bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of novel genetic variations in the folate‐related and ARID5B genes with the pharmacokinetics and toxicity of high‐dose methotrexate in paediatric acute lymphoblastic leukaemia
Authors: Csordas Katalin , Lautner‐Csorba Orsolya , Semsei Agnes F. , Harnos Andrea , Hegyi Marta , Erdelyi Daniel J. , Eipel Oliver T. , Szalai Csaba , Kovacs Gabor T. 
Published: April 2014

SummaryHigh‐dose methotrexate (HD‐MTX) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (ALL) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (SNPs) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of MTX and 7‐hydroxy‐methotrexate (7‐OH‐MTX). 63 SNPs of 14 genes were genotyped and a total of 463 HD‐MTX courses (administered according to the ALL‐BFM 95 and ALL IC‐BFM 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. SNPs (rs4948502, rs4948496, rs4948487) of the ARID5B gene were associated with the serum levels of MTX (P < 0·02), serum levels and area under the curve of 7‐OH‐MTX (P < 0·02) and with hypoproteinaemia (P = 0·004). SLCO1B1 rs4149056 also showed a significant association with serum MTX levels (P < 0·001). Our findings confirm the association of novel genetic variations in folate‐related and ARID5B genes with the serum MTX levels and acute toxicity.
Long‐term routine dental attendance: influence on tooth loss and oral health‐related quality of life in Swedish older adults
Authors: Åstrøm Anne N. , Ekback Gunnar , Ordell Sven , Nasir Elwalid 
Published: April 2014

AbstractObjectivesFew studies have investigated the effect of long‐term routine dental attendance on oral health between middle‐aged and older adults, using a prospective cohort design. This study aimed to assess routine dental attendance (attending dentist in the previous 12 months for dental checkups) from age 50 to 65 years. Moreover, this study examined whether long‐term routine dental attendance contributes to oral health‐related quality of life, OHRQoL, and major tooth loss independent of social factors and the type of treatment sector utilized. Whether oral health impacts of long‐term routine attendance varied with type of treatment sector utilized was also investigated.MethodIn 1992, a census of the 1942 cohort in two counties of Sweden participated in a longitudinal questionnaire survey conducted at age 50 and again after 5, 10, and 15 years. Information was collected on a wide range of health‐ and oral health‐related aspects. Of the 6346 subjects who completed the 1992 survey, 4143 (65%) completed postal follow‐ups in 1997, 2002, and 2007.ResultsRoutine dental attendance decreased from 69.1% at age 50–64.2% at age 65. Adjusted logistic regression analyses revealed that individuals reporting long‐term routine attendance (routine attendance in both 1992 and 2007) were 0.3 (95% CI 0.2–0.5) times less likely than their counterparts who were nonroutine attenders to report oral impacts. According to generalized estimating equations (GEE), individuals who reported long‐term routine attendance were 0.6 (95% CI 0.4–0.7) times less likely than nonroutine attenders to have major tooth loss across the survey years. The effect of long‐term routine attendance on OHRQoL was stronger in public than in private dental healthcare attenders.ConclusionRoutine attendance decreased from age 50–65 years. Long‐term routine attendance had positive impact on major tooth loss and OHRQoL supporting the principle of encouraging annual dental attendance for preventive checkups among older people.
Transnasal oesophagoscopy: diagnostic and management outcomes in a prospective cohort of 257 consecutive cases and practice implications
Authors: Abou‐Nader L. , Wilson J.A. , Paleri V. 
Published: April 2014

