bluuebunny/crossref_metadata_2025_split huggingface dataset:
WEE1 kinase polymorphism as a predictive biomarker for efficacy of platinum-gemcitabine doublet chemotherapy in advanced non-small cell lung cancer patients
Authors: Liu Di , Wu Chunyan , Jiao Yuli , Hou Likun , Lu Daru , Zheng Hui , Chen Chang , Qian Ji , Fei Ke , Su Bo 
Published: June 2015

AbstractDNA-damaging agents are commonly used for first-line chemotherapy of advanced non-small cell lung cancer (NSCLC). As a G2/M checkpoint kinase, Wee1 can phosphorylate CDC2-tyr15 and induce G2/M cell cycle arrest in response to DNA damage. The correlation of WEE1 polymorphisms to the efficacy of chemotherapy was tested in 663 advanced NSCLC patients. WEE1 rs3910384 genotype correlated to overall survival (OS) and progress-free survival (PFS) of NSCLC patients treated with platinum-based chemotherapy. Sub-group analysis revealed that rs3910384 was particularly associated with the efficacy of doublet chemotherapy combining two DNA-damaging agents, i.e. platinum and gemcitabine. NSCLC patients with the WEE1 rs3910384 G/G homozygote genotype showed 13.5 months extended OS, 3.2 months extended PFS and a 274% relative increase in their 3-year survival rate (from 7.4% to 27.7%) compared to the A/A+A/G genotype after treatment with platinum-gemcitabine regimen. This finding was reproduced in the validation cohort. We utilized a luciferase reporter assay and Electrophoretic Mobility Shift Assay (EMSA) to demonstrate that rs3910384-linked WEE1 promoter haplotype can mediate allele-specific transcriptional binding and WEE1 expression in DNA damage response. In conclusion, the WEE1 rs3910384 G/G homozygote genotype can be used as a selective biomarker for NSCLC patients to indicate treatment with platinum and gemcitabine regimen.
Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice
Authors: Levy R J , Kvajo M , Li Y , Tsvetkov E , Dong W , Yoshikawa Y , Kataoka T , Bolshakov V Y , Karayiorgou M , Gogos J A 
Published: June 2015

AbstractIn human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects of RAPGEF6 deletion in humans, we investigated the behavior and neural functions of a mouse lacking Rapgef6. Rapgef6 deletion resulted in impaired amygdala function measured as reduced fear conditioning and anxiolysis. Hippocampal-dependent spatial memory and prefrontal cortex-dependent working memory tasks were intact. Neural activation measured by cFOS phosphorylation demonstrated a reduction in hippocampal and amygdala activation after fear conditioning, while neural morphology assessment uncovered reduced spine density and primary dendrite number in pyramidal neurons of the CA3 hippocampal region of knockout mice. Electrophysiological analysis showed enhanced long-term potentiation at cortico–amygdala synapses. Rapgef6 deletion mice were most impaired in hippocampal and amygdalar function, brain regions implicated in schizophrenia pathophysiology. The results provide a deeper understanding of the role of the amygdala in schizophrenia and suggest that RAPGEF6 may be a novel therapeutic target in schizophrenia.
Lactoferrin and ovotransferrin contribute toward antioxidative effects of Edible Bird’s Nest against hydrogen peroxide-induced oxidative stress in human SH-SY5Y cells
Authors: Hou Zhiping , Imam Mustapha Umar , Ismail Maznah , Azmi Nur Hanisah , Ismail Norsharina , Ideris Aini , Mahmud Rozi 
Published: June 2015

