bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia
Authors: Ervik Arne Olav , Hafstad Solvang Stein-Erik , Nordrehaug Jan Erik , Ueland Per Magne , Midttun Øivind , Hildre Audun , McCann Adrian , Nygård Ottar , Aarsland Dag , Giil Lasse Melvaer 
Published: November 2019

Background: The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim: To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis. Methods: A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ε4 gene variant allele status was classified as one or more ε4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney U tests and linear mixed-effects models were used for statistical analysis. Results: There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOEε4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOEε4 compared to those with the APOEε4 allele ( P-value of the interactions < .05). Conclusions: Kynurenic acid, quinolinic acid, picolinic acid, and the kynurenine-to-tryptophan ratio were associated with a significant increase in cognitive decline when the APOEε4 variant was absent, whereas there was a relatively less decline when the APOEε4 variant was present.
Mussel Adhesive Protein as a Promising Alternative to Fibrin for Scaffold Fixation during Cartilage Repair Surgery
Authors: Ivarsson Mikael , Prenkert Malin , Cheema Annam , Wretenberg Per , Andjelkov Nenad 
Published: November 2019

Objective Fibrin has been used as a standard material for scaffold fixation during cartilage repair surgery. Most of the commercially available fibrin preparations need an additional method for scaffold fixation, most often with sutures, thus damaging the surrounding healthy cartilage. There is therefore a need to find alternatives to this method. In our study, we have investigated the potential possibility to use mussel adhesive protein as such an alternative. Methods In this study, hydrophobic plastic was coated with the mussel adhesive protein Mefp-1 as well as with other cell adhesives (poly-lysine, fibronectin, and collagen). Human keratinocytes and chondrocytes were seeded on these substrates at 37°C in culture medium, followed by analysis of attachment and proliferation by crystal violet staining and metabolic labelling. Performance of Mefp-1 and fibrin as tissue glues were estimated by tensional force resistance measurement of moist porcine dermis (as a correlate to scaffold) glued to dermis, cartilage, or bone at 37°C. Results Mefp-1 supported maximal cell attachment at a coating density of approximately 1 µg/cm2. This was at least as good as the other adhesives tested. In addition, it supported cell proliferation at least as good as regular tissue culture plastic over a 7-day period. Measurement of tensional force resistance showed that Mefp-1 performed equally well as fibrin when porcine dermis was glued to cartilage and bone at the same concentration. Separation of the moist tissues after 15-minute incubation required a force of approximately 1 N/cm2 for both compounds. Conclusions Mefp-1 show properties that qualify it as a compound that potentially could replace fibrin as a tissue glue for scaffold fixation. Given the possibilities to modify this protein by bioengineering, it is likely that the properties can be further improved.
Characteristics and firing behaviour of the under-Numidian clay deposits from the Jijel region (northeast Algeria): potential use in the ceramics industry
Authors: Baghdad Abdelmalek , Bouazi Rekia , Bouftouha Youcef , Hatert Frédéric , Fagel Nathalie 
Published: November 2019

AbstractThe Numidian Aquitano-Burdigalian nappe from the Jijel region (northeast Algeria) shows an important clay-rich basal series. In this study, seven representative clay samples were collected from the Djimla and El-Milia areas of this region in order to analyse their mineralogy using X-ray diffraction and Fourier-transform infrared spectroscopy, chemical composition by X-ray fluorescence, particle size, plasticity, morphology by scanning electron microscopy and their ceramic properties. Samples were prepared by pressing the clays and firing them at 800–1100°C, and bulk density, water absorption, linear firing shrinkage, weight loss and bending strength values were determined on the fired samples. The clays are mainly composed of kaolinite and illite, with a small amount of 10–14 Å interstratified clay minerals and chlorite, associated with quartz and feldspars. The main oxides in the samples were SiO2, Al2O3and Fe2O3. The clays may be classified as moderately plastic according to their Atterberg limits. Ceramic tiles have been produced by dry pressing. At all tested firing temperatures, the clays present the required standard values for linear firing shrinkage, weight loss, bulk density, water absorption and bending strength, and they are defect-free. The main transformations were observed at 1000°C with the appearance of new crystalline phases. The measured technological properties of the investigated deposits confirm that the Numidian clays from the Djimla and El-Milia regions are suitable materials for the production of high-quality structural ceramics.
Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder
Authors: Giri Neelam , Ravichandran Sandhiya , Wang Youjin , Gadalla Shahinaz M. , Alter Blanche P. , Fontana Joseph , Savage Sharon A. 
Published: November 2019

