bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study
Authors: Kanhai Danny A , de Kleijn Dominique P V , Kappelle L Jaap , Uiterwaal Cuno S P M , van der Graaf Yolanda , Pasterkamp Gerard , Geerlings Mirjam I , Visseren Frank L J ,   on behalf of the SMART Study Group
Published: January 2014

ObjectivesExtracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy.DesignCohort study; cross-sectional and prospective.SettingSingle centre, secondary and tertiary setting.Participants1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements.OutcomesWML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up.Statistical methodsThe relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years.ResultsHigher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (–0.14%/SD; –0.27 to –0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up.ConclusionsEV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.
Information needs of parents for acute childhood illness: determining ‘what, how, where and when’ of safety netting using a qualitative exploration with parents and clinicians
Authors: Jones Caroline H D , Neill Sarah , Lakhanpaul Monica , Roland Damian , Singlehurst-Mooney Hayley , Thompson Matthew 
Published: January 2014

ObjectiveTo explore the views of parents and clinicians regarding the optimal content, format and delivery of safety netting information for acute childhood illness.DesignQualitative study including semistructured focus groups and interviews.SettingFirst contact care settings, community centres, children's centres and nurseries in the Midlands, UK.Participants27 parents from a travelling community, Asian British community and white British community. Sixteen clinicians including 10 doctors and 6 nurses from a general practice surgery, an out-of-hours service and two emergency departments (paediatric and combined adult and paediatric).ResultsParticipants described a need for safety netting to contain information on signs and symptoms of serious and common illnesses, illness management and where and when to seek help. Resources should be basic, simple to use and contain simple symbols. A key criterion was professional endorsement of resources. Internet-based information was desired which is reliable, consistent and up-to-date. Participants described a need for different types of information: that which could be delivered during consultations, as well as more general information for parents to access before consulting a healthcare professional. Face-to-face education, written materials and digital media were suggested delivery mechanisms. Audiovisual material was preferred by families with low literacy. Participants commonly suggested internet-based and phone-based resources, but the travelling community was less comfortable with these approaches.ConclusionsA multifaceted and tailored approach to safety netting is needed so that effective resources are available for parents with varying information needs, literacy levels and ability to use information technology. We have identified key aspects of content, quality criteria, format and delivery mechanisms for safety netting information from the perspectives of clinicians and parents. Resources should be coproduced with parents and clinicians to ensure that they are valued and utilised by both groups.
Mobility decline in old age: the combined effect of mobility-related fatigue and socioeconomic position
Authors: Nilsson Charlotte Juul , Siersma Volkert , Mänty Minna , Avlund Kirsten , Vass Mikkel , Lund Rikke 
Published: January 2014

BackgroundMobility-related fatigue and low socioeconomic position predicts mobility limitations and disability in old age, but the interplay between these two factors is unknown. To evaluate whether mobility-related fatigue is a stronger risk factor for mobility limitations in certain socioeconomic groups, the aim of this study was to examine the combined effect of mobility-related fatigue and socioeconomic position on mobility limitations in a prospective study among older Danish men and women.MethodsMultivariate linear regression models with combined exposure variables using generalised estimating equations were performed using four waves of data on 2874 individuals without mobility limitations at baseline from The Danish Intervention Study on Preventive Home Visits.ResultsLow socioeconomic position and mobility-related fatigue are risk factors for mobility limitations in old age. The combined exposure to both factors additionally increased the risk, but there was no synergy effect between the two. Notably, fatigue predicted mobility decline at 3-year follow-up among those aged 80 years at baseline with a mean difference in number of mobility limitations from the joint reference category (high socioeconomic position and no fatigue) of −0.52, p<0.0001 among those in high socioeconomic position and −0.96, p<0.0001 among those in low socioeconomic position.ConclusionsMobility-related fatigue is not a significantly stronger risk factor for subsequent mobility limitations among those with concomitant exposure to low socioeconomic position, compared with those with high socioeconomic position. Preventive strategies must focus on vulnerable groups of older people with low socioeconomic position as well as on individuals with fatigue.
Fight like a ferret: a novel approach of using art therapy to reduce anxiety in stroke patients undergoing hospital rehabilitation
Authors: Ali Khalid , Gammidge Tony , Waller Diane 
Published: January 2014

