bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of various genetic polymorphisms on thiopurine treatment‐associated outcomes for Korean patients with Crohn's disease
Authors: Choi Rihwa , Lee Mi‐Na , Kim Kyunga , Baek Sun‐Young , Kim Tae Jun , Hong Sung Noh , Kim Young‐Ho , Lee Soo‐Youn 
Published: May 2020

AimsThis study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea.MethodsA total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia).ResultsThe median duration of thiopurine treatment was 47.0 months (range 6.0–153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti‐tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6‐thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05).ConclusionThe results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients.
Usefulness of therapeutic drug monitoring of rilpivirine and its relationship with virologic response and resistance in a cohort of naive and pretreated HIV‐infected patients
Authors: Néant Nadège , Lê Minh Patrick , Bouazza Naïm , Gattacceca Florence , Yazdanpanah Yazdan , Dhiver Catherine , Bregigeon Sylvie , Mokhtari Saadia , Peytavin Gilles , Tamalet Catherine , Descamps Diane , Lacarelle Bruno , Solas Caroline 
Published: May 2020

AimsThe purpose of this study was to assess the antiviral activity of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination and to describe the pharmacokinetics of rilpivirine and its association with resistance in clinical routine.MethodsA retrospective multicentre cohort study was performed in both naive and pretreated HIV patients receiving the once‐daily rilpivirine/emtricitabine/tenofovir disoproxil fumarate regimen. Immuno‐virologic and resistance data, and rilpivirine plasma trough concentrations were collected over the follow‐up. Statistical analyses were performed to evaluate the relationship between rilpivirine pharmacokinetics and virological response. Receiver operating characteristic (ROC) curve analysis was performed to determine the best target rilpivirine trough concentration.ResultsOverall, 379 patients were included. After a median follow‐up of 28 months, 26% of patients discontinued mainly due to toxicity and the virological success rate was 65.7%. Virological failure occurred in 5% of patients. A significant proportion of patients with HIV‐RNA > 40 copies/mL displayed rilpivirine plasma trough concentrations below the currently used 50 ng/mL efficacy threshold at both M6 (28%) and M12 (31%), in agreement with a significant lower median rilpivirine plasma trough concentration compared with patients virologically suppressed. Half of the patients with virologic failure who acquired rilpivirine resistance mutations had at least one suboptimal rilpivirine trough concentration. The optimal target for rilpivirine trough concentration was 70 ng/mL (sensitivity 75.4%; specificity 61.5%).ConclusionsThis study shows the impact of rilpivirine plasma trough concentration on both virological response and the emergence of rilpivirine mutations. Moreover, our results suggest that a higher target of rilpivirine trough concentration could be proposed in clinical practice.
Comparison of histomorphometry and microradiography of different implant designs to assess primary implant stability
Authors: Romanos Georgios , Damouras Michael , Veis Alexander A. , Hess Pablo , Schwarz Frank , Brandt Silvia 
Published: May 2020

AbstractObjectivesTo contribute toward optimizing the long‐term stability of dental implants. Our working hypothesis was that the degrees of immediate implant‐bone contact, and hence of primary stability, would demonstrably differ between implant systems due to their different external geometries and thread designs (macro‐design). This demonstration was provided in a bovine model (ex vivo) by employing and comparing histomorphometry and microradiography as evaluation methods.Materials and methodsA total of 120 implants, representing six different implant thread designs, were inserted following the recommended surgical protocol in ribs of freshly slaughtered cattle. Twenty specimens of implants with surrounding bone were prepared per system and were divided into two equally sized groups of 60 specimens for analysis by either histomorphometry or micro‐computed tomography. Data were analyzed by Mann‐Whitney U test (P ≤ .05).ResultsOne of the implant systems, featuring a slight tapered external geometry and a progressive thread design, consistently revealed the most favorable bone‐implant contacts in both histomorphometric and microradiographic evaluations. Overall, consistently higher values of bone‐implant contact were obtained with the microradiographic than the histomorphometric approach, and this difference reached statistical significance in three of the six implant systems tested.ConclusionsProgressive threads offering a bone‐condensing effect can significantly help to maximize implant‐bone contact percentages. Compared to histomorphometry, microradiography is likewise a suitable method to evaluate bone‐implant contact, offering the additional benefits of being noninvasive and less time consuming.
Life on a deadly trap: Buckleria paludum, a specialist herbivore of carnivorous sundew plants, licks mucilage from glands for defense
Authors: Osaki Haruka , Tagawa Kazuki 
Published: May 2020

