bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deoxycytidine kinase is downregulated under hypoxic conditions and confers resistance against cytarabine in acute myeloid leukaemia
Authors: Degwert Nicole , Latuske Emily , Vohwinkel Gabi , Stamm Hauke , Klokow Marianne , Bokemeyer Carsten , Fiedler Walter , Wellbrock Jasmin 
Published: November 2015

AbstractObjectivesLeukaemia initiating cells reside within specialised niches in the bone marrow where they undergo complex interactions with different stromal cell types. The bone marrow niche is characterised by a low oxygen content resulting in high expression of hypoxia‐inducible factor 1 α in leukaemic cells conferring a negative prognosis to patients with acute myeloid leukaemia (AML).Methods and ResultsIn the current study, we investigated the impact of hypoxic vs. normoxic conditions on the sensitivity of AML cell lines and primary AML blasts to cytarabine. AML cells cultured under 6% oxygen were significantly more resistant against cytarabine compared to cells cultured under normoxic conditions in proliferation and colony‐formation assays. Interestingly upon cultivation under hypoxia, the expression of the cytarabine‐activating enzyme deoxycytidine kinase was downregulated in all analysed AML cell lines and primary AML samples representing a possible mechanism for resistance to chemotherapy. Furthermore, the downregulation of deoxycytidine kinase could be associated with hypoxia‐inducible factor 1 α as treatment with its inhibitor BAY87‐2243 hampered the downregulation of deoxycytidine kinase expression under hypoxic conditions.ConclusionsIn conclusion, our data reveal that hypoxia‐induced downregulation of deoxycytidine kinase represents one stroma‐cell‐independent mechanism of drug resistance to cytarabine in acute myeloid leukaemia.
Subdivision of Broca's region based on individual‐level functional connectivity
Authors: Jakobsen Estrid , Böttger Joachim , Bellec Pierre , Geyer Stefan , Rübsamen Rudolf , Petrides Michael , Margulies Daniel S. 
Published: November 2015

AbstractBroca's region is composed of two adjacent cytoarchitectonic areas, 44 and 45, which have distinct connectivity to superior temporal and inferior parietal regions in both macaque monkeys and humans. The current study aimed to make use of prior knowledge of sulcal anatomy and resting‐state functional connectivity, together with a novel visualization technique, to manually parcellate areas 44 and 45 in individual brains in vivo. One hundred and one resting‐state functional magnetic resonance imaging datasets from the Human Connectome Project were used. Left‐hemisphere surface‐based correlation matrices were computed and visualized in brainGL. By observation of differences in the connectivity patterns of neighbouring nodes, areas 44 and 45 were manually parcellated in individual brains, and then compared at the group‐level. Additionally, the manual labelling approach was compared with parcellation results based on several data‐driven clustering techniques. Areas 44 and 45 could be clearly distinguished from each other in all individuals, and the manual segmentation method showed high test‐retest reliability. Group‐level probability maps of areas 44 and 45 showed spatial consistency across individuals, and corresponded well to cytoarchitectonic probability maps. Group‐level connectivity maps were consistent with previous studies showing distinct connectivity patterns of areas 44 and 45. Data‐driven parcellation techniques produced clusters with varying degrees of spatial overlap with the manual labels, indicating the need for further investigation and validation of machine learning cortical segmentation approaches. The current study provides a reliable method for individual‐level cortical parcellation that could be applied to regions distinguishable by even the most subtle differences in patterns of functional connectivity.
De novo DNM1 mutations in two cases of epileptic encephalopathy
Authors: Nakashima Mitsuko , Kouga Takeshi , Lourenço Charles Marques , Shiina Masaaki , Goto Tomohide , Tsurusaki Yoshinori , Miyatake Satoko , Miyake Noriko , Saitsu Hirotomo , Ogata Kazuhiro , Osaka Hitoshi , Matsumoto Naomichi 
Published: November 2015

