bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐4 receptor α blockade prevents sensitization and alters acute and long‐lasting effects of allergen‐specific immunotherapy of murine allergic asthma
Authors: Russkamp D. , Aguilar‐Pimentel A. , Alessandrini F. , Gailus‐Durner V. , Fuchs H. , Ohnmacht C. , Chaker A. , de Angelis M. H. , Ollert M. , Schmidt‐Weber C. B. , Blank S. 
Published: March 2019

AbstractBackgroundAllergen‐specific immunotherapy (AIT) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL‐4 and IL‐13 signaling on different phases of AIT were addressed.MethodsThe impact of the recombinantly produced IL‐4 and IL‐13 antagonist IL‐4 mutein (IL‐4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL‐4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post‐treatment.ResultsIntervention with IL‐4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL‐5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL4M‐supplemented AIT during allergen challenge. Additionally, IL4M markedly suppressed type‐2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post‐treatment. Intriguingly, here, IL‐4M induced a sustained decrease of Th2‐biased Tregs (ST2+FOXP3+GATA3intermediate).ConclusionsIL‐4 and IL‐13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT. Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease‐triggering Th2‐biased Tregs was further significantly decreased by IL‐4M treatment. Hence, IL‐4/IL13‐targeting therapies prime the immune memory in therapy success‐favoring manner.
Identification of an antigenic determinant of clavulanic acid responsible for IgE‐mediated reactions
Authors: Barbero Nekane , Fernández‐Santamaría Rubén , Mayorga Cristobalina , Martin‐Serrano Ángela , Salas María , Bogas Gador , Nájera Francisco , Pérez‐Sala Dolores , Pérez‐Inestrosa Ezequiel , Fernandez Tahia D. , Montañez María I. , Torres María J. 
Published: March 2019

AbstractBackgroundSelective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin‐CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis.MethodsBased on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD‐I (N‐protein, 3‐oxopropanamide) and AD‐II (N‐protein, 3‐aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches.ResultsTwo synthetic analogs of AD‐I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV‐treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls.ConclusionWe have identified AD‐I as one CLV antigenic determinant, which is the drug fragment that remains protein‐bound.
The antiviral effects of human microRNA miR‐302c‐3p against hepatitis B virus infection
Authors: Hamada‐Tsutsumi Susumu , Naito Yutaka , Sato Seiichi , Takaoka Akinori , Kawashima Keigo , Isogawa Masanori , Ochiya Takahiro , Tanaka Yasuhito 
Published: March 2019

SummaryBackgroundConventional treatments of chronic hepatitis B virus (HBV) infection rarely achieve a decline of serum hepatitis B surface antigen (HBsAg) levels and eradication of the virus.AimTo elucidate the antiviral mechanisms of a human microRNA, miR‐302c‐3p, against HBV replication.MethodsThe antiviral effect of miR‐302c‐3p was evaluated in vitro and in vivo by transfecting the miR‐302c‐3p mimic into HBV‐infected HepG2‐hNTCP‐C4 cells and HBV transgenic mice respectively.ResultsmiR‐302c‐3p decreased not only HBV replication but also production of HBsAg. Pregenomic RNA and HBsAg mRNA concentrations decreased in the cells treated with miR‐302c‐3p. Interestingly, the amount of cccDNA was significantly reduced in the miR‐302c‐3p‐treated cells, in association with disappearance of the HBV core protein. An RNA immunoprecipitation assay showed that miR‐302c‐3p decreased the binding of the HBV polymerase to the pregenomic RNA by hybridising with the ε‐loop region. A number of host genes were downregulated in miR‐302c‐3p‐treated cells, including BMPR2 and HNF4A. Knockdown of these two genes by corresponding siRNAs also suppressed HBV replication and HBsAg secretion. The antiviral effect of miR‐302c‐3p was also observed in HBV transgenic mice.ConclusionmiR‐302c‐3p had anti‐HBV activity, in vitro and in vivo, via several mechanisms.
Geographic space, relief, and soils predict plant community patterns of Asteraceae in rupestrian grasslands, Brazil
Authors: Chaves Daniel A. , Ribeiro‐Silva Suelma , Proença Carolyn E. B. , Oliveira Washington L. , Bringel João Bernardo A. , Medeiros Marcelo B. 
Published: March 2019

