julilili42/papers huggingface dataset:
Natural Diterpenoid Oridonin Ameliorates Experimental Autoimmune Neuritis by Promoting Anti-inflammatory Macrophages Through Blocking Notch Pathway
2019-04-02

The diterpenoid compound, Oridonin, extracted from the Chinese herb, <i>Rabdosia rubescens</i>, possesses multiple biological activities and properties. Oridonin exhibited efficient anti-inflammatory activity by inducing a switch in macrophage polarization to the anti-inflammatory phenotype through inhibition of the Notch pathway in our <i>in vitro</i> study; therefore, its potential therapeutic effects were further investigated in the animal model of human Guillain-Barré syndrome (GBS) and other polyneuropathies - experimental autoimmune neuritis (EAN). Either preventive or therapeutic treatments with Oridonin greatly attenuated disease peak severity, suppressed paraparesis, shortened disease duration, and even delayed EAN onset. Progression of neuropathic pain, demyelination, inflammatory cellular accumulations, and inflammatory cytokines in peripheral nerves were significantly attenuated. Meanwhile, accumulation of immune cells in the spinal roots and microglial activation in the lumbar spinal cord were also reduced. Interestingly, Oridonin treatment significantly increased the proportion of anti-inflammatory macrophages and made them locally dominant among all infiltrated macrophages in the peripheral nerves. The down-regulation of local Notch pathway proteins, together with our <i>in vitro</i> results indicated their possible involvement. Taken together, our results demonstrated that Oridonin effectively suppressed EAN by attenuating local inflammatory reaction and increasing the proportion of immune regulating macrophages in the peripheral nerves, possibly through blockage of the Notch pathway, which suggests Oridonin as a potential therapeutic candidate for human GBS and neuropathies.
Cryoballoon ablation for persistent atrial fibrillation in patients without left atrial fibrosis
2019-04-02

Abstract Introduction The role of cryoballoon (CB) pulmonary vein isolation (PVI) for patients with persistent atrial fibrillation (AF) is controversial, since long‐term success can be poor. We performed left atrial voltage mapping before CB PVI and determined AF‐free survival depending on the extent of low‐voltage areas (LVAs). Methods and Results We consecutively enrolled 60 patients with persistent AF (average age, 60.6 ± 12.9 years; CHA 2 DS 2 VASc score, 2.3 ± 1.6; and left atrial size 46.0 ± 5.2 mm) who were planned for CB PVI. Before ablation, we performed left atrial voltage mapping (Abbott EnSite Precision or Velocity). LVAs were defined if local bipolar signal amplitudes were less than 0.5 mV during sinus rhythm. Thirty‐seven patients did not show significant LVAs (&lt;10%), while 12 patients had LVAs between 10% and 30% and 11 patients showed substantial LVAs greater than 30% of the left atrial area. CB PVI could be successfully performed in all patients. A 7‐day holter monitoring was obtained 3, 6, and 12 months after ablation. After a 12‐month follow‐up time, 83.8% of patients without LVAs (&lt;10%) were free of atrial fibrillation, while 50.0% of patients with 10% to 30% LVAs and 9.1% of patients with LVAs more than 30% had stable sinus rhythm. The degree of atrial fibrosis correlated with the risk of AF recurrence. Conclusion In patients with persistent AF undergoing CB PVI, the extent of left atrial LVAs predicts an AF‐free survival. CB PVI seems to be a highly effective treatment for patients with persistent AF without atrial fibrosis.
A global approach to describe retinal defocus patterns
2019-04-02

The popularity of myopia treatments based on the peripheral defocus theory has risen. So far, little evidence has emerged around the questions which of these treatments are effective and why. In order to establish a framework that enables clinicians and researchers to acknowledge the possible interactions of different defocus patterns across the retina, different peripheral refractive errors (PRX) of subjects and different designs of optical treatments were evaluated. Dioptric defocus patterns on the retinal level have been obtained by merging the matrices of dioptric defocus maps of the visual field of different scenarios with individual peripheral refractive errors and different optical designs of multifocal contact lenses. The newly obtained matrices were statistically compared using a non-parametric test with familywise error algorithms and multi-comparison tests. Results show that asymmetric peripheral refractive error profiles (temporal or nasal positively skewed) appear to be less prone to be changed by the defocus imposition of multifocal contact lenses than those presenting symmetric patterns (relative peripheral myopia or hyperopia).
Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients
2019-04-02

