bluuebunny/crossref_metadata_2025_split huggingface dataset:
A polymorphism in the TH2 locus control region is associated with changes in DNA methylation and gene expression
Authors: Schieck M. , Sharma V. , Michel S. , Toncheva A. A. , Worth L. , Potaczek D. P. , Genuneit J. , Kretschmer A. , Depner M. , Dalphin J.‐C. , Riedler J. , Frei R. , Pekkanen J. , Tost J. , Kabesch M. 
Published: May 2014

AbstractBackgroundGenomewide association and epigenetic studies found a region within the RAD50 gene on chromosome 5q31 to be associated with total serum IgE levels and asthma. In mice, this region harbors a locus control region for nearby TH2 cytokines, which is characterized by four Rad50 DNase I hypersensitive sites (RHS4–7). Among these, RHS7 seems to have the strongest impact on TH2 differentiation. We investigated whether within the human homolog of RHS7, functional polymorphisms exist, which could affect DNA methylation or gene expression in the 5q31 locus and might have an influence on asthma status or IgE regulation.MethodsThe human RHS7 region was fine mapped using 1000 genomes database information. In silico analysis and electrophoretic mobility shift assays were used to assess SNP function. Allele‐specific effects on DNA methylation were evaluated in cord blood (n = 73) and at age of 4.5 years (n = 61) by pyrosequencing. Allele‐specific effects on RAD50, IL4, and IL13 expression were analyzed in 100 subjects. Associations with asthma and IgE levels were investigated in the MAGICS/ISAAC II population (n = 1145).ResultsPolymorphism rs2240032 in the RHS7 region is suggestive of allele‐specific transcription factor binding, affects methylation of the IL13 promoter region and influences RAD50 and IL4 expression (lowest P = 0.0027). It is also associated with total serum IgE levels (P = 0.0227).ConclusionA functional relevant polymorphism in the TH2 locus control region, equivalent to RHS7 in mice, affects DNA methylation and gene expression within 5q31 and influences total serum IgE on the population level.
Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459
Authors: Pettipher R. , Hunter M. G. , Perkins C. M. , Collins L. P. , Lewis T. , Baillet M. , Steiner J. , Bell J. , Payton M. A. 
Published: May 2014

AbstractBackgroundThe CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. A study was conducted to determine the effect of lower once daily doses of OC000459 and to define the phenotype of subjects most responsive to treatment.MethodsAdult subjects (percentage of predicted forced expiratory volume in 1 s (FEV1) 60–85%) were randomized to OC000459 at three dose levels (25 mg once daily, 200 mg once daily or 100 mg twice daily) or placebo for 12 weeks (n = 117–125 per group, full analysis set). The primary endpoint was the change from baseline in prebronchodilator FEV1, and secondary endpoints included Asthma Control Questionnaire (ACQ) and Standardised Asthma Quality of Life Questionnaire [AQLQ(S)], and incidence of exacerbations and respiratory tract infections.ResultsOC459 caused a significant improvement in FEV1 compared with placebo at a dose of 25 mg once daily (P = 0.028). A similar increase was observed in the other dose groups, and the mean change in FEV1 in the pooled dose groups at endpoint was 95 ml greater than placebo (P = 0.024). In a post hoc analysis of atopic eosinophilic subjects with uncontrolled asthma, a mean increase in FEV1 of 220 ml was observed compared with placebo (P = 0.005). The mean increase in FEV1 was more marked in younger subjects in this group: for subjects aged ≤40 years, there was a mean increase of 355 ml compared with placebo (P = 0.007). Improvements in ACQ and AQLQ(S) were observed in both the full analysis set and the atopic eosinophilic subgroup. There was a lower incidence of exacerbations and respiratory infections in subjects treated with OC000459. There were no drug‐related serious adverse events.ConclusionsOC000459 is a safe and effective oral anti‐inflammatory agent, which achieved clinically meaningful improvements in lung function and asthma control in allergic asthmatics with an eosinophil‐dominant form of the disease. A dose of 25 mg given once daily was as effective as the higher doses studied.
Loss of Sparc in p53‐null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival
Authors: Thomas Stacey L. , Schultz Chad R. , Mouzon Ezekiell , Golembieski William A. , Naili Reima El , Radakrishnan Archanna , Lemke Nancy , Poisson Laila M. , Gutiérrez Jorge A. , Cottingham Sandra , Rempel Sandra A. 
Published: May 2014

