bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-cultural study of caregiver burden for Alzheimer's disease in Japan and Taiwan: result from Dementia Research in Kumamoto and Tainan (DeReKaT)
Authors: Matsushita Masateru , Pai Ming-Chyi , Jhou Cai-Ying , Koyama Asuka , Ikeda Manabu 
Published: January 2016

ABSTRACTBackground:Caregiver burden (CB) of Alzheimer's disease (AD) in Taiwan is becoming an urgent social issue as well as that in Japan. The comparison of CB may explain how caregiver feels burden in each country.Methods:The participants were 343 outpatients with AD and their caregivers of Japan (n= 230) and Taiwan (n= 113). We assessed the CB using the Japanese and Chinese version of Zarit Caregiver Burden Interview (ZBI). The initial analysis was an exploratory factor analysis for each group to confirm the factor structure of ZBI. Then, the multiple-group structural equation modeling (MG-SEM) was used to assess the measurement invariance of ZBI such as configural, metric, and scalar invariances. Lastly, we compared the latent factor means of the ZBI between Japan and Taiwan.Results:In both groups, the confirmatory factor analysis extracted 3 factors which were labeled “Impact on caregiver's life”, “Embarrassed/anger”, and “Dependency”. The MG-SEM indicated an acceptable model fit, and established the partial scalar measurement invariance (comparative fit index (CFI) = 0.901, root mean square error of approximation (RMSEA) = 0.066). When we compared the latent factor means, the score of “Impact on caregiver's life” in Taiwanese caregivers was significantly higher than that in Japanese (p= 0.001). However, “Dependency” in Taiwanese caregivers was lower than that in Japanese (p< 0.001).Conclusions:Partial measurement invariance allowed comparing the latent factor mean across two countries. The results of comparisons suggested that there may be differences in the way of feeling CB between Japan and Taiwan.
Examination of level of knowledge in Italian general practitioners attending an education session on diagnosis and management of the early stage of Alzheimer's disease: pass or fail?
Authors: Veneziani Federica , Panza Francesco , Solfrizzi Vincenzo , Capozzo Rosa , Barulli Maria Rosaria , Leo Antonio , Lozupone Madia , Fontana Andrea , Arcuti Simona , Copetti Massimiliano , Cardinali Valentina , Grasso Alessandra , Tursi Marianna , Iurillo Annalisa , Imbimbo Bruno Pietro , Seripa Davide , Logroscino Giancarlo 
Published: January 2016

ABSTRACTBackground:We detected the general level of knowledge about the early diagnosis of Alzheimer's disease (AD) and subsequent care in general practitioners (GPs) from Southern Italy. We explored also the GP perception about their knowledge and training on diagnosis and management of AD.Methods:On a sample of 131 GPs, we administered two questionnaires: the GP-Knowledge, evaluating GPs’ expertise about AD epidemiology, differential diagnosis, and available treatments, and the GP-QUestionnaire on Awareness of Dementia (GP-QUAD), assessing the GPs’ attitudes, awareness, and practice regarding early diagnosis of dementia.Results:Specific screening tests or protocols to diagnose and manage dementia were not used by 53% of our GPs. The training on the recognition of early AD signs and symptoms was considered inadequate by 55% of the participants. Females were more likely to consider their training insufficient (58%) compared to males (53%). Female GPs were less likely to prescribe antipsychotic drugs to control neuropsychiatric symptoms (NPS) and suggest specialist advice in late stage of cognitive impairment. Multiple Correspondence Analysis (MCA) performed only on GP-QUAD suggested two dimensions explaining 26.1% (“GP attitude”) and 20.1% (“GP knowledge”) of the inertia for a total of 46.2%,Conclusion:In our survey on GP clinical practice, several problems in properly recognizing early AD symptoms and subsequently screening patients to be referred to secondary/tertiary care centers for diagnosis confirmation have emerged. In the future, specific training programs and educational projects for GPs should be implemented also in Italy to improve detection rates and management of dementia in primary care.
PICKWICK'S OTHER PAPERS: CONTINUALLY READING DICKENS
Authors: Han Carrie Sickmann 
Published: January 2016

