bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging Role of PML Nuclear Bodies in Innate Immune Signaling
Authors: Scherer Myriam , Stamminger Thomas 
Published: April 2016

ABSTRACT
Research in the last 2 decades has demonstrated that a specific organelle of the cell nucleus, termed PML nuclear body (PML-NB) or nuclear domain 10 (ND10), is frequently modified during viral infection. This correlates with antagonization of a direct repressive function of individual PML-NB components, such as the PML, hDaxx, Sp100, or ATRX protein, that are able to act as cellular restriction factors. Recent studies now reveal an emerging role of PML-NBs as coregulatory structures of both type I and type II interferon responses. This emphasizes that targeting of PML-NBs by viral regulatory proteins has evolved as a strategy to compromise intrinsic antiviral defense and innate immune responses.
T-wave inversions on ECG as primary manifestation of Hashimoto's disease
Authors: Araque Katherine A , Smith Michael J , Walsh Brooks M 
Published: April 2016

A middle-aged Hispanic woman presented to the emergency department (ED) reporting of acute new onset pressure-like chest pain developed at rest. It was radiated to the right arm and associated with malaise. Initial ECG demonstrated T-wave inversions (TWIs) in all anterior and lateral leads. Electrolytes, serial cardiac troponin and D-dimer were all normal. Comprehensive transthoracic echocardiogram and nuclear stress test did not reveal a cardiac cause of her symptoms.Serum thyroid-stimulating hormone was markedly elevated (207 mIU/L) and free thyroxine was low (FT4 0.07 ng/dL), consistent with severe primary hypothyroidism. Thyroperoxidase (TPO) antibodies were positive. Therapy with levothyroxine was started. No other cause of the TWIs was identified. A repeat ECG obtained 8 weeks later showed partial resolution of the TWIs. Our observations indicate that Hashimoto’s disease is the most likely primary cause of this patient's extensive and profound TWI, which improved after thyroid replacement therapy.
‘Physical Activity 4 Everyone’ school-based intervention to prevent decline in adolescent physical activity levels: 12 month (mid-intervention) report on a cluster randomised trial
Authors: Sutherland Rachel , Campbell Elizabeth , Lubans David R , Morgan Philip J , Okely Anthony D , Nathan Nicole , Wolfenden Luke , Wiese Jarrod , Gillham Karen , Hollis Jenna , Wiggers John 
Published: April 2016

BackgroundAdolescence is a recognised period of physical activity decline, particularly among low-income communities. We report the 12-month (midpoint) effects of a 2-year multicomponent physical activity intervention implemented in disadvantaged secondary schools.MethodsA cluster randomised trial was undertaken in 10 secondary schools located in disadvantaged areas in New South Wales, Australia. Students in Grade 7 were recruited, with follow-up in Grade 8. The intervention was guided by socioecological theory and included seven physical activity strategies, and six implementation adoption strategies. The primary outcome was mean minutes of moderate-to-vigorous physical activity (MVPA) per day assessed using Actigraph GT3X accelerometers. Outcome data were analysed using repeated measures linear mixed models.ResultsAt baseline, 1150 (93%) students participated in the data collection (mean age 12 years, 48% boys) and 1050 (79%) students participated at 12-month follow-up. By the 12-month follow-up, the six implementation adoption strategies had been used to support schools to deliver four of the seven physical activity elements. There was a significant group-by-time interaction for mean minutes of MVPA per day in favour of the intervention group (adjusted difference between groups at follow-up=3.85 min, 95% CI (0.79 to 6.91), p≤0.01), including significantly more vigorous physical activity (2.45 min, p≤0.01), equating to 27 min more MVPA per week.SummaryAt 12-month follow-up, the intervention had reduced the decline in physical activity among adolescents from disadvantaged schools. The intervention may assist students to meet physical activity guidelines.
NAP SACC UK: protocol for a feasibility cluster randomised controlled trial in nurseries and at home to increase physical activity and healthy eating in children aged 2–4 years
Authors: Kipping R , Jago R , Metcalfe C , White J , Papadaki A , Campbell R , Hollingworth W , Ward D , Wells S , Brockman R , Nicholson A , Moore L 
Published: April 2016

