bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic protection against acute flurothyl‐induced seizures by adjuvant treatment of the ketogenic diet with the type 2 diabetes drug pioglitazone
Authors: Simeone Timothy A. , Matthews Stephanie A. , Simeone Kristina A. 
Published: May 2017

SummaryObjectiveWe have previously found that the transcription factor peroxisome proliferator‐activated receptor γ (PPARγ) contributes to the mechanism of action of the ketogenic diet (KD), an established treatment for pediatric refractory epilepsy. We have found that the KD increases brain PPARγ and that inhibition or genetic loss of PPARγ prevents the antiseizure effects of the KD on (1) acutely induced seizures in nonepileptic mice and (2) spontaneous recurrent seizures in epileptic mice. Here, we tested the hypothesis that adjuvant treatment of KD‐treated mice with a PPARγ agonist, pioglitazone, would result in an additive effect.MethodsAcute seizures were induced in three groups of C57Bl/6 mice by inhalation exposure to flurothyl gas. In Group 1, mice were weaned onto either a standard diet or KD comprised of a fat:carbohydrate/protein ratio of either 6:1, 3:1, or 1:1 for 2 weeks. In Group 2, vehicle or pioglitazone (0.1, 1, 10, 80 mg/kg) was administered 4 h prior to flurothyl exposure. In Group 3, vehicle or increasing doses of pioglitazone were administered to KD‐treated mice 4 h prior to flurothyl exposure. Latency times to clonic seizures and generalized tonic–clonic (GTC) seizures were recorded, and isobolographic analysis was used to determine combinatorial interactions.ResultsNeither KD treatment nor pioglitazone alone or in combination affected clonic seizures. However, the latency to GTC seizures was dose‐dependently and significantly increased by both KD (~57%, p < 0.05) and pioglitazone (~28%, p < 0.05). Coadministration of an ineffective 1:1 KD and pioglitazone resulted in ~47–55% (p < 0.05) increase in latency to GTC. Isobolographic analysis indicated a synergistic interaction of the KD and pioglitazone.SignificanceThese results suggest coadministration may enable reduction of the KD ratio without loss of seizure protection. Such adjuvant treatment could improve quality of life and limit adverse effects of a classic KD or high‐dose pioglitazone.
Predictive value of different prostate‐specific antigen‐based markers in men with baseline total prostate‐specific antigen <2.0 ng/mL
Authors: Fujizuka Yuji , Ito Kazuto , Oki Ryo , Suzuki Rie , Sekine Yoshitaka , Koike Hidekazu , Matsui Hiroshi , Shibata Yasuhiro , Suzuki Kazuhiro 
Published: May 2017

ObjectivesTo investigate the predictive value of various molecular forms of prostate‐specific antigen in men with baseline prostate‐specific antigen <2.0 ng/mL.MethodsThe case cohort comprised 150 men with a baseline prostate‐specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate‐specific antigen‐ and age‐adjusted men who did not develop prostate cancer. Serum prostate‐specific antigen, free prostate‐specific antigen, and [−2] proenzyme prostate‐specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate‐specific antigen‐ and [−2] proenzyme prostate‐specific antigen‐related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated.ResultsThe baseline free to total prostate‐specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate‐specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [−2] proenzyme prostate‐specific antigen/free prostate‐specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores.ConclusionsFree to total prostate‐specific antigen ratio in men with low baseline prostate‐specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [−2] proenzyme prostate‐specific antigen‐related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance.
Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?
Authors: Moonen Avalon , Garsia Roger , Youssef Peter , Torzillo Paul , Corte Tamera , Boehm Christiane , Cordina Rachael , Celermajer David , Lau Edmund 
Published: May 2017

