Correlated memory resistor in epitaxial NdNiO3 heterostructures with asymmetrical proton concentration

The electronic devices using correlated transition metal oxides are the promising candidates to overcome the limitation of the current electronics due to the rich electronic phases and the extreme sensitivities. Here, we report proton-based resistive switching memory that uses correlated oxides, i.e., epitaxial NdNiO3 heterostructure with asymmetrical concentration of protons (H+) to obtain multilevel states. By designing such metal-NdNiO3-metal device structures with asymmetrical proton concentration, we demonstrate that the correlated oxides exhibit resistive switching by ionic transport of protons at the metal-hydrogenated NdNiO3 (H-NNO) interface. This finding will guide the development of energy-efficient switching devices for non-volatile memory and neuromorphic applications.open1184sciescopu

Portuguese validation of the Bergen Facebook Addiction Scale: an Empirical Study

Previous research on Social Networking Sites (SNSs) addiction have suggest the need to improve assessment of this behavioral addiction. The present study aimed at validating a Portuguese version of the Bergen Facebook Addiction Scale (BFAS), a widely used instrument to assess addiction to Facebook. A study was conducted in a sample of 509 Portuguese adolescent using an online survey. The psychometric properties (construct validity, criterion validity, and reliability) of the Portuguese BFAS was scrutinized. The results from the psychometric analyses suggested that the new validated instrument had excellent psychometric properties. The CFA confirmed the original one-factor solution of the BFAS and criterion validity was warranted. The reliability of the BFAS was supported by satisfactory levels of internal consistency as measured by the Cronbach’s alpha (α = .83), composite reliability (CR = .82), and factor determinacy (FD = .91). Overall, the results provided empirical support for the validity and reliability of the Portuguese BFAS. Moreover, the results were highly comparable with the findings of the original development study of the BFAS and cross-cultural support for the scale was obtained

Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Triple negative breast cancer (TNBC) has a poorer survival, despite a higher response rate to neoadjuvant chemotherapy. The purpose of this study was to identify the predictive or prognostic value of Ki-67 among patients with TNBC treated with neoadjuvant chemotherapy, and the role of Ki-67 in further classification of TNBC. Methods: A total of 105 TNBC patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were included in the present study. Pathologic complete response (pCR) rate, relapse-free survival (RFS), and overall survival (OS) were compared according to the level of Ki-67. Results: pCR was observed in 13.3% of patients. TNBC with high Ki-67 expression (>= 10%) showed a higher pCR rate to neoadjuvant chemotherapy than TNBC with low Ki-67 expression. None of the low Ki-67 group achieved pCR (18.2% in the high Ki-67 group vs. 0.0% in the low Ki-67 group, P = 0.019). However, a high Ki-67 expression was significantly associated with poor RFS and OS in TNBC, despite a higher pCR rate (P = 0.005, P = 0.019, respectively). In multivariate analysis, high Ki-67 was an independent prognostic factor for RFS in TNBC (hazard ratio = 7.82, P = 0.002). The high Ki-67 group showed a similar pattern of recurrence with overall TNBC, whereas the low Ki-67 group demonstrated a relatively constant hazard rate for relapse. Conclusions: TNBC with high Ki-67 was associated with a more aggressive clinical feature despite a higher pCR rate. High proliferation index Ki-67 can be used for further classification of TNBC into two subtypes with different responses and prognosis.

Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.</p> <p>Methods</p> <p>A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.</p> <p>Results</p> <p>Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative <it>vs</it>. 62.2% in non-triple negative, <it>p </it>= 0.012) and pathologic complete RR (17.0% in triple negative <it>vs</it>. 3.1% in non-triple negative, <it>p </it>= 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (<it>p </it>< 0.001, <it>p </it>= 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, <it>p </it>= 0.044).</p> <p>Conclusion</p> <p>Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.</p

Four Distances between Pairs of Amino Acids Provide a Precise Description of their Interaction

The three-dimensional structures of proteins are stabilized by the interactions between amino acid residues. Here we report a method where four distances are calculated between any two side chains to provide an exact spatial definition of their bonds. The data were binned into a four-dimensional grid and compared to a random model, from which the preference for specific four-distances was calculated. A clear relation between the quality of the experimental data and the tightness of the distance distribution was observed, with crystal structure data providing far tighter distance distributions than NMR data. Since the four-distance data have higher information content than classical bond descriptions, we were able to identify many unique inter-residue features not found previously in proteins. For example, we found that the side chains of Arg, Glu, Val and Leu are not symmetrical in respect to the interactions of their head groups. The described method may be developed into a function, which computationally models accurately protein structures

The West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study: a cluster randomised controlled trial testing the clinical effectiveness and cost-effectiveness of a multifaceted obesity prevention intervention programme targeted at children aged 6-7 years.

