bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined treatment with memantine and galantamine‐CR compared with galantamine‐CR only in antidementia drug naïve patients with mild‐to‐moderate Alzheimer's disease
Authors: Peters Oliver , Fuentes Manuel , Joachim Lisa Katharina , Jessen Frank , Luckhaus Christian , Kornhuber Johannes , Pantel Johannes , Hüll Michael , Schmidtke Klaus , Rüther Eckart , Möller Hans‐Jürgen , Kurz Alexander , Wiltfang Jens , Maier Wolfgang , Wiese Birgitt , Frölich Lutz , Heuser Isabella 
Published: October 2015

AbstractIntroductionSeveral studies have tested the N‐methyl‐D‐aspartate–receptor antagonist memantine as an add‐on to pre‐existing treatment with acetylcholinesterase inhibitors. The objective of this study was to evaluate the efficacy and safety of a combined memantine and galantamine‐CR de novo regimen compared with galantamine‐CR only treatment in never treated patients with mild‐to‐moderate Alzheimer's disease (AD).MethodsAntidementia drug–naïve participants (n = 232) with probable, mild‐to‐moderate AD, and mini‐mental state examination scores between 15 and 26 (inclusive) were randomized to receive either 20 mg/day memantine plus 24 mg/day galantamine‐CR or 24 mg/day galantamine‐CR plus placebo in a 52‐week, prospective, double‐blind, controlled trial. The primary outcome measurement was the change on the Alzheimer's disease assessment scale‐cognition score. Secondary measures comprised the Alzheimer's Disease Cooperative Study‐activities of daily living inventory and the clinical dementia rating.ResultsAt the end of the trial, there were no statistically significant differences between the galantamine‐CR/memantine combination and galantamine‐CR only group in primary and secondary outcome measurements. The incidence and the severity of adverse events were similar between the groups.DiscussionIn this trial, memantine in combination with galantamine‐CR did not show an advantage with respect to cognition, function, and behavior in previously never treated patients with mild‐to‐moderate AD. There were no significant differences in tolerability and safety between the groups. Thus, a de novo combination treatment results in no significant improvement in disease progression (current controlled trials number: NCT01921972).
Effects of phenol on metabolic activities and transcription profiles of cytochrome P450 enzymes inChironomus kiinensislarvae
Authors: Cao C.W. , Sun L.L. , Niu F. , Liu P. , Chu D. , Wang Z.Y. 
Published: October 2015

AbstractPhenol, also known as carbolic acid or phenic acid, is a priority pollutant in aquatic ecosystems. The present study has investigated metabolic activities and transcription profiles of cytochrome P450 enzymes inChironomus kiinensisunder phenol stress. Exposure ofC. kiinensislarvae to three sublethal doses of phenol (1, 10 and 100 µM) inhibited cytochrome P450 enzyme activity during the 96 h exposure period. The P450 activity measured after the 24 h exposure to phenol stress could be used to assess the level (low or high) of phenol contamination in the environment. To investigate the potential of cytochrome P450 genes as molecular biomarkers to monitor phenol contamination, the cDNA of ten CYP6 genes from the transcriptome ofC. kiinensiswere identified and sequenced. The open reading frames of the CYP6 genes ranged from 1266 to 1587 bp, encoding deduced polypeptides composed of between 421 and 528 amino acids, with predicted molecular masses from 49.01 to 61.94 kDa and isoelectric points (PI) from 6.01 to 8.89. Among the CYP6 genes, the mRNA expression levels of theCYP6EW3, CYP6EV9, CYP6FV1andCYP6FV2genes significantly altered in response to phenol exposure; therefore, these genes could potentially serve as biomarkers in the environment. This study shows that P450 activity combined with one or multipleCYP6genes could be used to monitor phenol pollution.
Dual congenital transmission ofToxoplasma gondiiandSarcocystis neuronain a late-term aborted pup from a chronically infected southern sea otter (Enhydra lutris nereis)
Authors: SHAPIRO KAREN , MILLER MELISSA A. , PACKHAM ANDREA E. , AGUILAR BEATRIZ , CONRAD PATRICIA A. , VANWORMER ELIZABETH , MURRAY MICHAEL J. 
Published: October 2015