While carefully crafting a valentine to his would-be-lover Mary, Sam Weller finishes rather abruptly, and his father, looking over his shoulder, asks, “That's rayther a sudden pull up, ain't it, Sammy?” Sam's response emblematizes the driving force of the serial novel: “Not a bit on it. . . she'll vish there wos more, and that's the great art o' letter writin'” (344; no. XII, ch. XXXIII). Charles Dickens's great art of serial writing aimed to leave his readers repeatedly wishing there was more: more pages, more plot, more world, and above all, more time with their favorite characters. This desire encouraged readers to imagine beyond the novel – to pursue characters outside the pages of The Pickwick Papers itself. Their desires were rewarded with a wide range of continuations that included theatrical adaptations, plagiarisms, or unauthorized sequels – anything that, like the valentine, could reunite readers with their beloved Sam.
Two Novel Psychomotor Tasks in Idiopathic Normal Pressure Hydrocephalus
Authors: Rossetti Maria A. , Piryatinsky Irene , Ahmed Fayeza S. , Klinge Petra M. , Relkin Norman R. , Salloway Stephen , Ravdin Lisa D. , Brenner Einat , Malloy Paul F. , Levin Bonnie E. , Broggi Michael , Gavett Rebecca , Maniscalco James S. , Katzen Heather 
Published: January 2016

AbstractObjective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. Methods: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). Results: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p≤.001) and SDT (p<.001). Conclusions: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. (JINS, 2016, 22, 341–349)
Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1
Authors: Qiu L , Wu J , Pan C , Tan X , Lin J , Liu R , Chen S , Geng R , Huang W 
Published: January 2016

AbstractDysregulated cell cycle progression has a critical role in tumorigenesis. Cell division cycle 27 (CDC27) is a core subunit of the anaphase-promoting complex/cyclosome, although the specific role of CDC27 in cancer remains unknown. In our study, we explored the biological and clinical significance of CDC27 in colorectal cancer (CRC) growth and progression and investigated the underlying molecular mechanisms. Results showed that CDC27 expression is significantly correlated with tumor progression and poor patient survival. Functional assays demonstrated that overexpression of CDC27 promoted proliferation in DLD1 cells, whereas knockdown of CDC27 in HCT116 cells inhibited proliferation both in vitro and in vivo. Further mechanistic investigation showed that CDC27 downregulation resulted in G1/S phase transition arrest via the significant accumulation of p21 in HCT116 cells, and the upregulation of CDC27 promoted G1/S phase transition via the attenuation of p21 in DLD1 cells. Furthermore, we also demonstrated that CDC27 regulated inhibitor of DNA binding 1 (ID1) protein expression in DLD1 and HCT116 cells, and rescue assays revealed that CDC27 regulated p21 expression through modulating ID1 expression. Taken together, our results indicate that CDC27 contributes to CRC cell proliferation via the modulation of ID1-mediated p21 regulation, which offers a novel approach to the inhibition of tumor growth. Indeed, these findings provide new perspectives for the future study of CDC27 as a target for CRC treatment.
X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity
Authors: Evans M K , Sauer S J , Nath S , Robinson T J , Morse M A , Devi G R 
Published: January 2016

AbstractInflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.
Amplification and generation of ultra-intense twisted laser pulses via stimulated Raman scattering
Authors: Vieira J. , Trines R. M. G. M. , Alves E. P. , Fonseca R. A. , Mendonça J. T. , Bingham R. , Norreys P. , Silva L. O. 
Published: January 2016

