bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation analysis of Swedish haemophilia B families – high frequency of unique mutations
Authors: Mårtensson A. , Letelier A. , Halldén C. , Ljung R. 
Published: November 2015

IntroductionHaemophilia B is caused by a heterogeneous spectrum of mutations. Mutation characterization is important in genetic counselling, prenatal diagnosis and to predict risk of inhibitor development.AimsTo study the mutation spectrum, frequency of unique recurrent mutations, genotype–phenotype association and inhibitor development in a population‐based study of the complete Swedish haemophilia B population.MethodsThe study included, facilitated by centralized DNA diagnostics, the complete registered Swedish haemophilia B population (113 families: 47 severe, 22 moderate and 44 mild), each represented by a single patient. Mutation characterization was performed by conventional sequencing of all exons and haplotyping by genotyping of single nucleotide variants and microsatellites.ResultsA mutation was found in every family: eight had large deletions, three had small deletions (<10 base pair) and 102 had single base pair substitutions (69 missense, 26 nonsense, four splice site and three promoter). Ten novel mutations were found and were predicted to be deleterious. Sixteen mutations (one total gene deletion, 14 substitutions and one acceptor splice site) were present in more than one family. Of the single nucleotide mutations (37/102), 36% arose at CpG sites. Haplotyping of families with identical mutations and present analyses showed that the frequency of unique mutations was at least 65%. Inhibitors developed in 9/47 (19%) patients with severe haemophilia B.ConclusionThe spectrum of haemophilia B mutations reveals at least 65% of the families carry a unique mutation, but with more inhibitor patients than reported internationally, probably as a result of many ‘null’ mutations.
Relevance of Helicobacter pylori vacA 3ʹ‐end Region Polymorphism to Gastric Cancer
Authors: Bakhti Seyedeh Zahra , Latifi‐Navid Saeid , Mohammadi Shiva , Zahri Saber , Bakhti Fatemeh Sadat , Feizi Farideh , Yazdanbod Abbas , Siavoshi Farideh 
Published: November 2015

AbstractBackgroundHelicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease.Materials and MethodsWe identified a novel polymorphic site in the 3ʹ‐end region of H. pylori vacA gene, denoted by c1/‐c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal‐ and diffuse‐type GC.ResultsThe vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03–9.08), 6.11 (2.63–14.19), 3.18 (1.49–6.76), 15.13 (5.86–39.01), and 2.59 (1.09–6.12), respectively. The vacA c1 genotype had an increased age‐ and sex‐adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60–222.29). This association was independent of and larger than the associations of the m‐, i‐, and d‐type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45–5.40) and 2.62 (1.23–5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92–14.03).ConclusionThe H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.
Efficacy of 10‐day Sitafloxacin‐Containing Third‐Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation
Authors: Mori Hideki , Suzuki Hidekazu , Matsuzaki Juntaro , Tsugawa Hitoshi , Fukuhara Seiichiro , Miyoshi Sawako , Hirata Kenro , Seino Takashi , Matsushita Misako , Masaoka Tatsuhiro , Kanai Takanori 
Published: November 2015

AbstractBackground and AimSitafloxacin‐containing Helicobacter pylori eradication therapy is a promising third‐line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10‐day sitafloxacin‐containing regimens. Here, we assessed the efficacy of 2 different 10‐day sitafloxacin‐containing rescue regimens.MethodsPatients who failed first‐ and second‐line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10‐day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test.ResultsAll patients with gyrA mutation‐negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation‐positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per‐protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483.ConclusionThere is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin‐containing rescue therapies.
Hp‐normogram (normo‐graham) for Assessing the Outcome of H. pylori Therapy: Effect of Resistance, Duration, and CYP2C19 Genotype
Authors: Graham David Y. 
Published: November 2015

AbstractThere have been hundreds of H. pylori eradication trials and yet doubt remains regarding the best regimen for any situation. With most regimens, treatment failure is the result of resistance to one component (e.g., clarithromycin). Thus, if one knows the treatment success with two groups (all with susceptible and with all with resistant infections), one can construct a normogram that provides a reliable estimate of the outcome at any prevalence of resistance. The same data can be used to estimate the prevalence of resistance in any clinical trial, the effects duration of therapy, and effects of any procedures to improve outcome (e.g., increasing the proton‐pump inhibitor dose, the duration of therapy, etc.). Because the Hp‐normo‐graham can reliably predict the outcome of clinical trials, it can also obviate the need for many clinical trials in populations where resistance is common. Here, we illustrate the construction of Hp‐normo‐graham and its use to describe the effects of resistance, duration of therapy, attempts to improve results, and the prevalence of resistance and to obviate the need for many clinical trials.
Empirical Advances in the Study of Early European Nationalisms
Authors: Kostantaras Dean 
Published: November 2015