AbstractBackgroundIn Australia, government‐subsidised treatment of pulmonary arterial hypertension (PAH) is limited to monotherapy. Recent international guidelines advocate that initial combination therapy be considered for all symptomatic PAH patients.AimTo characterise ‘real‐life’ outcomes in PAH patients initiated on monotherapy.MethodsWe performed a retrospective analysis of 100 consecutive PAH patients at a single centre who were commenced on monotherapy for PAH between 2004 and 2015. The composite clinical end‐point of ‘treatment failure’ was prospectively defined as (i) >15% fall in 6‐min walk distance (6MWD) on follow up, (ii) physician judgement of inadequate treatment response, (iii) adverse drug effect requiring cessation and (iv) death or transplantation.ResultsAt initiation of therapy, mean age was 54 ± 18 years, and underlying diagnoses included idiopathic (36%), connective tissue disease‐associated (37%) and congenital heart disease‐associated‐PAH (25%). Baseline 6MWD was 360 ± 140 m, and 75% were in either the New York Heart Association functional classes III or IV. Over a median follow up of 38 months (interquartile range 20–67), 62% of the subjects met the criteria for a clinical failure event. Median time to monotherapy failure was 24 months (95% confidence interval 14–34), with death or transplantation being the most common clinical failure event. Estimated 1‐, 3‐ and 5‐year survival rates from time of treatment initiation were 92, 75 and 66%.ConclusionThe majority of patients failed initial monotherapy therapy within 2 years of treatment initiation. Broader access to approved PAH agents is needed to enable combination therapy in line with evidence‐based international guidelines.
Effects of temperature and electric field on upconversion luminescence in Er3+‐Yb3+ codoped Ba0.8Sr0.2TiO3 ferroelectric ceramics
Authors: Sun Qiu , Wang Weihua , Pan Yunxing , Liu Zhikai , Chen Xiangqun , Ye Mao 
Published: May 2017

AbstractOptical and electrical properties of 1%Er3+ and different Yb3+ content (1ExY) codoped Ba0.8Sr0.2TiO3 (BST) ferroelectric ceramics fabricated by the solid‐phase reaction were investigated. Under 980 nm pump condition, two green emission bands at 525 and 549 nm wavelength corresponding to, 2H11/2→4I15/2 and 2S3/2→4I15/2 transitions, and two red emission bands at 655 and 668 nm wavelength attributed to 4F9/2→4I15/2 transition are observed. The temperature‐sensing behaviors, calculated by the intensity ratio I525/I549 suggested that, the maximum sensitivity of the green emission of the 1E8Y‐BST ceramics is 1.07×10−2 K‐1 at 293 K. Furthermore, the maximum sensitivity of 1E6Y‐BST and 1E11Y‐BST ceramics were obtained around the Curie temperature. The fluorescence lifetime of 1E8Y‐BST ceramics for 2H11/2 level and 2S3/2 level shortened with the increase in the temperatures. Moreover, the upconversion (UC) luminescence intensity of 1E8Y‐BST decreased with the increase in the external electric field and had a mutation at the coercive electric field (Ec) of about 1.24 kV/cm, which revealed that the electric field had influence on the UC luminescence.
Multilocus phylogeny of East African gerbils (Rodentia, Gerbilliscus) illuminates the history of the Somali‐Masai savanna
Authors: Aghová Tatiana , Šumbera Radim , Piálek Lubomír , Mikula Ondřej , McDonough Molly M. , Lavrenchenko Leonid A. , Meheretu Yonas , Mbau Judith S. , Bryja Josef 
Published: May 2017

