bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma
Authors: Hesse L. , Brouwer U. , Petersen A. H. , Gras R. , Bosman L. , Brimnes J. , Oude Elberink J. N. G. , van Oosterhout A. J. M. , Nawijn M. C. 
Published: May 2018

SummaryBackgroundBoth subcutaneous and sublingual allergen immunotherapy (SCIT and SLIT) have been shown to effectively suppress allergic manifestations upon allergen exposure, providing long‐term relief from symptoms in allergic disorders including allergic asthma. Clinical studies directly comparing SCIT and SLIT report a different kinetics and magnitude of immunological changes induced during treatment. Comparative studies into the mechanisms underlying immune suppression in SCIT and SLIT are lacking.ObjectiveWe aimed to establish an experimental model for grass pollen (GP) SCIT and SLIT that would allow a head‐to‐head comparison of the two treatments.MethodsBALB/c mice were sensitized with GP extract, followed by SCIT and SLIT treatments with various GP dosages. Subsequently, we challenged mice with GP and measured airway responsiveness (AHR), GP‐specific immunoglobulins, ear swelling tests (EST), eosinophilic inflammation in bronchoalveolar lavage fluid (BALF), and T cell cytokine release after restimulation of lung cells (IL‐5, IL‐10, and IL‐13).ResultsWe find that SLIT treatment was able to suppress allergen‐induced AHR, while allergic inflammation was not effectively suppressed even at the highest GP dose in this model. In contrast, SCIT treatment induced higher levels of GP‐specific IgG1, while SLIT was superior in inducing a GP‐specific IgG2a response, which was associated with increased Th1 activity in lung tissue after SLIT, but not SCIT treatment. Interestingly, SCIT was able to suppress Th2‐type cytokine production in lung cell suspensions, while SLIT failed to do so.Conclusions and clinical relevanceIn conclusion, GP‐SCIT suppresses Th2 inflammation and induced neutralizing antibodies, while GP‐SLIT suppresses the clinically relevant lung function parameters in an asthma mouse model, indicating that the two application routes depend on partially divergent mechanisms of tolerance induction. Interestingly, these data mirror observations in clinical studies, underscoring the translational value of these mouse models.
Experimental approach in research of Guillain–Barré syndrome: A range of pathogeneses mediated by molecular mimicry
Authors: Koga Michiaki 
Published: May 2018

AbstractMolecular mimicry between microbial antigens and host tissue is a highly attractive explanation for the pathogenesis of many autoimmune diseases. Among them, Guillain–Barré syndrome (GBS) is an excellent model to show the causal pathogenesis of molecular mimicry, because the epidemiological association of GBS with several infections has been established. The present review describes recent findings regarding the causative role of molecular mimicry in GBS that arises after infection with several different bacteria and viruses, including Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Haemophilus influenzae, Epstein–Barr virus, hepatitis E virus and Zika virus. Although many issues must be resolved to fully understand GBS pathogenesis, molecular mimicry is highly likely to be involved in the development of C. jejuni‐associated GBS and probably of M. pneumoniae‐associated GBS. Candidate autoantibodies that are generated in cytomegalovirus‐ and H. influenzae‐associated GBS types can also provide clues to the causal role of molecular mimicry. For other diseases associated with antecedent infections, clarification of pathogeneses is premature and warrants further research on molecular mimicry, as well as other autoimmune‐triggering mechanisms.
Retinoic acid‐inducible gene‐I, melanoma differentiation‐associated gene 5 and C‐X‐C motif chemokine ligand 10 are induced by a Toll‐like receptor 3 agonist in human brain microvascular endothelial cells
Authors: Imaizumi Tadaatsu , Arai Akine , Kawaguchi Shogo , Hayakari Ryo , Matsumiya Tomoh , Seya Kazuhiko , Yoshida Hidemi , Tanaka Hiroshi 
Published: May 2018