IntroductionSystematic reviews have identified the lack of intervention studies with young children to prevent obesity. This feasibility study examines the feasibility and acceptability of adapting the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) intervention in the UK to inform a full-scale trial.Methods and analysisA feasibility cluster randomised controlled trial in 12 nurseries in England, with 6 randomly assigned to the adapted NAP SACC UK intervention: nursery staff will receive training and support from an NAP SACC UK Partner to review the nursery environment (nutrition, physical activity, sedentary behaviours and oral health) and set goals for making changes. Parents will be invited to participate in a digital media-based home component to set goals for making changes in the home. As this is a feasibility study, the sample size was not based on a power calculation but will indicate the likely response rates and intracluster correlations. Measures will be assessed at baseline and 8–10 months later. We will estimate the recruitment rate of nurseries and children and adherence to the intervention and data. Nursery measurements will include the Environmental Policy Assessment and Observation score and the nursery staff's review of the nursery environment. Child measurements will include height and weight to calculate z-score body mass index (zBMI), accelerometer-determined minutes of moderate-to-vigorous physical activity per day and sedentary time, and diet using the Child and Diet Evaluation Tool. Questionnaires with nursery staff and parents will measure mediators. A process evaluation will assess fidelity of intervention delivery and views of participants.Ethics and disseminationEthical approval for this study was given by Wales 3 NHS Research Ethics Committee. Findings will be made available through publication in peer-reviewed journals, at conferences and to participants via the University of Bristol website. Data will be available from the University of Bristol Research Data Repository.Trial registration numberISRCTN16287377.
Stress and anxiety management strategies in health professions' simulation training: a review of the literature
Authors: Ignacio Jeanette , Dolmans Diana , Scherpbier Albert , Rethans Jan-Joost , Chan Sally , Liaw Sok Ying 
Published: April 2016

IntroductionSimulation training has been used to teach clinical skills to health profession trainees. Stress and/or anxiety occur in high-acuity scenarios in the clinical environment, and affect clinician performance and patient outcomes. To date, strategies that have been used in conjunction with simulation training for healthcare professionals that address stress management are limited. This paper reports a literature review conducted to explore strategies used with simulations to enhance the ability of health profession trainees in reducing acute stress and/or anxiety during high-acuity clinical events.MethodsDatabases searched included Scopus, PubMed, CINAHL, Web of Knowledge and Science Direct. The examples of the literature chosen were those published in the English language from January 2005 to March 2015, and were peer-reviewed empirical papers that focused on the strategies addressing stress and/or anxiety during simulation training for healthcare profession trainees.ResultsEight studies using various forms of stress/anxiety management strategies with simulations demonstrated varying degrees of effectiveness. Themes that emerged from these eight studies were excessive stress and clinical performance in simulation, emotional training strategies in simulation, and factors contributing to stress and anxiety reduction during simulation.ConclusionsExcessive stress and/or anxiety in the clinical setting have been shown to affect performance and could compromise patient outcomes. Health profession training curricula might benefit from a stress/anxiety reduction strategy integrated into the simulation programmes. This review showed that the stress/anxiety management strategies that have been used with simulations, mostly in surgical training, have various degrees of effectiveness.
Lenalidomide Stabilizes the Erythropoietin Receptor by Inhibiting the E3 Ubiquitin Ligase RNF41
Authors: Basiorka Ashley A. , McGraw Kathy L. , De Ceuninck Leentje , Griner Lori N. , Zhang Ling , Clark Justine A. , Caceres Gisela , Sokol Lubomir , Komrokji Rami S. , Reuther Gary W. , Wei Sheng , Tavernier Jan , List Alan F. 
Published: April 2016

