 (BAK1)‐interacting receptor‐like kinase 3 (BIR3). In the absence of BR, BIR3 forms complexes with BR insensitive 1 (BRI1) and BAK1. However, the biophysical and energetic requirements for complex formation in the absence of the ligand have yet to be determined. Using computational modeling, we simulated the potential complexes between the cytoplasmic domains of BAK1, BRI1 and BIR3. Our calculations and experimental data confirm the interaction of BIR3 with BAK1 and BRI1, with the BAK1 BIR3 interaction clearly favored. Furthermore, we demonstrate that BIR3 and BRI1 share the same interaction site with BAK1. This suggests a competition between BIR3 and BRI1 for binding to BAK1, which results in preferential binding of BIR3 to BAK1 in the absence of the ligand thereby preventing the active participation of BAK1 in BR signaling. Our model also suggests that BAK1 and BRI1 can interact even while BAK1 is in complex with BIR3 at an additional binding site of BAK1 that does not allow active BR signaling.
G‐CSF administration prior to donor lymphocyte apheresis promotes anti‐leukaemic effects in allogeneic HCT patients
2019-03-27

Summary Donor lymphocyte infusion (DLI) is an effective method to establish full donor chimerism or to prevent and treat relapse after allogeneic haematopoietic cell transplantation (allo‐HCT). Usually, DLIs are collected from naïve donors as steady‐state lymphocytes. When donor lymphocytes are collected during stem cell apheresis, donors are pre‐treated with granulocyte colony‐stimulating factor (G‐CSF). However, the impact of G‐CSF stimulation and the resulting composition of DLIs on beneficial anti‐leukaemic responses and survival remain elusive. Therefore, we performed a retrospective analysis to evaluate the role of G‐CSF‐DLIs: 44 patients received either steady‐state DLIs or G‐CSF‐DLIs to prevent and treat relapse or establish full donor chimerism after allo‐HCT. The G‐CSF‐DLI patient cohort showed an improved conversion to full donor chimerism and a lower cumulative incidence of relapse or disease progression without a significantly increased cumulative incidence of graft‐versus‐host disease (GVHD). CD34 + cells, monocytic myeloid‐derived suppressor cells and monocytes as well as donor age and the subsequent occurrence of chronic GVHD were identified as risk factors that significantly improve overall survival after DLI administration. In conclusion, our data suggest that administration of G‐CSF‐DLIs results in graft‐versus‐leukaemia effects without exacerbating GVHD, therefore, improving survival after DLIs.
Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR)
2019-03-27

Abstract Objectives We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients. Methods We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology–oncology departments. Patients colonized with ESBL-EC/KP received a 7 day antimicrobial regimen of oral colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) and fosfomycin (three administrations of 3 g every 72 h), or placebo. Faecal, throat and urine specimens were collected on day 0, 6 ± 2, 11 ± 2, 28 ± 4 and 42 ± 4 after treatment initiation, and the quantitative burden of ESBL-EC/KP, resistance genes and changes in intestinal microbiota were analysed. Clinicaltrials.gov: NCT01931592. Results As the manufacture of colistin powder was suspended worldwide, the study was terminated prematurely. Overall, 29 (18 verum/11 placebo) out of 47 patients were enrolled. The short-term intestinal eradication was marginal at day 6 (verum group 15/18, 83.3% versus placebo 2/11, 18.2%; relative risk 4.58, 95% CI 1.29–16.33; Fisher’s exact test P = 0.001) and not evident at later timepoints. Quantitative analysis showed a significant decrease of intestinal ESBL-EC/KP burden on day 6. Sustained intestinal eradication (day 28 + 42) was not achieved (verum, 38.9% versus placebo, 27.3%; P = 0.299). In the verum group, mcr-1 genes were detected in two faecal samples collected after treatment. Microbiome analysis showed a significant decrease in alpha diversity and a shift in beta diversity. Conclusions In this prematurely terminated study of a 7 day oral antimicrobial eradication regimen, short-term ESBL-EC/KP suppression was marginal, while an altered intestinal microbiota composition was clearly apparent.
Bayesian estimation of explained variance in ANOVA designs
2019-03-27