Influenza has been a long-running health problem and novel antiviral drugs are urgently needed. In pre-clinical studies, we demonstrated broad antiviral activity of D, L-lysine-acetylsalicylate glycine (LASAG) against influenza virus (IV) in cell culture and protection against lethal challenge in mice. LASAG is a compound with a new antiviral mode of action. It inhibits the NF-κB signal transduction module that is essential for IV replication. Our goal was to determine whether aerosolized LASAG would also show a therapeutic benefit in hospitalized patients suffering from severe influenza. The primary endpoint was time to alleviation of clinical influenza symptoms. The primary analysis was based on the modified intention-to-treat (MITT) population. This included all patients with confirmed influenza virus infection who received at least one treatment. The per protocol (PP) analysis set included all subjects from the MITT population who underwent at least 13 inhalations. In the MITT group, 48 (41.7%) participants (29 LASAG; 19 placebo) had severe influenza. The mean time to symptom alleviation was 56.2 h in the placebo group and 43.0 h in the LASAG group. The PP set consisted of 41 patients (24 LASAG; 17 placebo). The mean time to symptom alleviation in the LASAG group (38.3 h; <i>P = </i>0.0365) was lower than that in the placebo group (56.2 h). In conclusion, LASAG improved the time to alleviation of influenza symptoms in hospitalized patients. The present phase II proof-of-concept (PoC) study demonstrates that targeting an intra-cellular signaling pathway using aerosolized LASAG improves the time to symptom alleviation compared to standard treatment.
FAHN/SPG35: a narrow phenotypic spectrum across disease classifications
2019-04-03

The endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the 'WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers.
Early EEG correlates of word frequency and contextual predictability in reading
2019-04-03

Previous research into written language comprehension has been equivocal as to whether word frequency and contextual predictability effects share an early time course of processing. Target word frequency (low, high) and its predictability from prior context (low, high) were manipulated across two-sentence passages. Context sentences were presented in full, followed by word-by-word presentation (300 ms SOA) of target sentences. ERPs were analysed across left-to-right and anterior-to-posterior regions of interest within intervals from 50 to 550 ms post-stimulus. The onset of significant predictability effects (50–80 ms) preceded that of frequency (P1, 80–120 ms), while both main effects were generally sustained through the N400 (350–550 ms). Critically, the frequency-predictability interaction became significant in the P1 and was sustained through the N400, although the specific configuration of effects differed across components. The pattern of findings supports an early, chronometric locus of contextual predictability in recognising words during reading.
More than access: MOOCs and changes in Chinese higher education
2019-04-03

This paper presents an analysis of the conceptualization of massive open online courses (MOOCs) by major influencers in Chinese higher education. Using critical discourse analysis, predominantly from university resources, a map of the discursive construction of MOOCs is presented and interpreted. The centralized orientation of decision making in Chinese higher education is reflected in how MOOCs have been introduced, envisioned, and utilized in China. With the increase of Chinese MOOCs, elite universities are able to capitalize on their comparative advantages, which may be counter to the true intent of MOOCs, which is to raise teaching standards across sectors. This paper serves to illuminate how MOOCs may reinforce the status of elite universities, thereby having the opposite effect to their real intention of democratizing higher education for the masses. The strategy of using MOOCs to improve teaching quality and augment the worldwide reputation of Chinese institutions is central to China's reinvigorated focus on higher education, which counters the widely held perception, and intention, that MOOCs are vehicles for widening access.
Attitudes towards interprofessional collaboration in young healthcare professionals
2019-04-03

Successful interprofessional (IP) collaboration has great potential to improve healthcare delivery. The aim of this study was to evaluate and compare the attitudes towards IP collaboration in young health professionals who had not been exposed to IP learning activities. About one year after graduation from their vocational training, 387 graduates from various healthcare professions [Nurses (nursing and pediatric nursing), Therapists (physical therapy, speech and language therapy), Diagnostic professionals (biomedical science and radiography)], were invited to participate in an online survey. In total, data from 129 graduates were considered for data analyses. The University of Western England Interprofessional Questionnaire was administered to self-assess graduates individual attitude towards IP collaboration and learning using four scales. All health professional groups showed an overall positive attitude in communication and teamwork as well as in IP relationships and expressed a neutral attitude in IP learning and IP interactions. There were no significant differences in the overall scores between the health professional groups. In total, the three health professional groups showed similar attitudes towards IP collaboration and learning, despite their different scope of work. Results may help to design IP learning activities and this may contribute to better communication with and to know more about each other.
Gallium Methylene
2019-04-03