AbstractThis article discusses several recent monographs and edited volumes that reconsider the standing of ‘the nation’ in early modern European culture. The emphasis is placed on empirical interventions that condition the picture received from some famous works of the modernist‐constructivist school, while debunking older ‘dichotomies’ regarding presumed differences in the nature of Eastern and Western European thought. Although adhering themselves to a modernist perspective, the contributions cited below show that far from springing on the scene, as Benedict Anderson wrote ‘towards the late 18th century,’ the nation figured much earlier in European culture and it was from this inheritance that thinkers of Enlightenment‐era vintage obtained a number of conceptual and heuristic devices employed in their works. The nation enjoyed a particular rise in status on the basis of its serviceability, based again on older conventions, for the anthropological pursuits of the age. These insights offer a major advance for historians in narrative coherence by demonstrating the extent to which Enlightenment endeavors in this vein were culturally‐mediated and, in turn, influenced the terms of subsequent political debate.
A New Politics of the Middle Ages: A Global Middle Ages for a Global Modernity
Authors: McClure Julia 
Published: November 2015

AbstractThis paper outlines the new politics of the Middle Ages in an age of ‘global modernity’, a term coined by Arif Dirlik to describe the appearance of ‘alternative’ or ‘multiple’ modernities. The politics of the Middle Ages has been recognised by a number of medieval and postcolonial scholars who have understood the role that the category of the Middle Ages has played in the historic construction of Western modernity and Western imperialism. This political use of the Middle Ages in constructing Western imperialism and modernity was underpinned by the colonial discourse identified by Johannes Fabian as the ‘denial of coevalness’. Yet, in an age of multiple modernities, we need to understand the changing political frontiers of multiple medievalisms. This paper indicates the particular way in which radical Islamist movements, especially ISIL, use and relate to the Islamic past and calls for further analysis of the new politics of the Middle Ages. This paper discusses the global turn and the shift in the politics of the Middle Ages, from the denial of coevalness to contemporaneity, and signposts problems and future directions that this shift indicates for medieval history.
The Fourth Stage: Wole Soyinka and the Social Character of Ibadan.
Authors: Ibironke Olabode 
Published: November 2015

AbstractThis article traces the origin and development of modern African literature in Ibadan, in the 1960s. It argues that Soyinka's famous concept, the Fourth Stage, is his attempt to capture the unique and transformative character of the city of Ibadan. A major portion of African literary history is mostly available through writers' autobiographies such as Soyinka's Ibadan. This article promotes the idea of reading more of these autobiographies as literary history in order to recover the specificity and spirit of African literary production. Indeed, the ways in which the founding texts of African literature are reflective of the social character of the city might be lost if the history of local publication is not resurrected. By locating the origins of the idea of the Fourth Stage in Ibadan, I set the stage for the sequel to this paper that argues that although the African Writers Series published by Heinemann Educational Books canonized African literature, the process of that canonization was already well underway through Mbari publication that was located in Ibadan. Taken together, these two articles underscore the significance of Mbari publication as the outcome of literary activities centered on the Mbari literary club in the heart of Ibadan; the club and the publication were unique to the social character of the city as such.
Fission track and U–Pb zircon ages of psammitic rocks from the Harushinai unit, Kamuikotan metamorphic rocks, central Hokkaido, Japan: constraints on metamorphic histories
Authors: Okamoto Ayumi S. , Takeshita Toru , Iwano Hideki , Danhara Tohru , Hirata Takafumi , Nishido Hirotsugu , Sakata Shuhei 
Published: November 2015

AbstractAccurate pressure–temperature–time (P–T–t) paths of rocks from sedimentation through maximum burial to exhumation are needed to determine the processes and mechanisms that form high‐pressure and low‐temperature type metamorphic rocks. Here, we present a new method combining laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) U–Pb with fission track (FT) dates for detrital zircons from two psammitic rock samples collected from the Harushinai unit of the Kamuikotan metamorphic rocks. The concordant zircon U–Pb ages for these samples vary markedly, from 1980 to 95 Ma, with the youngest age clusters in both samples yielding Albian‐Cenomanian weighted mean ages of 100.8 ± 1.1 and 99.3 ± 1.0 Ma (2σ uncertainties). The zircon U–Pb ages were not reset by high‐P/T type metamorphism, because there is no indication of overgrowth within the zircons with igneous oscillatory zoning. Therefore, these weighted mean ages are indicative of the maximum age of deposition of protolithic material. By comparison, the zircon FT data yield a pooled age of ca. 90 Ma, which is almost the same as the weighted mean age of the youngest U–Pb age cluster. This indicates that the zircon FT ages were reset at ca. 90 Ma while still at their source, but have not been reset since. This conclusion is supported by recorded temperature conditions of less than about 300 °C (the closure temperature of zircon FTs), as estimated from microstructures in the deformed detrital quartz grains in psammitic rocks, and no shortening of fission track lengths in the zircon. Combining these new data with previously reported white mica K–Ar ages indicates that the Harushinai unit was deposited after ca. 100 Ma, and underwent burial to its maximum depth before being subjected to a localized thermal overprint during exhumation at ca. 58 Ma.
Recognition of shear heating on a long‐lived major fault using Raman carbonaceous material thermometry: implications for strength and displacement history of the MTL, SW Japan
Authors: Mori Hiroshi , Wallis Simon , Fujimoto Koichiro , Shigematsu Norio 
Published: November 2015