SUMMARYToxoplasma gondiiandSarcocystis neuronaare protozoan parasites with terrestrial definitive hosts, and both pathogens can cause fatal disease in a wide range of marine animals. Close monitoring of threatened southern sea otters (Enhydra lutris nereis) in California allowed for the diagnosis of dual transplacental transmission ofT. gondiiandS. neuronain a wild female otter that was chronically infected with both parasites. Congenital infection resulted in late-term abortion due to disseminated toxoplasmosis.Toxoplasma gondiiandS. neuronaDNA was amplified from placental tissue culture, as well as from fetal lung tissue. Molecular characterization ofT. gondiirevealed a Type X genotype in isolates derived from placenta and fetal brain, as well as in all tested fetal organs (brain, lung, spleen, liver and thymus). This report provides the first evidence for transplacental transmission ofT. gondiiin a chronically infected wild sea otter, and the first molecular and immunohistochemical confirmation of concurrent transplacental transmission ofT. gondiiandS. neuronain any species. Repeated fetal and/or neonatal losses in the sea otter dam also suggested thatT. gondiihas the potential to reduce fecundity in chronically infected marine mammals through parasite recrudescence and repeated fetal infection.
Characterizing social environment's association with neurocognition using census and crime data linked to the Philadelphia Neurodevelopmental Cohort
Authors: Moore T. M. , Martin I. K. , Gur O. M. , Jackson C. T. , Scott J. C. , Calkins M. E. , Ruparel K. , Port A. M. , Nivar I. , Krinsky H. D. , Gur R. E. , Gur R. C. 
Published: October 2015

BackgroundThe contribution of ‘environment’ has been investigated across diverse and multiple domains related to health. However, in the context of large-scale genomic studies the focus has been on obtaining individual-level endophenotypes with environment left for future decomposition. Geo-social research has indicated that environment-level variables can be reduced, and these composites can then be used with other variables as intuitive, precise representations of environment in research.MethodUsing a large community sample (N = 9498) from the Philadelphia area, participant addresses were linked to 2010 census and crime data. These were then factor analyzed (exploratory factor analysis; EFA) to arrive at social and criminal dimensions of participants' environments. These were used to calculate environment-level scores, which were merged with individual-level variables. We estimated an exploratory multilevel structural equation model (MSEM) exploring associations among environment- and individual-level variables in diverse communities.ResultsThe EFAs revealed that census data was best represented by two factors, one socioeconomic status and one household/language. Crime data was best represented by a single crime factor. The MSEM variables had good fit (e.g. comparative fit index = 0.98), and revealed that environment had the largest association with neurocognitive performance (β = 0.41, p < 0.0005), followed by parent education (β = 0.23, p < 0.0005).ConclusionsEnvironment-level variables can be combined to create factor scores or composites for use in larger statistical models. Our results are consistent with literature indicating that individual-level socio-demographic characteristics (e.g. race and gender) and aspects of familial social capital (e.g. parental education) have statistical relationships with neurocognitive performance.
Aphrodite Philommêdês in the Theogony
Authors: Bouchard Elsa 
Published: October 2015

Abstract:Discussion of Aphrodite’s epithet philommeidês/philommêdês in Hesiod Theogony 200. Hesiod’s aetiological account of this name suggests the meaning ‘wiles-loving’ as well as ‘genitals-loving’. This interpretation is supported by a number of episodes from Archaic poetry in which literary or mythical figures make use of a ruse to permit the fulfilment of their erotic longing, or conversely exploit someone else’s desire as a means to achieve supremacy in a power struggle.
One Health approach to controlling a Q fever outbreak on an Australian goat farm
Authors: BOND K. A. , VINCENT G. , WILKS C. R. , FRANKLIN L. , SUTTON B. , STENOS J. , COWAN R. , LIM K. , ATHAN E. , HARRIS O. , MACFARLANE-BERRY L. , SEGAL Y. , FIRESTONE S. M. 
Published: October 2015

