bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models
Authors: Cross A J , Widzowski D , Maciag C , Zacco A , Hudzik T , Liu J , Nyberg S , Wood M W 
Published: October 2015

Background and PurposeQuetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine.Experimental ApproachWe evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant‐like and anxiolytic‐like drug action.Key ResultsNorquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5‐HT1A receptors, and the anxiolytic‐like activity of norquetiapine in rat punished responding was blocked by the 5‐HT1A antagonist, WAY100635.Conclusions and ImplicationsQuetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5‐HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine.
Orienting Toward Face‐Like Stimuli in Early Childhood
Authors: Shah Punit , Happé Francesca , Sowden Sophie , Cook Richard , Bird Geoffrey 
Published: October 2015

Newborn infants orient preferentially toward face‐like or “protoface” stimuli and recent studies suggest similar reflexive orienting responses in adults. Little is known, however, about the operation of this mechanism in childhood. An attentional‐cueing procedure was therefore developed to investigate protoface orienting in early childhood. Consistent with the extant literature, 5‐ to 6‐year‐old children (n = 25) exhibited orienting toward face‐like stimuli; they responded faster when target location was cued by the appearance of a protoface stimulus than when location was cued by matched control patterns. The potential of this procedure to investigate the development of typical and atypical social perception is discussed.
Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency
Authors: Elgizouli M , Lowe D M , Speckmann C , Schubert D , Hülsdünker J , Eskandarian Z , Dudek A , Schmitt-Graeff A , Wanders J , Jørgensen S F , Fevang B , Salzer U , Nieters A , Burns S , Grimbacher B 
Published: October 2015

Summary
The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.
Awake Flexible Fiberoptic Laryngoscopy to diagnose glossoptosis in Robin Sequence patients
Authors: Basart H. , König A.M. , Bretschneider J.H. , Hoekstra C.E.L. , Oomen K.P.Q. , Pullens B. , Rinkel R.N.P.M. , van Gogh C.D.L. , van der Horst C.M.A.M. , Hennekam R.C. 
Published: October 2015

BackgroundRobin Sequence (RS) is usually defined as the combination of micrognathia, glossoptosis and upper airway obstruction. No objective criteria to diagnose RS exist. To compare management strategy results, a single RS definition using objective criteria is needed. The most frequently used primary diagnostic tool for glossoptosis is awake Flexible Fiberoptic Laryngoscopy (aFFL).ObjectivesTo determine the reliability of the aFFL videos as an independent diagnostic tool itself, rather than on the complete evaluation of a patient.Design, setting, participantsAll RS individuals from an existing cohort with an available aFFL video were included retrospectively. Thirty age‐matched patients without pathologic findings on aFFL were used as controls. aFFL videos were scored by six otolaryngologists as: a. Marked glossoptosis, b. Mild glossoptosis, c. Severity unknown, d. No glossoptosis, e. Insufficient video quality. Videos were anonymised and rated twice, in altered sequences, after a washout period of minimally 2 weeks.Main outcome measuresInter‐rater and intrarater agreement.ResultsTwenty‐six videos of 16 RS patients and 30 videos of controls were included. Inter‐rater agreement was fair in the whole group (κ: 0.320) and RS group (κ: 0.226), and fair to moderate in determining presence of glossoptosis (total group κ: 0.430; RS κ: 0.302; controls κ: 0.212). The intrarater agreement for the presence of glossoptosis in RS was moderate (κ: 0.541).ConclusionsaFFL offers fair to moderate inter‐rater agreement, with moderate intrarater agreement, in evaluating glossoptosis in RS. Using aFFL as the single tool in choosing management strategies in RS seems insufficient. There is need for a more reliable, patient friendly diagnostic tool or an internationally accepted aFFL scoring system, to diagnose glossoptosis in RS.
Fooled by Our Perceptions
Authors: Fatehi Kamal 
Published: October 2015

ABSTRACTMany people enjoy watching magicians perform magic acts and seemingly do the impossible. In many of these acts, magicians use sleight of hand, trickery, and special tools. There are, however, other occasions in which audience perceptions are used to make them see things differently. This exploits people's tendencies to see things based on their expectations and prior experience. One of these is perceptual readiness, the tendency for people to see what they expect or want to see. This article describes an exercise that illustrates that perceptions can be misleading.
Student Learning and Performance in Information Systems Courses: The Role of Academic Motivation
Authors: Herath Tejaswini C. 
Published: October 2015