AbstractAimThe rodent genus Gerbilliscus is widespread in savannas throughout sub‐Saharan Africa. The eastern clade comprises four species with distributions centred in the Somali‐Masai biogeographical region of East Africa. We investigated the genetic diversity of the group with a view to illuminating the historical (Plio‐Pleistocene) processes that formed contemporary biota of the understudied Somali‐Masai region.LocationSomali‐Masai savanna, East Africa.MethodsWe performed multilocus genetic analyses of 240 samples from 112 localities, combining genotyping of recently collected samples (N = 145), 454‐pyrosequencing of museum material (N = 34) and published sequences (N = 61). We used Bayesian and maximum likelihood approaches for phylogenetic reconstructions, and coalescent‐based methods to delimit species. We also estimated divergence times and modelled recent and past distributions to reconstruct the major evolutionary influences in the Somali‐Masai region during the Plio‐Pleistocene.ResultsGenetic analyses provided evidence for six lineages, possibly corresponding to distinct species. The two main species groups (with two and four putative species, respectively) have overlapping distributions, but species within each group are distributed parapatrically. The origin of the eastern clade dates back to the Pliocene, while individual species diverged in the Pleistocene. The distribution of genetic diversity and ecological niche modelling point to the importance of the Rift Valley and the presence of unsuitable xeric habitats in the allopatric diversification of Gerbilliscus in the Somali‐Masai savanna within the last 5 Myr.ConclusionsThis is the first detailed phylo(bio‐)geographical study of animals with predominant distribution in the Somali‐Masai region. It revealed currently underestimated diversity of eastern clade of Gerbilliscus and proposed a scenario of its evolution during Plio‐Pleistocene. Conspicuous genetic structure of these taxa can be now used to test detailed phylogeographical hypotheses related to Plio‐Pleistocene history of gerbils and, to some extent, also biota of Somali‐Masai bioregion in general.
Efficacy and tolerability of initial high vs low doses of S‐(‐)‐amlodipine in hypertension
Authors: Chen Qi , Huang Qi‐Fang , Kang Yuan‐Yuan , Xu Shao‐Kun , Liu Chang‐Yuan , Li Yan , Wang Ji‐Guang 
Published: May 2017

In an 8‐week randomized trial of patients with mild or moderate hypertension, the authors investigated the efficacy and tolerability of initial high (5.0 mg/d) vs low (2.5 mg/d) doses of S‐(‐)‐amlodipine (equivalent to 5 and 10 mg of racemic amlodipine, respectively). In the S‐(‐)‐amlodipine 2.5‐mg group (n=263), 24‐hour ambulatory systolic/diastolic blood pressure (±standard deviation) decreased from 131.5±15.0/82.1±10.7 mm Hg at baseline to 126.0±13.5/78.5±9.5 mm Hg at 8 weeks of follow‐up by a least square mean (±standard error) change of 6.0±0.6/3.8±0.4 mm Hg. In the S‐(‐)‐amlodipine 5‐mg group (n=260), the corresponding changes were from 133.6±13.7/83.1±9.9 mm Hg to 125.0±12.0/78.2±8.9 mm Hg by 8.1±0.6/4.7±0.4 mm Hg, respectively. The between‐group differences in changes in 24‐hour systolic/diastolic blood pressure were 2.1/0.9 (P=.02/.17) mm Hg. Similar trends were observed for daytime and nighttime ambulatory and clinic blood pressure. The incidence rate was similar for all adverse events. An initial high dose of S‐(‐)‐amlodipine improved ambulatory blood pressure control with similar tolerability as an initial low dose in hypertension.
Clinical and microbiological effects of the adjunctive use of probiotics in the treatment of gingivitis: A randomized controlled clinical trial
Authors: Montero Eduardo , Iniesta Margarita , Rodrigo Marta , Marín María José , Figuero Elena , Herrera David , Sanz Mariano 
Published: May 2017