ObjectivesTo determine the success rate, patient tolerability and impact of introducing transnasal oesophagoscopy on clinical practices.DesignProspective cohort with review of electronic patient records for outcomes.SettingUK tertiary centre Otolaryngology Department.ParticipantsThe cohort comprised of two hundred and fifty‐seven patients, 128 females (50%) and 129 males (50%) with an age range of 20–91 years; mean age 59 years (sd 13.6).Main outcome measuresSuccess rates, indications, findings and outcomes of patients undergoing transnasal oesophagoscopy and impact on rigid examinations of the pharynx and oesophagus were also considered.ResultsTransnasal oesophagoscopy has a high success rate of 97%; it is well tolerated by patients, and poor views are uncommon. Pathology was detected in 44% of patients. The most common indications for transnasal oesophagoscopy were unexplained throat symptoms (50%) and dysphagia (25%). Common positive findings were hiatus hernia (7%), Barrett's oesophagus (5%), dysmotility (5%) and oesophageal candidiasis (5%). Following transnasal oesophagoscopy, 59% of patients were discharged to their referring clinician, 17% continued to undergo otolaryngology follow‐up, and 13% were referred to our gastrointestinal colleagues. Following the introduction of transnasal oesophagoscopy, there was a reduction in the number of rigid examinations of the pharynx and oesophagus in the subsequent years, despite an increase in total referrals.ConclusionsTransnasal oesophagoscopy is a well‐tolerated procedure that allows otolaryngologists to make management decisions on common referrals swiftly in the clinic setting avoiding unnecessary investigations, follow‐up and referral.
Recommendation to increase the test concentration of methylchloroisothiazolinone/methylisothiazolinone in the European baseline patch test series – on behalf of the European Society of Contact Dermatitis and the European Environmental and Contact Dermatitis Research Group
Authors: Bruze Magnus , Goossens An , Isaksson Marléne 
Published: April 2014

SummaryBackgroundMethylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) in aqua is present in the European baseline patch test series at 100 ppm, whereas 200 ppm has been used in Sweden since 1986, in Spain in the late 1980s, and, in recent years, also in the United Kingdom and Ireland.ObjectivesWith regard to MCI/MI, to investigate the data on contact allergy rates in dermatitis patients, the frequencies of allergic contact dermatitis in the same group, and adverse reactions, particularly patch test sensitization in tested dermatitis patients, and to find the optimal patch test concentration as dose in mg/cm2.Materials and methodsWe performed a survey of the literature found via the National Library of Medicine (PubMed, http://www.ncbi.nlm.nih.gov/pubmed, last accessed 20 February 2014).ResultsMCI/MI at 200 ppm aq. diagnosis substantially more contact allergy and allergic contact dermatitis, without any registered increase in patch test sensitization, than the presently used concentration of 100 ppm.ConclusionMCI/MI at 200 ppm aq. is recommended to be included in the European baseline patch test series. To avoid patch test sensitization, a dose of 0.006 mg/cm2 must not be exceeded, which means a volume of 15 µl for Finn Chambers® (Ø 8 mm).
Neurogenin2‐d4Venus and Gadd45g‐d4Venus transgenic mice: Visualizing mitotic and migratory behaviors of cells committed to the neuronal lineage in the developing mammalian brain
Authors: Kawaue Takumi , Sagou Ken , Kiyonari Hiroshi , Ota Kumiko , Okamoto Mayumi , Shinoda Tomoyasu , Kawaguchi Ayano , Miyata Takaki 
Published: April 2014

To achieve highly sensitive and comprehensive assessment of the morphology and dynamics of cells committed to the neuronal lineage in mammalian brain primordia, we generated two transgenic mouse lines expressing a destabilized (d4) Venus controlled by regulatory elements of the Neurogenin2 (Neurog2) or Gadd45g gene. In mid‐embryonic neocortical walls, expression of Neurog2‐d4Venus mostly overlapped with that of Neurog2 protein, with a slightly (1 h) delayed onset. Although Neurog2‐d4Venus and Gadd45g‐d4Venus mice exhibited very similar labeling patterns in the ventricular zone (VZ), in Gadd45g‐d4Venus mice cells could be visualized in more basal areas containing fully differentiated neurons, where Neurog2‐d4Venus fluorescence was absent. Time‐lapse monitoring revealed that most d4Venus+ cells in the VZ had processes extending to the apical surface; many of these cells eventually retracted their apical process and migrated basally to the subventricular zone, where neurons, as well as the intermediate neurogenic progenitors that undergo terminal neuron‐producing division, could be live‐monitored by d4Venus fluorescence. Some d4Venus+ VZ cells instead underwent nuclear migration to the apical surface, where they divided to generate two d4Venus+ daughter cells, suggesting that the symmetric terminal division that gives rise to neuron pairs at the apical surface can be reliably live‐monitored. Similar lineage‐committed cells were observed in other developing neural regions including retina, spinal cord, and cerebellum, as well as in regions of the peripheral nervous system such as dorsal root ganglia. These mouse lines will be useful for elucidating the cellular and molecular mechanisms underlying development of the mammalian nervous system.
Social‐communicative abilities as treatment goals for preschool children with autism spectrum disorder: the importance of imitation, joint attention, and play
Authors: Warreyn Petra , van der Paelt Sara , Roeyers Herbert 
Published: April 2014