Abstract
There are reports of improved redox outcomes due to consumption of Edible Bird’s Nest (EBN). Many of the functional effects of EBN can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of aging and its related diseases like Alzheimer’s disease. In this study, the antioxidative potentials of EBN and its constituents, lactoferrin (LF) and ovotransferrin (OVF), were determined and protective effects against hydrogen peroxide (H2O2)- induced toxicity on SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange and propidium iodide (AO/PI) staining with microscopy were examined. Results showed that EBN and its constituents attenuated H2O2-induced cytotoxicity, and decreased radical oxygen species (ROS) through increased scavenging activity. Furthermore, LF, OVF, and EBN produced transcriptional changes in antioxidant related genes that tended towards neuroprotection as compared to H2O2-treated group. Overall, the results suggest that LF and OVF may produce synergistic or all-or-none antioxidative effects in EBN.
A multistate mark–recapture approach to estimating survival ofPIT‐tagged salamanders following timber harvest
Authors: Connette Grant M. , Semlitsch Raymond D. 
Published: June 2015

SummarySurvival is a critical component of individual fitness, population dynamics and the landscape ecology of organisms. Survival in animal populations is frequently estimated from capture–mark–recapture studies, yet these estimates are biased low when the permanent emigration of individuals is confounded with mortality. This systematic bias can limit the value of demographic information available for conservation and management efforts.We developed a novel multistate mark–recapture model for survival estimation in fossorial organisms that incorporates auxiliary passive integrated transponder (PIT‐tag) detection data to account for the possibility of permanent emigration from our study area as well as the imperfect detection of individuals. Our study provides a direct comparison of mortality, emigration and reduced ground surface activity as explanations for declines in terrestrial salamander counts which are commonly reported following timber harvest.Reduced ground surface activity was not supported as a likely cause for reduced counts of plethodontid salamanders after timber harvest. Instead, ground surface activity was predicted to be considerably higher after timber harvest, suggesting that surface counts would under‐represent the extent of population losses relative to control areas.Controlling for multiple causes for non‐detection of salamanders, we found evidence that survival probability was reduced while permanent emigration rates may also be elevated in the initial months after timber harvest. However, a substantial majority of salamanders were known to survive the process of initial forest stand entry and timber removal.Synthesis and applications. Our analysis of passive integrated transponder (PIT‐tag) detection data with a novel multistate mark–recapture model indicated that mortality and emigration are both potential causes for short‐term reductions in salamander abundance following timber harvest. We suggest that salamander mortality is likely tied to habitat or microclimate conditions in early successional timber cuts, rather than the physical process of timber removal.
Communicated Values as Informal Controls: Promoting Quality While Undermining Productivity?
Authors: Kachelmeier Steven J. , Thornock Todd A. , Williamson Michael G. 
Published: June 2015

AbstractWe find that the effectiveness of piece‐rate compensation relative to fixed pay in a laboratory letter‐search task hinges on the presence or absence of a nonbinding statement to participants that the experimenter values correct responses. In the absence of the value statement, participants with piece‐rate rewards for correct responses generate more correct and incorrect responses than do their counterparts with fixed pay, correcting errors as they go along to maximize compensation. Essentially, piece‐rate compensation acts as an output control, incentivizing participants to maximize correct responses through a “produce‐and‐improve” strategy. The value statement suppresses this strategy because participants appear to perceive it as an input constraint, prompting greater initial care at the expense of lower overall productivity. As a result, the value statement eliminates the gains in correct responses that piece‐rate incentivized participants otherwise realize. Thus, in settings in which individuals can gain efficiency by working expeditiously and improving quality when necessary, our results suggest the possibility that organizations could be better off just letting incentive schemes operate, rather than emphasizing quality in ways that could overly constrain productivity.
Proliferation and differentiation characteristics of neural stem cells during course of cerebral cortical histogenesis
Authors: Mitsuhashi Takayuki , Takahashi Takao 
Published: June 2015

