bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse axonal injury predicts neurodegeneration after moderate–severe traumatic brain injury
Authors: Graham Neil S N , Jolly Amy , Zimmerman Karl , Bourke Niall J , Scott Gregory , Cole James H , Schott Jonathan M , Sharp David J 
Published: August 2020

Abstract
Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer’s disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate–severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (&gt;50% for fractional anisotropy versus &lt;5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials.
Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration Along the White Matter
Authors: Lubart Alisa , Benbenishty Amit , Har-Gil Hagai , Laufer Hadas , Gdalyahu Amos , Assaf Yaniv , Blinder Pablo 
Published: August 2020

AbstractLoss of cognitive function with aging is a complex and poorly understood process. Recently, clinical research has linked the occurrence of cortical microinfarcts to cognitive decline. Cortical microinfarcts form following the occlusion of penetrating vessels and are considered to be restricted to the proximity of the occluded vessel. Whether and how such local events propagate and affect remote brain regions remain unknown. To this end, we combined histological analysis and longitudinal diffusion tensor imaging (DTI), following the targeted-photothrombotic occlusion of single cortical penetrating vessels. Occlusions resulted in distant tissue reorganization across the mouse brain. This remodeling co-occurred with the formation of a microglia/macrophage migratory path along subcortical white matter tracts, reaching the contralateral hemisphere through the corpus callosum and leaving a microstructural signature detected by DTI-tractography. CX3CR1-deficient mice exhibited shorter trail lengths, differential remodeling, and only ipsilateral white matter tract changes. We concluded that microinfarcts lead to brain-wide remodeling in a microglial CX3CR1-dependent manner.
Deficient or Excess Folic Acid Supply During Pregnancy Alter Cortical Neurodevelopment in Mouse Offspring
Authors: Harlan De Crescenzo Angelo , Panoutsopoulos Alexios A , Tat Lyvin , Schaaf Zachary , Racherla Shailaja , Henderson Lyle , Leung Kit-Yi , Greene Nicholas D E , Green Ralph , Zarbalis Konstantinos S 
Published: August 2020

AbstractFolate is an essential micronutrient required for both cellular proliferation through de novo nucleotide synthesis and epigenetic regulation of gene expression through methylation. This dual requirement places a particular demand on folate availability during pregnancy when both rapid cell generation and programmed differentiation of maternal, extraembryonic, and embryonic/fetal tissues are required. Accordingly, prenatal neurodevelopment is particularly susceptible to folate deficiency, which can predispose to neural tube defects, or when effective transport into the brain is impaired, cerebral folate deficiency. Consequently, adequate folate consumption, in the form of folic acid (FA) fortification and supplement use, is widely recommended and has led to a substantial increase in the amount of FA intake during pregnancy in some populations. Here, we show that either maternal folate deficiency or FA excess in mice results in disruptions in folate metabolism of the offspring, suggesting diversion of the folate cycle from methylation to DNA synthesis. Paradoxically, either intervention causes comparable neurodevelopmental changes by delaying prenatal cerebral cortical neurogenesis in favor of late-born neurons. These cytoarchitectural and biochemical alterations are accompanied by behavioral abnormalities in FA test groups compared with controls. Our findings point to overlooked potential neurodevelopmental risks associated with excessively high levels of prenatal FA intake.
Th17 associated cytokines in sputum samples from patients with cystic fibrosis
Authors: Oshalim Merna , Johansson Ewa , Rabe Hardis , Gilljam Marita , Lindblad Anders , Jönsson Bodil 
Published: August 2020

ABSTRACT
Cystic fibrosis (CF) is a genetic disease leading to chronic bacterial airway infection and inflammation. T helper 17 (Th17) cells are identified by their production of interleukin (IL)-17A, which recruit neutrophils to the site of airway infection. IL-23 is an important inducer of IL-17 and IL-22 production. The aim of this study was to study the role of Th17 cells in CF airway infection by measuring the levels of Th17 associated cytokines in sputum from CF patients with or without airway infection and by comparison with non-CF-controls. In a cross-sectional screening study, cytokine levels were measured with a Th17 multiplex cytokine ELISA. Significantly lower levels of IL-17A and IL-23 were found in sputa from infected CF patients. The lowest levels of IL-17A were found in patients chronically infected with P. aeruginosa, which also had the lowest IL-17/IL-22 ratio, while children had a higher ratio. Children also had higher IL-23 levels than adults. IL-1ß and IL-10 were significantly lower in CF sputum compared to controls. Thus, in our study CF patients with chronic infections had a lower production of Th17 associated cytokines in sputum compared with non-infected CF patients and infected patient without CF.
Interdependence of Approach and Avoidance Goals in Romantic Couples Over Days and Months
Authors: Nikitin Jana , Wünsche Jenna , Bühler Janina L , Weidmann Rebekka , Burriss Robert P , Grob Alexander 
Published: August 2020

