Miracle-dz/UniFAR-FTUs huggingface dataset:
A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis

Objective To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis. Design Pragmatic two arm cluster randomised controlled trial. Setting Hospitals within the United Kingdom. Participants Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis. Intervention An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components. Outcomes The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation. Results 13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%). Conclusion The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and education. Trial registration Controlled Trials: ISRCTN06886935.
Cross-linking the B7 Family Molecule B7-DC Directly Activates Immune Functions of Dendritic Cells

B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation. In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex–peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine. Furthermore, ex vivo treatment of DCs or systemic treatment of mice with sHIgM12 increases the number of transplanted DCs that reach draining lymph nodes and increases the ability of lymph node APCs to activate naive T cells. Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site. These findings implicate B7-DC expressed on DCs in bidirectional communication. In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.
Nervous system characterization during the development of a basal echinoderm, the feather star Antedon mediterranea

Neural development of echinoderms has always been difficult to interpret, as larval neurons degenerate at metamorphosis and a tripartite nervous system differentiates in the adult. Despite their key phylogenetic position as basal echinoderms, crinoids have been scarcely studied in developmental research. However, since they are the only extant echinoderms retaining the ancestral body plan of the group, crinoids are extremely valuable models to clarify neural evolution in deuterostomes. Antedon mediterranea is a feather star, endemic to the Mediterranean Sea. Its development includes a swimming lecithotrophic larva, the doliolaria, with basiepithelial nerve plexus, and a sessile filter‐feeding juvenile, the pentacrinoid, whose nervous system has never been described in detail. Thus, we characterized the nervous system of both these developmental stages by means of immunohistochemistry and, for the first time, in situ hybridization techniques. The results confirmed previous descriptions of doliolaria morphology and revealed that the larval apical organ contains two bilateral clusters of serotonergic cells while GABAergic neurons are localized under the adhesive pit. This suggested that different larval activities (e.g., attachment and metamorphosis) are under the control of different neural populations. In pentacrinoids, the analysis showed the presence of a cholinergic entoneural system while the ectoneural plexus appeared more composite, displaying different neural populations. The expression of three neural‐related microRNAs was described for the first time, suggesting that these are evolutionarily conserved also in basal echinoderms. Overall, our results set the stage for future investigations that will reveal new information on echinoderm evo‐devo neurobiology.
Estimated bioconcentration factors (BCFs) for the C4 through C8 perfluorinated alkylsulfonic acid (PFSA) and alkylcarboxylic acid (PFCA) congeners

Bioconcentration factors (BCFs) were estimated for all congeners in each of the C4 through C8 homologue groups for perfluorinated alkylsulfonic acids (PFSAs) and alkylcarboxylic acids (PFCAs). Predictive equations were developed between molecular areas and volumes using optimized gas-phase geometries from the AM1 and PM3 semiempirical computational basis sets and previously determined BCFs for representative straight-chain members of each contaminant class. Molecular area approaches for estimating PFSA and PFCA BCFs resulted in more variability both between and within homologue groups than the use of molecular volumes as proxies for hydrophobicity of the perfluoroalkyl chain. An increasing degree of perfluoroalkyl chain branching within each homologue group reduces the estimated BCF, suggesting that the more linear PFSA and PFCA congeners will display the highest BCFs in aquatic organisms.
Treatment of actinic keratosis through inhibition of cyclooxygenase‐2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5%

Cyclooxygenase‐2 (COX‐2) and its metabolic product prostaglandin E2 (PGE2) are induced in response to growth factors, inflammatory cytokines, tumor promoters, activated oncogenes, and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX‐2/PGE2 pathway in tumorigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) — common dysplastic lesions of the skin associated with UV radiation overexposure — considered as part of a continuum with skin cancer. Non‐steroidal anti‐inflammatory drugs (NSAIDs) exert their anti‐inflammatory, analgesic, and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemopreventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.
Dealing with flawed items in examinations: Using the compensation of disadvantage as used in German state examinations in items with partial credit scoring