AbstractRecent advancements in the research field of stem cell biology have enabled the realization of regenerative medicine in various systems of the body, including the central nervous system. However, fundamental knowledge regarding how neural stem cells divide and generate young neurons in mammals, especially in vivo, is still inadequate. In this article, we shall summarize the concept of cell cycle/division of neural stem cells that generate projection neurons in the murine cerebral cortex. We shall also review the molecular mechanisms that modulate the critical parameters related to the cell cycle regulatory mechanisms, with special reference to the cell cycle regulatory protein p27Kip1, an inhibitor of progression of the cell cycle at the G1 phase. A better understanding of the mechanisms controlling cell cycle progression is expected to contribute to the development of novel strategies to increase the efficiency of neural cell/tissue production, both in vivo and in vitro.
One ring (or two) to hold them all – on the structure and function of protein nanotubes
Authors: Angelucci Francesco , Bellelli Andrea , Ardini Matteo , Ippoliti Rodolfo , Saccoccia Fulvio , Morea Veronica 
Published: June 2015

Understanding the structural determinants relevant to the formation of supramolecular assemblies of homo‐oligomeric proteins is a traditional and central scope of structural biology. The knowledge thus gained is crucial both to infer their physiological function and to exploit their architecture for bionanomaterials design. Protein nanotubes made by one‐dimensional arrays of homo‐oligomers can be generated by either a commutative mechanism, yielding an ‘open’ structure (e.g. actin), or a noncommutative mechanism, whereby the final structure is formed by hierarchical self‐assembly of intermediate ‘closed’ structures. Examples of the latter process are poorly described and the rules by which they assemble have not been unequivocally defined. We have collected and investigated examples of homo‐oligomeric circular arrangements that form one‐dimensional filaments of stacked rings by the noncommutative mechanism in vivo and in vitro. Based on their quaternary structure, circular arrangements of protein subunits can be subdivided into two groups that we term Rings of Dimers (e.g. peroxiredoxin and stable protein 1) and Dimers of Rings (e.g. thermosome/rosettasome), depending on the sub‐structures that can be identified within the assembly (and, in some cases, populated in solution under selected experimental conditions). Structural analysis allowed us to identify the determinants by which ring‐like molecular chaperones form filamentous‐like assemblies and to formulate a novel hypothesis by which nanotube assembly, molecular chaperone activity and macromolecular crowding may be interconnected.
Reliable implementation of evidence: a qualitative study of antenatal corticosteroid administration in Ohio hospitals
Authors: Kaplan Heather C , Sherman Susan N , Cleveland Charlena , Goldenhar Linda M , Lannon Carole M , Bailit Jennifer L 
Published: June 2015

BackgroundAntenatal corticosteroids (ANCS) reduce complications of preterm birth; however, not all eligible women receive them. Many hospitals and providers do not have the right processes and conditions to enable ANCS administration with high reliability. The objective of this study was to understand conditions that enable delivery of ANCS with high reliability among hospitals participating in an Ohio Perinatal Quality Collaborative (OPQC) ANCS project.MethodsWe conducted focus groups and semistructured interviews with members of the OPQC project team (n=27) and other care providers (n=70) using a purposeful sample of 6 sites involved in the OPQC ANCS project. Participants including nurses (n=57), attending obstetricians (n=17), physician trainees (n=21) and certified nurse midwives (n=2) were asked to reflect on their experiences and to identify factors contributing to optimal use of ANCS. Focus groups and interviews were transcribed verbatim and were analysed by a multidisciplinary team using an iterative approach that combined inductive and deductive methods to identify and categorise themes.ResultsSix major themes supporting reliable implementation of ANCS at these hospitals emerged including: (1) presence of a high reliability culture, (2) processes that emphasise high reliability, (3) timely and efficient administration process, (4) multiple disciplines are involved, (5) evidence of benefit supports ANCS use and (6) benefit is recognised at all levels of the care team.ConclusionsOur findings identify the key processes and supports needed to ensure delivery of ASCS with high reliability and are reinforced by implementation and reliability science. They are useful for foundation of the successful implementation of other evidence-based practices at high levels of reliability.
Narrow Band Imaging
Authors: Dippold Sebastian , Becker Christoph , Nusseck Manfred , Richter Bernhard , Echternach Matthias 
Published: June 2015