AbstractObjectiveBrain microvascular endothelial cells (BMEC) are the major component of the blood–brain barrier, and play a critical role in protecting the brain from pathogens. Although Toll‐like receptor 3 (TLR3) is known as an important pattern‐recognition receptor against viral double‐stranded RNA, the downstream reactions of TLR3 in human BMEC are not fully characterized. The purpose of the present study was to investigate the role of TLR3 signaling in the expression of retinoic acid‐inducible gene‐I (RIG‐I), melanoma differentiation‐associated gene 5 (MDA5) and C‐X‐C motif chemokine ligand 10 (CXCL10) in human BMEC.MethodsThe hCMEC/D3 cells, a human BMEC cell line, were cultured and stimulated with polyinosinic‐polycytidylic acid, a synthetic TLR3 agonist. Quantitative real‐time reverse transcription polymerase chain reaction, western blotting and enzyme‐linked immunosorbent assay were used to examine the expression of interferon‐β, RIG‐I and CXCL10. RNA interference against TLR3, interferon‐β, RIG‐I or MDA5 was also carried out.ResultsExpression of RIG‐I, MDA5 and CXCL10 were induced by polyinosinic‐polycytidylic acid, and this was inhibited by knockdown of either TLR3 or interferon‐β. Knockdown of RIG‐I or MDA5 did not affect the CXCL10 expression in the early phase (4 h), but decreased the CXCL10 induction in the late phase (8 or 24 h).ConclusionsRIG‐I, MDA5 and CXCL10 are induced through TLR3 activation in hCMEC/D3 cells, and RIG‐I and MDA5 might function to enhance and/or prolong the reactions mediated by CXCL10. These molecules might play a distinct role in innate immune reactions against double‐stranded RNA viruses in human BMEC.
Perineal closure following extralevator abdominoperineal excision for cancer of the rectum
Authors: Barrie J. , Haque A. , Evans D. A. 
Published: May 2018

AbstractAimExtralevator abdominoperineal resection (ELAPE) may be complicated by perineal wound healing problems and herniation. We report a consecutive series of 38 such patients with selective use of a fasciocutaneous V‐Y buttock advancement flap (BAF).MethodData were collected on a series of patients undergoing ELAPE for rectal malignancy between August 2011 and July 2017. Demographics, management and outcomes were recorded prospectively. Perineal wound problems were considered as ‘major’ if they required packing; otherwise, they were classed as ‘minor’.ResultsThirty‐eight patients [eight female and 30 male; median age 63 (range: 35–89) years] underwent ELAPE. Thirty‐seven had an adenocarcinoma of the rectum and one had a malignant melanoma. The median tumour height (from the anal verge) was 30 (range: 0–80) mm. Sixteen patients had a BAF. The median length of stay was 10 (range: 6–25) days. Primary perineal healing occurred in 18 (47%) patients. Major wound breakdown occurred in three (10%) patients and minor wound breakdown in 17 (45%). Two of the 16 patients having a BAF had major wound breakdown: one wound took 9 weeks to heal completely and the other took 9 months. Of the 22 patients who did not have a BAF, one had a major wound breakdown which closed by 3 months. There were no perineal fistulae or chronic sinuses. There were two perineal herniae that were successfully repaired by perineal insertion of biological mesh (Permacol™; Covidien, Dublin, Ireland).ConclusionsSelective use of a BAF for perineal closure can give good results in terms of healing and an acceptably low early perineal herniation rate.
Prognostic impact of interhospital variation in adjuvant chemotherapy for patients with Stage II/III colorectal cancer: a nationwide study
Authors: Arakawa K. , Kawai K. , Tanaka T. , Hata K. , Sugihara K. , Nozawa H. 
Published: May 2018