We propose to use the squared multiple correlation coefficient as an effect size measure for experimental analysis‐of‐variance designs and to use Bayesian methods to estimate its posterior distribution. We provide the expressions for the squared multiple, semipartial, and partial correlation coefficients corresponding to four commonly used analysis‐of‐variance designs and illustrate our contribution with two worked examples.
REMP: A hybrid perturbation theory providing improved electronic wavefunctions and properties
2019-03-27

We propose a new perturbation theoretical approach to the electron correlation energy by choosing the zeroth order Hamiltonian as a linear combination of the corresponding “Retaining the Excitation degree” (RE) and the Møller-Plesset (MP) operators. In order to fulfill Kato cusp conditions, the RE and MP contributions are chosen to sum up to one. 15% ± 5% MP contribution is deduced to be in an optimal range from a fit of the first order REMP wavefunction to near full configuration interaction reference data. For closed shell systems, the same range of MP weights shows best performance for equilibrium bond distances and vibrational wavenumbers of diatomic molecules, the reaction energies in the spin component scaled MP2 fit set, the transition energies of the BHPERI test set, and the parameterized coupled cluster with singles and doubles (pCCSD) fit set. For these properties, REMP outperforms all other tested perturbation theories at second order and shows equal performance as the best coupled pair approaches or pCCSD methods as well as the best double hybrid density functionals. Furthermore, REMP is shown to fulfill all required fundamental boundary conditions of proper wavefunction based quantum chemical methods (unitary invariance and size consistency).
A systematic evaluation of interneuron morphology representations for cell type discrimination
2019-03-27

Abstract Quantitative analysis of neuronal morphologies usually begins with choosing a particular feature representation in order to make individual morphologies amenable to standard statistics tools and machine learning algorithms. Many different feature representations have been suggested in the literature, ranging from density maps to intersection profiles, but they have never been compared side by side. Here we performed a systematic comparison of various representations, measuring how well they were able to capture the difference between known morphological cell types. For our benchmarking effort, we used several curated data sets consisting of mouse retinal bipolar cells and cortical inhibitory neurons. We found that the best performing feature representations were two-dimensional density maps closely followed by morphometric statistics, which both continued to perform well even when neurons were only partially traced. The same representations performed well in an unsupervised setting, implying that they can be suitable for dimensionality reduction or clustering.
Using the past to estimate sensory uncertainty
2019-03-27

Abstract To form the most reliable percept of the environment, the brain needs to represent sensory uncertainty. Current theories of perceptual inference assume that the brain computes sensory uncertainty instantaneously and independently for each stimulus. In a series of psychophysics experiments human observers localized auditory signals that were presented in synchrony with spatially disparate visual signals. Critically, the visual noise changed dynamically over time with or without intermittent jumps. Our results show that observers integrate audiovisual inputs weighted by sensory reliability estimates that combine information from past and current signals as predicted by an optimal Bayesian learner or approximate strategies of exponential discounting Our results challenge classical models of perceptual inference where sensory uncertainty estimates depend only on the current stimulus. They demonstrate that the brain capitalizes on the temporal dynamics of the external world and estimates sensory uncertainty by combining past experiences with new incoming sensory signals.
Comparison of subjective evaluation versus objective algorithm in the interpretation of follow-up FDG-PET/CT scans after radiochemotherapy in head and neck cancer patients
2019-03-27

