bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kurzfassung der S2e-Leitlinie „Diagnostik und Therapie von exekutiven Dysfunktionen bei neurologischen Erkrankungen“ (AWMF-030/125)
Authors: Müller Sandra Verena , Klein Tilmann , Benke Thomas , Bohlhalter Stephan , Hildebrandt Helmut , Meiling Claudia , Hucke Birthe , Münte Thomas , Penner Iris-Katharina , Schwerdtfeger Karsten , Thöne-Otto Angelika , Wallesch Claus-W. 
Published: September 2020

Zusammenfassung. Exekutive Dysfunktionen treten besonders bei Erkrankungen, die zu einer Schädigung des präfrontalen und/oder orbitofrontalen Kortex oder subkortikaler Strukturen (insbesondere des Nucleus caudatus oder des Thalamus) führen, bzw. bei Schädigungen von Faserverbindungen zwischen relevanten kortikalen und subkortikalen Hirnstrukturen eines exekutiven Funktionsnetzwerks auf. Jede Untersuchung bei Verdacht auf exekutive Dysfunktion sollte mindestens je ein Verfahren zum Arbeitsgedächtnis und Monitoring, zur kognitiven Flüssigkeit und Flexibilität sowie zum planerischen und problemlösenden Denken umfassen. Die Verhaltensbeobachtung des Patienten und die umfassende Befragung der Angehörigen sind bei exekutiven Dysfunktionen zentrale Bestandteile der neuropsychologischen Untersuchung. Sie sind dabei vor allem für die Einschätzung der Auswirkungen möglicher Funktionsstörungen auf die Aktivitäten und die Teilhabe des Patienten von Relevanz. Für die Therapie von exekutiven Dysfunktionen ist eine sorgfältige Diagnostik Voraussetzung, da aufgrund der Verschiedenartigkeit der Symptome die Therapie spezifisch auf das jeweilige Defizit zugeschnitten sein muss. Exekutive Dysfunktionen können sehr vielgestaltig, teilweise sogar scheinbar gegensätzlich sein, daher wird die Art der Intervention durch die spezifischen Symptome bestimmt. Die Durchsicht und Bewertung der Therapiestudien nach den Evidenzkriterien für den Zeitraum von 2007 bis 2017 ergibt folgende Therapieempfehlungen für Patienten mit exekutiven Dysfunktionen: Kognitiv übende Verfahren allgemein sollen eingesetzt werden (Empfehlungsstärke A). Training des Arbeitsgedächtnisses soll eingesetzt werden (Empfehlungsstärke A). Therapieansätze zum planerischen Denken sollen eingesetzt werden (Empfehlungsstärke A). Kognitive Trainingsansätze mehrerer Funktionsbereiche unter Einschluss der Exekutivfunktionen sollen eingesetzt werden (Empfehlungsstärke A). Therapieansätze zum Problemlösetraining sollten eingesetzt werden (Empfehlungsstärke B). Zu den Ansätzen zur Modifikation und Manipulation der Umwelt liegen im aktuellen Suchzeitraum anders als in der Vorgängerleitlinie nur wenige Studien mit geringer Evidenzstärke vor, daher kann für den Untersuchungszeitraum keine Empfehlung ausgesprochen werden (Empfehlung offen). Pharmakologische Therapieansätze finden zunehmend Beachtung, aufgund ihrer Unterschiedlichkeit kann aktuell keine Empfehlung gegeben werden (Empfehlung offen).
A Complete Isotope (δ15N, δ18O, Δ17O) Investigation of Atmospherically Deposited Nitrate in Glacial‐Hydrologic Systems Across the Third Pole Region
Authors: Lin Mang , Hattori Shohei , Wang Kun , Kang Shichang , Thiemens Mark H. , Yoshida Naohiro 
Published: September 2020

AbstractThe Himalayas and Tibetan Plateau, identified as the Third Pole (TP), is a unique region because of its insertion into global environmental and climatic changes. Deposition of atmospheric nitrate in this region is one of the most important sources of reactive nitrogen to glacial‐hydrologic system and ecosystems. The isotopic composition of atmospherically deposited nitrate preserved in ice bodies plays a central role in delineating environmental and climatic changes, present, and past. Here, we provide an overview of the complete isotopic compositions (δ15N, δ18O, and Δ17O) of nitrate in aerosol, snow, ice, and water samples (n = 46) collected across the Southern, Southeastern, Central, and Northern TP to constrain complex nitrogen cycles of the atmosphere, cryosphere, hydrosphere, and, potentially, the biosphere. A large variability of snow nitrate isotopic compositions is observed across the TP at different spatial scales (from a single glacier to the entire plateau), likely due to the complex landscape and relevant physical and chemical processes across the TP. Large nitrate Δ17O values are observed in water samples collected from the Mt. Everest region, highlighting the considerable fraction (up to 45%) of atmospheric nitrate to the nitrate load in this Himalayan hydrologic system. Our work reveals the complex chemical, depositional, and postdepositional processes over the TP that are greater than previously thought and identifies further comprehensive investigations, which entail using nitrate isotopic compositions as an identifier for nitrate source apportionment in various ecosystems and understanding past atmospheric and climatic conditions in this region.
Size‐Resolved Mixing States and Sources of Amine‐Containing Particles in the East China Sea
Authors: Liu Zhe , Chen Hui , Li Qing , Sun Jianfeng , Wang Lin , Yang Xin , Xiao Hang , Li Mei , Chen Jianmin 
Published: September 2020

