bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study
Authors: Ulke Christine , Rullmann Michael , Huang Jue , Luthardt Julia , Becker Georg-Alexander , Patt Marianne , Meyer Philipp M. , Tiepolt Solveig , Hesse Swen , Sabri Osama , Strauß Maria 
Published: November 2019

AbstractThe norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[11C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right:F1,25 = 12.30,p = .002; regions on the left:F1,41 = 6.80,p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.
Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors
Authors: Guo Rongqun , Hu Fangxiao , Weng Qitong , Lv Cui , Wu Hongling , Liu Lijuan , Li Zongcheng , Zeng Yang , Bai Zhijie , Zhang Mengyun , Liu Yuting , Liu Xiaofei , Xia Chengxiang , Wang Tongjie , Zhou Peiqing , Wang Kaitao , Dong Yong , Luo Yuxuan , Zhang Xiangzhong , Guan Yuxian , Geng Yang , Du Juan , Li Yangqiu , Lan Yu , Chen Jiekai , Liu Bing , Wang Jinyong 
Published: November 2019

AbstractAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells (PSCs) is a central aim in T cell regenerative medicine. To date, preferentially reconstituting T lymphopoiesis in vivo from PSCs remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial-to-hematopoietic transition and hematopoietic maturation stages in a PSC differentiation scheme (iR9-PSC) in vitro induced preferential generation of engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSCs, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The induced T cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis restored immune surveillance in immunodeficient mice. Furthermore, gene-edited iR9-PSCs produced tumor-specific T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T cells from the unlimited and editable PSC source.
The indica nitrate reductase gene OsNR2 allele enhances rice yield potential and nitrogen use efficiency
Authors: Gao Zhenyu , Wang Yufeng , Chen Guang , Zhang Anpeng , Yang Shenglong , Shang Lianguang , Wang Danying , Ruan Banpu , Liu Chaolei , Jiang Hongzhen , Dong Guojun , Zhu Li , Hu Jiang , Zhang Guangheng , Zeng Dali , Guo Longbiao , Xu Guohua , Teng Sheng , Harberd Nicholas P. , Qian Qian 
Published: November 2019

AbstractTheindicaandjaponicarice (Oryza sativa) subspecies differ in nitrate (NO3−) assimilation capacity and nitrogen (N) use efficiency (NUE). Here, we show that a major component of this difference is conferred by allelic variation atOsNR2, a gene encoding a NADH/NADPH-dependent NO3−reductase (NR). Selection-driven allelic divergence has resulted in variantindicaandjaponica OsNR2alleles encoding structurally distinct OsNR2 proteins, withindicaOsNR2 exhibiting greater NR activity.Indica OsNR2also promotes NO3−uptake via feed-forward interaction withOsNRT1.1B, a gene encoding a NO3−uptake transporter. These properties enableindica OsNR2to confer increased effective tiller number, grain yield and NUE onjaponicarice, effects enhanced by interaction with an additionally introgressedindica OsNRT1.1Ballele. In consequence,indica OsNR2provides an important breeding resource for the sustainable increases injaponicarice yields necessary for future global food security.
In-fibre particle manipulation and device assembly via laser induced thermocapillary convection
Authors: Zhang Jing , Wang Zhe , Wang Zhixun , Zhang Ting , Wei Lei 
Published: November 2019

AbstractThe ability to manipulate in-fibre particles is of technological and scientific significance, yet particle manipulation inside solid environment remains fundamentally challenging. Here we show an accurately controlled, non-contact, size- and material-independent method for manipulating in-fibre particles based on laser-induced thermocapillary convection. The laser liquefaction process transforms the fibre from a solid media into an ideal fluid environment and triggers the in-fibre thermocapillary convection. In-fibre particles, with diameter from submicron to hundreds of microns, can be migrated toward the designated position. The number of particles being migrated, the particle migration velocity and direction can be precisely controlled. As a proof-of-concept, the laser-induced flow currents lead to the migration-to-contact of dislocated in-fibre p- and n-type semiconductor particles and the forming of dual-particle p-n homo- and heterojunction directly in a fibre. This approach not only enables in-fibre device assembly to achieve multi-component fibre devices, but also provide fundamental insight for in-solid particle manipulation.
Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A
Authors: Hall T. E. , Wood A. J. , Ehrlich O. , Li M. , Sonntag C. S. , Cole N. J. , Huttner I. G. , Sztal T. E. , Currie P. D. 
Published: November 2019

AbstractLaminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be “re-functionalised” prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.
Human mitochondrial DNA lineages in Iron-Age Fennoscandia suggest incipient admixture and eastern introduction of farming-related maternal ancestry
Authors: Översti Sanni , Majander Kerttu , Salmela Elina , Salo Kati , Arppe Laura , Belskiy Stanislav , Etu-Sihvola Heli , Laakso Ville , Mikkola Esa , Pfrengle Saskia , Putkonen Mikko , Taavitsainen Jussi-Pekka , Vuoristo Katja , Wessman Anna , Sajantila Antti , Oinonen Markku , Haak Wolfgang , Schuenemann Verena J. , Krause Johannes , Palo Jukka U. , Onkamo Päivi 
Published: November 2019

AbstractHuman ancient DNA studies have revealed high mobility in Europe’s past, and have helped to decode the human history on the Eurasian continent. Northeastern Europe, especially north of the Baltic Sea, however, remains less well understood largely due to the lack of preserved human remains. Finland, with a divergent population history from most of Europe, offers a unique perspective to hunter-gatherer way of life, but thus far genetic information on prehistoric human groups in Finland is nearly absent. Here we report 103 complete ancient mitochondrial genomes from human remains dated to AD 300–1800, and explore mtDNA diversity associated with hunter-gatherers and Neolithic farmers. The results indicate largely unadmixed mtDNA pools of differing ancestries from Iron-Age on, suggesting a rather late genetic shift from hunter-gatherers towards farmers in North-East Europe. Furthermore, the data suggest eastern introduction of farmer-related haplogroups into Finland, contradicting contemporary genetic patterns in Finns.
Data augmentation using generative adversarial networks (CycleGAN) to improve generalizability in CT segmentation tasks
Authors: Sandfort Veit , Yan Ke , Pickhardt Perry J. , Summers Ronald M. 
Published: November 2019

AbstractLabeled medical imaging data is scarce and expensive to generate. To achieve generalizable deep learning models large amounts of data are needed. Standard data augmentation is a method to increase generalizability and is routinely performed. Generative adversarial networks offer a novel method for data augmentation. We evaluate the use of CycleGAN for data augmentation in CT segmentation tasks. Using a large image database we trained a CycleGAN to transform contrast CT images into non-contrast images. We then used the trained CycleGAN to augment our training using these synthetic non-contrast images. We compared the segmentation performance of a U-Net trained on the original dataset compared to a U-Net trained on the combined dataset of original data and synthetic non-contrast images. We further evaluated the U-Net segmentation performance on two separate datasets: The original contrast CT dataset on which segmentations were created and a second dataset from a different hospital containing only non-contrast CTs. We refer to these 2 separate datasets as the in-distribution and out-of-distribution datasets, respectively. We show that in several CT segmentation tasks performance is improved significantly, especially in out-of-distribution (noncontrast CT) data. For example, when training the model with standard augmentation techniques, performance of segmentation of the kidneys on out-of-distribution non-contrast images was dramatically lower than for in-distribution data (Dice score of 0.09 vs. 0.94 for out-of-distribution vs. in-distribution data, respectively, p < 0.001). When the kidney model was trained with CycleGAN augmentation techniques, the out-of-distribution (non-contrast) performance increased dramatically (from a Dice score of 0.09 to 0.66, p < 0.001). Improvements for the liver and spleen were smaller, from 0.86 to 0.89 and 0.65 to 0.69, respectively. We believe this method will be valuable to medical imaging researchers to reduce manual segmentation effort and cost in CT imaging.
Identification of candidate cancer drivers by integrative Epi-DNA and Gene Expression (iEDGE) data analysis
Authors: Li Amy , Chapuy Bjoern , Varelas Xaralabos , Sebastiani Paola , Monti Stefano 
Published: November 2019

AbstractThe emergence of large-scale multi-omics data warrants method development for data integration. Genomic studies from cancer patients have identified epigenetic and genetic regulators – such as methylation marks, somatic mutations, and somatic copy number alterations (SCNAs), among others – as predictive features of cancer outcome. However, identification of “driver genes” associated with a given alteration remains a challenge. To this end, we developed a computational tool, iEDGE, to model cis and trans effects of (epi-)DNA alterations and identify potential cis driver genes, where cis and trans genes denote those genes falling within and outside the genomic boundaries of a given (epi-)genetic alteration, respectively. iEDGE first identifies the cis and trans gene expression signatures associated with the presence/absence of a particular epi-DNA alteration across samples. It then applies tests of statistical mediation to determine the cis genes predictive of the trans gene expression. Finally, cis and trans effects are annotated by pathway enrichment analysis to gain insights into the underlying regulatory networks. We used iEDGE to perform integrative analysis of SCNAs and gene expression data from breast cancer and 18 additional cancer types included in The Cancer Genome Atlas (TCGA). Notably, cis gene drivers identified by iEDGE were found to be significantly enriched for known driver genes from multiple compendia of validated oncogenes and tumor suppressors, suggesting that the remainder are of equal importance. Furthermore, predicted drivers were enriched for functionally relevant cancer genes with amplification-driven dependencies, which are of potential prognostic and therapeutic value. All the analyses results are accessible at https://montilab.bu.edu/iEDGE. In summary, integrative analysis of SCNAs and gene expression using iEDGE successfully identified known cancer driver genes and putative cancer therapeutic targets across 19 cancer types in the TCGA. The proposed method can easily be applied to the integration of gene expression profiles with other epi-DNA assays in a variety of disease contexts.
Quantitative Multilayer Cu(410) Structure and Relaxation Determined by QLEED
Authors: Ahmed Rezwan , Makino Takamasa , Gueriba Jessiel Siaron , Mizuno Seigi , Diño Wilson Agerico , Okada Michio 
Published: November 2019

