bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting time to dementia using a quantitative template of disease progression
Authors: Bilgel Murat , Jedynak Bruno M. ,   Alzheimer's Disease Neuroimaging Initiative
Published: February 2019

AbstractIntroductionCharacterization of longitudinal trajectories of biomarkers implicated in sporadic Alzheimer's disease (AD) in decades before clinical diagnosis is important for disease prevention and monitoring.MethodsWe used a multivariate Bayesian model to temporally align 1369 Alzheimer's disease Neuroimaging Initiative participants based on the similarity of their longitudinal biomarker measures and estimated a quantitative template of the temporal evolution of cerebrospinal fluid A, p‐, and t‐tau and hippocampal volume, brain glucose metabolism, and cognitive measurements. We computed biomarker trajectories as a function of time to AD dementia and predicted AD dementia onset age in a disjoint sample.ResultsQuantitative template showed early changes in verbal memory, cerebrospinal fluid Aβ1–42 and p‐tau181p, and hippocampal volume. Mean error in predicted AD dementia onset age was years.DiscussionOur method provides a quantitative approach for characterizing the natural history of AD starting at preclinical stages despite the lack of individual‐level longitudinal data spanning the entire disease timeline.
Supplier dependence and R&D intensity: The moderating role of network centrality and interconnectedness
Authors: Kim Dong‐Young , Zhu Pengcheng 
Published: February 2019

AbstractThis study examines whether financial dependence upon a few customers is negatively related to the allocation of innovation resources of supplier firms. Furthermore, this study investigates whether these negative effects of supplier dependence on research and development (R&D) intensity are reduced when the supplier leverages social capital conceptualized in terms of eigenvector centrality and interconnectedness. Using panel data, we find that a supplier firm's dependence upon major customers has a negative relationship with the supplier firm's R&D intensity. Our results, however, reveal that a dependent supplier having high eigenvector centrality or working with other companies that are densely connected to each other mitigates the negative effects of supplier dependence on R&D intensity. These findings highlight the importance of external information or resources being available in supply networks when suppliers that are dependent upon major customers explore and exploit opportunities for new product development.
Elephants and mammoths: the effect of an imperfect legal substitute on illegal activity
Authors: Farah Naima , Boyce John R. 
Published: February 2019

AbstractIn response to the CITES ban on trade in elephant ivory, mammoth ivory began to be produced in post-Soviet Russia. We investigate how this substitute to elephant ivory has affected the poaching of elephants. We argue that the early success of the 1989 ivory ban at increasing the African elephant population was driven in part by increasing supply of mammoth ivory. The more recent increases in poaching appear to be driven by increasing demand and falling African institutional quality. We find that absent the 80 tonnes of Russian mammoth ivory exports per annum 2010–2012, elephant ivory prices would have doubled from their $ 100 per kilogram level and that the current poaching level of 34,000 elephants per year may have increased by as many as 55,000 elephants per year on a population of roughly half a million animals.
Who knows best? Older people’s and practitioner contributions to understanding and preventing avoidable hospital admissions
Authors: Glasby Jon , Littlechild Rosemary , Le Mesurier Nick , Thwaites Rachel 
Published: February 2019

AbstractWhenever there are well-publicised pressures on acute care, there is a tendency for policy makers and the media to imply that a significant number of older people may be taking up hospital beds when they do not really need the services provided there. However, evidence to back up such claims is often lacking, and existing research tends to fail to engage meaningfully with older people themselves. In contrast, this research explores the emergency hospital admissions of older people in three English case study sites, drawing on the lived experience of older people and the practice wisdom of front-line staff to explore the appropriateness of each admission and scope for alternatives to hospital. Contrary to popular opinion, the study did not find evidence of large numbers of older people being admitted to hospital inappropriately. Indeed, some of the older people concerned delayed seeking help and only ended up at hospital as a very last resort, possibly due to concerns about being seen as a burden on scarce public resources. While older people and front-line staff identified a number of suggestions to improve services in future, there seemed few clear cut, easy answers to the longstanding dilemma of how best to reduce emergency admissions. Seeking to understand and potentially reduce emergency hospital admissions is complex, and it is important to consider the experiences and expertise of older people and front-line staff.
Simuliertes Glücksspiel im Internet
Authors: Hayer Tobias , Rosenkranz Moritz , Meyer Gerhard , Brosowski Tim 
Published: February 2019