Autism spectrum disorder (ASD) is a pervasive developmental disorder with a lifelong impact on multiple domains of functioning. Often, a diagnosis is possible by 3 years of age. Given the benefits of early intervention, it is advisable to start treatment as soon as possible after the diagnosis has been made. Among other factors, early intervention should focus on social‐communicative abilities such as imitation, joint attention, and play. In this review, the typical developmental course and functions of these social‐communicative abilities are described, and the problems young children with ASD experience in this domain. In addition, different approaches to promoting these abilities are explained. The authors recommend the inclusion of imitation, joint attention, and play as treatment goals in community settings for children with ASD.
Signature of subclinical femoral artery atherosclerosis in peripheral blood mononuclear cells
Authors: Llorente‐Cortés Vicenta , de Gonzalo‐Calvo David , Orbe Josune , Páramo Jose Antonio , Badimon Lina 
Published: April 2014

AbstractBackgroundPeripheral arterial disease is a relevant public health problem associated with increased risk of morbimortality. Most of the patients with this condition are asymptomatic. Therefore, the development of accessible biochemical markers seems to be necessary to anticipate diagnosis. Our hypothesis is that asymptomatic subjects with objectively confirmed femoral artery atherosclerosis could be distinguished from control subjects by gene expression analysis in peripheral blood mononuclear cells (PBMC).Materials and methodsA total of 37 asymptomatic males over 50 years old were recruited at the University Clinic of Navarra (Spain). Nineteen participants were free from atherosclerotic vascular disease and 18 participants presented subclinical femoral artery atherosclerosis defined by means of Doppler ultrasound. PBMC were isolated from blood and the RNA extracted. A panel of atherosclerotic‐related genes were evaluated by Taqman low‐density array.ResultsIn univariate logistic regression models, we found a direct relationship between IL4, ITGAM and TLR2 expression levels in PBMC and femoral atherosclerosis, even when the models were adjusted for age and hypertension prevalence. Multivariate logistic regression models showed that elevated IL4 expression levels were intimately associated with subclinical femoral atherosclerosis after adjusting for the same potential confounders.ConclusionsCurrent data suggest that gene expression in PBMC, in particular IL4 expression, could be a useful tool in the diagnosis of femoral artery atherosclerosis in asymptomatic patients. Furthermore, in patients with no differences in cardiovascular risk factors except for hypertension, the results point to the immune and inflammatory deregulation as a feature of subclinical peripheral atherosclerosis.
Confucius on Educational Failure: Three Types of Misguided Students
Authors: Black David W. 
Published: April 2014

AbstractIn this essay David Black claims that, if one pieces together the many sketches of educational decorum found in the Confucian Analects, one will discover three types of misguided student; that is, one will come to recognize that Confucius admonishes three types of insensitive learners who, due to the lure of personal advantage and social rhetoric, begin to mismanage the exchanges of respect particular to the educational process. These students misappropriate key rituals of decorum and dialogue, and consequently create a degree of disorder that, for Confucius, actually threatens the existence of civil society.
The Fundamental Ontology of Study
Authors: Lewis Tyson E. 
Published: April 2014