AbstractAimTo evaluate the efficacy of a probiotic combination in the treatment of gingivitis and to assess its impact on the subgingival microbiota.Materials and MethodsA placebo‐controlled clinical trial was conducted in gingivitis subjects during 6 weeks. Test treatment consisted of the administration of two oral tablets per day containing the probiotic strains Lactobacillus plantarum, Lactobacillus brevis and Pediococcus acidilactici; the control group received the same tablets but without live bacteria. The main outcome variable was the changes in gingival index (GI). Subgingival samples were collected and analysed by quantitative polymerase chain reaction (qPCR) for five putative periodontal pathogens. Outcome variables were compared between and within groups, and multiple regression analysis was performed.ResultsA total of 59 patients (29 tests, 30 placebos) were included in the analysis. Both treatment groups experienced a statistically significant improvement in mean GI (p < .0001), but no differences between treatment groups were found for any clinical index. A significantly higher reduction in the number of sites with higher GI scores (GI = 3 at baseline) was observed in the test group. In subgingival samples, a significant reduction in T. forsythia was significant only in the test group (p < .008).ConclusionsThe use of probiotic tablets containing L. plantarum, L. brevis and P. acidilactici did not lead to significant changes in mean GI; although a significant reduction occurred in the number of sites with severe inflammation. Furthermore, the adjunctive use of this probiotic promoted a significant microbiological impact.
Performance of a new real‐time continuous glucose monitoring system: A multicenter pilot study
Authors: Zhou Jian , Zhang Shuo , Li Liang , Wang Yufei , Lu Wei , Sheng Chunjun , Li Yiming , Bao Yuqian , Jia Weiping 
Published: May 2017

AbstractAims/IntroductionThe present study aimed to investigate the performance of a new real‐time continuous glucose monitoring system.Materials and MethodsInterstitial glucose levels were monitored for 7 days in 63 patients with type 1 or type 2 diabetes using the Medtrum A6 TouchCare® CGM System. Venous blood was collected on a randomized day of the wear period. Plasma glucose levels were measured as reference values.ResultsAmong 1,678 paired sensor–reference values, 90.5% (95% confidence interval 89.1–91.9%) were within ±20%/20 mg/dL of the reference values, with a mean absolute relative difference of 9.1 ± 8.7% (95% CI: 8.9–9.2%). The percentages of paired sensor–reference values falling within zone A and B of the Clarke error grid analysis (EGA) and the type 1 diabetes consensus EGA were 99.1 and 99.8%. Continuous EGA showed that the percentages of accurate readings, benign errors, and erroneous readings were 89.9, 6.3 and 3.8%, respectively. Surveillance EGA showed that 90.6, 9.2, and 0.2% of sensor–reference values with no, slight and lower moderate risk, respectively. The mean absolute relative difference was 16.6, and 96.0% of the sensor values fell within zones A and B of the consensus EGA for hypoglycemia. More than 85% of sensor values were within ±20%/20 mg/dL of reference values, the mean absolute relative difference was <11, and >99.5% of the sensor values fell in zones A and B of the consensus EGA.ConclusionsThe Medtrum real‐time continuous glucose monitoring system was numerically and clinically accurate over a large glucose range across 7 days of wear.
Phase I randomized study of KHK4083, an anti‐OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis
Authors: Papp K.A. , Gooderham M.J. , Girard G. , Raman M. , Strout V. 
Published: May 2017

AbstractBackgroundOX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40.ObjectiveThe primary aim of this first‐in‐human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity.MethodsIn phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double‐blind, placebo‐controlled, ascending single‐dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC.ResultsThere were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment‐related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose‐related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti‐KHK4083 antibodies following treatment. Mean elimination half‐life (t1/2) increased with dose, maximum serum concentration increased in a dose‐proportional manner, and area under the serum concentration–time curve increased in a more than dose‐proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC.ConclusionKHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose‐limiting AEs.
Describing mate preference functions and other function‐valued traits
Authors: Kilmer J. T. , Fowler‐Finn K. D. , Gray D. A. , Höbel G. , Rebar D. , Reichert M. S. , Rodríguez R. L. 
Published: May 2017