AbstractSingle‐particle aerosol mass spectrometry was employed during a cruise campaign from 3 to 27 June 2017 to investigate the mixing states and sources of amine‐containing particles in the East China Sea. A total of 271,160 particles were successfully identified, and 19,861 of these particles contained amines. Monomethylamine (MMA), trimethylamine (TMA), and diethylamine (DEA) were the most abundant amines. They accounted for 50%, 16%, and 29%, respectively, of the amine‐containing particles. The size distributions (mean ± geometric standard deviation) of the MMA‐, TMA‐, and DEA‐containing particles peaked at 0.58 ± 0.12, 0.56 ± 0.10, and 0.40 ± 0.10 μm, respectively. Using an adaptive resonance theory neural network algorithm, four major clusters of amine‐containing particles were categorized: carbon‐rich particles, K‐rich particles, Na‐rich particles, and metal‐rich particles. The MMA‐containing particles contained abundant elemental carbon‐, K‐, Mn‐, and Fe‐rich particles, which exhibit higher concentrations in land air masses, indicating that the MMA mainly originated from terrestrial anthropogenic sources. The TMA‐containing particles contained abundant organic and elemental carbon‐, EC‐, K‐, and V‐rich particles. High concentrations of TMA‐containing particles were measured near ports, indicating the significant contribution of the ports. The DEA‐containing particles contained abundant organic and elemental carbon‐, K‐, Mn‐, Cu‐, and Na‐rich particles, and high concentrations of DEA‐containing particles were observed in remote marine areas, suggesting that both terrestrial anthropogenic and marine sources are important contributors to DEA‐containing particles.
Probabilistic Flood Loss Models for Companies
Authors: Schoppa Lukas , Sieg Tobias , Vogel Kristin , Zöller Gert , Kreibich Heidi 
Published: September 2020

AbstractFlood loss modeling is a central component of flood risk analysis. Conventionally, this involves univariable and deterministic stage‐damage functions. Recent advancements in the field promote the use of multivariable and probabilistic loss models, which consider variables beyond inundation depth and account for prediction uncertainty. Although companies contribute significantly to total loss figures, novel modeling approaches for companies are lacking. Scarce data and the heterogeneity among companies impede the development of company flood loss models. We present three multivariable flood loss models for companies from the manufacturing, commercial, financial, and service sector that intrinsically quantify prediction uncertainty. Based on object‐level loss data (n = 1,306), we comparatively evaluate the predictive capacity of Bayesian networks, Bayesian regression, and random forest in relation to deterministic and probabilistic stage‐damage functions, serving as benchmarks. The company loss data stem from four postevent surveys in Germany between 2002 and 2013 and include information on flood intensity, company characteristics, emergency response, private precaution, and resulting loss to building, equipment, and goods and stock. We find that the multivariable probabilistic models successfully identify and reproduce essential relationships of flood damage processes in the data. The assessment of model skill focuses on the precision of the probabilistic predictions and reveals that the candidate models outperform the stage‐damage functions, while differences among the proposed models are negligible. Although the combination of multivariable and probabilistic loss estimation improves predictive accuracy over the entire data set, wide predictive distributions stress the necessity for the quantification of uncertainty.
The curvature of cucumber fruits is associated with spatial variation in auxin accumulation and expression of a YUCCA biosynthesis gene
Authors: Li Shengnan , Wang Chunhua , Zhou Xiuyan , Liu Dong , Liu Chunhong , Luan Jie , Qin Zhiwei , Xin Ming 
Published: September 2020