AbstractBoth the induction of SPARC expression and the loss of the p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival. This study determined whether the loss of Sparc in astrocytes that are null for p53 would result in reduced cell survival and tumor formation and increased tumor immunogenicity in an in vivo xenograft brain tumor model. In vitro, the loss of Sparc in p53‐null astrocytes resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7 days after intracranial implantation, Sparc‐null tumors had decreased tumor cell survival, proliferation and reduced tumor size. The loss of Sparc promoted microglia/macrophage activation and phagocytosis of tumor cells. Our results indicate that the loss of p53 by deletion/mutation in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance.
Allergic contact dermatitis caused by acrylates and methacrylates – a 7‐year study
Authors: Ramos Leonor , Cabral Rita , Gonçalo Margarida 
Published: May 2014

SummaryBackgoundAllergic contact dermatitis (ACD) caused by (meth)acrylates is traditionally an occupational disease among dentists, printers, and fibreglass workers. With the use of artificial nails, cases have been reported both in nail technicians and in users.ObjectivesThe aims of this study were to characterize ACD caused by (meth)acrylates, identify the responsible allergens, and assess the sensitivity of the patch test with 2‐hydroxyethyl methacrylate (HEMA) for diagnosis.MethodsAn observational and retrospective study (January 2006–April 2013) was performed, evaluating and correlating epidemiological and clinical parameters and positive patch test results with (meth)acrylates.ResultsAmong 2263 patch tested patients, 122 underwent aimed testing with an extended (meth)acrylate series, and 37 showed positive and relevant reactions. Twenty‐five cases (67.6%) were occupational. Hand eczema with pulpitis was observed in 32 patients. Twenty‐eight cases were related to artificial nails, 3 were related to dental materials, and 2 were industrial workers. Oral lesions associated with dental prostheses were observed in 4 patients. Thirty‐one patients reacted to more than one (meth)acrylate. In our sample, beauty technicians working with artificial nails were the most affected group (80% of occupational cases).ConclusionHEMA detected 80.6% of our cases, and may be considered a good screening allergen. However, to perform an accurate diagnosis, it is safer to use a broader series of allergens.
Clinical usefulness of novel tag‐less Agile patency capsule prior to capsule endoscopy for patients with suspected small bowel stenosis
Authors: Nakamura Masanao , Hirooka Yoshiki , Yamamura Takeshi , Miyahara Ryoji , Watanabe Osamu , Ando Takafumi , Ohmiya Naoki , Goto Hidemi 
Published: May 2014

Background and AimThe Agile patency capsule (PC; Given Imaging Ltd, Yoqneam, Israel) is used as a dummy prior to capsule endoscopy (CE) to avoid retention of the CE capsule. However, impaction of the PC's inner radio frequency identification (RFID) tag in a stricture could cause small‐bowel ileus. Recently, the RFID tag‐less PC was introduced into clinical practice. Herein, we aimed to retrospectively evaluate the usefulness of the tag‐less PC.MethodsOf 154 patients who were scheduled to undergo CE, 100 consecutive patients (65%) who underwent PC evaluation were enrolled in the present study. Primary study end point was the retention rate of the CE capsule after successful passage of the PC. Secondary end point was analysis of the significant factors affecting the passage of the PC.ResultsIn total, 87 patients (87%) had bowel patency confirmed by PC evaluation. There was no capsule retention in any of these 87 patients during CE. Abnormal findings were obtained from 60 CE, and 41 patients received new or modified treatment. Multivariate analysis of factors related to the confirmation of patency demonstrated that stenosis on imaging was the most influential factor (P = 0.002, odds ratio 16.387). The results confirmed that passage of the PC depends on stenosis on imaging.ConclusionsUse of the tag‐less PC confirmed gastrointestinal tract patency for most of the patients who did not have stenosis on imaging and allowed estimation of the patency for patients who did have stenosis on imaging.
Safety and efficacy of the dipeptidyl peptidase‐4 inhibitor linagliptin in elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331 individuals aged ≥ 65 years
Authors: Schernthaner G. , Barnett A. H. , Patel S. , Hehnke U. , von Eynatten M. , Woerle H.‐J. 
Published: May 2014