Abstract Aim Retrospective evaluation of serial FDG-PET/CT scans in head and neck squamous cell cancer (HNSCC) patient’s follow-up after primary radiochemotherapy (RCTx), to assess the diagnostic accuracy of an experienced observer vs. an objective classification compared to standard clinical follow-up examinations. Methods Sixty-nine patients with locally advanced HNSCC were included, who received curative RCTx. Follow-up included serial FDG-PET/CT at the following time intervals t1: ≤ 270 d, t2: 271–540 d, t3: &gt; 540 d after curative RCTx. The likelihood to detect local recurrences, nodal and distant metastases were compared between (i) experienced observer, (ii) an objective classification system by Zundel et al. 25, and (iii) routine clinical follow-up examinations. Results Twenty-two local recurrences, 7 nodal and 17 distant metastases were recorded during the follow-up. The diagnostic accuracy for local recurrence of the experienced observer vs. objective classification was 78 % vs. 77 % for t1, 83 % vs. 79 % for t2 and 100 % vs. 84 % for t3. The classification (ii) and the conventional follow-up (iii) resulted in a relatively high amount of equivocal findings reducing the diagnostic accuracy. Conclusion Evaluation of FDG-PET/CT by an experienced observer in follow-up of HNSCC patients after curative RCTx resulted in the highest diagnostic accuracy in comparison to an objective classification and to routine clinical examination. HNSCC is a malignant tumor with a high likelihood of recurrence, especially in the first two years after curative RCTx. Early detection of recurrence is of high clinical importance, since there are several effective second line therapies that may have curative potential in some patients.
Understanding Factors that Control the Structural (Dis)Assembly of Sulphur-Bridged Bimetallic Sites
2019-03-27

Bimetallic structures of the general type [M2(μ-S)2] are omnipresent in nature, for biological function [M2(μ-S)2] sites interconvert between electronically distinct, but isostructural, forms. Different from structure-function relationships, the current understanding of the mechanism of formation and persistence of [M2(μ-S)2] sites is poorly developed. This work reports on bimetallic model compounds of nickel that interconvert between functional structures [Ni2(μ-S)2]+/2+ and isomeric congeners [2{κ-S–Ni}]2+/+, S = Aryl-S−, in which the nickel ions are geometrically independent. Interconversion of the two sets of structures was studied quantitatively by UV–VIS absorption spectroscopy and cyclic voltammetry. Assembly of the [Ni2(μ-S)2]+ core from [2{κ-S–Ni}]+ is thermodynamically and kinetically highly preferred over the disassembly of [Ni2(μ-S)2]2+ into [2{κ-S–Ni}]2+. Labile Ni-η2/3-bonding to aromatic π-systems of the primary thiophenol ligand is critical for modeling (dis)assembly processes. A phosphine coligand mimics the role of anionic donors present in natural sites that saturate metal coordination. Three parameters have been identified as critical for structure formation and persistence. These are, first, the stereoelectronic properties of the metals ions, second, the steric demand of the coligand, and, third, the properties of the dative bond between nickel and coligand. The energies of transition states connecting functional and precursor forms have been found to depend on these parameters.
Natura 2000 in Bayern – Konflikte, Kompetenzen und Kommunikation
2019-03-27

Natura 2000 is a pan-European network of protected areas that contributes to nature conservation and conservation of biodiversity. The establishment of the network and the management of the areas did not always run their course without conflict. How about Natura 2000, specifically in the Free State of Bavaria? A media analysis and surveys of residents and stakeholders show us the challenges and potentials for acceptance, which can be promoted through, among other things, transparent communication (translated by the editors).
The Sleep-Immune Crosstalk in Health and Disease
2019-03-28

Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various immune parameters, is associated with a reduced infection risk, and can improve infection outcome and vaccination responses. The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade inflammation and is associated with various diseases that have an inflammatory component, like diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future research.
Dual energy computed tomography virtual monoenergetic imaging: technique and clinical applications
2019-03-28

Dual energy CT (DECT) has evolved into a commonly applied imaging technique in clinical routine due to its unique post-processing opportunities for improved evaluation of all body areas. Reconstruction of virtual monoenergetic imaging (VMI) series has shown beneficial effects for both non-contrast and contrast-enhanced DECT due to the flexibility to calculate low-keV VMI reconstructions to increase contrast and iodine attenuation, or to compute high-keV VMI reconstructions to reduce beam-hardening artefacts. The goal of this review article is to explain the technical background of VMI and noise-optimized VMI+ algorithms and to give an overview of useful clinical applications of the VMI technique in DECT of various body regions.