AbstractTwisted Laguerre–Gaussian lasers, with orbital angular momentum and characterized by doughnut-shaped intensity profiles, provide a transformative set of tools and research directions in a growing range of fields and applications, from super-resolution microcopy and ultra-fast optical communications to quantum computing and astrophysics. The impact of twisted light is widening as recent numerical calculations provided solutions to long-standing challenges in plasma-based acceleration by allowing for high-gradient positron acceleration. The production of ultra-high-intensity twisted laser pulses could then also have a broad influence on relativistic laser–matter interactions. Here we show theoretically and with ab initio three-dimensional particle-in-cell simulations that stimulated Raman backscattering can generate and amplify twisted lasers to petawatt intensities in plasmas. This work may open new research directions in nonlinear optics and high–energy-density science, compact plasma-based accelerators and light sources.
Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
Authors: Imamura Minako , Takahashi Atsushi , Yamauchi Toshimasa , Hara Kazuo , Yasuda Kazuki , Grarup Niels , Zhao Wei , Wang Xu , Huerta-Chagoya Alicia , Hu Cheng , Moon Sanghoon , Long Jirong , Kwak Soo Heon , Rasheed Asif , Saxena Richa , Ma Ronald C. W. , Okada Yukinori , Iwata Minoru , Hosoe Jun , Shojima Nobuhiro , Iwasaki Minaka , Fujita Hayato , Suzuki Ken , Danesh John , Jørgensen Torben , Jørgensen Marit E. , Witte Daniel R. , Brandslund Ivan , Christensen Cramer , Hansen Torben , Mercader Josep M. , Flannick Jason , Moreno-Macías Hortensia , Burtt Noël P. , Zhang Rong , Kim Young Jin , Zheng Wei , Singh Jai Rup , Tam Claudia H. T. , Hirose Hiroshi , Maegawa Hiroshi , Ito Chikako , Kaku Kohei , Watada Hirotaka , Tanaka Yasushi , Tobe Kazuyuki , Kawamori Ryuzo , Kubo Michiaki , Cho Yoon Shin , Chan Juliana C. N. , Sanghera Dharambir , Frossard Philippe , Park Kyong Soo , Shu Xiao-Ou , Kim Bong-Jo , Florez Jose C. , Tusié-Luna Teresa , Jia Weiping , Tai E Shyong , Pedersen Oluf , Saleheen Danish , Maeda Shiro , Kadowaki Takashi 
Published: January 2016

AbstractGenome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10−8), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency
Authors: Song Jun , Yang Dongshan , Xu Jie , Zhu Tianqing , Chen Y. Eugene , Zhang Jifeng 
Published: January 2016

AbstractZinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.
Follicular regulatory T cells can be specific for the immunizing antigen and derive from naive T cells
Authors: Aloulou Meryem , Carr Edward J. , Gador Mylène , Bignon Alexandre , Liblau Roland S. , Fazilleau Nicolas , Linterman Michelle A. 
Published: January 2016

AbstractT follicular regulatory (Tfr) cells are a subset of Foxp3+ regulatory T (Treg) cells that form in response to immunization or infection, which localize to the germinal centre where they control the magnitude of the response. Despite an increased interest in the role of Tfr cells in humoral immunity, many fundamental aspects of their biology remain unknown, including whether they recognize self- or foreign antigen. Here we show that Tfr cells can be specific for the immunizing antigen, irrespective of whether it is a self- or foreign antigen. We show that, in addition to developing from thymic derived Treg cells, Tfr cells can also arise from Foxp3− precursors in a PD-L1-dependent manner, if the adjuvant used is one that supports T-cell plasticity. These findings have important implications for Tfr cell biology and for improving vaccine efficacy by formulating vaccines that modify the Tfr:Tfh cell ratio.
Facile Access to Graphene Oxide from Ferro-Induced Oxidation
Authors: Yu Chao , Wang Cai-Feng , Chen Su 
Published: January 2016

AbstractMethods allowing the oxidation of graphite to graphene oxide (GO) are vital important for the production of graphene from GO. This oxidation reaction has mainly relied on strong acid strategy for 174 years, which circumvents issues associated with toxicity of reagent and product, complex post-treatment, high cost and waste generation. Here, we report a green route for performing this oxidization reaction via a ferro-induced strategy, with use of water, potassium ferrate (Fe(VI)) and hydrogen peroxide (H2O2) as reagents, to produce about 65% yield of GO (vs. 40% for Hummers’ method, the most commonly used concentrated acid strategy) and non-toxic by-products. Moreover, GO produced from this new method shows equivalent performance to those reported previously. This H2SO4-free strategy makes it possible to process graphite into GO in a safe, low-cost, time-saving, energy-efficient and eco-friendly pathway, opening a promising avenue for the large-scale production of GO and GO-based materials.
All-atom molecular dynamics analysis of multi-peptide systems reproduces peptide solubility in line with experimental observations
Authors: Kuroda Yutaka , Suenaga Atsushi , Sato Yuji , Kosuda Satoshi , Taiji Makoto 
Published: January 2016