AbstractWe investigated the effects of geographic distance and environmental heterogeneity on Asteraceae communities in the rupestrian grasslands of the Espinhaço Range, southeastern Brazil. Asteraceae species composition and relative abundance were sampled in 21–1 ha plots distributed across park conservation units, comprising an environmental gradient in soils and relief (elevation and slope). We found high levels of heterogeneity overall in assemblages of herbaceous and woody Asteraceae species at the intermediate spatial scale of this study (10–100 km). We found that both relief and soil properties (texture and total exchangeable bases) explained significant proportions of variation in community composition, suggesting that definitions or expansions of conservation units should span the highest possible variability in observed relief and soil values. We also found that Asteraceae distribution exhibited strong spatial structure independent of environmental variation, reinforcing the need to consider conservation across larger areas. Considering the dystrophic character of the soils found in the Espinhaço Range and the few differences in the fertility observed between the sampling units, our results also support the hypothesis that plant distributions in the tropics are controlled by a hierarchy of environmental gradients, where variables such as altitude and exchangeable bases and Al texture are important predictors in low‐fertility soils. We suggest that Asteraceae could be a model family for conservation planning in other countries and regions because it is particularly well represented in open and montane areas of the Neotropics in general.Abstract in Portuguese is available with online material.
Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia
Authors: Ji Linong , Liu Yanmei , Miao Heng , Xie Yongli , Yang Ming , Wang Wei , Mu Yuting , Yan Ping , Pan Sharon , Lauring Brett , Liu Shu , Huyck Susan , Qiu Yanping , Terra Steven G. 
Published: March 2019

AimPhase III, randomized, double‐blind study evaluating the efficacy and safety of ertugliflozin in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin, including evaluation in the China subpopulation.Materials and methodsA 26‐week, double‐blind study of 506 Asian patients (80.2% from mainland China), randomized 1:1:1 to placebo, ertugliflozin 5‐ or 15 mg, was performed. Primary endpoint was change from baseline in HbA1c at week 26. Secondary endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight (BW), systolic/diastolic blood pressure (SBP/DBP), and proportion of patients with HbA1c <7.0%. Hypotheses for the primary endpoint and FPG and BW secondary endpoints were tested in the China subpopulation.ResultsAt week 26, least squares mean (95% CI) change from baseline HbA1c was significantly greater with ertugliflozin 5‐ and 15 mg versus placebo: −1.0% (−1.1, −0.9), −0.9% (−1.0, −0.8), −0.2% (−0.3, −0.1), respectively. Ertugliflozin significantly reduced FPG, BW and SBP. Reductions in DBP with ertugliflozin were not significant. At week 26, 16.2%, 38.2% and 40.8% of patients had HbA1c <7.0% with placebo, ertugliflozin 5‐ and 15 mg, respectively. 59.3%, 56.5% and 53.3% of patients experienced adverse events with placebo, ertugliflozin 5‐ and 15 mg, respectively. Incidence of symptomatic hypoglycaemia was higher for ertugliflozin 15 mg vs placebo. Results in the China subpopulation were consistent.ConclusionsErtugliflozin significantly improved glycaemic control and reduced BW and SBP in Asian patients with T2DM. Ertugliflozin was generally well‐tolerated. Results in the China subpopulation were consistent with the overall population.ClinicalTrials.gov: NCT02630706.
Eco‐Fashion Consumption: Cognitive‐Experiential Self‐Theory
Authors: Fu Wei , Kim Youn‐Kyung 
Published: March 2019