Pulmonary fibrosis and pulmonary arteriovenous malformations are known manifestations of dyskeratosis congenita (DC), a telomere biology disorder (TBD) and inherited bone marrow failure syndrome caused by germline mutations in telomere maintenance genes resulting in very short telomeres. Baseline pulmonary function tests (PFTs) and long-term clinical outcomes have not been thoroughly studied in DC/TBDs.In this retrospective study, 43 patients with DC and 67 unaffected relatives underwent baseline PFTs and were followed for a median of 8 years (range 1–14). Logistic regression and competing risk models were used to compare PFT results in relation to clinical and genetic characteristics, and patient outcomes.Restrictive abnormalities on spirometry and moderate-to-severe reduction in diffusing capacity of the lung for carbon monoxide were significantly more frequent in patients with DC than relatives (42%versus12%; p=0.008). The cumulative incidence of pulmonary disease by age 20 years was 55% in patients with DC with baseline PFT abnormalities compared with 17% in those with normal PFTs (p=0.02). None of the relatives developed pulmonary disease. X-linked recessive, autosomal recessive inheritance or heterozygousTINF2variants were associated with early-onset pulmonary disease that mainly developed after haematopoietic cell transplantation (HCT). Overall, seven of 14 patients developed pulmonary disease post-HCT at a median of 4.7 years (range 0.7–12). The cumulative incidence of pulmonary fibrosis in patients with heterozygous non-TINF2pathogenic variants was 70% by age 60 years.Baseline PFT abnormalities are common in patients with DC and associated with progression to significant pulmonary disease. Prospective studies are warranted to facilitate clinical trial development for patients with DC and related TBDs.
Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene
Authors: Barbieri R. , Bertelli S. , Pusch M. , Gavazzo P. 
Published: November 2019

Abstract
Background
Familial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na+ channel Nav1.1, and FHM caused by mutations of SCN1A is named FHM3. For 7 of the 12 known FHM3-causing SCNA1 mutations functional consequences have been investigated, and even if gain of function effect seems to be a predominant phenotype, for several mutations conflicting results have been obtained and the available data do not reveal a univocal FHM3 pathomechanism.

Methods
To obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems.

Results
With the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na+ current blocker, on the above mentioned mutants as well as on previously characterized ones (L1649Q, L1670 W, F1774S). GS967 inhibited persistent currents of all SCNA1 FMH3-related mutants and dramatically slowed the recovery from fast inactivation of WT and mutants, consistent with the hypothesis that GS967 specifically binds to and thereby stabilizes the fast inactivated state.
Simulation of neuronal firing showed that enhanced persistent currents cause an increase of ionic fluxes during action potential repolarization and consequent accumulation of K+ and/or exhaustion of neuronal energy resources. In silico application of GS967 largely reduced net ionic currents in neurons without impairing excitability.

Conclusion
In conclusion, late Na+ current blockers appear a promising specific pharmacological treatment of FHM3.
Optimized grouping to increase accuracy of prediction of breeding values based on group records in genomic selection breeding programs
Authors: Chu Thinh T. , Bastiaansen John W. M. , Berg Peer , Komen Hans 
Published: November 2019

AbstractBackgroundPhenotypic records of group means or group sums are a good alternative to individual records for some difficult to measure, but economically important traits such as feed efficiency or egg production. Accuracy of predicted breeding values based on group records increases with increasing relationships between group members. The classical way to form groups with more closely-related animals is based on pedigree information. When genotyping information is available before phenotyping, its use to form groups may further increase the accuracy of prediction from group records. This study analyzed two grouping methods based on genomic information: (1) unsupervised clustering implemented in the STRUCTURE software and (2) supervised clustering that models genomic relationships.ResultsUsing genomic best linear unbiased prediction (GBLUP) models, estimates of the genetic variance based on group records were consistent with those based on individual records. When genomic information was available to constitute the groups, genomic relationship coefficients between group members were higher than when random grouping of paternal half-sibs and of full-sibs was applied. Grouping methods that are based on genomic information resulted in higher accuracy of genomic estimated breeding values (GEBV) prediction compared to random grouping. The increase was ~ 1.5% for full-sibs and ~ 11.5% for paternal half-sibs. In addition, grouping methods that are based on genomic information led to lower coancestry coefficients between the top animals ranked by GEBV. Of the two proposed methods, supervised clustering was superior in terms of accuracy, computation requirements and applicability. By adding surplus genotyped offspring (more genotyped offspring than required to fill the groups), the advantage of supervised clustering increased by up to 4.5% compared to random grouping of full-sibs, and by 14.7% compared to random grouping of paternal half-sibs. This advantage also increased with increasing family sizes or decreasing genome sizes.ConclusionsThe use of genotyping information for grouping animals increases the accuracy of selection when phenotypic group records are used in genomic selection breeding programs.
Didelphis albiventris: an overview of unprecedented transcriptome sequencing of the white-eared opossum
Authors: dos Santos Íria Gabriela Dias , de Oliveira Mendes Tiago Antônio , Silva Gerluza Aparecida Borges , Reis Amanda Maria Sena , Monteiro-Vitorello Cláudia Barros , Schaker Patricia Dayane Carvalho , Herai Roberto Hirochi , Fabotti André Brait Carneiro , Coutinho Luiz Lehmann , Jorge Erika Cristina 
Published: November 2019