AbstractThe extent to which movement on major faults causes long term shear heating is a contentious issue and an important aspect in the debate about the strength of major faults in the crust. Comparing the results of experimental work on the kinetics of crystallization of carbonaceous material with results of thermal modeling show that the Raman carbonaceous material (CM) geothermometer is well suited to studying shear heating on geological time scales in suitable lithologies exposed around exhumed major fault zones. The Median Tectonic Line (MTL), SW Japan, is the largest on‐land fault in Japan with a length of > 800 km. Application of Raman CM thermometry to pelitic schist adjacent to the fault reveals the presence of a rise in peak temperature of around 60 °C over a distance of around 150 m perpendicular to the MTL fault plane. The spatial association of this thermal anomaly with the fault implies it is due to shear heating. Thermal modeling shows the recorded thermal anomaly and steep temperature gradient is compatible with very high rates of displacement over time scales of a few thousand years. However, the implied displacement rates lie outside those generally observed. An alternative explanation is that an originally broader thermal anomaly that developed during strike slip faulting was shortened due to the effects of normal faulting. Constraints on displacement rate, width of the original anomaly, duration of heating and peak temperature imply a coefficient of friction, μ, greater than 0.4.
The development and validation of the student response system benefit scale
Authors: Hooker J.F. , Denker K.J. , Summers M.E. , Parker M. 
Published: November 2015

AbstractPrevious research into the benefits student response systems (SRS) that have been brought into the classroom revealed that SRS can contribute positively to student experiences. However, while the benefits of SRS have been conceptualized and operationalized into a widely cited scale, the validity of this scale had not been tested. Furthermore, subsequent research found the scale to be unreliable. Therefore, this project used two studies and created a reliable and valid SRS benefit scale. First, iterative exploratory factor analysis (EFA) was conducted to determine whether the stated conceptual definitions matched the operational definitions reflected in student responses to survey items. The results of this statistical analysis showed an 8‐item, two‐factor scale demonstrating the benefits of SRS in the large lecture classroom. Study 2 used a new sample for confirmatory factor analysis that confirmed the results of the EFA suggested a good model fit with excellent scale reliability. Implications for future assessment of the benefits of SRS were discussed.
Nrdp1S, short variant of Nrdp1, inhibits human glioma progression by increasing Nrdp1‐mediated ErbB3 ubiquitination and degradation
Authors: Wu Yuxuan , Wang Lei , Bao Hanmo , Zou Shenshan , Fu Chunling , Gong Hui , Gao Yong , Tang Yuan , Yu Rutong , Shi Hengliang 
Published: November 2015

AbstractThe ubiquitin ligase neuregulin receptor degradation protein 1 (Nrdp1) is involved in the induction of apoptosis and suppression of tumour formation. We previously showed that it was expressed at lower levels in human glioma tissues compared with normal brain tissues. However, the mechanism underlying this is unclear. Here, we reported that a novel short variant (Nrdp1S), lacking 71 amino acids at the N‐terminal, was expressed in normal human brain tissue, but absent from glioma tissues. Similar to Nrdp1, Nrdp1S could be degraded by the proteasomal pathway, but exhibited an even longer half‐life than Nrdp1. Nrdp1S was also shown to form a heterodimer with Nrdp1, which increased its stability, thereby augmenting the Nrdp1‐mediated ubiquitination and degradation of ErbB3. EdU incorporation, MTT assay and in vitro colony formation demonstrated that Nrdp1S significantly inhibited the cell tumourigenicity. These results together suggest that Nrdp1S is a tumour suppressor that which potentiates the Nrdp1‐mediated ubiquitination and degradation of ErbB3. An Nrdp1S deficiency may also be an important factor in the loss of Nrdp1.
Fast‐scan cyclic voltammetry demonstrates that L‐DOPA produces dose‐dependent, regionally selective bimodal effects on striatal dopamine kinetics in vivo
Authors: Harun Rashed , Hare Kristin M. , Brough Elizabeth M. , Munoz Miranda J. , Grassi Christine M. , Torres Gonzalo E. , Grace Anthony A. , Wagner Amy K. 
Published: November 2015