AbstractObjectivesDespite the centrality of people’s approach goals (i.e., approach toward positive outcomes) and avoidance goals (i.e., avoidance of negative outcomes) in romantic relationships, little is known about the interdependence of approach and avoidance relationship goals between partners. Assuming that short-term, state-level goals accumulate into general goal tendencies, the present research tested whether partners’ daily (i.e., state level) and aggregated daily (i.e., trait level) approach and avoidance goals are mutually predictive in the short term (after one day) and the long term (after 10–12 months). In addition, we explored whether goal interdependence unfolds differently across adulthood and in relationships of different duration.MethodApproach and avoidance goals were assessed daily on two 14-day measurement-burst occasions that were conducted 10–12 months apart. The sample consisted of N = 456 female–male couples (age: M = 33.6, SD = 13.8 years; relationship duration: M = 9.6, SD = 10.7 years).ResultsWe observed significant short- and long-term partner effects in the prediction of couple members’ approach and avoidance goals. These partner effects were restricted to trait level and they did not emerge at the state level. Almost all effects were independent of age and relationship duration.DiscussionThe present research underscores the importance of disentangling state- and trait-level goal tendencies when investigating the interdependence of approach and avoidance goals within romantic relationships.
A reduced order approach for probabilistic inversions of 3-D magnetotelluric data I: general formulation
Authors: Manassero M C , Afonso J C , Zyserman F , Zlotnik S , Fomin I 
Published: August 2020

SUMMARYSimulation-based probabilistic inversions of 3-D magnetotelluric (MT) data are arguably the best option to deal with the nonlinearity and non-uniqueness of the MT problem. However, the computational cost associated with the modelling of 3-D MT data has so far precluded the community from adopting and/or pursuing full probabilistic inversions of large MT data sets. In this contribution, we present a novel and general inversion framework, driven by Markov Chain Monte Carlo (MCMC) algorithms, which combines (i) an efficient parallel-in-parallel structure to solve the 3-D forward problem, (ii) a reduced order technique to create fast and accurate surrogate models of the forward problem and (iii) adaptive strategies for both the MCMC algorithm and the surrogate model. In particular, and contrary to traditional implementations, the adaptation of the surrogate is integrated into the MCMC inversion. This circumvents the need of costly offline stages to build the surrogate and further increases the overall efficiency of the method. We demonstrate the feasibility and performance of our approach to invert for large-scale conductivity structures with two numerical examples using different parametrizations and dimensionalities. In both cases, we report staggering gains in computational efficiency compared to traditional MCMC implementations. Our method finally removes the main bottleneck of probabilistic inversions of 3-D MT data and opens up new opportunities for both stand-alone MT inversions and multi-observable joint inversions for the physical state of the Earth’s interior.
The burden of cardiovascular diseases in Ethiopia from 1990 to 2017: evidence from the Global Burden of Disease Study
Authors: Ali Solomon , Misganaw Awoke , Worku Asnake , Destaw Zelalem , Negash Legesse , Bekele Abebe , Briant Paul S , Johnson Catherine O , Alam Tahiya , Odell Chris , Roth Gregory A , Naghavi Mohsen , Abate Ebba , Mirkuzie Alemnesh H 
Published: August 2020