AbstractIn an effort to disrupt the hegemonic dominance of learning theory, in this article Tyson Lewis explores the unique educational logic of studying. Drawing on the work of Giorgio Agamben, we can understand the operation of study as one of suspension through three modes: preferring not; no longer, not yet; and as not. But the relationship between the operation of suspension and the everyday mode of learning remains an open question requiring further analysis. In order to accomplish this task, it is important to remember that for Agamben, study is a kind of profanation or improper life. Through examining Heidegger's analytic of Dasein's everyday being, Lewis demonstrates that the nature of study is always already saturated with the everyday, and is itself a contaminated process that is neither simply everyday living nor “authentic” existence. To be absolutely precise, the studier engages in idle talk, is curious, and is caught up in ambiguity in order to explore the seemingly uninhabitable zone that rests between everyday falling and authentically standing. Lewis concludes by offering Agamben's own work as a paradigm of study, illustrating how the smallest of freedoms opens to the studier: the freedom to dwell in potentiality.
On Consumerism, Collective Action, and Whether Art Teaches Anything
Authors: Ruitenberg Claudia W. 
Published: April 2014

AbstractIn this review essay, Claudia Ruitenberg discusses Trevor Norris's Consuming Schools, René Arcilla's Mediumism, and Martha Nussbaum's Not for Profit. While the primary focus of each book is different — with Norris concentrating on the pressures of consumerism and commercialism on K–12 schooling, Arcilla analyzing modernist art and existentialist education, and Nussbaum emphasizing the role of the humanities in educating for democratic citizenship — each of the books in some way addresses the question of how people can be educated to resist consumerism and how education itself can resist being absorbed by consumerism. Here, Ruitenberg considers this common theme as well as the more specific question of what special role — if any — the arts might play in anticonsumerist education.
Temperature–growth patterns of individually tagged anadromousArctic charrSalvelinus alpinusinUngava andLabrador,Canada
Authors: Murdoch Alyssa , Dempson J. Brian , Martin Francois , Power Michael 
Published: April 2014

AbstractIndividual measurements of annual, or within‐season growth were determined from tag‐recapturedArctic charr and examined in relation to summer sea surface temperatures and within‐season capture timing in theUngava andLabrador regions of EasternCanada. Differences between two years of growth (2010–2011) were significant forUngavaBayArctic charr, with growth being higher in the warmer year. Growth ofLabradorArctic charr did not vary significantly among years (1982–1985). Regional comparisons demonstrated thatUngavaArctic charr had significantly higher annual growth rates and experienced warmer temperatures thanLabradorArctic charr. The higher annual growth ofUngavaBayArctic charr was attributed to the high sea surface temperatures experienced in 2010–2011 and the localised differences in nearshore productivity as compared toLabrador. Within‐season growth rates ofLabradorArctic charr peaked inJune, declined towardsAugust and were negatively correlated with the length of time spent at sea and mean experienced sea surface temperatures. A quadratic model relating growth rate to temperature best explained the pattern of within‐season growth. Collectively, results suggest that increases in water temperature may have profound consequences for Arctic charr growth in theCanadian sub‐Arctic, depending on the responses of local marine productivity to those same temperature increases.
The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview
Authors: Lecca Salvatore , Meye Frank J. , Mameli Manuel 
Published: April 2014

AbstractThe lateral habenula (LHb) is an epithalamic region with a crucial role in the regulation of midbrain monoaminergic systems. Over the past few years a renewed interest in the LHb has emerged due to studies highlighting its central role in encoding rewarding and aversive aspects of stimuli. Moreover, an increasing number of functional as well as behavioral indications provide substantial evidence supporting a role of LHb in neuropsychiatric diseases, including mood disorders and drug addiction. Cellular and synaptic adaptations in the LHb may therefore represent a critical phenomenon in the etiology of these diseases. In the current review we describe the anatomical and functional connections allowing the LHb to control the dopamine and serotonin systems, as well as possible roles of these connections in motivated behaviors and neuropsychiatric disorders. Finally, we discuss how drug exposure and stressful conditions alter the cellular physiology of the LHb, highlighting a role for the LHb in the context of drug addiction and depression.
Reversal of activity‐mediated spine dynamics and learning impairment in a mouse model of Fragile X syndrome
Authors: Boda Bernadett , Mendez Pablo , Boury‐Jamot Benjamin , Magara Fulvio , Muller Dominique 
Published: April 2014