RationaleThe holistic aspect of stroke rehabilitation to include psychological well-being is currently neglected, with more emphasis placed on physical recovery despite anxiety and depression being common poststroke. From the limited amount of current literature, it seems that creative strategies such as art therapy (AT) can be beneficial in reducing isolation and anxiety among stroke patients.MethodsStroke patients (able to consent) in a hospital rehabilitation unit were invited to participate in two weekly AT sessions for 6 weeks, facilitated by an art psychotherapist using paints, crayons, clay, a camera and an iPad. Hospital anxiety and depression scales (HAD) and therapy outcome measures (TOM) were measured at the beginning and end of the study.ResultsSix male patients were recruited, average age 69 years (38–85). Group discussions allowed patients to express openly feelings of frustration as well as hope for physical and emotional recovery: ‘fight like a ferret’, an expression used by a group member. The group produced several art objects and photographic images that were collated using stop-frame animation to produce a 10 min film. Median HAD score for the group was eight points upon entering the study and six points on finishing the study.Key conclusionsThere is little attention to the emotional needs of stroke patients in rehabilitation. Properly designed research studies exploring the role of AT in addressing anxiety and depression poststroke are needed. Our study showed that AT was a feasible intervention that helped patients explore the sequel of stroke in an open supportive environment.
Palaeohurricane reconstructions from sedimentary archives along the Gulf of Mexico, Caribbean Sea and western North Atlantic Ocean margins
Authors: Wallace Davin J. , Woodruff Jonathan D. , Anderson John B. , Donnelly Jeffrey P. 
Published: January 2014

Abstract
Hurricanes annually threaten the Atlantic Ocean margins. Historical hurricane records are relatively short and palaeohurricane sedimentary archives provide a geological and climatic context that sheds light on future hurricane activity. Here we review palaeo-trends in hurricane activity elucidated from sedimentary archives. We discuss dating methods, site selection and statistics associated with previously published records. These archives have been useful for understanding the long-term evolution of coastal systems and the response of intense hurricane activity to climatic changes. Regional shifts in hurricane overwash on centennial to millennial timescales have been linked to various climatic modes of variability, including El Niño/Southern Oscillation and the North Atlantic Oscillation, but could also reflect regional-scale controls on hurricane activity.
Immunoglobulin Fc Domain Fusion to TRAIL Significantly Prolongs Its Plasma Half-Life and Enhances Its Antitumor Activity
Authors: Wang Haizhen , Davis Jennifer S. , Wu Xiangwei 
Published: January 2014

Abstract
TRAIL (Apo2L) is a potent inducer of cell death. Interest in TRAIL has increased, following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and when grown as xenografts. Therefore, TRAIL has been proposed as a promising anticancer agent and currently is being tested in clinical trials. However, recombinant TRAIL has a very short plasma half-life, which limits its therapeutic potential. To overcome this limitation, we investigated the ability of the human IgG1 fragment crystallizable region (Fc) to enhance TRAIL stability. In this report, we show that Fc-TRAIL chimeric protein displays higher specific activity in vitro and a significantly longer half-life in mice than recombinant human TRAIL (rh-TRAIL). No short-term toxicity, especially liver toxicity, was observed. More importantly, Fc-TRAIL was much more effective in inhibiting tumor growth in a xenograft tumor model compared with rh-TRAIL. Our data suggest that fusion of Fc to TRAIL is able to improve the bioavailability and activity of TRAIL both in vitro and in vivo, and Fc-TRAIL may be explored for future clinical applications in cancer treatment and prevention. Mol Cancer Ther; 13(3); 643–50. ©2014 AACR.
Synuclein γ Compromises Spindle Assembly Checkpoint and Renders Resistance to Antimicrotubule Drugs
Authors: Miao Suyu , Wu Kejin , Zhang Bo , Weng Ziyi , Zhu Mingjie , Lu Yunshu , Krishna Ramadas , Shi Yuenian Eric 
Published: January 2014