In the written part of German state exams, multiple choice questions which inherit a flaw are not always excluded but taken into consideration when awarding a grade to any individual candidate, if this is advantageous to the candidate. This process of elimination and compensation of disadvantage in flawed questions, as applied by the Institut für medizinische und pharmazeutische Prüfungsfragen (IMPP), can lead to different items being taken into consideration in the grading in individual cases and to the application of different pass and grade boundaries in individual cases. This procedure is applied here to examinations containing items with partial credit scoring. A simple numerical rule can be applied which can be used to decide whether a flawed item has be taken into account in the grading procedure in order to achieve a pass or a particular grade for a candidate. This rule – as in the state examinations – must take account of the individual number of scores achieved in the flawed item and, if the relative pass threshold ("automatic adjustment clause") is applied, the average score achieved in the item by all candidates. In addition, however, it also includes the grade boundaries.
Evaluating the Effectiveness and Safety of the Electroencephalogram-Based Brain-Machine Interface Rehabilitation System for Patients With Severe Hemiparetic Stroke: Protocol for a Randomized Controlled Trial (BEST-BRAIN Trial)

Background We developed a brain-machine interface (BMI) system for poststroke patients with severe hemiplegia to detect event-related desynchronization (ERD) on scalp electroencephalogram (EEG) and to operate a motor-driven hand orthosis combined with neuromuscular electrical stimulation. ERD arises when the excitability of the ipsi-lesional sensorimotor cortex increases. Objective The aim of this study was to evaluate our hypothesis that motor training using this BMI system could improve severe hemiparesis that is resistant to improvement by conventional rehabilitation. We, therefore, planned and implemented a randomized controlled clinical trial (RCT) to evaluate the effectiveness and safety of intensive rehabilitation using the BMI system. Methods We conducted a single blind, multicenter RCT and recruited chronic poststroke patients with severe hemiparesis more than 90 days after onset (N=40). Participants were randomly allocated to the BMI group (n=20) or the control group (n=20). Patients in the BMI group repeated 10-second motor attempts to operate EEG-BMI 40 min every day followed by 40 min of conventional occupational therapy. The interventions were repeated 10 times in 2 weeks. Control participants performed a simple motor imagery without servo-action of the orthosis, and electrostimulation was given for 10 seconds for 40 min, similar to the BMI intervention. Overall, 40 min of conventional occupational therapy was also given every day after the control intervention, which was also repeated 10 times in 2 weeks. Motor functions and electrophysiological phenotypes of the paretic hands were characterized before (baseline), immediately after (post), and 4 weeks after (follow-up) the intervention. Improvement in the upper extremity score of the Fugl-Meyer assessment between baseline and follow-up was the main outcome of this study. Results Recruitment started in March 2017 and ended in July 2018. This trial is currently in the data correcting phase. This RCT is expected to be completed by October 31, 2018. Conclusions No widely accepted intervention has been established to improve finger function of chronic poststroke patients with severe hemiparesis. The results of this study will provide clinical data for regulatory approval and novel, important understanding of the role of sensory-motor feedback based on BMI to induce neural plasticity and motor recovery. Trial Registration UMIN Clinical Trials Registry UMIN000026372; https://upload.umin. ac.jp/cgi-open-bin/ctr_e/ctr_view. cgi? recptno=R000030299 (Archived by WebCite at http://www.webcitation.org/743zBJj3D) International Registered Report Identifier (IRRID) DERR1-10.2196/12339
High Baseline Vitamin C Levels Do Not Prevent a Positive Outcome of a Lifestyle Intervention

Reactive oxygen species (ROS) generated by oxidative stress induced by physical activity are important mediators responsible for adaptive processes in skeletal muscle (1). ROS induce the production of myokines (muscle-derived cytokines) that mediate systemic metabolic effects (1) and induce an increase in the expression of genes involved in mitochondrial biogenesis (2). Therefore, the oxidative stress induced by exercise may play an important role in the cellular responses occurring within skeletal muscle after training. Supplementation with the antioxidant vitamin C pharmacologically inhibits positive effects of exercise on the parameters of glucose metabolism (3). However, these data conflict with the finding that high levels of vitamin C also reduce the risk of type 2 diabetes (4). Therefore, we …
Early Weight Gain in Infants With Cleft Lip and Palate Treated With and Without Nasoalveolar Molding: A Retrospective Study