AimsTo investigate individual patient data from a comprehensive trials programme to evaluate the safety and efficacy of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin across a range of glucose‐lowering regimens in a large elderly population with type 2 diabetes mellitus (T2DM).MethodsData were pooled from individuals aged ≥65 years, who participated in seven phase III, placebo‐controlled clinical trials of linagliptin (24–52 weeks). Safety was assessed by incidence and severity of adverse events (AEs) with a focus on hypoglycaemia. The primary efficacy endpoint was change in glycated haemoglobin (HbA1c).ResultsIn total, 841 subjects received linagliptin 5 mg once a day and 490 received placebo. At baseline, the population had a mean ± s.d. age of 71.0 ± 4.6 years and a mean HbA1c concentration of 8.0 ± 0.8%; 63.5% of subjects received ≥2 antidiabetes drugs. Overall AEs and drug‐related AEs were experienced by similar proportions of patients (linagliptin 71.3, placebo 73.3; linagliptin 18.1, placebo 19.8%, respectively). The incidence of investigator‐reported hypoglycaemia was 21.4% with linagliptin and 25.7% with placebo. Severe hypoglycaemic events were rare and there were fewer in the linagliptin group (1.0 vs. 1.8%). At week 24, the placebo‐corrected adjusted mean ± s.e. reduction in HbA1c with linagliptin was −0.62 ± 0.06% (95% CI: −0.73, −0.51).ConclusionsData from this large cohort show that linagliptin is a well‐tolerated and efficacious therapy for elderly patients with T2DM. Treatment with linagliptin may support individualized treatment goals, while effectively managing the risk of hypoglycaemia or drug‐related side effects.
Orthogonal array design for optimization of an artificial medium for in vitro rearing of Trichogramma dendrolimi
Authors: Lü Xin , Han Shichou , De Clercq Patrick , Dai Jianqing , Li Liying 
Published: May 2014

AbstractSuccessful complete development of Trichogramma species on artificial media is also related to the presence and proportions of ingredients other than host insect‐derived components. In this study, an orthogonal array with six factors at three levels was performed and parameters of parasitism, larval development, pupation, and adult emergence were monitored to reveal the most important components of an artificial medium and to improve the medium for in vitro mass rearing of Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae). Results indicated that biological parameters of T. dendrolimi were affected differently by six ingredients of the artificial medium: pupal hemolymph of Antheraea pernyi (Guérin‐Méneville) (Lepidoptera: Saturniidae), egg yolk, 10% malted milk solution, Neisenheimer's salt solution, trehalose, and sterile water. Statistical analysis indicated that trehalose and Neisenheimer's salt solution, 10% malted milk solution, and pupal hemolymph of A. pernyi were the main ingredients of the artificial medium based on rates of parasitism and pupation, the number of larvae developing in each artificial egg, adult emergence rate, and the number of normal adults produced. A follow‐up bioassay with a selection of optimized formulas confirmed the validity of the optimization as predicted by the orthogonal array analysis, indicating the usefulness of this method for selecting artificial diets for entomophagous insects. Adult emergence rate of the parasitoid and total number of normal adults produced per egg card (each containing 20 artificial eggs) averaged 88.8% and 956 females on the best performing optimized artificial medium, consisting of 3 ml pupal hemolymph of A. pernyi, 2.5 ml egg yolk, 1 ml 10% malted milk solution, 1 ml Neisenheimer's salt solution, 0.1 g trehalose, and 1.5 ml sterile water. The latter medium was superior to any formerly developed medium and may thus have potential for the in vitro mass rearing of T. dendrolimi.
Participants' perceived benefits of family intervention following a first episode of psychosis: a qualitative study
Authors: Nilsen Liv , Frich Jan C. , Friis Svein , Norheim Irene , Røssberg Jan Ivar 
Published: May 2014

AbstractAimTo explore the perceived benefits for patients and family members of psychoeducational family intervention following a first episode of psychosis.MethodsA qualitative exploratory study using data from interviews with 12 patients and 14 family members who participated in a psychoeducational multi‐ or single‐family treatment programme. Semi‐structured interviews were digitally recorded and transcribed verbatim with slight modifications, after which they were analysed by systematic text condensation.ResultsPatients and family members reported benefits that could be classified in five categories: (i) developing insight and acceptance requires understanding of the fact that the patient has an illness, and recognizing the need for support; (ii) recognizing warning signs requires an understanding of early signs of deterioration in the patient; (iii) improving communication skills is linked to new understanding and better communication both within the family and in groups; (iv) Learning to plan and solve problems requires the ability to solve problems in new ways; (v) becoming more independent requires patients to take responsibility for their own life.ConclusionThe study suggests that developing insight and acceptance, learning about warning signs, improving communications skills, learning to plan and solve problems, and becoming more independent are perceived as benefits of a psychoeducational family intervention.
Fixational saccade‐related activity of pedunculopontine tegmental nucleus neurons in behaving monkeys
Authors: Okada Ken‐ichi , Kobayashi Yasushi 
Published: May 2014