Zusammenfassung. Die vorliegende Studie beschäftigt sich mit simulierten Internet-Glücksspielen und folglich mit neuartigen Spielangeboten, die an der Schnittstelle von Computer- und Glücksspielen anzusiedeln sind. Erstmals werden für Deutschland in diesem Zusammenhang differenzierte Daten zum Nachfrageverhalten sowie zu teilnahmefördernden Bedingungen vorgelegt. Grundlage der Datenanalyse ist eine quantitative Erhebung mit N = 1 905 Schülern und Schülerinnen der Klassenstufen 6 bis 10 ( M = 13.8 Jahre) aus drei norddeutschen Großstädten. Die Ergebnisse zeigen, dass etwa die Hälfte aller Befragten in den letzten 12 Monaten am simulierten Internet-Glücksspiel teilgenommen hat. Dabei dominieren Spielerfahrungen innerhalb von Videospielen. Darüber hinaus variieren die Prädiktoren einer Spielteilnahme in Abhängigkeit konkreter Spielvarianten (innerhalb von Videospielen, über Apps, in sozialen Netzwerken, als Demospiele). Abschließend werden weiterführende Handlungsbedarfe in Bezug auf Prävention, Regulation und Forschung diskutiert.
Differenzielle Analysen zum Zusammenhang zwischen Kreativität und ADHS bei Kindern und Jugendlichen
Authors: Lüdeke Sören , Linderkamp Friedrich , Cevani Isabelle 
Published: February 2019

Zusammenfassung. Befunde zur Kreativität bei Kindern und Jugendlichen mit ADHS sind widersprüchlich. Zur Erfassung von Kreativität wird oft auf quantitative Leistungsmaße wie divergentes Denken in Speed-Tests zurückgegriffen anstelle von qualitativen Aspekten wie Unkonventionalität und Humor. Diese Studie untersucht, ob sich Kinder und Jugendliche mit ADHS hinsichtlich quantitativer und qualitativer Kreativitätsmerkmale von einer Kontrollgruppe unterscheiden. Die Stichprobe schließt N = 71 Kinder und Jugendliche (10 – 14 Jahre) ein, davon 17 mit klinischer ADHS-Diagnose und 16 mit ADHS-Symptomen gemäß DISYPS-II. In einem standardisierten Kreativitätstest erreichen die ADHS-Gruppen unabhängig von Alter und Geschlecht signifikant bessere Gesamtleistungen als die Kontrollgruppe. Unterschiede bestehen vor allem in den Bereichen Humor und emotionale Expressivität zeichnerischer Darstellungen. Die Ergebnisse unterstreichen die Bedeutung ressourcenorientierter Perspektiven auf Kinder und Jugendliche mit ADHS.
Deformation, Annealing, Melt‐Rock Interaction, and Seismic Properties of an Old Domain of the Equatorial Atlantic Lithospheric Mantle
Authors: Liu Shiran , Tommasi Andréa , Vauchez Alain , Mazzucchelli Maurizio 
Published: February 2019

AbstractWe analyzed a set of mantle xenoliths from the Fernando de Noronha archipelago to constrain the roles of deformation, cooling, annealing, and melt percolation in the evolution of the mantle lithosphere of the equatorial Atlantic. The peridotites are dominantly lherzolites with coarse granular or porphyroclastic microstructures. Equilibrium temperatures range between 850 and 1,000 °C. Olivine crystal preferred orientations (CPO) have mainly orthorhombic patterns characterized by clear [100] and [010] point maxima or a fiber‐[100] tendency; these patterns imply deformation by dislocation creep with dominant activation of the [100](010) slip system. Olivine fiber‐[010] patterns are less common; they probably result from recrystallization or melt‐rock interaction. Annealing after deformation partially recovered the microstructures and reduced the olivine CPO strength. Pyroxene CPOs often have weak consistency with olivine CPO, implying post‐deformation refertilization. Chemical compositions are systematically more fertile than those from abyssal peridotites from the Mid‐Atlantic Ridge. These compositions together with the microstructures suggest two stages of melt‐rock interaction. An early refertilization of the base of the lithosphere due to continuous percolation of small melt fractions and later, more important, but local chemical changes (both refertilization and dunitization) as well as recrystallization due to reactive melt percolation likely associated with the Cenozoic volcanism. By comparing the calculated seismic properties with existing seismological data we argue that the moderate seismic anisotropy displayed by the Fernando de Noronha mantle xenoliths likely records past horizontal asthenospheric flow parallel to the spreading direction frozen in the lithospheric mantle as the plate cooled.
The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG)
Authors: Kyriakou Charalampia , Molloy Sean , Vrionis Frank , Alberico Ronald , Bastian Leonard , Zonder Jeffrey A. , Giralt Sergio , Raje Noopur , Kyle Robert A. , Roodman David G. D. , Dimopoulos Meletios A. , Rajkumar S. Vincent , Durie Brian B. G. , Terpos Evangelos 
Published: February 2019

AbstractMultiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing, efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs.
Regulation of senescence escape by TSP1 and CD47 following chemotherapy treatment
Authors: Guillon Jordan , Petit Coralie , Moreau Marie , Toutain Bertrand , Henry Cécile , Roché Henry , Bonichon-Lamichhane Nathalie , Salmon Jean Paul , Lemonnier Jérôme , Campone Mario , Verrièle Véronique , Lelièvre Eric , Guette Catherine , Coqueret Olivier 
Published: February 2019

AbstractSenescence is a tumor-suppressive mechanism induced by telomere shortening, oncogenes, or chemotherapy treatment. Although it is clear that this suppressive pathway leads to a permanent arrest in primary cells, this might not be the case in cancer cells that have inactivated their suppressive pathways. We have recently shown that subpopulations of cells can escape chemotherapy-mediated senescence and emerge as more transformed cells that induce tumor formation, resist anoikis, and are more invasive. In this study, we characterized this emergence and showed that senescent cells favor tumor growth and metastasis, in vitro and in vivo. Senescence escape was regulated by secreted proteins produced during emergence. Among these, we identified thrombospondin-1 (TSP1), a protein produced by senescent cells that prevented senescence escape. Using SWATH quantitative proteomic analysis, we found that TSP1 can be detected in the serum of patients suffering from triple-negative breast cancer and that its low expression was associated with treatment failure. The results also indicate that senescence escape is explained by the emergence of CD47low cells that express a reduced level of CD47, the TSP1 receptor. The results show that CD47 expression is regulated by p21waf1. The cell cycle inhibitor was sufficient to maintain senescence since its downregulation in senescent cells increased cell emergence. This leads to the upregulation of Myc, which then binds to the CD47 promoter to repress its expression, allowing the generation of CD47low cells that escape the suppressive arrest. Altogether, these results uncovered a new function for TSP1 and CD47 in the control of chemotherapy-mediated senescence.
Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway
Authors: Yang Wei , Wu Peng-fei , Ma Jian-xing , Liao Mao-jun , Wang Xu-hui , Xu Lun-shan , Xu Min-hui , Yi Liang 
Published: February 2019

AbstractHigh aggressiveness is a hallmark of glioblastoma and predicts poor prognosis of patients with glioblastoma. The expression level of sortilin has been preliminarily reported to be elevated in high-grade glioma; however, the potential significance of sortilin in glioblastoma progression has not been elucidated. In this study, we investigated the oncogenic effect of sortilin in glioblastoma. Increased levels of sortilin were noted in the mesenchymal subtype of glioblastoma and highly aggressive subtypes of glioblastoma tissues and cell lines. In addition, high levels of sortilin predicted poor prognoses in patients with glioblastoma. Sortilin knockdown or inhibition with AF38469 (an orally bioavailable inhibitor of sortilin) significantly suppressed migration and invasion by inhibiting EMT-like mesenchymal transition in glioblastoma cells. Furthermore, we proved that sortilin promoted cell invasion mainly via Glycogen synthase kinase 3 beta (GSK-3β)/β-catenin/Twist-induced EMT-like mesenchymal transition in glioblastoma. Taken together, our results demonstrate a critical role of sortilin in glioblastoma invasion and EMT-like mesenchymal transition, indicating that sortilin contributes to glioblastoma progression. These data also highlight the dramatic antitumor effects of AF38469 in glioblastoma, suggesting that AF38469 is a potentially powerful antitumor agent for sortilin-overexpressing human glioblastoma.
PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation
Authors: Tong Lei , Wang Long , Yao Shuangshuang , Jin Lina , Yang Jian , Zhang Yifei , Ning Guang , Zhang Zhiguo 
Published: February 2019

AbstractPeroxisome proliferator-activated receptor δ (PPARδ) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPARδ is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPARδ is a potent stimulator of hepatic autophagic flux. The expression levels of PPARδ and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPARδ expression and activity were achieved in obese transgenic db/db and high fat diet-fed mice. Using genetic, pharmacological and metabolic approaches, we demonstrate that PPARδ reduces intrahepatic lipid content and stimulates β-oxidation in liver and hepatic cells by an autophagy–lysosomal pathway involving AMPK/mTOR signalling. These results provide novel insight into the lipolytic actions of PPARδ through autophagy in the liver and highlight its potential beneficial effects in NAFLD.
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Authors: Hess Daniel L. , Kelly-Goss Molly R. , Cherepanova Olga A. , Nguyen Anh T. , Baylis Richard A. , Tkachenko Svyatoslav , Annex Brian H. , Peirce Shayn M. , Owens Gary K. 
Published: February 2019