AbstractParkinson's disease (PD) is a debilitating condition that is caused by a relatively specific degeneration of dopaminergic (DAergic) neurons of the substantia nigra pars compacta. L‐DOPA was introduced as a viable treatment option for PD over 40 years ago and still remains the most common and effective therapy for PD. Though the effects of L‐DOPA to augment striatal DA production are well known, little is actually known about how L‐DOPA alters the kinetics of DA neurotransmission that contribute to its beneficial and adverse effects. In this study, we examined the effects of L‐DOPA administration (50 mg/kg carbidopa + 0, 100, and 250 mg/kg L‐DOPA) on regional electrically stimulated DA response kinetics using fast‐scan cyclic voltammetry in anesthetized rats. We demonstrate that L‐DOPA enhances DA release in both the dorsal striatum (D‐STR) and nucleus accumbens (NAc), but surprisingly causes a delayed inhibition of release in the D‐STR. In both regions, L‐DOPA progressively attenuated reuptake kinetics, predominantly through a decrease in Vmax. These findings have important implications on understanding the pharmacodynamics of L‐DOPA, which may be informative for understanding its therapeutic effects and also common side effects like L‐DOPA‐induced dyskinesias (LID).
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L‐DOPA is commonly used to treat Parkinsonian symptoms, but little is known about how it affects presynaptic DA neurotransmission. Using in vivo fast‐scan cyclic voltammetry, we show L‐DOPA inhibits DA reuptake in a region‐specific and dose‐dependent manner, and L‐DOPA has paradoxical effects on release. These findings may be important when considering mechanisms for L‐DOPA's therapeutic benefits and adverse side‐effects.
Sex‐Dependent Effects of Prenatal Stress on Social Memory in Rats: A Role for Differential Expression of Central Vasopressin‐1a Receptors
Authors: Grundwald N. J. , Benítez D. P. , Brunton P. J. 
Published: November 2015

Prenatal stress (PNS) affects a number of traits in the offspring, including stress axis regulation, emotionality and cognition; however, much less is known about the effects of PNS on social memory and the underlying central mechanisms. In the present study, we investigated social preference, social memory under basal and stress conditions and olfactory memory for social and nonsocial odours in the adult offspring of dams exposed to social stress during late pregnancy. Given the key roles that the central oxytocin and vasopressin systems play in facilitating social memory, we further investigated the effects of PNS on the central expression of mRNA for oxytocin (Oxtr) and vasopressin‐1a (Avpr1a) receptors. PNS did not affect social preference in either sex; however, social memory was impaired under basal conditions in PNS females but not PNS males. Accordingly, Avpr1a mRNA expression in the lateral septum and bed nucleus of stria terminalis (BNST) was unaltered in males but was significantly lower in PNS females compared to controls. No differences in Oxtr mRNA expression were detected between control and PNS offspring in either sex in any of the brain regions examined. Social memory deficits in PNS females persisted when social odours were used; however, this does not appear to be a result of impaired olfaction because memory for nonsocial odours was similar in control and PNS females. Under acute stress conditions, deficits in social memory were observed in both male and female control offspring; however, PNS males were unaffected. Moreover, acute stress facilitated social memory in PNS females and this was associated with an up‐regulation of Avpr1a mRNA in the lateral septum and BNST. Our data support a role for altered signalling via central Avpr1a in PNS‐induced sex‐dependent changes in social memory and may have implications for understanding the aetiology of neurodevelopmental disorders characterised by social behaviour deficits in humans.
The Anatomical Society core regional anatomy syllabus for undergraduate medicine
Authors: Smith C.F. , Finn G.M. , Stewart J. , Atkinson M.A. , Davies D.C. , Dyball R. , Morris J. , Ockleford C. , Parkin I. , Standring S. , Whiten S. , Wilton J. , McHanwell S. 
Published: November 2015

AbstractThe Anatomical Society's core syllabus for anatomy (2003 and later refined in 2007) set out a series of learning outcomes that an individual medical student should achieve on graduation. The core syllabus, with 182 learning outcomes grouped in body regions, referenced in the General Medical Council's Teaching Tomorrow's Doctors, was open to criticism on the grounds that the learning outcomes were generated by a relatively small group of anatomists, albeit some of whom were clinically qualified. We have therefore used a modified Delphi technique to seek a wider consensus. A Delphi panel was constructed involving ‘experts’ (n = 39). The revised core syllabus of 156 learning outcomes presented here is applicable to all medical programmes and may be used by curriculum planners, teachers and students alike in addressing the perennial question: ‘What do I need to know ?’