Objectives: Narrow band imaging (NBI) is supposed to be a technique for a better visualization of vessel structures in superficial tissue as it selects the wavelengths of hemoglobin. It was hypothesized that, in the regular follow-up examination of patients with recurrent laryngeal papillomatosis, NBI enables a better detection of laryngeal papillomatosis in contrast to normal white light endoscopy. Methods: Eleven patients, 10 with a known recurrent papillomatosis (8 with a relapse, 2 without) and 1 with a primary diagnosis of papillomatosis, were examined with normal white light and NBI endoscopy. Twenty-six video sequences (11 white, 11 NBI, 4 doubled for validity) were generated and randomly presented to 20 otolaryngologists who rated the videos in terms of lesions seen and number of lesions identified. Results were compared with the histopathologic findings of microlaryngoscopy. Results: Detection of papillomatosis and the correct number of lesions identified were more accurate with NBI than with normal white light endoscopy. There was a significantly higher probability of detecting laryngeal papillomata with NBI. Conclusions: NBI endoscopy enables a more accurate detection of laryngeal papillomatosis than white light endoscopy.
Post-traumatic headaches correlate with migraine symptoms in youth with concussion
Authors: Heyer Geoffrey L , Young Julie A , Rose Sean C , McNally Kelly A , Fischer Anastasia N 
Published: June 2015

Objective The term “post-traumatic migraine” (PTM) has been used to describe post-traumatic headaches (PTHs) that have associated migraine features, but studies of this relationship are lacking. The objective of the present study was to determine whether PTH correlates strongly with migraine symptoms among youth with concussion. Methods Twenty-three symptoms were analyzed from a retrospective cohort of 1953 pediatric patients with concussion. A principal component analysis (PCA) with oblique Promax rotation was conducted to explore underlying symptom relationships in the full cohort and in subcohorts stratified by the presence ( n = 414) or absence ( n = 1526) of premorbid headache. Results The mean patient age was 14.1 years; 63% were male. Headache was the most common postconcussion symptom, acknowledged by 69.4% of patients. When considering the full cohort, the PCA demonstrated clustering of headache with photophobia, phonophobia, nausea, dizziness, and neck pain. Similar clustering was present among patients without premorbid headaches. Repeating the analysis in the patients with preconcussion headaches led to elimination of neck pain from the cluster. Conclusions PTH correlates strongly with other migraine symptoms among youth with concussion, regardless of premorbid headaches. This clustering of migraine symptoms supports the existence of PTM as a distinct clinical entity in some patients.
A Case of Lichen Sclerosus et Atrophicus With Distinct Erythematous Borders
Authors: Surkan Megan , Hull Peter 
Published: June 2015

Background: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory and fibrosing condition that mostly affects the genital mucosa. Nongenital skin may be affected either in isolation or in association with genital involvement. A distinct, brightly red border may be seen but is poorly documented in major dermatology texts. In the case presented, such a border was noted in all of the patient’s very extensive lesions. Objective: To draw attention to this clinical manifestation and to stimulate future observations as to its clinical and prognostic significance. Methods and Results: A 67-year-old woman presented with disseminated LSA with genital involvement. All the lesions had a distinct red border. A review of major textbooks available to the authors revealed that the presence of a marginal erythema is regularly not mentioned. Conclusion: An erythematous border to LSA may be a notable feature. Its frequency and clinical significance remain to be determined.
Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis
Authors: Ling Martin R , Chapple Iain LC , Matthews John B 
Published: June 2015