SummaryDynamin 1 (DNM1) is a large guanosine triphosphatase involved in clathrin‐mediated endocytosis. In recent studies, de novo mutations in DNM1 have been identified in five individuals with epileptic encephalopathy. In this study, we report two patients with early onset epileptic encephalopathy possessing de novo DNM1 mutations. Using whole exome sequencing, we detected the novel mutation c.127G>A (p.Gly43Ser) in a patient with Lennox‐Gastaut syndrome, and a recurrent mutation c.709C>T (p.Arg237Trp) in a patient with West syndrome. Structural consideration of DNM1 mutations revealed that both mutations would destabilize the G domain structure and impair nucleotide binding, dimer formation, and/or GTPase activity of the G domain. These and previous cases of DNM1 mutations were reviewed to verify the phenotypic spectrum. The main clinical features of DNM1 mutations include intractable seizures, intellectual disability, developmental delay, and hypotonia. Most cases showed development delay before the onset of seizures. A patient carrying p.Arg237Trp in this report showed a different developmental status from that of a previously reported case, together with characteristic extrapyramidal movement.
Contracted endodontic cavities: the foundation for less invasive alternatives in the management of apical periodontitis
Authors: Bóveda Carlos , Kishen Anil 
Published: November 2015

Compromised structural or mechanical integrity of teeth results in different types of tooth fractures, which are known to be one of the most common causes for tooth extraction. Minimally invasive concepts and procedures are currently advocated as less invasive alternatives to traditional treatments. Recent advances in the available resources and technologies have made a significant impact on endodontic treatment procedures, allowing minimally invasive treatment procedures such as contracted endodontic cavities for preserving coronal and radicular tooth structure. The purpose of this article is to provide a framework for understanding the clinical reasoning for contracted endodontic cavities and their possible benefits in contemporary endodontics.
Rapid evolution of increased vulnerability to an insecticide at the expansion front in a poleward‐moving damselfly
Authors: Dinh Khuong Van , Janssens Lizanne , Therry Lieven , Gyulavári Hajnalka A. , Bervoets Lieven , Stoks Robby 
Published: November 2015

AbstractMany species are too slow to track their poleward‐moving climate niche under global warming. Pesticide exposure may contribute to this by reducing population growth and impairing flight ability. Moreover, edge populations at the moving range front may be more vulnerable to pesticides because of the rapid evolution of traits to enhance their rate of spread that shunt energy away from detoxification and repair. We exposed replicated edge and core populations of the poleward‐moving damselfly Coenagrion scitulum to the pesticide esfenvalerate at low and high densities. Exposure to esfenvalerate had strong negative effects on survival, growth rate, and development time in the larval stage and negatively affected flight‐related adult traits (mass at emergence, flight muscle mass, and fat content) across metamorphosis. Pesticide effects did not differ between edge and core populations, except that at the high concentration the pesticide‐induced mortality was 17% stronger in edge populations. Pesticide exposure may therefore slow down the range expansion by lowering population growth rates, especially because edge populations suffered a higher mortality, and by negatively affecting dispersal ability by impairing flight‐related traits. These results emphasize the need for direct conservation efforts toward leading‐edge populations for facilitating future range shifts under global warming.
The Second Crusade, 1145–49: Damascus, Lisbon and the Wendish Campaigns
Authors: Roche Jason T. 
Published: November 2015

AbstractThe Second Crusade (1145–49) is thought to have encompassed near simultaneous Christian attacks on Muslim towns and cities in Syria and Iberia and pagan Wend strongholds around the southern shore of the Baltic Sea. The motivations underpinning the attacks on Damascus, Lisbon and – taken collectively – the Wendish strongholds have come in for particular attention. The doomed decision to assault Damascus in 1148 rather than recover Edessa, the capital of the first so‐called crusader state, was once thought to be ill‐conceived. Historians now believe the city was attacked because Damascus posed a significant threat to the Latin kingdom of Jerusalem when the Second Crusaders arrived in the East. The assault on Lisbon and the Wendish strongholds fell into a long‐established pattern of regional, worldly aggression and expansion; therefore, historians tend not to ascribe any spiritual impulses behind the native Christians' decisions to attack their enemies. Indeed, the siege of Lisbon by an allied force of international crusaders and those of the Portuguese ruler, Afonso Henriques, is perceived primarily as a politico‐strategic episode in the on‐going Christian–Muslim conflict in Iberia – commonly referred to as thereconquista. The native warrior and commercial elite undoubtedly had various temporal reasons for engaging in warfare in Iberia and the Baltic region between 1147 and 1149, although the article concludes with some notes of caution before clinically construing motivation from behaviour in such instances.
Fine‐scale climatic variation drives altitudinal niche partitioning of tabanid flies in a tropical montane cloud forest, Ecuadorian Chocó
Authors: Cárdenas Rafael E. 
Published: November 2015