AbstractFruit curving lowers the commercial value of cucumber and leads to significant economic losses. The mechanism driving the abnormal curving of cucumber is largely unknown. Through our previous work, we discovered that 2 days post-anthesis (DPA) was the key time point at which various phenotypic and genotypic characteristics of cucumber fruits are determined. Here, we analyzed the transcriptome of the concave (C1) and convex (C2) sides of curved fruits at 2 DPA by Gene Ontology (GO) enrichment and functional pathway enrichment analyses and identified auxin as a putative factor influencing fruit curvature. Changes in the curve angle in the fruits and exogenous auxin treatment analyses showed that asymmetric auxin distribution induces fruit curving. Identification of differentially expressed genes (DEGs) related to auxin and qPCR validation showed that CsYUC10b had the most significant differential expression when both sides of the curved fruits were compared. Gene functional analysis showed that the transcript levels of CsYUC10b and the auxin concentration were even on both sides of the fruit in CsYUC10b-overexpressing plants, which in turn contributed to an equal rate of growth of both sides of cucumber fruits and resulted in a straight shape of the fruits. Thus, we conclude that CsYUC10b promotes the formation of straight cucumber fruits, with possible applications in the production and breeding of cucumber.
Imaging nodal knots in momentum space through topolectrical circuits
Authors: Lee Ching Hua , Sutrisno Amanda , Hofmann Tobias , Helbig Tobias , Liu Yuhan , Ang Yee Sin , Ang Lay Kee , Zhang Xiao , Greiter Martin , Thomale Ronny 
Published: September 2020

AbstractKnots are intricate structures that cannot be unambiguously distinguished with any single topological invariant. Momentum space knots, in particular, have been elusive due to their requisite finely tuned long-ranged hoppings. Even if constructed, probing their intricate linkages and topological "drumhead” surface states will be challenging due to the high precision needed. In this work, we overcome these practical and technical challenges with RLC circuits, transcending existing theoretical constructions which necessarily break reciprocity, by pairing nodal knots with their mirror image partners in a fully reciprocal setting. Our nodal knot circuits can be characterized with impedance measurements that resolve their drumhead states and image their 3D nodal structure. Doing so allows for reconstruction of the Seifert surface and hence knot topological invariants like the Alexander polynomial. We illustrate our approach with large-scale simulations of various nodal knots and an experiment which maps out the topological drumhead region of a Hopf-link.
Atomically-precise dopant-controlled single cluster catalysis for electrochemical nitrogen reduction
Authors: Yao Chuanhao , Guo Na , Xi Shibo , Xu Cong-Qiao , Liu Wei , Zhao Xiaoxu , Li Jing , Fang Hanyan , Su Jie , Chen Zhongxin , Yan Huan , Qiu Zhizhan , Lyu Pin , Chen Cheng , Xu Haomin , Peng Xinnan , Li Xinzhe , Liu Bin , Su Chenliang , Pennycook Stephen J. , Sun Cheng-Jun , Li Jun , Zhang Chun , Du Yonghua , Lu Jiong 
Published: September 2020

AbstractThe ability to precisely engineer the doping of sub-nanometer bimetallic clusters offers exciting opportunities for tailoring their catalytic performance with atomic accuracy. However, the fabrication of singly dispersed bimetallic cluster catalysts with atomic-level control of dopants has been a long-standing challenge. Herein, we report a strategy for the controllable synthesis of a precisely doped single cluster catalyst consisting of partially ligand-enveloped Au4Pt2 clusters supported on defective graphene. This creates a bimetal single cluster catalyst (Au4Pt2/G) with exceptional activity for electrochemical nitrogen (N2) reduction. Our mechanistic study reveals that each N2 molecule is activated in the confined region between cluster and graphene. The heteroatom dopant plays an indispensable role in the activation of N2 via an enhanced back donation of electrons to the N2 LUMO. Moreover, besides the heteroatom Pt, the catalytic performance of single cluster catalyst can be further tuned by using Pd in place of Pt as the dopant.
AmpliconReconstructor integrates NGS and optical mapping to resolve the complex structures of focal amplifications
Authors: Luebeck Jens , Coruh Ceyda , Dehkordi Siavash R. , Lange Joshua T. , Turner Kristen M. , Deshpande Viraj , Pai Dave A. , Zhang Chao , Rajkumar Utkrisht , Law Julie A. , Mischel Paul S. , Bafna Vineet 
Published: September 2020

AbstractOncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary driver of focal copy number amplification (fCNA) - enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA’s structure is a first step in deciphering the mechanisms of its genesis and the fCNA’s subsequent biological consequences. We introduce a computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150 kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating its performance through multiple simulation strategies, AR reconstructed fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, a breakage-fusion-bridge and other complex rearrangements. By reconstructing the rearrangement signatures associated with an fCNA’s generative mechanism, AR enables a more thorough understanding of the origins of fCNAs.
Inhibitors of BRAF dimers using an allosteric site
Authors: Cotto-Rios Xiomaris M. , Agianian Bogos , Gitego Nadege , Zacharioudakis Emmanouil , Giricz Orsi , Wu Yang , Zou Yiyu , Verma Amit , Poulikakos Poulikos I. , Gavathiotis Evripidis 
Published: September 2020