Abstract
In a subset of patients with non-del(5q) myelodysplastic syndrome (MDS), lenalidomide promotes erythroid lineage competence and effective erythropoiesis. To determine the mechanism by which lenalidomide promotes erythropoiesis, we investigated its action on erythropoietin receptor (EpoR) cellular dynamics. Lenalidomide upregulated expression and stability of JAK2-associated EpoR in UT7 erythroid cells and primary CD71+ erythroid progenitors. The effects of lenalidomide on receptor turnover were Type I cytokine receptor specific, as evidenced by coregulation of the IL3-Rα receptor but not c-Kit. To elucidate this mechanism, we investigated the effects of lenalidomide on the E3 ubiquitin ligase RNF41. Lenalidomide promoted EpoR/RNF41 association and inhibited RNF41 auto-ubiquitination, accompanied by a reduction in EpoR ubiquitination. To confirm that RNF41 is the principal target responsible for EpoR stabilization, HEK293T cells were transfected with EpoR and/or RNF41 gene expression vectors. Steady-state EpoR expression was reduced in EpoR/RNF41 cells, whereas EpoR upregulation by lenalidomide was abrogated, indicating that cellular RNF41 is a critical determinant of drug-induced receptor modulation. Notably, shRNA suppression of CRBN gene expression failed to alter EpoR upregulation, indicating that drug-induced receptor modulation is independent of cereblon. Immunohistochemical staining showed that RNF41 expression decreased in primary erythroid cells of lenalidomide-responding patients, suggesting that cellular RNF41 expression merits investigation as a biomarker for lenalidomide response. Our findings indicate that lenalidomide has E3 ubiquitin ligase inhibitory effects that extend to RNF41 and that inhibition of RNF41 auto-ubiquitination promotes membrane accumulation of signaling competent JAK2/EpoR complexes that augment Epo responsiveness. Cancer Res; 76(12); 3531–40. ©2016 AACR.
Loss of Tet1-Associated 5-Hydroxymethylcytosine Is Concomitant with Aberrant Promoter Hypermethylation in Liver Cancer
Authors: Thomson John P. , Ottaviano Raffaele , Unterberger Elif B. , Lempiäinen Harri , Muller Arne , Terranova Remi , Illingworth Robert S. , Webb Shaun , Kerr Alastair R.W. , Lyall Marcus J. , Drake Amanda J. , Wolf C. Roland , Moggs Jonathan G. , Schwarz Michael , Meehan Richard R. 
Published: April 2016

Abstract
Aberrant hypermethylation of CpG islands (CGI) in human tumors occurs predominantly at repressed genes in the host tissue, but the preceding events driving this phenomenon are poorly understood. In this study, we temporally tracked epigenetic and transcriptomic perturbations that occur in a mouse model of liver carcinogenesis. Hypermethylated CGI events in the model were predicted by enrichment of the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone H3 modification H3K27me3 at silenced promoters in the host tissue. During cancer progression, selected CGIs underwent hypo-hydroxymethylation prior to hypermethylation, while retaining H3K27me3. In livers from mice deficient in Tet1, a tumor suppressor involved in cytosine demethylation, we observed a similar loss of promoter core 5hmC, suggesting that reduced Tet1 activity at CGI may contribute to epigenetic dysregulation during hepatocarcinogenesis. Consistent with this possibility, mouse liver tumors exhibited reduced Tet1 protein levels. Similar to humans, DNA methylation changes at CGI in mice did not appear to be direct drivers of hepatocellular carcinoma progression, rather, dynamic changes in H3K27me3 promoter deposition correlated strongly with tumor-specific activation and repression of transcription. Overall, our results suggest that loss of promoter-associated 5hmC in liver tumors licenses reprograming of DNA methylation at silent CGI during progression. Cancer Res; 76(10); 3097–108. ©2016 AACR.
Evidence-Based Policy Making: Assessment of the American Heart Association’s Strategic Policy Portfolio
Authors: Labarthe Darwin R. , Goldstein Larry B. , Antman Elliott M. , Arnett Donna K. , Fonarow Gregg C. , Alberts Mark J. , Hayman Laura L. , Khera Amit , Sallis James F. , Daniels Stephen R. , Sacco Ralph L. , Li Suhui , Ku Leighton , Lantz Paula M. , Robinson Jennifer G. , Creager Mark A. , Van Horn Linda , Kris-Etherton Penny , Bhatnagar Aruni , Whitsel Laurie P. 
Published: April 2016

Background—
American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA’s policies to determine how well they address the association’s 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development.