Abstract

In montane systems, global warming may lead communities to disassemble by forcing organisms to shift their distributions to higher elevations or by causing the extinction of those that are unable to adapt. To predict which species are most at risk from environmental change, physiological responses to multiple factors must be measured in natural conditions at fine spatial and temporal scales.

To examine the potential drivers of elevational distributions in tabanid flies, specimens were exhaustively sampled at three altitudes within a tropical montane cloud forest in Western Ecuador. Observed abundances were then correlated with seven environmental variables measured in situ. It was hypothesised that (1) tabanid distributions were significantly associated with particular environmental conditions measured in each altitudinal habitat, and (2) a greater proportion of lowland species were limited to a specific elevation than highland species.

Most species occupied well‐defined altitudinal niches corresponding to optimal climatic conditions. Colder weather, higher daily temperature variability, and higher levels of moisture seemed to limit most species from establishing in high elevation sites of this mountainous ecosystem.

Despite the high dispersal potential of tabanids within the study area, results suggest that most tabanid flies are limited to the subset of altitudes where their climatic requirements are satisfied.
Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes
Authors: Kobayashi Kazuhiro , Saito Toshihiro , Kitamura Yasuo , Bilim Vladimir , Toba Tomotaka , Kawasaki Takashi , Hara Noboru , Tanikawa Toshiki , Tomita Yoshihiko 
Published: November 2015

ObjectivesTo determine the effect of preoperative chemotherapy on survival in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.MethodsWe retrospectively analyzed 55 consecutive patients who received radical nephroureterectomy with or without preoperative chemotherapy for upper urinary tract urothelial carcinoma clinically involving regional lymph nodes at a single institution between January 1991 and December 2013.ResultsMedian follow up was 18 months (range 2–193). Of 55 patients, 24 (43.6%) received preoperative chemotherapy (study group) and 31 (56.4%) underwent primary surgery (control group). Preoperative chemotherapy consisted of two to four cycles (median 3) of cisplatin‐containing regimens. The fraction of patients with lower pathological T stage and N stage than clinical T stage and N stage was higher in the study group (29.2% and 54.2%) compared with the control group (3.2% and 16.1%; P = 0.013 and 0.010, respectively). The 5‐year overall survival rate was significantly higher in the study group than in the control group (44.0% vs 12.9%, log–rank, P = 0.003). In multivariate analysis incorporating age at diagnosis, Eastern Cooperative Oncology Group Performance Status, clinical N stage and the number of removed lymph nodes, preoperative chemotherapy was a predictor of better overall survival (P = 0.047, HR 0.47, 95% CI 0.22–0.99).ConclusionsPreoperative chemotherapy might provide better survival outcomes in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.
The Federal Reserve: The Weakest Lender of Last Resort Among Its Peers
Authors: Scott Hal S. 
Published: November 2015

AbstractThis article for the first time compares the Federal Reserve's powers as lender of last resort (‘LLR’) and its ability to fight contagion, with its three major peers, the Bank of England (the ‘BOE’), the European Central Bank (the ‘ECB’) and the Bank of Japan (the ‘BOJ’). It concludes that the Federal Reserve (the ‘Fed’) is currently the weakest of the four, largely due to a hostile political environment for LLR powers, which are equated with bailouts, and restrictions placed by the 2010 Dodd–Frank Act on the Fed's ability to loan to non‐banks, whose role in the financial system is ever‐increasing. This is a concern for the global as well as the US financial system, given the economic importance of the United States and the use of the dollar as a reserve currency.
Increased risk of A(H1N1)pdm09 influenza infection in UK pig industry workers compared to a general population cohort
Authors: Fragaszy Ellen , Ishola David A. , Brown Ian H. , Enstone Joanne , Nguyen‐Van‐Tam Jonathan S. , Simons Robin , Tucker Alexander W. , Wieland Barbara , Williamson Susanna M. , Hayward Andrew C. ,   the Flu Watch Group, Wood James L. N. ,   the Combating Swine Influenza (COSI) Consortium
Published: November 2015