AbstractBackgroundThe white-eared opossum (Didelphis albiventris) is widely distributed throughout Brazil and South America. It has been used as an animal model for studying different scientific questions ranging from the restoration of degraded green areas to medical aspects of Chagas disease, leishmaniasis and resistance against snake venom. As a marsupial,D. albiventriscan also contribute to the understanding of the molecular mechanisms that govern the different stages of organogenesis. Opossum joeys are born after only 13 days, and the final stages of organogenesis occur when the neonates are inside the pouch, depending on lactation. As neither the genome of this opossum species nor its transcriptome has been completely sequenced, the use ofD. albiventrisas an animal model is limited. In this work, we sequenced theD. albiventristranscriptome by RNA-seq to obtain the first catalogue of differentially expressed (DE) genes and gene ontology (GO) annotations during the neonatal stages of marsupial development.ResultsTheD. albiventristranscriptome was obtained from whole neonates harvested at birth (P0), at 5 days of age (P5) and at 10 days of age (P10). The de novo assembly of these transcripts generated 85,338 transcripts. Approximately 30% of these transcripts could be mapped against the amino acid sequences ofM. domestica, the evolutionarily closest relative ofD. albiventristo be sequenced thus far. Among the expressed transcripts, 2077 were found to be DE between P0 and P5, 13,780 between P0 and P10, and 1453 between P5 and P10. The enriched GO terms were mainly related to the immune system, blood tissue development and differentiation, vision, hearing, digestion, the CNS and limb development.ConclusionsThe elucidation of opossum transcriptomes provides an out-group for better understanding the distinct characteristics associated with the evolution of mammalian species. This study provides the first transcriptome sequences and catalogue of genes for a marsupial species at different neonatal stages, allowing the study of the mechanisms involved in organogenesis.
Qualifying and quantifying the precision medicine rhetoric
Authors: Lee Jasmine , Hamideh Dina , Nebeker Camille 
Published: November 2019

Abstract
Background
With the rise of precision medicine efforts worldwide, our study objective was to describe and map the emerging precision medicine landscape. A Google search was conducted between June 19, 2017 to July 20, 2017 to examine how “precision medicine” and its analogous terminology were used to describe precision medicine efforts. Resulting web-pages were reviewed for geographic location, data type(s), program aim(s), sample size, duration, and the key search terms used and recorded in a database. Descriptive statistics were applied to quantify terminology used to describe specific precision medicine efforts. Qualitative data were analyzed for content and patterns.

Results
Of the 108 programs identified through our search, 84% collected only biospecimen(s) and, of those that collected at least two data types, 42% mentioned both Electronic Health Records (EHR) and biospecimen. Given the majority of efforts limited to biospecimen(s) use, genetic research seems to be prioritized in association with precision medicine. Roughly, 54% were found to collect two or more data types, which limits the output of information that may contribute to understanding of the interplay of genetic, lifestyle, and environmental factors. Over half were government-funded with roughly a third being industry-funded. Most initiatives were concentrated in the United States, Europe, and Asia.

Conclusions
To our knowledge, this is the first study to map and qualify the global precision medicine landscape. Our findings reveal that precision medicine efforts range from large model cohort studies involving multidimensional, longitudinal data to biorepositories with a collection of blood samples. We present a spectrum where past, present, and future PM-like efforts can fall based on their scope and potential impact. If precision medicine is based on genes, lifestyle and environmental factors, we recommend programs claiming to be precision medicine initiatives to incorporate multidimensional data that can inform a holistic approach to healthcare.
Population genomics and morphological features underlying the adaptive evolution of the eastern honey bee (Apis cerana)
Authors: Yancan Li , Tianle Chao , Yunhan Fan , Delong Lou , Guizhi Wang 
Published: November 2019