AbstractIndustrially relevant catalytically active surfaces exhibit defects. These defects serve as active sites; expose incoming adsorbates to both high and low coordinated surface atoms; determine morphology, reactivity, energetics, and surface relaxation. These, in turn, affect crystal growth, oxidation, catalysis, and corrosion. Systematic experimental analyses of such surface defects pose challenges, esp., when they do not exhibit order. High Miller index surfaces can provide access to these features and information, albeit indirectly. Here, we show that with quantitative low-energy electron diffraction (QLEED) intensity analyses and density functional theory (DFT) calculations, we can visualize the local atomic configuration, the corresponding electron distribution, and local reactivity. The QLEED-determined Cu(410) structure (Pendry reliability factor RP ≃ 0.0797) exhibits alternating sequences of expansion (+) and contraction (−) (of the first 16 atomic interlayers) relative to the bulk-truncated interlayer spacing of ca. 0.437 Å. The corresponding electron distribution shows smoothening relative to the bulk-determined structure. These results should aid us to further gain an atomic-scale understanding of the nature of defects in materials.
Contrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality
Authors: Ribitsch Werner , Horina Joerg H. , Quehenberger Franz , Rosenkranz Alexander R. , Schilcher Gernot 
Published: November 2019

AbstractThe existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min−1·1.73 m−2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.
Understanding controversies in the α-ω and ω-β phase transformations of zirconium from nonhydrostatic thermodynamics
Authors: Zhang Lin , Li Ying-Hua , Gu Yan-Qin , Cai Ling-Cang 
Published: November 2019

AbstractSignificant debate has been noted in the α-ω and ω-β phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to 7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-β phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-β triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-β phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.
High-throughput screening against protein:protein interaction interfaces reveals anti-cancer therapeutics as potent modulators of the voltage-gated Na+ channel complex
Authors: Wadsworth Paul A. , Folorunso Oluwarotimi , Nguyen Nghi , Singh Aditya K. , D’Amico Daniela , Powell Reid T. , Brunell David , Allen John , Stephan Clifford , Laezza Fernanda 
Published: November 2019

AbstractMultiple voltage-gated Na+ (Nav) channelopathies can be ascribed to subtle changes in the Nav macromolecular complex. Fibroblast growth factor 14 (FGF14) is a functionally relevant component of the Nav1.6 channel complex, a causative link to spinocerebellar ataxia 27 (SCA27) and an emerging risk factor for neuropsychiatric disorders. Yet, how this protein:channel complex is regulated in the cell is still poorly understood. To search for key cellular pathways upstream of the FGF14:Nav1.6 complex, we have developed, miniaturized and optimized an in-cell assay in 384-well plates by stably reconstituting the FGF14:Nav1.6 complex using the split-luciferase complementation assay. We then conducted a high-throughput screening (HTS) of 267 FDA-approved compounds targeting known mediators of cellular signaling. Of the 65 hits initially detected, 24 were excluded based on counter-screening and cellular toxicity. Based on target analysis, potency and dose-response relationships, 5 compounds were subsequently repurchased for validation and confirmed as hits. Among those, the tyrosine kinase inhibitor lestaurtinib was highest ranked, exhibiting submicromolar inhibition of FGF14:Nav1.6 assembly. While providing evidence for a robust in-cell HTS platform that can be adapted to search for any channelopathy-associated regulatory proteins, these results lay the potential groundwork for repurposing cancer drugs for neuropsychopharmacology.
Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia
Authors: Henning Carina , Branopolski Anna , Schuler Dominik , Dimitroulis Dimitrios , Huelsemann Patrik , Nicolaus Christopher , Sansone Roberto , Ludolf Postma Jelle , Eberhard Daniel , Le Noble Ferdinand , Kelm Malte , Lammert Eckhard , Heiss Christian 
Published: November 2019

AbstractAn acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.