BackgroundPigs are mixing vessels for influenza viral reassortment, but the extent of influenza transmission between swine and humans is not well understood.ObjectivesTo assess whether occupational exposure to pigs is a risk factor for human infection with human and swine‐adapted influenza viruses.MethodsUK pig industry workers were frequency‐matched on age, region, sampling month, and gender with a community‐based comparison group from the Flu Watch study. HI assays quantified antibodies for swine and human A(H1) and A(H3) influenza viruses (titres ≥ 40 considered seropositive and indicative of infection). Virus‐specific associations between seropositivity and occupational pig exposure were examined using multivariable regression models adjusted for vaccination. Pigs on the same farms were also tested for seropositivity.ResultsForty‐two percent of pigs were seropositive to A(H1N1)pdm09. Pig industry workers showed evidence of increased odds of A(H1N1)pdm09 seropositivity compared to the comparison group, albeit with wide confidence intervals (CIs), adjusted odds ratio after accounting for possible cross‐reactivity with other swine A(H1) viruses (aOR) 25·3, 95% CI (1·4–536·3), P = 0·028.ConclusionThe results indicate that A(H1N1)pdm09 virus was common in UK pigs during the pandemic and subsequent period of human A(H1N1)pdm09 circulation, and occupational exposure to pigs was a risk factor for human infection. Influenza immunisation of pig industry workers may reduce transmission and the potential for virus reassortment.
The Impact of Dividend Covenants on Investment and Operating Performance
Authors: Jung Boochun , Lee Woo‐Jong , Yang Yanhua Sunny 
Published: November 2015

AbstractThis paper examines the influence of dividend covenants in corporate bonds on investment and operating performance. Prior literature analytically demonstrates that by limiting dividend distribution to shareholders, dividend restrictions effectively place a minimum on investment expenditures. This suggests a positive relation between dividend covenants and investment. The literature also conjectures that the influence of dividend covenants on investment (1) mitigates the under‐investment problem associated with debt financing; or (2) exacerbates over‐investment. We empirically document that the presence of dividend covenants is associated with a higher level of investment and poorer future performance. Further analyses confirm that the higher level of investment is consistent with dividend covenants exacerbating over‐investment, not mitigating under‐investment. Our results shed light on the cost aspect of dividend covenants proposed in prior literature.
Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up‐regulation of lysyl oxidase‐like 2
Authors: de Jong Olivier G. , van Balkom Bas W. M. , Gremmels Hendrik , Verhaar Marianne C. 
Published: November 2015

AbstractExosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome‐ECM interactions is limited. Here, we investigate whether the exosome‐associated lysyl oxidase family member lysyl oxidase‐like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)‐derived exosomes, placing it in direct vicinity of the ECM. It is up‐regulated twofold in EC‐derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome‐producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC‐derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia‐regulated focal ECM remodelling, a key process in both fibrosis and wound healing.
Price-Level Changes and the Redistribution of Nominal Wealth across the Euro Area
Authors: Adam Klaus , Zhu Junyi 
Published: November 2015