AbstractCaterpillars of Buckleria spp. (Lepidoptera: Pterophoridae) have a unique feeding habit of eating trap leaves of carnivorous sundew plants (Drosera spp.). We observed the foraging behavior of Buckleria paludum on trap leaves of Drosera spp. and discussed how the moth species avoided being caught by trap leaves. In 81.5% (66/81) of encounters with glandular hairs on adaxial surfaces of Drosera trap leaves, B. paludum larvae licked mucilage and crawled on the processed hairs. The frequency of licking mucilage was significantly higher than the frequency of other behaviors such as eating glandular hairs, chewing bases of them without eating and ignoring when encountering secreted mucilage. Licking mucilage enables the caterpillars to move safely on trap leaves and prevents bending of glandular hairs.
Translational cognitive neuroscience of dementia with touchscreen operant chambers
Authors: Lee Ji Han , Cho So Yeon , Kim Eosu 
Published: May 2020

AbstractTranslational cognitive neuroscience of dementia involves mainly two areas: the validation of newly developed dementia animal models and the preclinical assessment of novel drug candidates in such model animals. To validate new animal models, a multidomain panel (battery) approach is essential in that dementia is, by definition, not merely a memory disorder but rather a multidomain cognitive/behavior disorder: animal modeling with a certain type of dementia would develop cognitive impairments in multiple (two at minimum) domains in a specific order according to unique spreading patterns of its neuropathology. In new drug development, the availability of highly sensitive tools assessing animal cognition is crucial to the detection of cognitive decline at the earliest stage of the disease, which may be an optimal time point to test a drug candidate. Using interspecies translatable (analogous) cognitive tasks would also be necessary to successfully predict the efficacy of drug candidates in subsequent clinical trials. Currently, this translational prediction is seriously limited given discrepancies in behavioral assessment methods between animals and humans in the preclinical and clinical trials, respectively. Since neurodegenerative diseases are often accompanied by not only cognitive but also affective and movement disorders, simultaneous assessment of task‐relevant locomotor behavior and motivation is also important to rule out the effects of potential confounders. The touchscreen operant platform may satisfy these needs by offering several advantages over conventional methodology. In this review, we discuss the touchscreen operant chamber system and highlight some of its qualities as a promising and desirable tool for translational research of dementia.
Human‐induced globalization of insular herpetofaunas
Authors: Capinha César , Marcolin Fabio , Reino Luís 
Published: May 2020

AbstractAimThe aim was to document the impact of the globalization of human activity on the biodiversity and biogeographical patterns of reptilian and amphibian faunas across islands worldwide.LocationIslands worldwide.Time periodFrom the 15th century to the present time.Major taxa studiedReptiles and amphibians.MethodsWe compiled lists of the reptilian and amphibian species that occurred on islands before the 15th century and of those that occur currently. For each species group, we calculated differences in species richness and in compositional similarities among islands, between the two periods. Regression models were used: (a) to associate the observed differences with spatial patterns of geographical, climatic, biotic and human factors; and (b) to quantify changes in the relative importance of non‐human factors in explaining the spatial patterns of species richness and compositional similarity.ResultsThe richness of reptile and amphibian species increased consistently across islands worldwide. Hotspots of increase were detected in the Caribbean and the Indian Ocean. The composition of species assemblages was substantially homogenized; this was particularly true for amphibians within the Caribbean Sea and for reptiles within the Caribbean Sea and Indian Ocean and between the Indian and the Pacific Oceans. Our results showed that spatial patterns of change in species richness and compositional similarity are driven by human and natural factors. The driving role of mean annual temperature is particularly consistent, and current reptile richness and compositional similarity patterns for both species groups are increasingly being shaped by the global temperature gradient.Main conclusionsThe globalization of human activity is eroding the regionalized character of insular herpetofaunas and leading to the emergence of global‐scale gradients of taxonomic composition and species richness. Projections of increasing rates of biological invasions, extinctions and climate change suggest that these changes are likely to be aggravated even further in the coming decades.
Patient and Public Involvement of young people with a chronic condition in projects in health and social care: A scoping review
Authors: van Schelven Femke , Boeije Hennie , Mariën Veerle , Rademakers Jany 
Published: May 2020