SUMMARYA recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping ofCoxiella burnetiiDNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.
Murine models provide insight to the development of non-alcoholic fatty liver disease
Authors: Reid D. T. , Eksteen B. 
Published: October 2015

AbstractAssociated with the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) has become the leading liver disease in North America. Approximately 30 % of patients with NAFLD may develop non-alcoholic steatohepatitis (NASH) that can lead to cirrhosis and hepatocellular carcinoma (HCC). Frequently animal models are used to help identify underlying factors contributing to NAFLD including insulin resistance, dysregulated lipid metabolism and mitochondrial stress. However, studying the inflammatory, progressive nature of NASH in the context of obesity has proven to be a challenge in mice. Although the development of effective treatment strategies for NAFLD and NASH is gaining momentum, the field is hindered by a lack of a concise animal model that reflects the development of liver disease during obesity and the metabolic syndrome. Therefore, selecting an animal model to study NAFLD or NASH must be done carefully to ensure the optimal application. The most widely used animal models have been reviewed highlighting their advantages and disadvantages to studying NAFLD and NASH specifically in the context of obesity.
Characteristics of exceptional responders to lenalidomide-based therapy in multiple myeloma
Authors: Vu T , Gonsalves W , Kumar S , Dispenzieri A , Lacy M Q , Buadi F , Gertz M A , Rajkumar S V 
Published: October 2015

AbstractWe studied all patients at our institution with a diagnosis of multiple myeloma (MM), from 1 January 2004 to 1 July 2009, who received lenalidomide–dexamethasone (Rd) as initial therapy and had a time to progression of 72 months or longer. Of 240 patients, we identified 33 exceptional responders. Twenty-five patients received primary therapy with Rd and eight patients received Rd induction followed by early stem cell transplantation (SCT). Seven of the eight patients who received SCT did not receive maintenance therapy; one patient received 9 months of lenalidomide post transplant. Fifteen (45%) patients had known clonal plasma cell disorder before the diagnosis of MM. The dominant mode of clinical presentation was with lytic lesions in 28 patients. Of those with informative cytogenetics (n=24), trisomies were present in 19 (79%), including one patient with concurrent trisomies and t(11;14). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). None of these exceptional responders had high-risk cytogenetic features at baseline. Twenty-five patients (76%) had a complete response (CR), whereas eight patients (24%) achieved the exceptional response state without ever achieving a CR. We identify a cohort of exceptional responders to Rd-based therapy, representing ~10–15% newly diagnosed MM patients with normal renal function.
Effects of low temperature on tropical and temperate isolates of marine Synechococcus
Authors: Varkey Deepa , Mazard Sophie , Ostrowski Martin , Tetu Sasha G , Haynes Paul , Paulsen Ian T 
Published: October 2015