AbstractFragile X syndrome (FXS) is characterized by intellectual disability and autistic traits, and results from the silencing of the FMR1 gene coding for a protein implicated in the regulation of protein synthesis at synapses. The lack of functional Fragile X mental retardation protein has been proposed to result in an excessive signaling of synaptic metabotropic glutamate receptors, leading to alterations of synapse maturation and plasticity. It remains, however, unclear how mechanisms of activity‐dependent spine dynamics are affected in Fmr knockout (Fmr1‐KO) mice and whether they can be reversed. Here we used a repetitive imaging approach in hippocampal slice cultures to investigate properties of structural plasticity and their modulation by signaling pathways. We found that basal spine turnover was significantly reduced in Fmr1‐KO mice, but markedly enhanced by activity. Additionally, activity‐mediated spine stabilization was lost in Fmr1‐KO mice. Application of the metabotropic glutamate receptor antagonist α‐Methyl‐4‐carboxyphenylglycine (MCPG) enhanced basal turnover, improved spine stability, but failed to reinstate activity‐mediated spine stabilization. In contrast, enhancing phosphoinositide‐3 kinase (PI3K) signaling, a pathway implicated in various aspects of synaptic plasticity, reversed both basal turnover and activity‐mediated spine stabilization. It also restored defective long‐term potentiation mechanisms in slices and improved reversal learning in Fmr1‐KO mice. These results suggest that modulation of PI3K signaling could contribute to improve the cognitive deficits associated with FXS.
The synapse in schizophrenia
Authors: Pocklington Andrew J. , O'Donovan Michael , Owen Michael J. 
Published: April 2014

AbstractIt has been several decades since synaptic dysfunction was first suggested to play a role in schizophrenia, but only in the last few years has convincing evidence been obtained as progress has been made in elucidating the genetic underpinnings of the disorder. In the intervening years much has been learned concerning the complex macromolecular structure of the synapse itself, and genetic studies are now beginning to draw upon these advances. Here we outline our current understanding of the genetic architecture of schizophrenia and examine the evidence for synaptic involvement. A strong case can now be made that disruption of glutamatergic signalling pathways regulating synaptic plasticity contributes to the aetiology of schizophrenia.
Stress andVTAsynapses: implications for addiction and depression
Authors: Polter Abigail M. , Kauer Julie A. 
Published: April 2014

AbstractWhile stressful experiences are a part of everyone's life, they can also exact a major toll on health. Stressful life experiences are associated with increased substance abuse, and there exists significant co‐morbidity between mental illness and substance use disorders [N.D. Volkow & T.K. Li (2004)Nat. Rev. Neurosci.,5, 963–970; G. Koob & M.J. Kreek (2007)Am. J. Psych.,164, 1149–1159; R. Sinha (2008)Annals N.Y. Acad. Sci.,1141, 105–130]. The risk for development of mood or anxiety disorders after stress is positively associated with the risk for substance use disorders [R. Sinha (2008)Annals N.Y. Acad. Sci.,1141, 105–130], suggesting that there are common substrates for vulnerability to addictive and affective disorders. Understanding the molecular and physiological substrates of stress may lead to improved therapeutic interventions for the treatment of substance use disorders and mental illnesses.
Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system
Authors: Randall Andrew D. , Kurihara Mai , Brandon Nicholas J. , Brown Jon T. 
Published: April 2014

AbstractThe disrupted in schizophrenia 1 (DISC1) gene is found at the breakpoint of an inherited chromosomal translocation, and segregates with major mental illnesses. Its potential role in central nervous system (CNS) malfunction has triggered intensive investigation of the biological roles played by DISC1, with the hope that this may shed new light on the pathobiology of psychiatric disease. Such work has ranged from investigations of animal behavior to detailed molecular‐level analysis of the assemblies that DISC1 forms with other proteins. Here, we discuss the evidence for a role of DISC1 in synaptic function in the mammalian CNS.