AbstractIn order to investigate the contribution of individual amino acids to protein and peptide solubility, we carried out 100 ns molecular dynamics (MD) simulations of 106 Å3 cubic boxes containing ~3 × 104 water molecules and 27 tetra-peptides regularly positioned at 23 Å from each other and composed of a single amino acid type for all natural amino acids but cysteine and glycine. The calculations were performed using Amber with a standard force field on a special purpose MDGRAPE-3 computer, without introducing any “artificial” hydrophobic interactions. Tetra-peptides composed of I, V, L, M, N, Q, F, W, Y and H formed large amorphous clusters and those containing A, P, S and T formed smaller ones. Tetra-peptides made of D, E, K and R did not cluster at all. These observations correlated well with experimental solubility tendencies as well as hydrophobicity scales with correlation coefficients of 0.5 to > 0.9. Repulsive Coulomb interactions were dominant in ensuring high solubility, whereas both Coulomb and van der Waals (vdW) energies contributed to the aggregations of low solubility amino acids. Overall, this very first all-atom molecular dynamics simulation of a multi-peptide system appears to reproduce the basic properties of peptide solubility, essentially in line with experimental observations.
Nucleosome architecture throughout the cell cycle
Authors: Deniz Özgen , Flores Oscar , Aldea Martí , Soler-López Montserrat , Orozco Modesto 
Published: January 2016

AbstractNucleosomes provide additional regulatory mechanisms to transcription and DNA replication by mediating the access of proteins to DNA. During the cell cycle chromatin undergoes several conformational changes, however the functional significance of these changes to cellular processes are largely unexplored. Here, we present the first comprehensive genome-wide study of nucleosome plasticity at single base-pair resolution along the cell cycle in Saccharomyces cerevisiae. We determined nucleosome organization with a specific focus on two regulatory regions: transcription start sites (TSSs) and replication origins (ORIs). During the cell cycle, nucleosomes around TSSs display rearrangements in a cyclic manner. In contrast to gap (G1 and G2) phases, nucleosomes have a fuzzier organization during S and M phases, Moreover, the choreography of nucleosome rearrangements correlate with changes in gene expression during the cell cycle, indicating a strong association between nucleosomes and cell cycle-dependent gene functionality. On the other hand, nucleosomes are more dynamic around ORIs along the cell cycle, albeit with tighter regulation in early firing origins, implying the functional role of nucleosomes on replication origins. Our study provides a dynamic picture of nucleosome organization throughout the cell cycle and highlights the subsequent impact on transcription and replication activity.
Nonlinear dynamics induced anomalous Hall effect in topological insulators
Authors: Wang Guanglei , Xu Hongya , Lai Ying-Cheng 
Published: January 2016

AbstractWe uncover an alternative mechanism for anomalous Hall effect. In particular, we investigate the magnetisation dynamics of an insulating ferromagnet (FM) deposited on the surface of a three-dimensional topological insulator (TI), subject to an external voltage. The spin-polarised current on the TI surface induces a spin-transfer torque on the magnetisation of the top FM while its dynamics can change the transmission probability of the surface electrons through the exchange coupling and hence the current. We find a host of nonlinear dynamical behaviors including multistability, chaos and phase synchronisation. Strikingly, a dynamics mediated Hall-like current can arise, which exhibits a nontrivial dependence on the channel conductance. We develop a physical understanding of the mechanism that leads to the anomalous Hall effect. The nonlinear dynamical origin of the effect stipulates that a rich variety of final states exist, implying that the associated Hall current can be controlled to yield desirable behaviors. The phenomenon can find applications in Dirac-material based spintronics.
Estimating the minimum control count of random network models
Authors: Ruths Derek , Ruths Justin 
Published: January 2016

AbstractThe study of controllability of complex networks has introduced the minimum number of controls required for full controllability as a new network measure of interest. This network measure, like many others, is non-trivial to compute. As a result, establishing the significance of minimum control counts (MCCs) in real networks using random network null models is expensive. Here we derive analytic estimates for the expected MCCs of networks drawn from three commonly-used random network models. Our estimates show good agreement with exact control counts. Furthermore, the analytic expressions we derive offer insights into the structures within each random network model that induce the need for controls.