ABSTRACTDespite the need for information technology knowledge in the business world today, enrollments in information systems (IS) courses have been consistently declining. Student performance in lower level IS courses and student assumptions about the level of difficulty of the courses seem to be reasons for lower enrollments. To understand how student motivation may explain learning outcomes in introductory IS courses, this study investigates the impact of intrinsic and extrinsic academic motivations as framed by self‐determination theory on two measures of learning outcomes: (1) student self‐reported measures of learning and (2) actual grades obtained in courses and course components. Using 269 student responses collected in a second‐year undergraduate core course and a first‐year MBA core course, both of which are offered in a traditional face‐to‐face classroom environment, study hypotheses are analyzed. Results indicate that the motivational model explains both the affective and cognitive perceptions of learning held by students. In examining overall grades and grades in course components, the motivational model, however, was unable to sufficiently explain student performance. Data also indicate that there are significant differences between undergraduate and graduate students in terms of their motivation and learning outcomes.
Sublethal effects of Bt toxin and chlorpyrifos on various Spodoptera exigua populations
Authors: Su Hong‐Hua , Jiang Li‐Li , Wang Hai‐Tao , Yang Ting‐Zhang , Harvey‐Samuel Tim , Zhou Qiu‐Xia , Lü Yao‐Bin , Yang Yi‐Zhong 
Published: October 2015

AbstractBt cotton (Cry1Ac) has been commercially grown in China since 1997, saving China's cotton production from attack by Bt‐target pests and also tremendously reducing pesticide usage. In recent years, however, Bt cotton, with 4.2 million ha of cultivation, has suffered from a secondary target pest, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae). In China, growers have even had to re‐adopt conventional pesticides to control the pest, and this practice has already caused serious pesticide residue. In order to clarify the sublethal effects of chemical pesticide, the responses of a Bt‐susceptible and a Bt‐tolerant (Bt10) S. exigua strain to three treatment combinations were examined, including Bt toxin, sublethal chlorpyrifos, and Bt + sublethal chlorpyrifos. The susceptible and the Bt10 strain responded differently to dual pressure. Bt toxin + sublethal chlorpyrifos treatment lowered larval mortality and stimulated population increase of the susceptible S. exigua, whereas it delayed growth and development of the Bt10 strain. Under dual pressure, although larvae of the Bt10 strain developed faster than larvae of the susceptible strain, the Bt10 population experienced higher larval mortality, prolonged pupal duration, decreased pupal weight, decreased emergence rate, and shortened adult longevity. Compared with the susceptible strain, the Bt10 strain was deleteriously affected by sublethal chlorpyrifos. The Bt‐tolerant/resistant S. exigua population was more vulnerable to chemical pesticides like chlorpyrifos regardless of whether it was exposed to Bt toxin or not. Our study provides a reference for increasing the efficacy of control of S. exigua in Bt‐cotton planting areas.
The effects of phylogenetic relatedness on invasion success and impact: deconstructing Darwin's naturalisation conundrum
Authors: Li Shao‐peng , Cadotte Marc W. , Meiners Scott J. , Hua Zheng‐shuang , Shu Hao‐yue , Li Jin‐tian , Shu Wen‐sheng 
Published: October 2015

AbstractDarwin's naturalisation conundrum describes the paradox that the relatedness of exotic species to native residents could either promote or hinder their success through opposing mechanisms: niche pre‐adaptation or competitive interactions. Previous studies focusing on single snapshots of invasion patterns have provided support to both sides of the conundrum. Here, by examining invasion dynamics of 480 plots over 40 years, we show that exotic species more closely related to native species were more likely to enter, establish and dominate the resident communities, and that native residents more closely related to these successful exotics were more likely to go locally extinct. Therefore, non‐random displacement of natives during invasion could weaken or even reverse the negative effects of exotic–native phylogenetic distances on invasion success. The scenario that exotics more closely related to native residents are more successful, but tend to eliminate their closely related natives, may help to reconcile the 150‐year‐old conundrum.
Traumatic brain injury in Africa in 2050: a modeling study
Authors: Wong J. C. , Linn K. A. , Shinohara R. T. , Mateen F. J. 
Published: October 2015