BACKGROUND: Systematic reviews suggest that school-based interventions can be effective in preventing childhood obesity, but better-designed trials are needed that consider costs, process, equity, potential harms and longer-term outcomes. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of the WAVES (West Midlands ActiVe lifestyle and healthy Eating in School children) study intervention, compared with usual practice, in preventing obesity among primary school children. DESIGN: A cluster randomised controlled trial, split across two groups, which were randomised using a blocked balancing algorithm. Schools/participants could not be blinded to trial arm. Measurement staff were blind to allocation arm as far as possible. SETTING: Primary schools, West Midlands, UK. PARTICIPANTS: Schools within a 35-mile radius of the study centre and all year 1 pupils (aged 5-6 years) were eligible. Schools with a higher proportion of pupils from minority ethnic populations were oversampled to enable subgroup analyses. INTERVENTIONS: The 12-month intervention encouraged healthy eating/physical activity (PA) by (1) helping teachers to provide 30 minutes of additional daily PA, (2) promoting 'Villa Vitality' (interactive healthy lifestyles learning, in an inspirational setting), (3) running school-based healthy cooking skills/education workshops for parents and children and (4) highlighting information to families with regard to local PA opportunities. MAIN OUTCOME MEASURES: The primary outcomes were the difference in body mass index z-scores (BMI-zs) between arms (adjusted for baseline body mass index) at 3 and 18 months post intervention (clinical outcome), and cost per quality-adjusted life-year (QALY) (cost-effectiveness outcome). The secondary outcomes were further anthropometric, dietary, PA and psychological measurements, and the difference in BMI-z between arms at 27 months post intervention in a subset of schools. RESULTS: Two groups of schools were randomised: 27 in 2011 (n = 650 pupils) [group 1 (G1)] and another 27 in 2012 (n = 817 pupils) [group 2 (G2)]. Primary outcome data were available at first follow-up (n = 1249 pupils) and second follow-up (n = 1145 pupils) from 53 schools. The mean difference (MD) in BMI-z between the control and intervention arms was -0.075 [95% confidence interval (CI) -0.183 to 0.033] and -0.027 (95% CI -0.137 to 0.083) at 3 and 18 months post intervention, respectively. The main analyses showed no evidence of between-arm differences for any secondary outcomes. Third follow-up included data on 467 pupils from 27 G1 schools, and showed a statistically significant difference in BMI-z (MD -0.20, 95% CI -0.40 to -0.01). The mean cost of the intervention was £266.35 per consented child (£155.53 per child receiving the intervention). The incremental cost-effectiveness ratio associated with the base case was £46,083 per QALY (best case £26,804 per QALY), suggesting that the intervention was not cost-effective. LIMITATIONS: The presence of baseline primary outcome imbalance between the arms, and interschool variation in fidelity of intervention delivery. CONCLUSIONS: The primary analyses show no evidence of clinical effectiveness or cost-effectiveness of the WAVES study intervention. A post hoc analysis, driven by findings at third follow-up, suggests a possible intervention effect, which could have been attenuated by baseline imbalances. There was no evidence of an intervention effect on measures of diet or PA and no evidence of harm. FUTURE WORK: A realist evidence synthesis could provide insights into contextual factors and strategies for future interventions. School-based interventions need to be integrated within a wider societal framework and supported by upstream interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 8. See the NIHR Journals Library website for further project information

Stem cells in liver regeneration and therapy

The liver has adapted to the inflow of ingested toxins by the evolutionary development of unique regenerative properties and responds to injury or tissue loss by the rapid division of mature cells. Proliferation of the parenchymal cells, i.e. hepatocytes and epithelial cells of the bile duct, is regulated by numerous cytokine/growth-factor-mediated pathways and is synchronised with extracellular matrix degradation and restoration of the vasculature. Resident hepatic stem/progenitor cells have also been identified in small numbers in normal liver and implicated in liver tissue repair. Their putative role in the physiology, pathophysiology and therapy of the liver, however, is not yet precisely known. Hepatic stem/progenitor cells also known as “oval cells” in rodents have been implicated in liver tissue repair, at a time when the capacity for hepatocyte and bile duct replication is exhausted or experimentally inhibited (facultative stem/progenitor cell pool). Although much more has to be learned about the role of stem/progenitor cells in the physiology and pathophysiology of the liver, experimental analysis of the therapeutic value of these cells has been initiated. Transplantation of hepatic stem/progenitor cells or in vivo pharmacological activation of the pool of hepatic stem cells may provide novel modalities for the therapy of liver diseases. In addition, extrahepatic stem cells (e.g. bone marrow cells) are being investigated for their contribution to liver regeneration. Hepatic progenitor cells derived from embryonic stem cells are included in this review, which also discusses future perspectives of stem cell-based therapies for liver diseases

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities

Uridylation and adenylation of RNAs

The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3′ ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone mRNAs, mRNA fragments, U6 snRNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area