AbstractThe stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration and recruitment during angiogenesis. Knockout of Oct4 in perivascular cells significantly impairs perivascular cell migration, increases perivascular cell death, delays endothelial cell migration, and promotes vascular leakage following corneal angiogenic stimulus. Knockout of Oct4 in perivascular cells also impairs perfusion recovery and decreases angiogenesis following hindlimb ischemia. Transcriptomic analyses demonstrate that expression of the migratory gene Slit3 is reduced following loss of Oct4 in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle. Together, these results provide evidence that Oct4 plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis.
Viral pathogens hitchhike with insect sperm for paternal transmission
Authors: Mao Qianzhuo , Wu Wei , Liao Zhenfeng , Li Jiajia , Jia Dongsheng , Zhang Xiaofeng , Chen Qian , Chen Hongyan , Wei Jing , Wei Taiyun 
Published: February 2019

AbstractArthropod-borne viruses (arboviruses) can be maternally transmitted by female insects to their offspring, however, it is unknown whether male sperm can directly interact with the arbovirus and mediate its paternal transmission. Here we report that an important rice arbovirus is paternally transmitted by the male leafhoppers by hitchhiking with the sperm. The virus-sperm binding is mediated by the interaction of viral capsid protein and heparan sulfate proteoglycan on the sperm head surfaces. Mating experiments reveal that paternal virus transmission is more efficient than maternal transmission. Such paternal virus transmission scarcely affects the fitness of adult males or their offspring, and plays a pivotal role in maintenance of viral population during seasons unfavorable for rice hosts in the field. Our findings reveal that a preferred mode of vertical arbovirus transmission has been evolved by hitchhiking with insect sperm without disturbing sperm functioning, facilitating the long-term viral epidemic and persistence in nature.
Man-made microbial resistances in built environments
Authors: Mahnert Alexander , Moissl-Eichinger Christine , Zojer Markus , Bogumil David , Mizrahi Itzhak , Rattei Thomas , Martinez José Luis , Berg Gabriele 
Published: February 2019

AbstractAntimicrobial resistance is a serious threat to global public health, but little is known about the effects of microbial control on the microbiota and its associated resistome. Here we compare the microbiota present on surfaces of clinical settings with other built environments. Using state-of-the-art metagenomics approaches and genome and plasmid reconstruction, we show that increased confinement and cleaning is associated with a loss of microbial diversity and a shift from Gram-positive bacteria, such as Actinobacteria and Firmicutes, to Gram-negative such as Proteobacteria. Moreover, the microbiome of highly maintained built environments has a different resistome when compared to other built environments, as well as a higher diversity in resistance genes. Our results highlight that the loss of microbial diversity correlates with an increase in resistance, and the need for implementing strategies to restore bacterial diversity in certain built environments.
A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT
Authors: Talavera Ariel , Tamman Hedvig , Ainelo Andres , Konijnenberg Albert , Hadži San , Sobott Frank , Garcia-Pino Abel , Hõrak Rita , Loris Remy 
Published: February 2019

AbstractBacterial toxin-antitoxin (TA) modules are tightly regulated to maintain growth in favorable conditions or growth arrest during stress. A typical regulatory strategy involves the antitoxin binding and repressing its own promoter while the toxin often acts as a co-repressor. Here we show that Pseudomonas putida graTA-encoded antitoxin GraA and toxin GraT differ from other TA proteins in the sense that not the antitoxin but the toxin possesses a flexible region. GraA auto-represses the graTA promoter: two GraA dimers bind cooperatively at opposite sides of the operator sequence. Contrary to other TA modules, GraT is a de-repressor of the graTA promoter as its N-terminal disordered segment prevents the binding of the GraT2A2 complex to the operator. Removal of this region restores operator binding and abrogates Gr	aT toxicity. GraTA represents a TA module where a flexible region in the toxin rather than in the antitoxin controls operon expression and toxin activity.
Persistent DNA-break potential near telomeres increases initiation of meiotic recombination on short chromosomes
Authors: Subramanian Vijayalakshmi V. , Zhu Xuan , Markowitz Tovah E. , Vale-Silva Luis A. , San-Segundo Pedro A. , Hollingsworth Nancy M. , Keeney Scott , Hochwagen Andreas 
Published: February 2019

AbstractFaithful meiotic chromosome inheritance and fertility rely on the stimulation of meiotic crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation of crossover repair. In Saccharomyces cerevisiae, this regulation requires the removal of the conserved DSB-promoting protein Hop1/HORMAD during chromosome synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all telomeres that escape DSB down-regulation. These regions retain Hop1 and continue to break in pachynema despite normal synaptonemal complex deposition. Differential retention of Hop1 requires the disassemblase Pch2/TRIP13, which preferentially removes Hop1 from telomere-distant sequences, and is modulated by the histone deacetylase Sir2 and the nucleoporin Nup2. Importantly, the uniform size of EARs among chromosomes contributes to disproportionately high DSB and repair signals on short chromosomes in pachynema, suggesting that EARs partially underlie the curiously high recombination rate of short chromosomes.