Background and purposeOur aim was to provide estimates of traumatic brain injury (TBI) in 2050 for the African population by region, sex and age strata.MethodsA literature search was performed in October 2014 in PubMed for population‐based studies of TBI in different geographical locations. Articles were selected from Kenya (model 1), New Zealand (model 2) and the USA (model 3). In model 1, rates of road traffic injury in Kenya were used to estimate TBI rates in the African continent. Models 2 and 3 used existing TBI incidence estimates from other locations to estimate the burden of TBI for Africa in 2050. The 2050 African population, as projected by the United Nations, was used as a base population.ResultsBased on rates from model 1, the estimated total TBI count in Africa in 2050 is 5.98 ± 0.03 million, with the highest count in eastern (2.04 ± 0.01 million) and lowest count in southern (0.15 ± 0.00 million) Africa. A higher TBI count is predicted by models 2 (14.25 ± 0.75 million) and 3 (10.40 ± 0.02 million). Estimated TBI count is highest for males aged 15–34 (5.47 ± 0.55 million in model 2 and 3.21 ± 0.13 million in model 3).ConclusionsProjected estimates of TBI in Africa are high, with a burden of anywhere between approximately 6 and 14 million new cases in 2050. This emphasizes the importance of developing accurate surveillance systems of TBI at a population level and public health measures to mitigate the risk and burden of TBI.
Selection on oxidative phosphorylation and ribosomal structure as a multigenerational response to ocean acidification in the common copepod Pseudocalanus acuspes
Authors: De Wit Pierre , Dupont Sam , Thor Peter 
Published: October 2015

AbstractOcean acidification is expected to have dramatic impacts on oceanic ecosystems, yet surprisingly few studies currently examine long‐term adaptive and plastic responses of marine invertebrates to pCO2 stress. Here, we exposed populations of the common copepod Pseudocalanus acuspes to three pCO2 regimes (400, 900, and 1550 μatm) for two generations, after which we conducted a reciprocal transplant experiment. A de novo transcriptome was assembled, annotated, and gene expression data revealed that genes involved in RNA transcription were strongly down‐regulated in populations with long‐term exposure to a high pCO2 environment, even after transplantation back to control levels. In addition, 747 000 SNPs were identified, out of which 1513 showed consistent changes in nucleotide frequency between replicates of control and high pCO2 populations. Functions involving RNA transcription and ribosomal function, as well as ion transport and oxidative phosphorylation, were highly overrepresented. We thus conclude that pCO2 stress appears to impose selection in copepods on RNA synthesis and translation, possibly modulated by helicase expression. Using a physiological hypothesis‐testing strategy to mine gene expression data, we herein increase the power to detect cellular targets of ocean acidification. This novel approach seems promising for future studies of effects of environmental changes in ecologically important nonmodel organisms.
An anatomical study of the dorsal and ventral nasal conchal bullae in normal horses: Computed tomographic anatomical and morphometric findings
Authors: Liuti T. , Reardon R. , Smith S. , Dixon P. M. 
Published: October 2015

SummaryReasons for performing studyInfection of the dorsal nasal conchal bulla and ventral nasal conchal bulla has recently been shown to cause clinical disease in horses, but the anatomy of these 2 structures is poorly documented.ObjectivesTo describe the anatomical features, dimensions and relationships to adjacent structures of the dorsal conchal bulla and ventra conchal bulla in normal horses using computed tomography (CT).Study designDescriptive imaging study using cadavers.MethodsComputed tomographic images acquired from 60 equine cadaver heads that were shown to be free of sinonasal disease were categorised into 3 age groups (0–5; 6–15; >16 years old). Linear and volumetric measurements and descriptive anatomical assessments of the dorsal conchal bulla and ventral conchal bulla were produced from these CT images and the anatomical relationships between the dorsal conchal bulla and ventral conchal bulla and the adjacent structures, particularly the maxillary cheek teeth, were examined. The associations between bullae dimensions with horse ages and skull dimensions were assessed using linear regression.ResultsMean (range) dorsal conchal bulla measurements were: length 7.5 cm (4.6–14), width 1.9 cm (1.3–2.5), height 2.8 cm (1.8–4), volume 24 cm3 (5.9–50.5). Mean ventral conchal bulla measurements were: length 5.7 cm (2.5–8.5), width 1.6 cm (0.7–2.9), height 2.4 cm (0.8–3.7), volume 15 cm3 (0.4–30). In both dorsal conchal bulla and ventral conchal bulla, there were significant differences in sizes between the different age groups (smaller in younger animals). In the ventral conchal bulla, this was probably related to protrusion of the large dental alveoli of younger horses into the lateral nasal cavity. Measures of bullae size and volume were significantly associated with head size. The anatomical positions (rostro‐caudal boundaries) of the dorsal conchal bulla and ventral conchal bulla were closely associated with specific maxillary cheek teeth.ConclusionsComputed tomography was a useful technique to establish the linear and volumetric dimensions of the nasal conchal bullae in normal horses. Both dorsal conchal bulla and ventral conchal bulla sizes increased with animal age. Relatively consistent anatomical relationships were shown between the rostral and caudal limits of the bullae and certain maxillary cheek teeth, which would be of diagnostic value with conventional radiography and act as landmarks in the surgical treatment of nasal bulla disease.
The possible interaction between periostin expressed by cancer stroma and tumor‐associated macrophages in developing mycosis fungoides
Authors: Furudate Sadanori , Fujimura Taku , Kakizaki Aya , Kambayashi Yumi , Asano Masayuki , Watabe Akiko , Aiba Setsuya 
Published: October 2015