AbstractFixational saccades are small, involuntary eye movements that occur during attempted visual fixation. Recent studies suggested that several cognitive processes affect the occurrence probability of fixational saccades. Thus, there might be an interaction between fixational saccade‐related motor signals and cognitive signals. The pedunculopontine tegmental nucleus (PPTN) in the brainstem has anatomical connections with numerous saccade‐related and limbic areas. Previously, we reported that a group of PPTN neurons showed transient phasic bursts or a pause in activity during large visually guided and spontaneous saccades, and also showed sustained tonic changes in activity with task context. We hypothesised that single PPTN neurons would relay both fixational saccade‐related and task context‐related signals, and might function as an interface between the motor and limbic systems. We recorded the activity of PPTN neurons in behaving monkeys during a reward‐biased task, and analysed neuronal activity for small fixational saccades during visual fixation, and compared it with the activity for large visually guided targeting saccades and large spontaneous saccades during intertrial intervals. A population of PPTN neurons exhibited a fixational saccade‐related phasic increase in activity, and the majority of them also showed activity modulation with large targeting saccades. In addition, a group of these neurons showed a task‐related tonic increase in activity during the fixation period, and half of them relayed the saccade signal only when the neuron exhibited higher tonic activity during the task execution period. Thus, fixational saccade‐related signals of PPTN neurons overlap with tonic task‐related signals, and might contribute to the cognitive modulation of fixational saccades.
Long‐term safety of perampanel and seizure outcomes in refractory partial‐onset seizures and secondarily generalized seizures: Results from phase III extension study 307
Authors: Krauss Gregory L. , Perucca Emilio , Ben‐Menachem Elinor , Kwan Patrick , Shih Jerry J. , Clément Jean‐François , Wang Xuefeng , Bagul Makarand , Gee Michelle , Zhu Jin , Squillacote David 
Published: May 2014

SummaryObjectiveTo evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment.MethodsPatients ≥12 years old with partial‐onset seizures despite treatment with 1–3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open‐label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions.ResultsAmong 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy‐related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure‐free for the entire year.SignificanceNo new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Cleaning Up After a Meal: The Consequences of Prey Disposal for Pit‐Building Antlion Larvae
Authors: Beponis Lucy M. , O'Dea Rose E. , Ohl Valérie‐Anne , Ryan Mitchell P. , Backwell Patricia R. Y. , Binning Sandra A. , Haff Tonya M. 
Published: May 2014

AbstractPredators use a variety of strategies for capturing prey. Trap‐building predators can save on searching and encountering costs by investing in the construction and maintenance of traps such as webs and pits. However, what to do with partially consumed prey poses a potential problem. Antlion larvae (Myrmeleon acer) catch ants in conical pits, and dispose of partially consumed carcasses by flicking them a short distance away. We tested whether this prey‐disposal behaviour affects the effectiveness of antlion pits. We observed ant behaviour around artificially constructed pits and compared falls into pits with clean margins to those with conspecific ant carcasses or control objects around the pit edge. The presence of objects near pits affected the behaviour of live ants, and reduced the effectiveness of pits. Live ants spent the most time examining fresh ant carcasses, but the presence of any object near pits deterred pitfalls. Ants fell into pits significantly more often when pit edges were clean, suggesting that antlions could incur a prey capture cost from flicking carcasses from pits as well as from the accumulation of other debris around pit margins.
Infectious disease, shifting climates, and opportunistic predators: cumulative factors potentially impacting wild salmon declines
Authors: Miller Kristina M. , Teffer Amy , Tucker Strahan , Li Shaorong , Schulze Angela D. , Trudel Marc , Juanes Francis , Tabata Amy , Kaukinen Karia H. , Ginther Norma G. , Ming Tobi J. , Cooke Steven J. , Hipfner J. Mark , Patterson David A. , Hinch Scott G. 
Published: May 2014

AbstractEmerging diseases are impacting animals under high‐density culture, yet few studies assess their importance to wild populations. Microparasites selected for enhanced virulence in culture settings should be less successful maintaining infectivity in wild populations, as once the host dies, there are limited opportunities to infect new individuals. Instead, moderately virulent microparasites persisting for long periods across multiple environments are of greatest concern. Evolved resistance to endemic microparasites may reduce susceptibilities, but as barriers to microparasite distributions are weakened, and environments become more stressful, unexposed populations may be impacted and pathogenicity enhanced. We provide an overview of the evolutionary and ecological impacts of infectious diseases in wild salmon and suggest ways in which modern technologies can elucidate the microparasites of greatest potential import. We present four case studies that resolve microparasite impacts on adult salmon migration success, impact of river warming on microparasite replication, and infection status on susceptibility to predation. Future health of wild salmon must be considered in a holistic context that includes the cumulative or synergistic impacts of multiple stressors. These approaches will identify populations at greatest risk, critically needed to manage and potentially ameliorate the shifts in current or future trajectories of wild populations.