Objective: To assess weight gain of infants with cleft lip and/or palate (CL ± P) treated with nasoalveolar molding (NAM). Design: Retrospective, case–control chart review. Setting: Doernbecher Children’s Hospital, Oregon Health & Science University, Portland, Oregon. Patients, Participants: Infants with nonsyndromic CL ± P and noncleft controls. Interventions: Prior to primary lip surgery, NAM was either included (+NAM) or not included (−NAM) in the cleft treatment protocol. Main Outcome Measure(s): Weight gain and percentage weight gain relative to initial weight were compared among +NAM, −NAM, and control groups from birth to 7 months and from birth to 36 months. Results: Comparing +NAM and −NAM groups, no significant difference in weight or percentage weight gain was found in either time window. Compared to controls, from birth to 7 months, both CL ± P groups weighed less (P < .001), while percentage weight gain was greater for the +NAM (P < .001) and did not differ for −NAM. From birth to 36 months relative to controls, weight for +NAM showed no significant difference and −NAM weighed less (P < .01), while percentage weight gain was greater for both CL ± P groups (P < .001). Conclusions: Comparisons of CL ± P infants treated with and without NAM showed that with the NAM appliance, despite its added complexity, there was no adverse impact on weight gain. Comparisons to noncleft, control infants suggests that NAM treatment may have a beneficial impact on weight gain.
The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia

Purpose: Ketamine is widely used in pediatric anesthesia. Recent studies have demonstrated that excessive application of ketamine leads to cortical neurodegeneration in neonatal brains. The present study aims to characterize the functional role of neuronal microRNA, miR-124, in regulating ketamine-induced neurotoxicity in mouse hippocampus. Methods: Real-time quantitative PCR (RT-PCR) was used to examine the effect of high-dosage ketamine on the expression of miR-124 in murine hippocampus in vitro. Downregulation of hippocampal miR-124 was achieved by lentivirual transfection, and its effects on protecting ketamine-induced hippocampal neurodegeneration were examined both in vitro and in vivo. Results: Hippocampal miR-124 was upregulated by ketamine treatment. Knocking down miR-124 in vitro reduced ketamine-induced apoptosis in hippocampal CA1 neurons, upregulated AMPA receptors phosphorylation and activated the protein kinase C/extracellular signal-regulated kinases (PKC/ERK) pathway. In the in vivo Morris water maze test, following ketamine-induced hippocampal neurodegeneration, mice subjected to hippocampal miR-124 inhibition showed improved memory performance. Conclusions: Our study demonstrated that miR-124 played an important role in regulating ketamine-induced hippocampal neurodegeneration. Inhibiting miR-124 may provide a molecular target to improve memory performance in both human and animals suffering from overanesthetizing-related neurotoxicity.
Special collection: Pesticide Exposure in Non-Honey Bees Pesticide Exposure Assessment Paradigm for Stingless Bees

Although the importance of bees as the pollinators responsible for maintaining gene flow for many native and cultivated plants in ecosystems around the world is recognized, much of their biodiversity and behavior remains to be discovered. Stingless bees are considered key pollinators for several plant species in tropical and subtropical ecosystems and they also provide pollination services for economically important agricultural crops. Many countries are using the honey bee (Apis mellifera Linnaeus, 1758, Hymenoptera: Apidae) as a surrogate to evaluate the risk of pesticides to all species of bees. However, there is uncertainty regarding the extent to which honey bees can serve as surrogates for non-Apis bee species in the risk assessment for pesticides. This paper provides a short overview of the life history traits relevant in risk assessment of stingless bees. It summarizes what is known about stingless bee exposure to pesticides compared to that of honey bees and presents criteria for potential candidate species from Brazil for use in pesticide risk assessment in tropical environments. This paper also identifies gaps in knowledge of bee biology and pesticide exposure routes not covered by the current honey bee exposure assessment paradigm. Based on these gaps, research is needed on life history traits, estimates of nectar and pollen consumption, mud, resin, and water collection and available protocols to adequately assess toxic effects of pesticides to stingless bees. This review is part of a series of papers on the risk of exposure of non-Apis bees to pesticides.
Oncolytic adenovirus: A tool for cancer therapy in combination with other therapeutic approaches

Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue‐ or tumor‐specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach.
Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: A longitudinal β‐CIT SPECT study