AbstractMate preferences are important causes of sexual selection. They shape the evolution of sexual ornaments and displays, sometimes maintaining genetic diversity and sometimes promoting speciation. Mate preferences can be challenging to study because they are expressed in animal brains and because they are a function of the features of potential mates that are encountered. Describing them requires taking this into account. We present a method for describing and analysing mate preference functions, and introduce a freely available computer program that implements the method. We give an overview of how the program works, and we discuss how it can be used to visualize and quantitatively analyse preference functions. In addition, we provide an informal review of different methods of testing mate preferences, with recommendations for how best to set up experiments on mate preferences. Although the program was written with mate preferences in mind, it can be used to study any function‐valued trait, and we hope researchers will take advantage of it across a broad range of traits.
Interspecific competition counteracts negative effects of dispersal on adaptation of an arthropod herbivore to a new host
Authors: Alzate A. , Bisschop K. , Etienne R. S. , Bonte D. 
Published: May 2017

AbstractDispersal and competition have both been suggested to drive variation in adaptability to a new environment, either positively or negatively. A simultaneous experimental test of both mechanisms is however lacking. Here, we experimentally investigate how population dynamics and local adaptation to a new host plant in a model species, the two‐spotted spider mite (Tetranychus urticae), are affected by dispersal from a stock population (no‐adapted) and competition with an already adapted spider mite species (Tetranychus evansi). For the population dynamics, we find that competition generally reduces population size and increases the risk of population extinction. However, these negative effects are counteracted by dispersal. For local adaptation, the roles of competition and dispersal are reversed. Without competition, dispersal exerts a negative effect on adaptation (measured as fecundity) to a novel host and females receiving the highest number of immigrants performed similarly to the stock population females. By contrast, with competition, adding more immigrants did not result in a lower fecundity. Females from populations with competition receiving the highest number of immigrants had a significantly higher fecundity than females from populations without competition (same dispersal treatment) and than the stock population females. We suggest that by exerting a stronger selection on the adapting populations, competition can counteract the migration load effect of dispersal. Interestingly, adaptation to the new host does not significantly reduce performance on the ancestral host, regardless of dispersal rate or competition. Our results highlight that assessments of how species can adapt to changing conditions need to jointly consider connectivity and the community context.
Three‐dimensional stereophotogrammetric analysis of 50 smiles: A study of dento‐facial proportions
Authors: Ceinos R. , Lupi L. , Tellier A. , Bertrand M. F. 
Published: May 2017

AbstractObjectivesThe purpose of this study was to analyze 50 smiles using 3D stereophotogrammetry (3D‐spg)‐based facial reconstruction, to calculate ratios involving measurements of the distances between dental and facial landmarks and to compare these ratios with the golden ratio φ (1.618).Materials and MethodsFifty subjects with no obvious malocclusion participated in this study. For each subject, 4 photographs were acquired using the LifeViz Mini™, an absolute calibration 3D‐spg system. Facial and dental landmarks (based on Farkas' definitions) were fixed, and 8 distances were measured. Four ratios were then calculated and compared with the value of 1.618.ResultsThe ratio “incisal edge of the maxillary central incisor—lower border of the chin/subnasal point—incisal edge of the maxillary central incisor” (IE‐Me/SN‐IE) was 1.693 ± 0.190, the ratio “right endocanthion—left endocanthion/right exocanthion—right endocanthion” was 1.582 ± 0.173, the ratio “incisal edge of the maxillary central incisor—distal edge of the right canine/distal edge of the right canine—right labial commissure” was 1.670 ± 0.355, and the ratio “right labial commissure—left labial commissure/distal edge of the right canine—distal edge of the left canine” was 1.602 ± 0.136. In contrast, the vertical ratio IE‐Me/SN‐IE significantly differed from the golden ratio (1 sample t test, P = .009).ConclusionThis study revealed that the observed ratios were surprisingly close to the golden ratio. Only the vertical ratio differed from the golden ratio, whereas the horizontal ratios appear to be adequately approximated by φ.CLINICAL SIGNIFICANCEIf the distances from reference points of the face to teeth within a harmonious smile exhibited recurring esthetic proportions, knowledge of such ratios would provide an additional tool for the elaboration of esthetic treatment plans. In addition, this knowledge could provide guidance when planning tooth positions and dental proportions by encouraging consideration of the global nature of the oro‐facial sphere.