AbstractBackgroundThe adaptation of organisms to changing environments is self-evident, with the adaptive evolution of organisms to environmental changes being a fundamental problem in evolutionary biology. Bees can pollinate in various environments and climates and play important roles in maintaining the ecological balance of the earth.ResultsWe performed an analysis of 462Apis cerana(A. cerana) specimens from 31 populations in 11 regions and obtained 39 representative morphological features. We selected 8A. ceranasamples from each population and performed 2b-RAD simplified genome sequencing. A total of 11,506 high-quality single nucleotide polymorphism (SNP) loci were obtained. For these SNPs, the minor allele frequency (MAF) was > 1%, the average number of unique labels for each sample was 49,055, and the average depth was 72.61x. The ratios of the unique labels of all samples were 64.27–86.33%.ConclusionsUsing 39 morphological characteristics as the data set, we proposed a method for the rapid classification ofA. cerana. Using genomics to assess population structure and genetic diversity, we found thatA. ceranahas a large genetic difference at the ecotype level. A comparison ofA. ceranain North China revealed that some physical obstacles, especially the overurbanization of the plains, have isolated the populations of this species. We identified several migration events in North China and Central China. By comparing the differences in the environmental changes in different regions, we found thatA. ceranahas strong potential for climate change and provides a theoretical basis for investigating and protectingA. cerana.
Foliar application of sodium selenate induces regulation in yield formation, grain quality characters and 2-acetyl-1-pyrroline biosynthesis in fragrant rice
Authors: Luo Haowen , Du Bin , He Longxin , Zheng Axiang , Pan Shenggang , Tang Xiangru 
Published: November 2019

Abstract
Background
Selenium (Se) is a beneficial element for higher plants and essential for mammals. To study the effect of the foliar application of sodium selenate on fragrant rice performance, a pot experiment was conducted in Guangdong, China. At the initial heading stage, one-time foliar application of sodium selenate with concentrations of 0, 10, 20, 30, 40 and 50 μmol·L− 1 (named CK, Se1, Se2, Se3, Se4 and Se5, respectively) were foliar applied on two fragrant rice varieties, ‘Meixiangzhan-2’ and ‘Xiangyaxiangzhan’.

Results
Selenate application at the initial heading stage not only improved the grain yield of fragrant rice by increasing the seed-setting rate and grain weight, but also promoted the grain quality by increasing crude protein contents and lowering the chalky rice rate. Furthermore, Se applications enhanced the biosynthesis of 2-acetyl-1- pyrroline (2-AP), the main aromatic compound, by increasing the contents of precursors (△1- pyrroline, proline and pyrroline-5-carboxylic acid (P5C)) and the activities of enzymes (proline dehydrogenase (PRODH), △1-pyrroline-5-carboxylic acid synthetase (P5CS), and ornithine aminotransferase (OAT)) in fragrant rice. The results also showed that foliar application of sodium selenate enhanced the antioxidant system of both varieties by promoting the activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and reducing the contents of malondialdehyde (MDA). Furthermore, the real-time PCR analyses depicted that foliar application of selenate up-regulated the GPX1, GPX4 and CATC transcripts. The higher antioxidative enzymatic activities might strength the stress resistant to ensure the stability of yield in fragrant rice form abiotic stress.

Conclusions
Foliar applications of sodium selenate at the initial heading stage increased the grain 2-AP content by enhancing the biosynthesis-related enzymes and precursors. The grain yield and quality of fragrant rice also increased due to selenate application. Furthermore, foliar application of selenate promoted the activities of enzymes such as POD, SOD and CAT and up-regulated the expression of gene GPX4, GPX1 and CATC.
Modeling perinatal mortality in twins via generalized additive mixed models: a comparison of estimation approaches
Authors: Mullah Muhammad Abu Shadeque , Hanley James A. , Benedetti Andrea 
Published: November 2019

AbstractBackgroundThe analysis of twin data presents a unique challenge. Second-born twins on average weigh less than first-born twins and have an elevated risk of perinatal mortality. It is not clear whether the risk difference depends on birth order or their relative birth weight. This study evaluates the association between birth order and perinatal mortality by birth order-specific weight difference in twin pregnancies.MethodsWe adopt generalized additive mixed models (GAMMs) which are a flexible version of generalized linear mixed models (GLMMs), to model the association. Estimation of such models for correlated binary data is challenging. We compare both Bayesian and likelihood-based approaches for estimating GAMMs via simulation. We apply the methods to the US matched multiple birth data to evaluate the association between twins’ birth order and perinatal mortality.ResultsPerinatal mortality depends on both birth order and relative birthweight. Simulation results suggest that the Bayesian method with half-Cauchy priors for variance components performs well in estimating all components of the GAMM. The Bayesian results were sensitive to prior specifications.ConclusionWe adopted a flexible statistical model, GAMM, to precisely estimate the perinatal mortality risk differences between first- and second-born twins whereby birthweight and gestational age are nonparametrically modelled to explicitly adjust for their effects. The risk of perinatal mortality in twins was found to depend on both birth order and relative birthweight. We demonstrated that the Bayesian method estimated the GAMM model components more reliably than the frequentist approaches.