AbstractAimClinical guidelines recommend adjuvant chemotherapy for high‐risk patients with Stage II–III colorectal cancer. However, chemotherapeutic administration rates differ significantly between hospitals. We assessed the prognostic benefit of adjuvant chemotherapy in patients with Stage IIb/c colorectal cancer, and the prognostic impact of interhospital variations in the administration of adjuvant chemotherapy for Stage II–III colorectal cancer.MethodWe conducted a multicentre, retrospective study of 17 757 patients with Stage II–III colorectal cancer treated between 1997 and 2008 in 23 hospitals in Japan. Hospitals were classified as high‐rate (rate > 42.8%) or low‐rate (rate ≤ 42.8%), chemotherapy prescribing clinics.ResultsThe 5‐year overall survival (OS) of patients with Stage II–III colorectal cancer receiving adjuvant chemotherapy was significantly higher than for those not receiving adjuvant chemotherapy (85.7% vs 79.2%, P < 0.01 and 79.9% vs 72.5%, P < 0.01, respectively). For patients with Stage II disease, adjuvant chemotherapy was an independent factor for longer OS (P < 0.01, hazard ratio = 0.71). Both adjuvant chemotherapy and high‐rate hospital independently improved OS for patients with Stage III colorectal cancer (both P < 0.01; hazard ratio = 0.68 and 0.87, respectively).ConclusionSignificant prognostic benefit was found for patients with Stage IIb/c colorectal cancer who received adjuvant chemotherapy, with patients who were treated in hospitals with high adjuvant chemotherapy rates demonstrating better prognoses.
Slow treatment promotes control of harmful species by multiple agents
Authors: Lampert Adam , Hastings Alan , Sanchirico James N. 
Published: May 2018

AbstractThe management of harmful species, including invasive species, pests, parasites, and diseases, is a major, global challenge. Harmful species cause severe damage to ecosystems, biodiversity, agriculture, and human health. The control of harmful species is challenging and often requires cooperation among multiple agents, such as land‐owners, agencies, and countries. Agents may have incentives to contribute less, leaving more work for other agents, which can result in inefficient treatment. Here we present a dynamic game theory model and we show that slow treatment may promote a stable solution (Markovian Nash equilibrium) where all agents cooperate to remove the harmful species. The efficiency of this solution depends critically on the life history of the harmful species that determines the speed of optimal treatment. Furthermore, this cooperative equilibrium may coexist with other Nash equilibria, including one dictating no treatment of the harmful species, which implies that coordination among agents is critical for successful control.
The difficulty in interpreting gene expression profiling in BAP‐negative melanocytic tumors
Authors: Fischer Andrew S. , High Whitney A. 
Published: May 2018

BackgroundBAP‐negative melanocytic tumors were unrecognized in the medical literature until 2011. While the clinical significance of these tumors is poorly understood, there is concern such lesions represent processes in transition, and malignant degeneration is a concern. We investigated use of a 23‐gene expression profiling (23‐GEP) test for distinction from melanoma with the aim of better characterizing the biologic potential of such tumors.MethodsTwenty BAP‐negative melanocytic tumors, subjected to 23‐GEP (Myriad Genetic Laboratories, Inc. [Salt Lake City, Utah]) testing, were retrospectively analyzed.ResultsTumors exhibited varying degrees of atypia and aberrant immunohistochemical profiles. 23‐GEP testing revealed a “malignant” genetic signature in four cases, a “benign” signature in 15 cases, and an “indeterminate” signature in one case. Array‐based comparative genomic hybridization (aCGH) testing was performed for two cases with a “malignant” 23‐GEP signature, but the aCGH result conflicted with 23‐GEP, and supported benignity. Conversely, in one case with a “benign” 23‐GEP result, aCGH testing supported assessment as melanoma. Moreover, evolving melanoma could not be wholly excluded by histopathological analysis in 2 “benign” cases.ConclusionsBAP‐negative melanocytic tumors remain a diagnostic dilemma for dermatopathologists. A widely marketed 23‐GEP test may not be useful in distinguishing these tumors from spitzoid melanoma, at least in comparison to aCGH technology.
Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro
Authors: Breining Peter , Jensen Jonas B. , Sundelin Elias I. , Gormsen Lars C. , Jakobsen Steen , Busk Morten , Rolighed Lars , Bross Peter , Fernandez‐Guerra Paula , Markussen Lasse K. , Rasmussen Nanna E. , Hansen Jacob B. , Pedersen Steen B. , Richelsen Bjørn , Jessen Niels 
Published: May 2018