Abstract
We show that unexpected price-level movements generate sizable wealth redistribution in the Euro Area (EA), using sectoral accounts and newly available data from the Household Finance and Consumption Survey. The EA as a whole is a net loser of unexpected price-level decreases, with Italy, Greece, Portugal, and Spain losing most in per capita terms, and Belgium and Malta being net winners. Governments are net losers of deflation, while the household (HH) sector is a net winner in the EA as a whole. HHs in Belgium, Ireland, Malta, and Germany experience the biggest per capita gains, while HHs in Finland and Spain turn out to be net losers. Considerable heterogeneity exists also within the HH sector: relatively young middle class HHs are net losers of deflation, while older and richer HHs are winners. As a result, wealth inequality in the EA increases with unexpected deflation, although in some countries (Austria, Germany, and Malta) inequality decreases due to the presence of relatively few young borrowing HHs. We document that HHs’ inflation exposure varies systematically across countries, with HHs in high-inflation EA countries holding systematically lower nominal exposures.
Quantitative immunoenzymatic detection of viral encephalopathy and retinopathy virus (betanodavirus) in sea bass Dicentrarchus labrax
Authors: Nuñez‐Ortiz N , Stocchi V , Toffan A , Pascoli F , Sood N , Buonocore F , Picchietti S , Papeschi C , Taddei A R , Thompson K D , Scapigliati G 
Published: November 2015

AbstractViral encephalopathy and retinopathy disease caused by betanodavirus, genus of the family Nodaviridae, affects marine, wild and farmed species including sea bass, one of the most important farmed species in Europe. This work describes a reliable and sensitive indirect ELISA assay to detect betanodavirus in biological samples using a polyclonal antiserum (pAb 283) against the 283/I09 virus strain, the most common red‐spotted grouper nervous necrosis virus (RGNNV) genotype in the Mediterranean area, and a capture‐based ELISA using a monoclonal antibody (mAb 4C3) specific to a common epitope present on the capsid protein. Using adsorbed, purified VERv preparation, the detection limit of indirect ELISA was 2 μg mL−1 (3 × 105 TCID50 per mL), whereas for capture‐based ELISA, the sensitivity for the antigen in solution was 17 μg mL−1 (35 × 105 TCID50 per mL). The capture‐based ELISA was employed to detect VERv in brain homogenates of in vivo infected sea bass and resulted positive in 22 of 32 samples, some of these with a high viral load estimates (about 1.1 × 108 TCID50 per mL). The ELISA system we propose may be helpful in investigations where coupling of viral content in fish tissues with the presence of circulating VERv‐specific IgM is required, or for use in samples where PCR is difficult to perform.
Qualitative Analysis of the American College of Nurse‐Midwives Student Reports, 2005 to 2014
Authors: Doherty Mary Ellen 
Published: November 2015

IntroductionThe Patient Protection and Affordable Care Act (ACA) is changing the health care landscape in the United States. It is now more important than ever to understand the needs of students who are preparing for roles as health care providers. The purpose of this study was to describe and analyze the American College of Nurse‐Midwives (ACNM) Student Reports from 2005 through 2014 to acquire a better understanding of student needs in light of the historic change in health care reform.MethodsA document analysis was conducted to review and evaluate 10 student reports using qualitative content analysis. Data were coded, categories were formed, and themes were discovered. The interpretation of the student reports elicited meaning, gained understanding, and developed empirical knowledge.ResultsEight themes emerged from the data contained in the 10 student reports. These were: 1) public awareness and marketing; 2) midwifery education; 3) funding for midwifery education; 4) preceptor issues; 5) communication and professional issues; 6) diversity and inclusion; 7) transition to practice; and 8) the ACNM Annual Meeting.DiscussionStudents bring a unique perspective to the profession of midwifery and ACNM. This study revealed 8 themes emanating from the student reports spanning 10 years. Each theme showcased in this study is presented through a student lens and was deemed important enough to be mentioned in the majority of the student reports. These themes identify key areas affecting students such as education program content and clinical experiences, diversity and inclusion, preceptor availability and relationships, funding for graduate school and for attending the ACNM Annual Meeting, and a myriad of other significant topics. These students will begin their new careers with the changing structure of the health care industry under the ACA. At this complex and vulnerable time, it is imperative that student voices be heard and that their professional organization remains receptive to their concerns. A continuing dialogue between students and midwifery leadership, faculty, and preceptors will be beneficial to move our profession in the direction of achieving access to high‐quality health care for all.