Abstract
In Ethiopia, evidence on the national burden of cardiovascular diseases (CVDs) is limited. To address this gap, this systematic analysis estimated the burden of CVDs in Ethiopia using the Global Burden of Disease (GBD) 2017 study data. The age-standardized CVD prevalence, disability-adjusted life years (DALYs) and mortality rates in Ethiopia were 5534 (95% uncertainty interval [UI] 5310.09 - 5774.0), 3549.6 (95% UI 3229.0 - 3911.9) and 182.63 (95% UI 165.49 - 203.9) per 100 000 population, respectively. Compared with 1990, the age-standardized CVD prevalence rate in 2017 showed no change. But significant reductions were observed in CVD mortality (54.7%), CVD DALYs (57.7%) and all-cause mortality (53.4%). The top three prevalent CVDs were ischaemic heart disease, rheumatic heart disease and stroke in descending order. The reduction in the mortality rate due to CVDs is slower than for communicable, maternal, neonatal and nutritional disease mortalities. As a result, CVDs are the leading cause of mortality in Ethiopia. These findings urge Ethiopia to consider CVDs as a priority public health problem.
Optimizing Application Rates ofMetarhizium brunneum(Hypocreales: Clavicipitaceae) Microsclerotia for Infecting the Invasive Asian Longhorned Beetle (Coleoptera: Cerambycidae)
Authors: Clifton Eric H , Gardescu Sana , Behle Robert W , Hajek Ann E 
Published: August 2020

AbstractThe Asian longhorned beetle (Anoplophora glabripennis [Motschulsky]) is an invasive wood-boring beetle that threatens urban trees and forests in North America and Europe. The entomopathogenic fungus Metarhizium brunneum Petch strain F52 can infect and kill A. glabripennis adults. Products containing this fungus were available for commercial use in the United States but not registered for Asian longhorned beetle. This study tested different formulations and application rates of M. brunneum F52 microsclerotial granules for their potential development for management of A. glabripennis adults. Three application rates of M. brunneum microsclerotial granules relative to a 1× formulation from previous experiments (0.03 g/cm2; 2× = 0.06 g/cm2 and 3× = 0.09 g/cm2) were exposed on tree trunks for 4-wk periods during May–September. Increased application rates had better retention (% of initial g applied) than the 1× rate, rather than greater weathering loss. Microsclerotia at the 2× application produced 5.05 × 106 conidia/cm2, which was 18 times more conidia than the 1× application. Since A. glabripennis is under active eradication, bioassays with adult beetles were carried out in a quarantine laboratory, using the formulation samples from field exposures. The 2× application resulted in faster beetle mortality. The 3× and 2× rates were not significantly different in retention of the formulation, conidial production, or mortality, but 2× produced the most conidia per gram applied (3.92 × 109 conidia/g). An augmented formulation containing 70% M. brunneum by weight, rather than 50%, produced significantly more conidia and faster beetle mortality than the 50% formulation.
Use of Digital Video Cameras to Determine the Efficacy of Two Trap Types for CapturingRhynchophorus palmarum(Coleoptera: Curculionidae)
Authors: Milosavljević Ivan , Hoddle Christina D , Mafra-Neto Agenor , Gómez-Marco Francesc , Hoddle Mark S 
Published: August 2020

AbstractThe efficacies of two trap types, bucket and Picusan traps, for capturing and retaining Rhynchophorus palmarum (L.), an invasive palm pest responsible for killing thousands of ornamental Canary Islands date palms (Phoenix canariensis Chabaud [Arecales: Arecaceae]) in San Diego County, CA, were compared. Digital video data were analyzed to determine how R. palmarum behavior toward each trap type affected capture and retention rates. Videography was conducted 24 h/d, 7 d/wk, for more than 7 mo resulting in 20,211 h of digital data for analysis. Weevil attraction to traps was observed only during daylight hours and no patterns in diel activity were found. Neither trap type tested captured 100% of weevils attracted to traps. Bucket traps suspended 1.5 m above the ground attracted 30% more weevils than ground deployed Picusan traps. Of those weevils attracted to bucket traps, 89% entered, 82% escaped, and 18% that entered traps were retained. Weevils that were not retained spent an average of 19 min 20 s entering and exiting entry holes and walking and flying around the bucket trap. By contrast, Picusan traps captured 89% of weevils that entered the trap. The time between weevils arriving (via walking or flight) on the sides of the Picusan trap and retention in the trap ranged between 90 and 376 s. These visual observations suggest that Picusan traps are more efficient than bucket traps for R. palmarum capture.
The Wicked Problem of Diffuse Nutrient Pollution from Agriculture
Authors: Sharma Annabel 
Published: August 2020