Drawing upon cognitive‐experiential self‐theory (CEST), this study examined how individuals’ differences in emotion‐driven dispositions (i.e., need for variety and fashion interest) and logic‐driven dispositions (i.e., ecological consciousness and social consciousness) can influence their information processing and decision making in the context of eco‐fashion. A focus group of nine participants and an online questionnaire involving 657 participants were used to accomplish the purpose of the study. Structural equation modeling (SEM) was used to test the hierarchical relationships among individual differences, responses, and consumer behavioral tendencies. The results indicated that consumers’ need for variety positively influenced their affective responses, purchase intention, and willingness to pay more for eco‐fashion. Consumers’ ecological consciousness and social consciousness positively influenced their cognitive responses and eventually their purchase intentions and willingness to pay more for eco‐fashion. Furthermore, cognitive responses had strong impacts on affective responses.
Elevational richness patterns of sphingid moths support area effects over climatic drivers in a near‐global analysis
Authors: Bärtschi Florian , McCain Christy M. , Ballesteros‐Mejia Liliana , Kitching Ian J. , Beerli Nicolas , Beck Jan 
Published: March 2019

AbstractAimWe test hypotheses on the environmental control of elevational richness patterns of sphingid moths for their global applicability and generality. Specifically, we compare effects of area with climate‐related drivers, such as primary productivity and temperature, while also considering direct effects of precipitation.Major taxaSphingid moths (Lepidoptera).LocationEighty‐six mountain ranges of the Old World and the Australia/Pacific region, from Scandinavia and Siberia through the African and Australasian tropics to South Africa and Southern Australia.MethodsWe used a large compilation of point locality records for 744 species, in addition to fine‐grained range maps derived from species distribution modelling of these records, to characterize the elevational pattern of species richness in 86 custom‐delineated mountain regions. For both types of data, we compared the effects of environmental drivers on richness by comparing standardized coefficients of multivariate models for pooled data after accounting for between‐region variation in richness.ResultsWe observed varying patterns of elevational richness across the research region, with a higher prevalence of midpeaks in arid regions. We found overwhelming support for area as a main determinant of richness, modulated by temperature and productivity, whereas we detected no effect of precipitation.Main conclusionsArea, productivity and temperature are the main environmental predictors explaining a large proportion of variability in sphingid richness. This is consistent not only with other elevational studies, but also with empirical and theoretical biodiversity research in a non‐elevational context (with the caveat of some unresolved issues in elevational area effects). However, distinct differences in elevational patterns remain even within the same mountain ranges when comparing with other Lepidoptera, that is, geometrid moths, which highlights the importance of understanding higher clade differentiation in ecological responses, within insects and in other groups.
An RCVS Spectrum Disorder? New Daily Persistent Headache Starting as a Single Thunderclap Headache (3 New Cases)
Authors: Jamali Sheheryar A. , Rozen Todd D. 
Published: March 2019

ObjectiveTo describe 3 new cases of new daily persistent headache (NDPH) starting as a single thunderclap headache.BackgroundNDPH is a form of chronic daily headache that is unique in its temporal profile of onset. Distinct subtypes of NDPH are being described with specific efficacious treatments. A single case of NDPH starting as a single thunderclap headache has been previously reported but no further cases have been documented in the literature. New cases need to be published to better define the syndrome.MethodsTo report a case series of patients diagnosed with this unique NDPH subtype at an academic headache center from 2016 to 2018.ResultsThree new cases of NDPH starting as a single thunderclap headache at onset were diagnosed. All patients were female with an average age of onset of 46 years. All presented with neurologic symptoms/stroke‐like spells at headache onset. No defined triggering events were noted in any of the patients. There is a possible seasonal predilection to develop the syndrome around the fall clock change to the winter solstice. Neuroimaging was normal in the case patients. All patients rapidly responded to nimodipine. The duration of headache prior to nimodipine therapy ranged from 3 months to 4 years.ConclusionThis NDPH subtype appears to be rare. The key to diagnosis is asking about the temporal profile of the onset of the first ever NDPH headache. None of the case patients had been asked about the initial headache and its pattern of onset. Nimodipine seems to be very effective in treating this NDPH subtype. This syndrome is most likely precipitated by persistent or intermittent cerebral artery vasospasm. It is possibly a subform of the reversible cerebral vasoconstriction syndrome.
Synthetic fayalite Fe2SiO4 by kinetically controlled reaction between hematite and silicon carbide
Authors: Pinto Rui G. , Yaremchenko Aleksey A. , Baptista Miguel F. , Tarelho Luís A. C. , Frade Jorge R. 
Published: March 2019