AbstractDefects in the spindle assembly checkpoint (SAC) have been proposed to contribute to the chromosomal instability in human cancers. One of the major mechanisms underlying antimicrotubule drug (AMD) resistance involves acquired inactivation of SAC. Synuclein γ (SNCG), previously identified as a breast cancer–specific gene, is highly expressed in malignant cancer cells but not in normal epithelium. Here, we show that SNCG is sufficient to induce resistance to AMD-caused apoptosis in breast cancer cells and cancer xenografts. SNCG binds to spindle checkpoint kinase BubR1 and inhibits its kinase activity. Specifically, the C-terminal (Gln106-Asp127) of SNCG binds to the N-terminal TPR (tetratricopeptidelike folds) motif of BubR1. SNCG–BubR1 interaction induces a structure change of BubR1, attenuates its interaction with other key checkpoint proteins of Cdc20, and thus compromises SAC function. SNCG expression in breast cancers from patients with a neoadjuvant clinical trial showed that SNCG-positive tumors are resistant to chemotherapy-induced apoptosis. These data show that SNCG renders AMD resistance by inhibiting BubR1 activity and attenuating SAC function. Mol Cancer Ther; 13(3); 699–713. ©2014 AACR.
JAK2 Expression Is Associated with Tumor-Infiltrating Lymphocytes and Improved Breast Cancer Outcomes: Implications for Evaluating JAK2 Inhibitors
Authors: Miller Chris P. , Thorpe Jason D. , Kortum Amanda N. , Coy Catherine M. , Cheng Wei-Yi , Yang Tai-Hsien Ou , Anastassiou Dimitris , Beatty J. David , Urban Nicole D. , Blau C. Anthony 
Published: January 2014

Abstract
Janus kinase-2 (JAK2) supports breast cancer growth, and clinical trials testing JAK2 inhibitors are under way. In addition to the tumor epithelium, JAK2 is also expressed in other tissues including immune cells; whether the JAK2 mRNA levels in breast tumors correlate with outcomes has not been evaluated. Using a case–control design, JAK2 mRNA was measured in 223 archived breast tumors and associations with distant recurrence were evaluated by logistic regression. The frequency of correct pairwise comparisons of patient rankings based on JAK2 levels versus survival outcomes, the concordance index (CI), was evaluated using data from 2,460 patients in three cohorts. In the case–control study, increased JAK2 was associated with a decreasing risk of recurrence (multivariate P = 0.003, n = 223). Similarly, JAK2 was associated with a protective CI (&lt;0.5) in the public cohorts: NETHERLANDS CI = 0.376, n = 295; METABRIC CI = 0.462, n = 1,981; OSLOVAL CI = 0.452, n = 184. Furthermore, JAK2 was strongly correlated with the favorable prognosis LYM metagene signature for infiltrating T cells (r = 0.5; P &lt; 2 × 10−16; n = 1,981) and with severe lymphocyte infiltration (P = 0.00003, n = 156). Moreover, the JAK1/2 inhibitor ruxolitinib potently inhibited the anti-CD3–dependent production of IFN-γ, a marker of the differentiation of Th cells along the tumor-inhibitory Th1 pathway. The potential for JAK2 inhibitors to interfere with the antitumor capacities of T cells should be evaluated. Cancer Immunol Res; 2(4); 301–6. ©2014 AACR.
Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support
Authors: Yang Kai-Chien , Yamada Kathryn A. , Patel Akshar Y. , Topkara Veli K. , George Isaac , Cheema Faisal H. , Ewald Gregory A. , Mann Douglas L. , Nerbonne Jeanne M. 
Published: January 2014

Background—
Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD).

Methods and Results—

Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that
cis
-gene regulation represents a major mechanism of action of human cardiac lncRNAs.

Conclusions—
The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.
A new species of Nemacerota Hampson, [1893] (Lepidoptera, Thyatiridae) from Tibet, China
Authors: PAN ZHAO-HUI , RONKAY GÁBOR , RONKAY LÁSZLÓ , HAN HUI-LIN 
Published: January 2014

The genus Nemacerota Hampson, [1893] includes 14 species worldwide, which are mainly distributed from Pakistan along the main Himalayan chain, the eastern frontier of the Tibetan plateau and the Central Chinese mountains to the northern Pacific regions. Ten species have been recorded from China. Among them, only N. tancrei (Graeser, 1888) occurs in NE China, whereas all other taxa inhabit mountainous areas in Central China, the eastern frontier of the Tibetan plateau or Tibet. N. igorkostjuki Laszlo, Ronkay, Ronkay & Witt, 2007 is found only in the southern edge of Tibet (Nyalam = Nielamu); N. mandibulata Laszlo, Ronkay, Ronkay & Witt, 2007, N. taurina Laszlo, Ronkay, Ronkay & Witt, 2007, N. stueningi Laszlo, Ronkay, Ronkay & Witt, 2007, N. pectinata (Houlbert, 1921), N. inouei Laszlo, Ronkay, Ronkay & Witt, 2007 and N. owadai Laszlo, Ronkay, Ronkay & Witt, 2007 are known from Mt. Taibaishan, Shaanxi Province; N. griseobasalis (Sick, 1941), N. decorata (Sick, 1941) and N. pectinata (Houlbert, 1921) occur in the northwestern parts of Yunnan Province (and, possibly, also in southern Sichuan). Here we describe a new species from the Linzhi area, Autonomous Region Xizang (Tibet), China. Specimens were dissected and examined using standard methods; adult photographs were photographed with a Nikon D700; genitalic slides were photographed using the Qcapture pro system, and processed in Adobe Photoshop CS5 software.
Variations of the North Pacific Subtropical Mode Water from Direct Observations
Authors: Rainville Luc , Jayne Steven R. , Cronin Meghan F. 
Published: January 2014