AbstractBackgroundThe involvement of young people with a chronic condition in research and implementation projects in health and social care receives growing attention. Yet, there is a lack of conceptual clarity of this so‐called ‘Patient and Public Involvement’ (PPI) and methods to systematically evaluate it are absent. This scoping review aimed to gain insight into developments in the existing literature on PPI of young people with a chronic condition by mapping reported definitions, goals, activities, experiences and impact.MethodsWe conducted searches in Cinahl, Embase, PsycINFO, PubMed and Scopus. Included articles described involvement of young people with a chronic condition in research and implementation projects, contained empirical data, were written in English and were published after 1990. Two researchers independently carried out the data extraction.ResultsTwenty‐three studies out of 4993 initial hits met the inclusion criteria. We found great variation in definitions and operationalizations of PPI. Reflections of authors on the process of PPI and its impact were similar and did not change over the years.Discussion and conclusionLimited progress in the evidence base of the impact of PPI with young people with a chronic condition was found. Over the years, studies continue to report similar experiences and challenges. In order to move forward, we suggest future research to make connections to existing work instead, to include thorough descriptions of what is understood by PPI and how this is translated into activities, and to use systematic and objective, but also flexible, methods to measure its impact.
Environmental barrier coatings using low pressure plasma spray process
Authors: Chen Dianying , Pegler Aaron , Dorfman Mitch 
Published: May 2020

AbstractYb2Si2O7/Si bilayer environmental barrier coatings (EBCs) on SiC ceramic substrate were produced by low pressure plasma spray (LPPS) process. Phase composition, microstructure, and thermal durability of LPPS Yb2Si2O7/Si coating were investigated. XRD analysis indicated that the coating is mainly composed of Yb2Si2O7 with ~15.5v% Yb2SiO5 phases. The LPPS EBCs have a dense microstructure with porosity less than 4%. Adhesion strength measurement indicated the LPPS EBCs have an average adhesion strength of 29.1 ± 0.8 MPa. Furnace cycle test (FCT) on the coatings in air at 1316°C was performed and the test ran for 900 cycles and there was no coating spallation/failure for LPPS Yb2Si2O7/Si EBCs. The FCT results demonstrated the excellent thermal cycle durability of LPPS EBCs. Oxidation kinetics investigation of LPPS EBCs in flowing 90% H2O (g)+10% air at 1316°C showed that the thermally grown oxide (TGO) growth rate is close to the oxidation rate of pure Si in dry air and is significantly lower than that in water vapor environment. The LPPS process is promising in making highly durable Yb2Si2O7‐based dense EBCs by impeding diffusion and ingression of water vapor/O2.
Natural antiviral compound silvestrol modulates human monocyte‐derived macrophages and dendritic cells
Authors: Blum Leonard , Geisslinger Gerd , Parnham Michael J. , Grünweller Arnold , Schiffmann Susanne 
Published: May 2020

AbstractOutbreaks of infections with viruses like Sars‐CoV‐2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona‐, Ebola‐, Zika‐, Picorna‐, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down‐regulated several pro‐ and anti‐inflammatory cytokines (IL‐6, IL‐8, IL‐10, CCL2, CCL18) and increased TNF‐α during differentiation and activation of M1‐macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti‐inflammatory potential of M2‐macrophages by increasing expression of anti‐inflammatory surface markers CD206, TREM2 and reducing release of pro‐inflammatory IL‐8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down‐regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status.
Influence of adult diet on fitness and reproductive traits of the egg parasitoid Anagrus virlai (Hymenoptera: Mymaridae), a potential biocontrol agent against the corn leafhopper
Authors: Hill Jorge Guillermo , Aguirre María Belén , Bruzzone Octavio Augusto , Virla Eduardo Gabriel , Luft Albarracin Erica 
Published: May 2020