AbstractThe present work explores the preparation of fayalite α‐Fe2SiO4, the iron‐rich end‐member of the olivine solid‐solution series, as a tar removal catalyst for biomass gasification. The synthetic procedure was developed starting from the stoichiometric mixture of hematite and micrometer size silicon carbide and employing thermal treatments in controlled atmospheres at 1000‐1100°C supported by thermodynamic modeling to assess the required redox conditions. The treatments in dry and humidified inert gas yielded phase mixtures containing metallic Fe as one of the main phases, thus emphasizing a shortage of oxygen supply. XRD and TGA studies of precursor mixtures on heating in dry CO2 demonstrated a multistep mechanism of the overall reaction including (a) fast reactivity between silicon carbide and hematite at ~920°C with formation of metallic Fe and amorphous silica followed by (b) formation of fayalite involving oxygen supplied in the form of CO2 and competing with (c) over‐oxidation to thermodynamically favorable Fe3O4+SiO2 mixture. Comparative studies of reactivity in powdered and pelletized samples emphasized the importance of the kinetic factor in the formation of Fe2SiO4 while preventing further oxidation. The preferential formation of fayalite in the CO2 atmosphere is shown to be favored by shorter treatments of compacted samples at higher temperatures. The procedure was designed (2‐step heating to 1100°C in CO2 followed by fast cooling) for the preparation of pelletized fayalite α‐Fe2SiO4 catalyst with only minor traces of surface over‐oxidation which can be suppressed by adding 10 vol.% of forming gas to CO2 flow.
Assisting Wild Animals Vulnerable to Climate Change: Why Ethical Strategies Diverge
Authors: Palmer Clare 
Published: March 2019

AbstractMany individual sentient wild animals are vulnerable to anthropogenic climate change. In this article, I suggest that animal ethicists who take sentient animals’ moral status seriously are likely to agree that, other things being equal, we have moral responsibilities to assist wild animals made vulnerable to climate change. However, I also argue that these ethicists are likely to diverge in terms of the strategies they believe would actually fulfil such moral responsibilities, depending on whether their primary concern is rectificatory justice or duties of beneficence. To support this argument, I consider three plausible strategies for helping wild animals vulnerable to climate change: rescue and rehabilitation, habitat restoration, and assisted migration. I argue that different theoretical approaches to animal ethics are likely to diverge on aspects of all these strategies. These differences mean that the process of creating wide agreement among animal ethicists on climate adaptation strategies to assist vulnerable wild animals faces significant hurdles.
Workflow description of additively manufactured clear silicone indexes for injected provisional restorations: A novel technique
Authors: Revilla‐León Marta , Fountain Joshua , Piedra Cascón Wenceslao , Özcan Mutlu , Zandinejad Amirali 
Published: March 2019

AbstractObjectiveThe present article describes the digital workflow protocol for additive manufacturing (AM) of a clear silicone index to be used for an injected provisional restoration fabrication.Clinical considerationsThe incorporation of CAD software and AM technologies have allowed the integration of a new way to fabricate conventional diagnostic wax‐ups and silicone indexes for preparing diagnostic mock ups, direct composite restorations, or provisional restorations. Although the conventional concept remains, the protocol differs.ConclusionsThis workflow provides a more efficient and accurate procedure with the reduction of time and cost compared to conventional technique.Clinical SignificanceThe digital workflow protocol described for AM of a clear silicone index to be used for an injected provisional restoration fabrication is time and cost efficient compared to conventional procedures.
Long‐term efficacy and safety of CT‐P13, a biosimilar of infliximab, in patients with inflammatory bowel disease: A retrospective multicenter study
Authors: Kim Nam Hee , Lee Ji Hyun , Hong Sung Noh , Yoon Hyuk , Kang Hyoun Woo , Lee Suck‐Ho , Im Jong Pil , Cha Jae Myung , Eun Chang Soo , Kim Ji Won , Choi Chang Hwan , Park Dong Il 
Published: March 2019