Abstract Despite the eminent importance of metal alkylidene species for organic synthesis and industrial catalytic processes, molecular homoleptic metal methylene compounds [M(CH 2 ) n ] as the simplest representatives, have remained elusive. Reports on this topic date back to 1955 when polymeric [Li 2 (CH 2 )] n and [Mg(CH 2 )] n were accessed by pyrolysis of methyllithium and dimethylmagnesium, respectively. However, the insoluble salt‐like composition of these compounds has impeded their application as valuable reagents. We report that rare‐earth metallocene methyl complexes [(C 5 Me 5 ) 2 Ln{(μ‐Me) 2 GaMe 2 }] (Ln=Lu, Y) trigger the formation of homoleptic gallium methylene [Ga 8 (μ‐CH 2 ) 12 ] from trimethylgallium [GaMe 3 ] (Me=methyl) via a cascade C−H bond activation involving the dodecametallic clusters [(C 5 Me 5 ) 6 Ln 3 (μ 3 ‐CH 2 ) 6 Ga 9 (μ‐CH 2 ) 9 ] as crucial intermediates. Such gallium methylene compounds feature a reversible [Ga 8 (μ‐CH 2 ) 12 ]/[Ga 6 (μ‐CH 2 ) 9 ] oligomer switch in donor solvents and act as Schrock‐type methylene‐transfer reagents.
In vitro neuronal network activity as a new functional diagnostic system to detect effects of Cerebrospinal fluid from autoimmune encephalitis patients
2019-04-03

Abstract The intent of this study was to investigate if cerebrospinal fluid (CSF) from autoimmune encephalitis (AE) patients regulates in vitro neuronal network activity differentially to healthy human control CSF (hCSF). To this end, electrophysiological effects of CSF from AE patients or hCSF were measured by in vitro neuronal network activity (ivNNA) recorded with microelectrode arrays (MEA). CSF from patients with either N-methyl-D-aspartate-receptor-antibody (pCSF NMDAR , n = 7) or Leucine-rich-glioma-inactivated-1-Ab (pCSF LGI1 , n = 6) associated AE suppressed global spiking activity of neuronal networks by a factor of 2.17 ( p &lt; 0.05) or 2.42 ( p &lt; 0.05) compared to hCSF. The former also suppressed synchronous network bursting by a factor of 1.93 ( p &lt; 0.05) in comparison to hCSF (n = 13). As a functional diagnostic test, this parameter reached a sensitivity of 86% for NMDAR-Ab- and 100% for LGI1-Ab-associated AE vs. hCSF at a specificity of 85%. To explore if modulation at the NMDAR influences effects of hCSF or pathological CSF, we applied the NMDAR-antagonist 2-Amino-5-phosphono-pentanoic acid (AP5). In CSF from NMDAR-Ab-associated AE patients, spike rate reduction by AP5 was more than 2-fold larger than in hCSF ( p &lt; 0.05), and network burst rate reduction more than 18-fold ( p &lt; 0.01). Recording ivNNA might help discriminating between functional effects of CSF from AE patients and hCSF, and thus could be used as a functional diagnostic test in AE. The pronounced suppression of ivNNA by CSF from NMDAR-Ab-associated AE patients and simultaneous antagonism at the NMDAR by AP5, particularly in burst activity, compared to hCSF plus AP5, confirms that the former contains additional ivNNA-suppressing factors.
On the semantics of non-words and their lexical category
2019-04-03

Using computational simulations, this work demonstrates that it is possible to learn a systematic relation between words’ sound and their meanings. The sound-meaning relation was learned from a corpus of phonologically transcribed child-directed speech by using the Linear Discriminative Learning (LDL) framework (Baayen, Chuang, Shafaei-Bajestan, &amp;amp; Blevins, 2019), which implements linear mappings between words’ form vectors and semantic vectors. Presented with the form vectors of 16 non-words, taken from a study on word learning (Fitneva, Christiansen, &amp;amp; Monaghan, 2009), the network generated the estimated semantic vectors of the non-words. As half of these non-words were created to phonologically resemble English nouns and the other half were phonologically similar to English verbs, we assessed whether the estimated semantic vectors for these non-words reflect this word category difference. In seven different simulations, Linear Discriminant Analysis (LDA) successfully discriminated between noun-like non-words and verb-like non-words, based on their semantic relation to the words in the lexicon. Furthermore, how well LDA categorized a non-word correlated well with a phonological typicality measure (i.e., the degree of its form being noun-like or verb-like) and with children’s performance in an entity/action discrimination task. On the one hand, the results suggest that children can infer the implicit meaning of a word directly from its sound. On the other hand, this study shows that non-words do land in semantic space, such that children can capitalize on their semantic relations with other elements in the lexicon to decide whether a non-word is more likely to denote an entity or an action.
Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection
2019-04-04