AbstractDalbulus maidis is the most important leafhopper pest of maize in the Americas. Anagrus virlai is an egg parasitoid commonly associated with the corn leafhopper. We evaluated whether the performance of A. virlai is dependent on different diets provided during 24 hr or throughout adult female lifetime. Additionally, functional response of A. virlai on D. maidis eggs using maize leaves containing honeydew plus honey was described. A. virlai is a mostly pro‐ovigenic autogenic species whose females are able to parasitize eggs immediately after emergence. We found that wasps oviposit the majority of their eggs in the first day of their adult life. Realized lifetime fecundity and lifetime potential fecundity did not differ significantly among treatments, but longevity and egg production increased when honey was added to diet. Data were consistent with an intermediate functional response between type II and III, but closer to type II, indicating a high parasitism rate at low host densities and a decrease in the oviposition rate at high host densities, due to a possible egg limitation. Our results suggest that carbohydrate food sources (honeydew and honey) might not be the factor limiting reproductive success during the first 24 hr. Food supply, however, might influence egg maturation and survivorship of wasps, thus potentially enhancing biological pest control when hosts are scarce in the course of the first few days of adulthood.
Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes
Authors: Huang Yan , Mao Qian‐Ying , Shi Xi‐Jin , Cong Xin , Zhang Yan , Wu Li‐Ling , Yu Guang‐Yan , Xiang Ruo‐Lan 
Published: May 2020

AbstractTight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes‐induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type‐2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin‐1 (Cldn1) and claudin‐3 (Cldn3) were increased, whereas those of claudin‐4 (Cldn4), occludin (Ocln), and zonula occludens‐1 (ZO‐1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin‐10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes‐induced hyposalivation.
Predicting MGMT Promoter Methylation of Glioblastoma from Dynamic Susceptibility Contrast Perfusion: A Radiomic Approach
Authors: Crisi Girolamo , Filice Silvano 
Published: May 2020

ABSTRACTBACKGROUND AND PURPOSEThis study aims to investigate whether radiomic quantitative image features (IFs) from perfusion dynamic susceptibility contrast magnetic resonance imaging (DSC‐MRI) retain sufficient strength to predict O6‐methylguanine–DNA methyltransferase promoter methylation (MGMT_pm) in newly diagnosed glioblastoma (GB) patients.METHODSWe retrospectively reviewed the perfusion DSC‐MRI of 59 patients with GB. Patients were classified into three groups: (1) unmethylated if MGMT_pm ≤ 9% (UM); (2) intermediate‐methylated if MGMT_pm ranged between 10% and 29% (IM); (3) methylated if MGMT_pm ≥ 30% (M). A total of 92 quantitative IFs were obtained from relative cerebral blood volume and relative cerebral blood flow maps. The Mann‐Whitney U‐test was applied to assess whether there were statistical differences in IFs between patient groups. Those IFs showing significant difference between two patient groups were termed relevant IFs (rIFs). rIFs were uploaded to a machine learning model to predict the MGMT_pm.RESULTSNo rIFs were found between UM and IM groups. Fourteen rIFs were found among UM‐M, IM‐M, and (UM + IM)‐M groups. We built a multilayer perceptron deep learning model that classified patients as belonging to UM + IM and M group. The model performed well with 75% sensitivity, 85% specificity, and an area under the receiver‐operating curve of .84.CONCLUSIONrIFs from perfusion DSC‐MRI are potential biomarkers in GBs with a ≥30% MGMT_pm. Otherwise, unmethylated and intermediate‐methylated GBs lack of rIFs. Five of 14 rIFs show sufficient strength to build an accurate prediction model of MGMT_pm.
Bootstrap procedures for detecting multiple persistence shifts in heteroskedastic time series
Authors: Kejriwal Mohitosh , Yu Xuewen , Perron Pierre 
Published: May 2020

This article proposes new bootstrap procedures for detecting multiple persistence shifts in a time series driven by non‐stationary volatility. The assumed volatility process can accommodate discrete breaks, smooth transition variation as well as trending volatility. We develop wild bootstrap sup‐Wald tests of the null hypothesis that the process is either stationary [I(0)] or has a unit root [I(1)] throughout the sample. We also propose a sequential procedure to estimate the number of persistence breaks based on ordering the regime‐specific bootstrap p‐values. The asymptotic validity of the advocated procedures is established both under the null of stability and a variety of persistence change alternatives. A comparison with existing tests that assume homoskedasticity illustrates the finite sample improvements offered by our methods. An application to OECD inflation rates highlights the empirical relevance of the proposed approach and weakens the case for persistence change relative to existing procedures.