AimsTo test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11C]‐metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes.Materials and methodsTissue‐specific uptake of metformin was assessed in mice by PET/CT imaging after injection of [11C]‐metformin. Human brown adipose tissue was obtained from elective neck surgery and metformin transporter expression levels in human and murine BAT were determined by qPCR. Oxygen consumption in metformin‐treated human brown adipocyte cell models was assessed by Seahorse XF technology.ResultsInjected [11C]‐metformin showed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was similar to hepatic exposure. Non‐specific inhibition of the organic cation transporter (OCT) protein by cimetidine administration eliminated BAT exposure to metformin, demonstrating OCT‐mediated uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose‐dependent manner.ConclusionThese results support BAT as a putative metformin target.
Roles of the right temporo‐parietal and premotor cortices in self‐location and body ownership
Authors: Convento Silvia , Romano Daniele , Maravita Angelo , Bolognini Nadia 
Published: May 2018

AbstractIn the rubber hand illusion (RHI), the feeling that a fake hand belongs to oneself can be induced by the simultaneous, congruent touch of the fake visible hand and one's own hidden hand. This condition is also associated with a recalibration of the perceived location of the real hand. A cortical network, including premotor and temporo‐parietal areas, has been proposed as the basis of the RHI. However, the causal contribution of these areas to the discrete illusory components remains unclear. We used transcranial direct current stimulation (tDCS) to assess the contribution of the right premotor cortex (rPMc) and the right temporo‐parietal junction (rTPJ) to the RHI and explored the role of these areas in modulating the subjective experience of embodiment and the misperception of the hand position. We found that anodal tDCS of both rPMc and rTPJ increased the misjudgement of the real hand location towards the fake hand. Crucially, the difference in proprioceptive displacement evoked by the congruent and incongruent visuo‐tactile stroking was minimised when tDCS was applied over the rPMc, while it was amplified when the rTPJ was targeted. The parietal effects of tDCS also extended to the self‐report components of the RHI. These findings suggest that the tDCS of rTPJ modulates the RHI depending on the temporal congruency of the visuo‐tactile stimulation, while the tDCS of rPMc induces a general recalibration of hand coordinates, regardless of the visuo‐tactile congruency. The present results are discussed in the view of a multicomponent model of the RHI.
Distinct neural mechanisms for reading Arabic vs. verbal numbers: An ERP study
Authors: Proverbio Alice Mado , Bianco Marco , De Benedetto Francesco 
Published: May 2018

AbstractIn this electroencephalogram/event‐related potential (EEG/ERP) study, 16 volunteers were asked to compare the numerical equality of 360 pairs of multidigit numbers presented in Arabic or verbal format. Behavioural data showed faster and more accurate responses for digit targets, with a right hand/left hemisphere advantage only for verbal numerals. Occipito‐temporal N1, peaking at approximately 180 ms, was strongly left‐lateralized during verbal number processing and bilateral during digit processing. A LORETA (low‐resolution electromagnetic tomography) source reconstruction performed at the N1 latency stage (155–185 ms) revealed greater brain activation during coding of Arabic than of verbal stimuli. Digit perceptual coding was associated with the activation of the right angular gyrus (rAG), the left fusiform gyrus (FG,BA37), and left and right superior and medial frontal areas. N1 sources for verbal numerals included the left FG (BA37), the precuneus (BA31), the parahippocampal area and a small right prefrontal activation. In addition, verbal numerals elicited a late frontocentral negativity, possibly reflecting stimulus unfamiliarity or complexity. Overall, the data suggest distinct mechanisms for number reading through ciphers (digits) or words. Information about quantity was accessed earlier and more accurately if numbers were in a nonlinguistic code. Indeed, it can be speculated that numerosity processing would involve circuits originally involved in processing space (i.e., rAG/rIPS).
Valproic acid inhibits ATP‐triggered Ca2+ release via a p38‐dependent mechanism in bEND.3 endothelial cells
Authors: Leong Iat‐Lon , Tsai Tien‐Yao , Wong Kar‐Lok , Shiao Lian‐Ru , Cheng Ka‐Shun , Chan Paul , Leung Yuk‐Man 
Published: May 2018

AbstractValproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling are hitherto unreported. In this report, we examined the effects of VA on agonist‐triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μm) did not cause an acute inhibition of ATP‐triggered Ca2+ signaling, a 30‐min VA treatment strongly suppressed ATP‐triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size. VA‐activated p38 signaling, and VA‐induced inhibition of ATP‐triggered Ca2+ release was prevented by SB203580, a p38 inhibitor, suggesting VA caused the inhibition by activating p38. Remarkably, VA treatment did not affect acetylcholine‐triggered Ca2+ release, suggesting VA may not inhibit inositol 1,4,5‐trisphosphate‐induced Ca2+ release per se, and may not act directly on Gq or phospholipase C. Taken together, our results suggest VA treatment, via a p38‐dependent mechanism, led to an inhibition of purinergic receptor‐effector coupling.
Cannabis smoking impairs driving performance on the simulator and real driving: a randomized, double‐blind, placebo‐controlled, crossover trial
Authors: Micallef Joëlle , Dupouey Julien , Jouve Elisabeth , Truillet Romain , Lacarelle Bruno , Taillard Jacques , Daurat Agnès , Authié Colas , Blin Olivier , Rascol Olivier , Philip Pierre , Mestre Daniel 
Published: May 2018

AbstractDriving experiments in real conditions are considered as a ‘gold standard’ to evaluate the effects of drugs on driving performance. Several constraints are difficult to manage in these conditions, so driving simulation appears as the best alternative. A preliminary comparison is crucial before being able to use driving simulation as a valid evaluation method. The aim of this study was to design a driving simulation method for assessing drug effects on driving. We used cannabis (THC) as a positive control and assessed whether THC affects driving performance in simulation conditions and whether these effects are consistent with performance in real driving conditions. A double‐blind, placebo‐controlled, two successive two‐way crossover design was performed using cigarettes containing 20 mg of THC. Healthy occasional users of THC, aged 25–35 years, who had a consistent driving experience were included. The first two sessions were realized in simulation conditions, and the last two sessions were in real driving conditions. Driving performance was estimated through inappropriate line crossings (ILC) and the standard deviation of the vehicle's lateral position. Participants felt significantly drowsier and more tired after THC, whatever the driving condition. Driving stability was significantly impaired after THC, both in simulated and real driving conditions. We also found that ILC were significantly more numerous in driving simulation conditions, as compared to real driving. In conclusion, the driving simulator was proven to be more sensitive for demonstrating THC‐induced effects on driving performances. Driving simulation appears to be a good qualitative predictor of driving safety after drug intake.
Effects of Intraborehole Flow on Purging and Sampling Long‐Screened or Open Wells
Authors: Poulsen David L. , Cook Peter G. , Simmons Craig T. , McCallum James L. , Dogramaci Shawan 
Published: May 2018

AbstractHydraulic head differences across the screened or open interval of a well significantly influence the sampled water mixture. Sample bias can occur due to an insufficient pumping rate and/or due to native groundwater displacement by intraborehole flow (IBF). Proper understanding of the sampled water mixture is crucial for accurate interpretation of environmental tracers and groundwater chemistry data, and hence groundwater characterization. This paper uses numerical modeling to quantify sample bias caused by IBF in an un‐pumped high‐yield well, and the influence of pumping rate and heterogeneity on the volume of pumpage required to purge an IBF plume. The results show that (1) the pumping rate must be at least an order of magnitude greater than the IBF rate to achieve permeability‐weighted yield, (2) purge volume was 2.2 to 20.6 times larger than the IBF plume volume, with the ratio depending on plume location relative to hydraulic conductivity and head distributions, and (3) after an example 1000‐day un‐pumped period, purging required removal of at least three orders of magnitude more water than the common practice of three to five well volumes. These results highlight the importance of knowing the borehole flow regime to identify IBF inflow and outflow zones, estimate IBF rates, and to develop a strategic sampling approach.