Methods and Results—
The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust evidence base. For CVH metrics, the distinction between policies for adults (age ≥20 years) and children (<20 years) was often not considered, although policy approaches may differ importantly by age. Inclusion of all those <20 years of age as a single group also ignores important differences in policy needs for infants, children, adolescents, and young adults. For CVD management indicators, specific quantitative targets analogous to criteria for ideal, intermediate, and poor CVH are lacking but needed to assess progress toward the 2020 goal to reduce deaths from CVDs and stroke. New research in support of current policies needs to focus on the evaluation of their translation and implementation through expanded application of implementation science. Focused basic, clinical, and population research is required to expand and strengthen the evidence base for the development of new policies. Evaluation of the impact of targeted improvements in population health through strengthened surveillance of CVD and stroke events, determination of the cost-effectiveness of policy interventions, and measurement of the extent to which vulnerable populations are reached must be assessed for all policies. Additional attention should be paid to the social determinants of health outcomes.

Conclusions—
AHA’s public policies are generally robust and well aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy development to fill gaps, overarching research strategies, and topic-specific priority areas are proposed.
Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy
Authors: Cannon John E. , Su Li , Kiely David G. , Page Kathleen , Toshner Mark , Swietlik Emilia , Treacy Carmen , Ponnaberanam Anie , Condliffe Robin , Sheares Karen , Taboada Dolores , Dunning John , Tsui Steven , Ng Choo , Gopalan Deepa , Screaton Nicholas , Elliot Charlie , Gibbs Simon , Howard Luke , Corris Paul , Lordan James , Johnson Martin , Peacock Andrew , MacKenzie-Ross Robert , Schreiber Benji , Coghlan Gerry , Dimopoulos Kostas , Wort Stephen J. , Gaine Sean , Moledina Shahin , Jenkins David P. , Pepke-Zaba Joanna 
Published: April 2016

Background—
Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA.

Methods and Results—

Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s
−1
·cm
−5
at reassessment correlated with worse long-term survival.

Conclusions—
Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.
Prasugrel, a Platelet P2Y
12
Receptor Antagonist, Improves Abnormal Gait in a Novel Murine Model of Thrombotic Hindlimb Ischemia
Authors: Ohno Kousaku , Tomizawa Atsuyuki , Mizuno Makoto , Jakubowski Joseph A. , Sugidachi Atsuhiro 
Published: April 2016

Background

The efficacy of P2Y
12
inhibition for the prevention of cardiovascular events in patients with peripheral arterial disease (
PAD
) has been established. However, the therapeutic effects on ischemic limb complications are less clear. Accordingly, we aimed to develop a novel murine model of thrombotic hindlimb ischemia to reflect that found in patients with
PAD
exhibiting ischemic limb symptoms. We further investigated the effects of P2Y
12
deficiency and P2Y
12
inhibition by prasugrel in this model.

Methods and Results

Thrombus formation induced by application of ferric chloride to the femoral artery resulted in a significant reduction in blood flow in the injured limb. In gait analysis using the CatWalk system, moderate difficulties in grounding and weight bearing of the ischemic limb, including reduction of maximum contact area and stance phase duration and increasing in swing phase duration in the ischemic limb, were observed in this model. Blood flow reduction and gait abnormalities gradually recovered over 21 days to levels present before arterial injury. Compared to wild‐type (
WT
) mice, significant increases in blood flow and improvement in gait were observed in P2Y
12
‐deficient mice. In addition, daily oral administration of prasugrel (3 mg/kg per day) to
WT
mice resulted in significant inhibition of blood flow reduction and gait abnormalities to levels found in P2Y
12
deficient mice.