AbstractBRAF kinase, a critical effector of the ERK signaling pathway, is hyperactivated in many cancers. Oncogenic BRAFV600E signals as an active monomer in the absence of active RAS, however, in many tumors BRAF dimers mediate ERK signaling. FDA-approved RAF inhibitors poorly inhibit BRAF dimers, which leads to tumor resistance. We found that Ponatinib, an FDA-approved drug, is an effective inhibitor of BRAF monomers and dimers. Ponatinib binds the BRAF dimer and stabilizes a distinct αC-helix conformation through interaction with a previously unrevealed allosteric site. Using these structural insights, we developed PHI1, a BRAF inhibitor that fully uncovers the allosteric site. PHI1 exhibits discrete cellular selectivity for BRAF dimers, with enhanced inhibition of the second protomer when the first protomer is occupied, comprising a novel class of dimer selective inhibitors. This work shows that Ponatinib and BRAF dimer selective inhibitors will be useful in treating BRAF-dependent tumors.
Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak
Authors: Dingens Adam S. , Crawford Katharine H. D. , Adler Amanda , Steele Sarah L. , Lacombe Kirsten , Eguia Rachel , Amanat Fatima , Walls Alexandra C. , Wolf Caitlin R. , Murphy Michael , Pettie Deleah , Carter Lauren , Qin Xuan , King Neil P. , Veesler David , Krammer Florian , Dickerson Jane A. , Chu Helen Y. , Englund Janet A. , Bloom Jesse D. 
Published: September 2020

AbstractChildren are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.
An orphan protein of Fusarium graminearum modulates host immunity by mediating proteasomal degradation of TaSnRK1α
Authors: Jiang Cong , Hei Ruonan , Yang Yang , Zhang Shijie , Wang Qinhu , Wang Wei , Zhang Qiang , Yan Min , Zhu Gengrui , Huang Panpan , Liu Huiquan , Xu Jin-Rong 
Published: September 2020

AbstractFusarium graminearum is a causal agent of Fusarium head blight (FHB) and a deoxynivalenol (DON) producer. In this study, OSP24 is identified as an important virulence factor in systematic characterization of the 50 orphan secreted protein (OSP) genes of F. graminearum. Although dispensable for growth and initial penetration, OSP24 is important for infectious growth in wheat rachis tissues. OSP24 is specifically expressed during pathogenesis and its transient expression suppresses BAX- or INF1-induced cell death. Osp24 is translocated into plant cells and two of its 8 cysteine-residues are required for its function. Wheat SNF1-related kinase TaSnRK1α is identified as an Osp24-interacting protein and shows to be important for FHB resistance in TaSnRK1α-overexpressing or silencing transgenic plants. Osp24 accelerates the degradation of TaSnRK1α by facilitating its association with the ubiquitin-26S proteasome. Interestingly, TaSnRK1α also interacts with TaFROG, an orphan wheat protein induced by DON. TaFROG competes against Osp24 for binding with the same region of TaSnRKα and protects it from degradation. Overexpression of TaFROG stabilizes TaSnRK1α and increases FHB resistance. Taken together, Osp24 functions as a cytoplasmic effector by competing against TaFROG for binding with TaSnRK1α, demonstrating the counteracting roles of orphan proteins of both host and fungal pathogens during their interactions.
Tracking the COVID-19 pandemic in Australia using genomics
Authors: Seemann Torsten , Lane Courtney R. , Sherry Norelle L. , Duchene Sebastian , Gonçalves da Silva Anders , Caly Leon , Sait Michelle , Ballard Susan A. , Horan Kristy , Schultz Mark B. , Hoang Tuyet , Easton Marion , Dougall Sally , Stinear Timothy P. , Druce Julian , Catton Mike , Sutton Brett , van Diemen Annaliese , Alpren Charles , Williamson Deborah A. , Howden Benjamin P. 
Published: September 2020

AbstractGenomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global diversity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential samples from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number (Re) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally.
Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration
Authors: Zysset-Burri Denise C. , Keller Irene , Berger Lieselotte E. , Largiadèr Carlo R. , Wittwer Matthias , Wolf Sebastian , Zinkernagel Martin S. 
Published: September 2020

AbstractAge-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a shotgun metagenomics analysis of 57 neovascular AMD and 58 healthy controls as well as of 16 complement C3-deficient mice and 16 wildtypes was performed. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and species Bacteroides had a significantly higher prevalence in persons without AMD. Similar taxonomic features were identified that distinguished wildtype mice from C3-deficient mice. Moreover, several purine signaling pathways were associated with both, neovascular AMD and C3 deficiency. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with neovascular AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. This study suggests an association between the intestinal microbiome and the complement system in neovascular AMD.