AbstractBackground and AimA biosimilar of infliximab, CT‐P13 (Remsima®) has the potential to reduce treatment costs and enhance access to biological therapy for inflammatory bowel disease (IBD) patients. However, long‐term clinical data on its use for IBD treatment are currently sparse. We aimed to investigate the long‐term efficacy and safety of CT‐P13 therapy in a large, real‐life IBD cohort.MethodsA total of 368 IBD patients (227 with Crohn's disease [CD] and 141 with ulcerative colitis [UC]) treated with CT‐P13 at 16 referral hospitals in Korea between July 2012 and December 2017 were retrospectively analyzed.ResultsThe cumulative retention rates at years 1, 3, and 5 were 86.1%, 68.5%, and 58.7% and 69.7%, 46.0%, and 26.7% in anti‐tumor necrosis factor (TNF)‐naïve CD and UC patients, respectively. The clinical response and remission rates at week 14 and at years 1, 3, and 5 were 94.3%, 92.7%, 76.8%, and 17.6% and 78.6%, 82.4%, 72.2%, and 17.6% in anti‐TNF‐naïve CD and 85.6%, 80.0%, 55.2%, and 6.7% and 42.6%, 59.8%, 44.2%, and 6.7% in anti‐TNF‐naïve UC patients, respectively. Among patients who switched from the biologic originator to CT‐P13, the cumulative retention rates at years 1, 3, and 5 were 88.5%, 66.1%, and 44.8% in CD, and 73.9%, 42.5%, and 42.5% in UC patients, respectively. Significant improvements in disease activity scores were accompanied by marked reductions in inflammatory marker levels, and no unexpected adverse events including death or malignancy occurred during the study period.ConclusionsLong‐term treatment with CT‐P13 is effective in inducing and maintaining disease improvement and is well‐tolerated in patients with IBD. CT‐P13 may be a promising treatment option for IBD.
Crosstalk between mitochondria, calcium channels and actin cytoskeleton modulates noradrenergic activity of locus coeruleus neurons
Authors: de Oliveira Ramatis B. , Petiz Lyvia L. , Lim Rebecca , Lipski Janusz , Gravina Fernanda S. , Brichta Alan M. , Callister Robert J. , Leão Richardson N. , van Helden Dirk F. 
Published: March 2019

AbstractLocus coeruleus (LC) is the name of a group of large sized neurons located at the brain stem, which provides the main source of noradrenaline to the central nervous system, virtually, innervating the whole brain. All noradrenergic signalling provided by this nucleus is dependent on an intrinsic pacemaker process. Our study aims to understand how noradrenergic neurons finely tune their pacemaker processes and regulate their activities. Here we present that mitochondrial perturbation in the LC from mice, inhibits spontaneous firing by a hyperpolarizing response that involves Ca2+ entry via L‐type Ca2+ channels and the actin cytoskeleton. We found that pharmacological perturbation of mitochondria from LC neurons using the protonophore carbonyl cyanide m‐chlorophenylhydrazone (CCCP), induced a dominant hyperpolarizing response when electrophysiological approaches were performed. Surprisingly, the CCCP‐induced hyperpolarizing response was dependent on L‐type Ca2+ channel‐mediated Ca2+ entry, as it was inhibited by: the removal of extracellular Ca2+; the addition of Cd2+; nifedipine or nicardipine; but not by the intracellular dialysis with the Ca2+ chelator 1,2‐Bis(2‐Aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid, the latter indicating that the response was not because of a global change in [Ca2+]c but does not exclude action at intracellular microdomains. Further to this, the incubation of slices with cytochalasin D, an agent that depolymerises the actin cytoskeleton, inhibited the hyperpolarizing response indicating an involvement of the actin cytoskeleton. The data are consistent with the hypothesis that there is a crosstalk between mitochondria and L‐type Ca2+ channels leading to modulation of noradrenergic neuronal activity mediated by the actin cytoskeleton.Open Science BadgesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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