Abstract
Temperature is an important factor influencing the distribution of marine picocyanobacteria. However, molecular responses contributing to temperature preferences are poorly understood in these important primary producers. We compared the temperature acclimation of a tropical Synechococcus strain WH8102 with temperate strain BL107 at 18 °C relative to 22 °C and examined their global protein expression, growth patterns, photosynthetic efficiency and lipid composition. Global protein expression profiles demonstrate the partitioning of the proteome into major categories: photosynthesis (&gt;40%), translation (10–15%) and membrane transport (2–8%) with distinct differences between and within strains grown at different temperatures. At low temperature, growth and photosynthesis of strain WH8102 was significantly decreased, while BL107 was largely unaffected. There was an increased abundance of proteins involved in protein biosynthesis at 18 °C for BL107. Each strain showed distinct differences in lipid composition with higher unsaturation in strain BL107. We hypothesize that differences in membrane fluidity, abundance of protein biosynthesis machinery and the maintenance of photosynthesis efficiency contribute to the acclimation of strain BL107 to low temperature. Additional proteins unique to BL107 may also contribute to this strain’s improved fitness at low temperature. Such adaptive capacities are likely important factors favoring growth of temperate strains over tropical strains in high latitude niches.
Scalable fabrication of a hybrid field-effect and acousto-electric device by direct growth of monolayer MoS2/LiNbO3
Authors: Preciado Edwin , Schülein Florian J.R. , Nguyen Ariana E. , Barroso David , Isarraraz Miguel , von Son Gretel , Lu I-Hsi , Michailow Wladislaw , Möller Benjamin , Klee Velveth , Mann John , Wixforth Achim , Bartels Ludwig , Krenner Hubert J. 
Published: October 2015

AbstractLithium niobate is the archetypical ferroelectric material and the substrate of choice for numerous applications including surface acoustic wave radio frequencies devices and integrated optics. It offers a unique combination of substantial piezoelectric and birefringent properties, yet its lack of optical activity and semiconducting transport hamper application in optoelectronics. Here we fabricate and characterize a hybrid MoS2/LiNbO3 acousto-electric device via a scalable route that uses millimetre-scale direct chemical vapour deposition of MoS2 followed by lithographic definition of a field-effect transistor structure on top. The prototypical device exhibits electrical characteristics competitive with MoS2 devices on silicon. Surface acoustic waves excited on the substrate can manipulate and probe the electrical transport in the monolayer device in a contact-free manner. We realize both a sound-driven battery and an acoustic photodetector. Our findings open directions to non-invasive investigation of electrical properties of monolayer films.
Multimaterial magnetically assisted 3D printing of composite materials
Authors: Kokkinis Dimitri , Schaffner Manuel , Studart André R. 
Published: October 2015

Abstract3D printing has become commonplace for the manufacturing of objects with unusual geometries. Recent developments that enabled printing of multiple materials indicate that the technology can potentially offer a much wider design space beyond unusual shaping. Here we show that a new dimension in this design space can be exploited through the control of the orientation of anisotropic particles used as building blocks during a direct ink-writing process. Particle orientation control is demonstrated by applying low magnetic fields on deposited inks pre-loaded with magnetized stiff platelets. Multimaterial dispensers and a two-component mixing unit provide additional control over the local composition of the printed material. The five-dimensional design space covered by the proposed multimaterial magnetically assisted 3D printing platform (MM-3D printing) opens the way towards the manufacturing of functional heterogeneous materials with exquisite microstructural features thus far only accessible by biological materials grown in nature.
Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids
Authors: Freedman Benjamin S. , Brooks Craig R. , Lam Albert Q. , Fu Hongxia , Morizane Ryuji , Agrawal Vishesh , Saad Abdelaziz F. , Li Michelle K. , Hughes Michael R. , Werff Ryan Vander , Peters Derek T. , Lu Junjie , Baccei Anna , Siedlecki Andrew M. , Valerius M. Todd , Musunuru Kiran , McNagny Kelly M. , Steinman Theodore I. , Zhou Jing , Lerou Paul H. , Bonventre Joseph V. 
Published: October 2015

AbstractHuman-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications.
A new mutually reinforcing network node and link ranking algorithm
Authors: Wang Zhenghua , Dueñas-Osorio Leonardo , Padgett Jamie E. 
Published: October 2015