Atypical parkinsonian syndromes (APS) such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration are characterized by poor response to antiparkinsonian medication and rapid clinical deterioration. We used SPECT and [123I]β‐CIT as a label of dopamine transporters to study the progression of presynaptic dopaminergic degeneration in Parkinson's disease (PD) and APS. Twenty‐four PD patients with short disease duration (2.4 ± 1.5 years), 12 PD patients with long disease duration (9.2 ± 2.6 years), 10 patients with APS (disease duration 2.1 ± 1.5 years), and nine patients with essential tremor (ET) underwent sequential [123I]β‐CIT SPECT imaging with an interval of 25.5 ± 10.3 (13–63) months. The age‐related decline of striatal β‐CIT binding was studied cross‐sectionally in 30 healthy subjects. The ratio of striatum/cerebellum −1 at 20 hours after tracer injection, reflecting specific‐to‐nondisplaceable binding, was used as the primary SPECT outcome measure. At scan 1, striatal β‐CIT binding was reduced in PD patients with short disease duration (−42% compared with age‐corrected normal values) and long disease duration (−51%), and APS (−36%), but normal in ET. During the observation period striatal β‐CIT binding significantly declined in patients with APS (14.9% per year) and short duration PD (7.1% per year), whereas PD patients with long disease duration and patients with ET showed no significant change of striatal β‐CIT binding between scans 1 and 2. The relative annual reduction from age‐corrected normal values at the time of scan 1 was significantly higher in patients with APS than in PD patients with short disease duration (9.6 vs. 4.3%, P = 0.004). These results demonstrate a rapid decline of striatal β‐CIT binding in patients with atypical parkinsonian syndromes, exceeding the reduction in PD. The dopaminergic degeneration in PD appears to slow down during the course of the disease. SPECT with [123I]β‐CIT is a sensitive marker of disease progression in parkinsonian disorders. © 2001 Movement Disorder Society.
Assessing the bipotency of in vitro-derived neuromesodermal progenitors

Retrospective clonal analysis in the mouse has demonstrated that the posterior spinal cord neurectoderm and paraxial mesoderm share a common bipotent progenitor. These neuromesodermal progenitors (NMPs) are the source of new axial structures during embryonic rostrocaudal axis elongation and are marked by the simultaneous co-expression of the transcription factors T(Brachyury) (T(Bra)) and Sox2. NMP-like cells have recently been derived from pluripotent stem cells in vitro following combined stimulation of Wnt and fibroblast growth factor (FGF) signaling. Under these conditions the majority of cultures consist of T(Bra)/Sox2 co-expressing cells after 48-72 hours of differentiation. Although the capacity of these cells to generate posterior neural and paraxial mesoderm derivatives has been demonstrated at the population level, it is unknown whether a single in vitro-derived NMP can give rise to both neural and mesodermal cells. Here we demonstrate that T(Bra) positive cells obtained from mouse epiblast stem cells (EpiSCs) after culture in NMP-inducing conditions can generate both neural and mesodermal clones. This finding suggests that, similar to their embryonic counterparts, in vitro-derived NMPs are truly bipotent and can thus be exploited as a model for studying the molecular basis of developmental cell fate decisions.
Neuropeptides SP and CGRP Underlie the Electrical Properties of Acupoints

Electrical skin measurements at acupuncture points (acupoints) have been utilized as a diagnostic and therapeutic aid for more than 50 years. Although acupoints are described as having distinct electrical properties, such as high conductance and low impedance, the underlying mechanisms are currently unknown. The present study investigated in a rat model of hypertension whether the high conductance at acupoints is a result of the release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) during neurogenic inflammation in the referred pain area. When plasma extravasation from neurogenic inflammation was examined by exploring the leakage of intravenously injected Evans blue dye (EBD) to the skin, extravasated EBD was found most frequently in acupoints on the wrist. The increased conductance and temperature at these acupoints occurred during the development of hypertension. The increase in conductance and plasma extravasation at acupoints in hypertensive rats was ablated by cutting median and ulnar nerves, blocking small diameter afferent fibers with resiniferatoxin (RTX) injection into median and ulnar nerves, or antagonizing SP or CGRP receptors in acupoints. In turn, intradermal injection of SP or CGRP resulted in increased conductance and plasma extravasation in naïve rats. Elevated levels of SP and CGRP were found in the acupoints of hypertensive rats. These findings suggest that the high conductance at acupoints is due to vascular leakage following local release of SP and CGRP during neurogenic inflammation.