Conclusions

Acute femoral artery thrombosis resulted in hindlimb ischemia and moderate gait abnormalities in mice. In addition, the present study suggests a possible role of P2Y
12
in the complications with thrombotic limb ischemia.
Effects of Restoration of Blood Flow on the Development of Aortic Atherosclerosis in ApoE
−/−
Mice With Unilateral Renal Artery Stenosis
Authors: Pathak Alokkumar S. , Huang Jianhua , Rojas Mauricio , Bazemore Taylor C. , Zhou Ruihai , Stouffer George A. 
Published: April 2016

Background

Chronic unilateral renal artery stenosis (
RAS
) causes accelerated atherosclerosis in apolipoprotein E–deficient (ApoE
−/−
) mice, but effects of restoration of renal blood flow on aortic atherosclerosis are unknown.

Methods and Results

Male ApoE
−/−
mice underwent sham surgery (n=16) or had partial ligation of the right renal artery (n=41) with the ligature being removed 4 days later (D4
LR
; n=6), 8 days later (D8
LR
; n=11), or left in place for 90 days (chronic
RAS
; n=24). Ligature removal at 4 or 8 days resulted in improved renal blood flow, decreased plasma angiotensin
II
levels, a return of systolic blood pressure to baseline, and increased plasma levels of neutrophil gelatinase associated lipocalin. Chronic
RAS
resulted in increased lipid staining in the aortic arch (33.2% [24.4, 47.5] vs 11.6% [6.1, 14.2];
P
<0.05) and descending thoracic aorta (10.2% [6.4, 25.9] vs 4.9% [2.8, 7.8];
P
<0.05), compared to sham surgery. There was an increased amount of aortic arch lipid staining in the D8
LR
group (22.7% [22.1, 32.7]), compared to sham‐surgery, but less than observed with chronic
RAS
. Lipid staining in the aortic arch was not increased in the D4
LR
group, and lipid staining in the descending aorta was not increased in either the D8
LR
or D4
LR
groups. There was less macrophage expression in infrarenal aortic atheroma in the D4
LR
and D8
LR
groups compared to the chronic
RAS
group.

Conclusions

Restoration of renal blood flow at either 4 or 8 days after unilateral
RAS
had a beneficial effect on systolic blood pressure, aortic lipid deposition, and atheroma inflammation.
Does Transcranial Direct Current Stimulation Improve Healthy Working Memory?: A Meta-analytic Review
Authors: Mancuso Lauren E. , Ilieva Irena P. , Hamilton Roy H. , Farah Martha J. 
Published: April 2016

Abstract
Transcranial direct current stimulation (tDCS) has been reported to improve working memory (WM) performance in healthy individuals, suggesting its value as a means of cognitive enhancement. However, recent meta-analyses concluded that tDCS has little or no effect on WM in healthy participants. In this article, we review reasons why these meta-analyses may have underestimated the effect of tDCS on WM and report a more comprehensive and arguably more sensitive meta-analysis. Consistent with our interest in enhancement, we focused on anodal stimulation. Thirty-one articles matched inclusion criteria and were included in four primary meta-analyses assessing the WM effects of anodal stimulation over the left and right dorsolateral pFC (DLPFC) and right parietal lobe as well as left DLPFC stimulation coupled with WM training. These analyses revealed a small but significant effect of left DLPFC stimulation coupled with WM training. Left DLPFC stimulation alone also enhanced WM performance, but the effect was reduced to nonsignificance after correction for publication bias. No other effects were significant, including a variety of tested moderators. Additional meta-analyses were undertaken with study selection criteria based on previous meta-analyses, to reassess the findings from these studies using the analytic methods of this study. These analyses revealed a mix of significant and nonsignificant small effects. We conclude that the primary WM enhancement potential of tDCS probably lies in its use during training.