Abstract
Diffuse nutrient pollution from agriculture has been the concern of policymakers for several decades, and yet it remains a persistent environmental issue. The current approach to mitigating the problem is predominantly via command and control regulation within the Nitrates Directive and the Water Framework Directive. This article will set out how diffuse pollution can be considered a wicked policy problem which acts as an explanation of how it has eluded the current regulatory regime. It will further establish that the traditional planning process overlooked the complexity of the problem. Finally, it will illustrate the ineffectiveness of the current regulatory framework to mitigate the problem. This will be exemplified through the legal framework of Northern Ireland.
Embryo-Like Features in Developing Bacillus subtilis Biofilms
Authors: Futo Momir , Opašić Luka , Koska Sara , Čorak Nina , Široki Tin , Ravikumar Vaishnavi , Thorsell Annika , Lenuzzi Maša , Kifer Domagoj , Domazet-Lošo Mirjana , Vlahoviček Kristian , Mijakovic Ivan , Domazet-Lošo Tomislav 
Published: August 2020

Abstract
Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny−ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny−ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.
IDDB: a comprehensive resource featuring genes, variants and characteristics associated with infertility
Authors: Wu Jing , Li Danjun , Liu Xinyi , Li Qian , He Xinheng , Wei Jiale , Li Xinyi , Li Mingyu , Rehman Ashfaq Ur , Xia Yujia , Wu Chengwei , Zhang Jian , Lu Xuefeng 
Published: August 2020

Abstract
Infertility is a complex multifactorial disease that affects up to 10% of couples across the world. However, many mechanisms of infertility remain unclear due to the lack of studies based on systematic knowledge, leading to ineffective treatment and/or transmission of genetic defects to offspring. Here, we developed an infertility disease database to provide a comprehensive resource featuring various factors involved in infertility. Features in the current IDDB version were manually curated as follows: (i) a total of 307 infertility-associated genes in human and 1348 genes associated with reproductive disorder in 9 model organisms; (ii) a total of 202 chromosomal abnormalities leading to human infertility, including aneuploidies and structural variants; and (iii) a total of 2078 pathogenic variants from infertility patients’ samples across 60 different diseases causing infertility. Additionally, the characteristics of clinically diagnosed infertility patients (i.e. causative variants, laboratory indexes and clinical manifestations) were collected. To the best of our knowledge, the IDDB is the first infertility database serving as a systematic resource for biologists to decipher infertility mechanisms and for clinicians to achieve better diagnosis/treatment of patients from disease phenotype to genetic factors. The IDDB is freely available at http://mdl.shsmu.edu.cn/IDDB/.
TERT and DNMT1 expression predict sensitivity to decitabine in gliomas
Authors: Park Jong-Whi , Sahm Felix , Steffl Bianca , Arrillaga-Romany Isabel , Cahill Daniel , Monje Michelle , Herold-Mende Christel , Wick Wolfgang , Turcan Şevin 
Published: August 2020

Abstract

Background
Decitabine (DAC) is an FDA-approved DNA methyltransferase (DNMT) inhibitor that is used in the treatment of patients with myelodysplastic syndromes. Previously, we showed that DAC marks antitumor activity against gliomas with isocitrate dehydrogenase 1 (IDH1) mutations. Based on promising preclinical results, a clinical trial has been launched to determine the effect of DAC in IDH-mutant gliomas. The next step is to comprehensively assess the efficacy and potential determinants of response to DAC in malignant gliomas.

Methods
The expression and activity of telomerase reverse transcriptase (TERT) and DNMT1 were manipulated in patient-derived IDH1-mutant and -wildtype glioma lines, followed by assessment of cell proliferation with DAC treatment alone or in combination with telomerase inhibitors. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and correlation analysis were performed.

Results
IDH1-mutant glioma tumorspheres with hemizygous codeletion of chromosome arms 1p/19q were particularly sensitive to DAC and showed significant inhibition of DNA replication genes. Our transcriptome analysis revealed that DAC induced expression of cyclin-dependent kinase inhibitor 1A/p21 (CDKN1A), along with downregulation of TERT. These molecular changes were also observed following doxorubicin treatment, supporting the importance of DAC-induced DNA damage in contributing to this effect. We demonstrated that knockdown of p21 led to TERT upregulation. Strikingly, TERT overexpression increased DNMT1 levels and DAC sensitivity via a telomerase-independent mechanism. Furthermore, RNA inhibition (RNAi) targeting of DNMT1 abrogated DAC response in TERT-proficient glioma cells.

Conclusions
DAC downregulates TERT through p21 induction. Our data point to TERT and DNMT1 levels as potential determinants of response to DAC treatment.