Abstract
Mooring measurements from the Kuroshio Extension System Study (June 2004–June 2006) and from the ongoing Kuroshio Extension Observatory (June 2004–present) are combined with float measurements of the Argo network to study the variability of the North Pacific Subtropical Mode Water (STMW) across the entire gyre, on time scales from days, to seasons, to a decade. The top of the STMW follows a seasonal cycle, although observations reveal that it primarily varies in discrete steps associated with episodic wind events. The variations of the STMW bottom depth are tightly related to the sea surface height (SSH), reflecting mesoscale eddies and large-scale variations of the Kuroshio Extension and recirculation gyre systems. Using the observed relationship between SSH and STMW, gridded SSH products and in situ estimates from floats are used to construct weekly maps of STMW thickness, providing nonbiased estimates of STMW total volume, annual formation and erosion volumes, and seasonal and interannual variability for the past decade. Year-to-year variations are detected, particularly a significant decrease of STMW volume in 2007–10 primarily attributable to a smaller volume formed. Variability of the heat content in the mode water region is dominated by the seasonal cycle and mesoscale eddies; there is only a weak link to STMW on interannual time scales, and no long-term trends in heat content and STMW thickness between 2002 and 2011 are detected. Weak lagged correlations among air–sea fluxes, oceanic heat content, and STMW thickness are found when averaged over the northwestern Pacific recirculation gyre region.
Millennial Variability in an Idealized Ocean Model: Predicting the AMOC Regime Shifts
Authors: Sévellec Florian , Fedorov Alexey V. 
Published: January 2014

AbstractA salient feature of paleorecords of the last glacial interval in the North Atlantic is pronounced millennial variability, commonly known as Dansgaard–Oeschger events. It is believed that these events are related to variations in the Atlantic meridional overturning circulation and heat transport. Here, the authors formulate a new low-order model, based on the Howard–Malkus loop representation of ocean circulation, capable of reproducing millennial variability and its chaotic dynamics realistically. It is shown that even in this chaotic model changes in the state of the meridional overturning circulation are predictable. Accordingly, the authors define two predictive indices which give accurate predictions for the time the circulation should remain in the on phase and then stay in the subsequent off phase. These indices depend mainly on ocean stratification and describe the linear growth of small perturbations in the system. Thus, monitoring particular indices of the ocean state could help predict a potential shutdown of the overturning circulation.
Influence of Kuroshio Path Variation South of Japan on Formation of Subtropical Mode Water
Authors: Sugimoto Shusaku , Hanawa Kimio 
Published: January 2014

Abstract
Distributions of subtropical mode water (STMW) in the northwestern part of the North Pacific Subtropical Gyre were investigated, using temperature–salinity profiles from 2005 to 2011, with particular reference to the Kuroshio meander and non-meander path states, south of Japan. In spring of meander years, warm STMW with a potential temperature of 19°–20°C (potential density anomaly of 24.6–24.9 kg m−3) was found in the Shikoku Basin, whereas cold STMW below 19°C was distributed throughout the southern region of Japan in non-meander years. The warm STMW was formed in a spatially isolated and warm winter mixed layer (ML) in the Shikoku Basin, where a local recirculation developed in association with the Kuroshio meander path; both the absence of horizontal mixing with a cold ML south of the Kuroshio Extension because of the spatially isolated ML and an increase in horizontal heat advection due to the westward flow associated with this local recirculation caused the ML warming in the Shikoku Basin. After the spring shoaling of the ML, the warm STMW was preserved under the seasonal pycnocline until midsummer at a depth of 100–250 dbar; its thickness was approximately half that of the cold STMW in the Shikoku Basin in non-meander years. The warm STMW was rapidly eroded between the late summer and the following winter.