AbstractMycosis fungoides (MF) starts as an indolent disease, progresses from a patch stage to confluent plaques and ultimately develops skin tumors. Tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF. The purpose of this study was to elucidate the involvement of TAMs in the lesional skin of different stages of MF. First, we immunohistologically examined the percentage of CD163+ macrophages and CD206+ cells, as well as the levels of periostin and IL‐4 in cancer stroma. The percentage of CD206+ cells increased in parallel with tumor progression, while there was no significant difference in the percentage of CD163+ cells. Periostin was prominent in the stromal area at the patch and plaque stages but decreased at the tumor stage. In contrast, IL‐4 was prominently stained at both plaque and tumor stages. To further elucidate the molecular mechanisms of the effects of these stromal factors on TAMs, we examined their effects on mRNA expression in monocyte‐derived macrophages in vitro. Based on microarray analysis and gene ontology, we examined a series of chemokines and MMPs whose expression was strongly connected with periostin stimulation. The DNA microarray results were verified in M2 macrophages using real‐time PCR. We further examined the mRNA expression of these chemokines and MMPs in the presence of periostin and IL‐4 to simulate the advanced stages of MF and validated their protein expression by ELISA. Our present report suggests possible roles of periostin on TAMs in establishing the tumor microenvironment in MF.
Iron and iron‐binding ligands as cofactors that limit cyanobacterial biomass across a lake trophic gradient
Authors: Sorichetti Ryan J. , Creed Irena F. , Trick Charles G. 
Published: October 2015

Summary

The frequency and intensity of cyanobacterial blooms (cyanoblooms) is increasing globally. While cyanoblooms in eutrophic (nutrient‐rich) freshwater lakes are expected to persist and worsen with climate change projections, many of the ‘new’ cyanobloom reports pertain to oligotrophic (nutrient‐poor) freshwater lakes with no prior history of cyanobloom occurrence.

Iron (Fe) is required in nearly all pathways of cyanobacterial macronutrient use, although its precise role in regulating cyanobacterial biomass across a lake trophic gradient is not fully understood.

In all lakes sampled representing a gradient in trophic status from oligotrophic to hypereutrophic (2.2–561.2 μg L−1 total phosphorus), the relative cyanobacterial biomass was highest at low predicted Fe bioavailability in eutrophic Alberta lakes (<1.0 × 10−22 mol L−1) and low Fe concentration in oligotrophic Ontario Lakes (<3.2 μg L−1).

Fe‐binding organic ligands were measured within this range of low bioavailable Fe. Concentrations of ligands with reactive hydroxamate moieties were positively correlated to cyanobacterial biomass in lakes with low Fe bioavailability and supply, suggesting a possible cellular origin (i.e. siderophores) mediated by low Fe.

These findings suggest that Fe serves as a possible cofactor that maintains cyanobacterial biomass across a lake trophic gradient and that cyanobacteria invoke a similar Fe‐scavenging system to overcome Fe limitation in lakes of all trophic states.
In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs
Authors: Fensham R.J. , Silcock J.L. , Powell O. , Habermehl M.A. 
Published: October 2015

AbstractGroundwater springs are significant landscape features for humans and the biota that occupies their habitat. Many springs become inactive where groundwater exploitation by humans has lowered the water table or artesian pressure. In order to assess this impact, it is important to identify and locate active, and with more difficulty, inactive springs. Using a variety of archival, environmental and field‐based data, this study presents a protocol for the determination of the location and status of springs across the Great Artesian Basin of Australia. This protocol underpins a database of springs, which is not only important for the assessment of spring ecosystems, but also contributes to understand groundwater extraction impacts and hydrogeological processes. The database indicates that 30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely inactive and another 11.8% are partially inactive. For the outcrop (gravity) springs of the Basin, only 1.9% are entirely inactive and 7.4% partially inactive, and for the outcrop springs in the Tertiary sandstone overlying the Basin 30.9% are inactive and 18.2% are partially inactive.