AbstractThis study proposes a novel Normalized Wide network Ranking algorithm (NWRank) that has the advantage of ranking nodes and links of a network simultaneously. This algorithm combines the mutual reinforcement feature of Hypertext Induced Topic Selection (HITS) and the weight normalization feature of PageRank. Relative weights are assigned to links based on the degree of the adjacent neighbors and the Betweenness Centrality instead of assigning the same weight to every link as assumed in PageRank. Numerical experiment results show that NWRank performs consistently better than HITS, PageRank, eigenvector centrality and edge betweenness from the perspective of network connectivity and approximate network flow, which is also supported by comparisons with the expensive N-1 benchmark removal criteria based on network efficiency. Furthermore, it can avoid some problems, such as the Tightly Knit Community effect, which exists in HITS. NWRank provides a new inexpensive way to rank nodes and links of a network, which has practical applications, particularly to prioritize resource allocation for upgrade of hierarchical and distributed networks, as well as to support decision making in the design of networks, where node and link importance depend on a balance of local and global integrity.
TUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis
Authors: Yokoi Setsuri , Ishihara Naoko , Miya Fuyuki , Tsutsumi Makiko , Yanagihara Itaru , Fujita Naoko , Yamamoto Hiroyuki , Kato Mitsuhiro , Okamoto Nobuhiko , Tsunoda Tatsuhiko , Yamasaki Mami , Kanemura Yonehiro , Kosaki Kenjiro , Kojima Seiji , Saitoh Shinji , Kurahashi Hiroki , Natsume Jun 
Published: October 2015

AbstractTUBA1A mutations cause a wide spectrum of lissencephaly and brain malformations. Here, we report two patients with severe cortical dysgeneses, one with an extremely thin cerebral parenchyma apparently looking like hydranencephaly and the other with lissencephaly accompanied by marked hydrocephalus, both harbouring novel de novo missense mutations of TUBA1A. To elucidate how the various TUBA1A mutations affect the severity of the phenotype, we examined the capacity of the mutant protein to incorporate into the endogenous microtubule network in transfected COS7 cells by measuring line density using line extraction in an immunofluorescence study. The mutants responsible for severe phenotypes were found to incorporate extensively into the network. To determine how each mutant alters the microtubule stability, we examined cold-induced microtubule depolymerisation in fibroblasts. The depolymerisation of patients’ fibroblasts occurred earlier than that of control fibroblasts, suggesting that microtubules bearing mutated tubulins are unstable. Both mutations are predicted to participate in lateral interactions of microtubules. Our data suggest that the TUBA1A mutations disrupting lateral interactions have pronounced dominant-negative effects on microtubule dynamics that are associated with the severe end of the lissencephaly spectrum.
Phosphatidic Acid (PA) can Displace PPARα/LXRα Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells
Authors: Mahankali Madhu , Farkaly Terry , Bedi Shimpi , Hostetler Heather A. , Gomez-Cambronero Julian 
Published: October 2015

AbstractThe expression of the epidermal growth factor receptor (EGFR) is highly regulated in normal cells, whereas some cancer cells have high constitutive levels. Understanding naturally-occurring ways of downregulating EGFR in cancer cells was investigated. Phosphatidic acid (PA) or Nuclear Receptors (NR) PPARα/RXRα/LXRα, enhance EGFR expression, mediated by the promoter region -856(A) to -226(T). Unexpectedly, the combination of NRs and PA caused repression. PA induces a conformational change in the nuclear receptor PPARα (increase of alpha-helices at the expense of decreasing beta-sheets), as evidenced by circular dichroism. This represses the naturally-enhancing capability of PPARα on EGFR transcription. PPARα-overexpressing cells in the presence of PA > 300 nM or the enzyme that produces it, phospholipase D (PLD), downregulate EGFR expression. The reasons are two-fold. First, PA displaces PPARα binding to the EGFR promoter at those concentrations. Second, NR heterodimer-dependent promoter activity is weakened in the presence of PA in vivo. Since other genes considered (β-catenin, cyclin D3, PLD2 and ACOX-1) are also downregulated with a PA + PPARα combination, the transrepression appears to be a global phenomenon. Lastly, the reported effect is greater in MCF-7 than in MDA-MB-231 breast cancer cells, which could provide a novel basis for regulating excessive expression of EGFR in luminal cancer cells.