Background Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5–9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. Methods Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0–6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63–2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). Conclusions Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
The Role of Pre-existing Cross-Reactive Central Memory CD4 T-Cells in Vaccination With Previously Unseen Influenza Strains
2019-04-04

Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains-a process called original antigenic sin. The role of this pre-existing cellular immunity in this process is, despite some hints from animal models, not clear. Here, we analyzed cellular and humoral immunity in healthy individuals before and after vaccination with seasonal influenza vaccine. Based on influenza-specific hemagglutination inhibiting (HI) titers, vaccinees were grouped into HI-negative and -positive cohorts followed by in-depth cytometric and TCR repertoire analysis. Both serological groups revealed cross-reactive T-cell memory to the vaccine strains at baseline that gave rise to the majority of vaccine-specific T-cells post vaccination. On the contrary, very limited number of vaccine-specific T-cell clones was recruited from the naive pool. Furthermore, baseline quantity of vaccine-specific central memory helper T-cells and clonotype richness of this population directly correlated with the vaccination efficacy. Our findings suggest that the deliberate recruitment of pre-existing cross-reactive cellular memory might help to improve vaccination outcome.
1,3‐Diene Polymerization Promoted by Half‐Sandwich Rare‐Earth‐Metal Dimethyl Complexes: Active Species Clustering and Cationization/Deactivation Processes
2019-04-04

Abstract When activated with fluorinated borate cocatalysts the trimetallic complexes [Cp*LnMe 2 ] 3 (Ln=Y, Lu; Cp*=C 5 Me 5 ) promote efficiently the formation of high‐ cis polybutadiene. Respective polyisoprenes instead bear much less pronounced microstructures, but reveal crosslinked products at lower polymerization temperatures. Varying the amount of cocatalyst, the emerging active species were examined by NMR spectroscopic techniques (incl. 1 H DOSY). The occurrence of donor‐solvent and thermally induced degradation products of the highly reactive precatalyst [Cp*YMe 2 ] 3 and derived catalyst species was revealed by the elucidation of methylidene clusters [Cp* 3 Y 3 Me 4 (CH 2 )(thf) 2 ] and [Cp* 6 Y 6 Me 4 (CH 2 ) 4 ], as well as [(Cp*Y) 2 Me 2 (N(Me) 2 (C 6 H 4 )] n [B(C 6 F 5 ) 4 ] n , implying a multimetallic active species.
Zoster Vaccination in Older Adults: Efficacy and Public Health Implications
2019-04-04

Abstract Shingles and its most common disabling complication, post-herpetic neuralgia, represent a serious public health challenge in the older population. The decline in the T-cell-mediated immune response to varicella zoster virus after age 50 is clearly associated with increased risk of viral reactivation, causing an acutely painful zoster rash, which may have a severe prodrome of dermatomal pain and persist as seriously debilitating post-herpetic neuralgia well beyond the resolution of the rash. However, new vaccines and adjuvants are being developed and trialed and are now more effective in preventing shingles and the sequelae of post-herpetic neuralgia. Those vaccines that possess the ability to enhance antigen presentation and reverse memory T-cell exhaustion, as well as diminish the immune suppressive effects of regulatory T cells, are most likely to be effective in older adults.
Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?
2019-04-05

ABSTRACT Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non‐synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system, which mediates both synaptic and non‐synaptic signaling via ionotropic and metabotropic glutamate receptors. Intriguingly, neurons establish glutamatergic synapses also with oligodendrocyte precursor cells (NG2 + ‐glia). Moreover, neuronal activity and glutamate receptors play an important role in the development and functionality of oligodendrocytes and their precursors in vivo. Yet, molecular characteristics and functional significance of neuron–glia synapses remain poorly understood, and it is unclear how glutamate receptors mediate the effects of neuronal activity on the oligodendrocyte lineage cells. In this review, we discuss what is known with regard to synaptic and non‐synaptic glutamatergic signaling between neurons and oligodendrocyte lineage cells, what can be suggested based on the current state of knowledge, and what is fully unknown and requires new research.