Pro-inflammatory cytokine release (IL-8, IL-6, TNF-α, IL-1β) by peripheral blood neutrophils, isolated from periodontitis patients (before/after therapy) and matched controls, was determined after 18 h culture in the presence/absence of Escherichia coli LPS, opsonised Staphylococcus aureus, heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis. All cultures demonstrated differences in the amounts of each cytokine detected ( P < 0.0001), with a clear release pattern (IL-8 > IL-6 > TNF-α = IL-1β). Median cytokine release from unstimulated patient neutrophils was consistently, but non-significantly, higher than from control cells. Stimulated cytokine release from untreated patient neutrophils was also consistently higher than from control cells. This hyper-reactivity was significant for all tested cytokines when data for all stimuli were combined ( P < 0.016). In terms of individual stimuli, significant hyper-reactivity was detected with LPS (IL-8), F. nucleatum (IL-8, TNF-α), opsonised S. aureus (IL-8, TNF-α, IL-1β) and P. gingivalis (IL-8, IL-1β). Cytokine production by patient neutrophils did not reduce following successful non-surgical periodontal therapy and, except for responses to F. nucleatum, the cytokine hyper-reactivity detected pre-therapy was retained. These data demonstrate that chronic periodontitis is characterised by neutrophils that constitutively exhibit cytokine hyper-reactivity, the effects of which could modulate local and systemic inflammatory-immune responses and influence the risk and severity of periodontitis-associated systemic inflammatory diseases.
Influence of Glycosylation on Diagnostic and Prognostic Accuracy of N-Terminal Pro–B-Type Natriuretic Peptide in Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study
Authors: Røsjø Helge , Dahl Mai Britt , Jørgensen Marit , Røysland Ragnhild , Brynildsen Jon , Cataliotti Alessandro , Christensen Geir , Høiseth Arne Didrik , Hagve Tor-Arne , Omland Torbjørn 
Published: June 2015

AbstractBACKGROUNDThe N-terminal part of pro–B-type natriuretic peptide (NT-proBNP) is glycosylated, but whether glycosylation influences the diagnostic and prognostic accuracy of NT-proBNP measurements is not known.METHODSWe measured NT-proBNP concentrations of 309 patients with acute dyspnea by use of standard EDTA tubes and EDTA tubes pretreated with deglycosylation enzymes. The primary cause of dyspnea was classified as heart failure (HF) or non-HF, and the diagnosis was adjudicated by 2 independent physicians. We collected information on all-cause mortality during follow-up.RESULTSIn all, 142 patients (46%) were diagnosed with HF. NT-proBNP concentrations in nondeglycosylated samples distinguished HF patients from patients with non-HF related dyspnea [median 3588 (quartiles 1–3 1578–8404) vs 360 (126–1139) ng/L, P &lt; 0.001], but concentrations were markedly higher in samples pretreated with deglycosylation enzymes (total NT-proBNP) [7497 (3374–14 915) vs 798 (332–2296) ng/L, P &lt; 0.001]. The AUC to separate HF patients from patients with non-HF related dyspnea was 0.871 (95% CI 0.829–0.907) for total NT-proBNP compared with 0.852 (0.807–0.890) for NT-proBNP measurements in standard EDTA plasma. During a median follow-up of 816 days, 112 patients (36%) died. Both NT-proBNP and total NT-proBNP concentrations were associated with mortality in separate multivariate models, but only total NT-proBNP concentrations provided added value to the basic risk model of our dataset as assessed by the net reclassification index: 0.24 (95% CI 0.003–0.384). There was a graded increase in risk across total NT-proBNP quartiles, in contrast with the results for NT-proBNP measurements.CONCLUSIONSNT-proBNP concentrations were higher, and diagnostic and prognostic accuracy was improved, by pretreating tubes with deglycosylation enzymes.
Increasing Energy Storage in Activated Carbon based Electrical Double Layer Capacitors through Plasma Processing
Authors: Muriel Marcelis L. , Narayanan Rajaram , Bandaru Prabhakar R. 
Published: June 2015

ABSTRACTWe present a methodology to enhance the electrical capacitance of activated carbon (AC) electrodes based on the introduction of electrically charged defects through argon plasma processing. Extensive characterization using electrochemical techniques incorporating cyclic voltammetry, constant current charge/discharge, and electrical impedance spectroscopy indicated a close to seven-fold increase in capacitance with respect to untreated AC electrodes, not subject to plasma processing.