bluuebunny/crossref_metadata_2025_split huggingface dataset:
A UK survey of rehabilitation following critical illness: implementation of NICE Clinical Guidance 83 (CG83) following hospital discharge
Authors: Connolly Bronwen , Douiri A , Steier J , Moxham J , Denehy L , Hart N 
Published: May 2014

ObjectiveTo determine the implementation of National Institute for Health and Care Excellence guidance (NICE CG83) for posthospital discharge critical illness follow-up and rehabilitation programmes.DesignClosed-question postal survey.SettingAdult intensive care units (ICUs) across the UK, identified from national databases of organisations. Specialist-only and private ICUs were not included.ParticipantsSenior respiratory critical care physiotherapy clinicians.ResultsA representative sample of 182 surveys was returned from the 240 distributed (75.8% (95% CI 70.4 to 81.2)). Only 48 organisations (27.3% (95% CI 20.7 to 33.9)) offered a follow-up service 2–3 months following hospital discharge, the majority (n=39, 84.8%) in clinic format. 12 organisations reported posthospital discharge rehabilitation programmes (6.8% (95% CI 3.1 to 10.5)), albeit only 10 of these operated on a regular basis. Lack of funding was reported as the most frequent (n=149/164, 90%) and main barrier (n=99/156, 63.5%) to providing services. Insufficient resources (n=71/164, 43.3%) and lack of priority by the clinical management team (n=66/164, 40.2%) were also highly cited barriers to service delivery.ConclusionsNICE CG83 has been successful in profiling the importance of rehabilitation for survivors of critical illness. However, 4 years following publication of CG83 there has been limited development of this clinical service across the UK. Strategies to support delivery of such quality improvement programmes are urgently required to enhance patient care.
The effect of information about overdetection of breast cancer on women's decision-making about mammography screening: study protocol for a randomised controlled trial
Authors: Hersch Jolyn , Barratt Alexandra , Jansen Jesse , Houssami Nehmat , Irwig Les , Jacklyn Gemma , Dhillon Haryana , Thornton Hazel , McGeechan Kevin , Howard Kirsten , McCaffery Kirsten 
Published: May 2014

IntroductionWomen are largely unaware that mammography screening can cause overdetection of inconsequential disease, leading to overdiagnosis and overtreatment of breast cancer. Evidence is lacking about how information on overdetection affects women's breast screening decisions and experiences. This study investigates the consequences of providing information about overdetection of breast cancer to women approaching the age of invitation to mammography screening.Methods and analysisThis is a randomised controlled trial with an embedded longitudinal qualitative substudy. Participants are a community sample of women aged 48–50 in New South Wales, Australia, recruited in 2014. Women are randomly allocated to either quantitative only follow-up (n=904) or additional qualitative follow-up (n=66). Women in each stream are then randomised to receive either the intervention (evidence-based information booklet including overdetection, breast cancer mortality reduction and false positives) or a control information booklet (including mortality reduction and false positives only). The primary outcome is informed choice about breast screening (adequate knowledge, and consistency between attitudes and intentions) assessed via telephone interview at 2 weeks postintervention. Secondary outcomes measured at this time include decision process (decisional conflict and confidence) and psychosocial outcomes (anticipated regret, anxiety, breast cancer worry and perceived risk). Women are further followed up at 6 months, 1 and 2 years to assess self-reported screening behaviour and long-term psychosocial outcomes (decision regret, quality of life). Participants in the qualitative stream undergo additional in-depth interviews at each time point to explore the views and experiences of women who do and do not choose to have screening.Ethics and disseminationThe study has ethical approval, and results will be published in peer-reviewed journals. This research will help ensure that information about overdetection may be communicated clearly and effectively, using an evidence-based approach, to women considering breast cancer screening.Trial registration numberAustralian New Zealand Clinical Trials Registry ACTRN12613001035718.
Measuring hydraulic conductivity and swelling pressure under high hydraulic gradients
Authors: Hausmannova Lucie , Vasicek Radek 
Published: May 2014

Abstract
The concept of a deep geological repository for high-level waste in the Czech Republic is based on disposal in a granite environment. The construction of an engineered barrier between the rock and canister is considered, and compacted swelling clay (bentonite) is chosen as the most suitable material for such a barrier. The most important geotechnical properties of bentonite in this context are low hydraulic conductivity and high swelling pressure. Measuring these parameters in such a low-permeable material requires much time. This study focuses on combined measurements of hydraulic conductivity and swelling pressure and on the impact of using high hydraulic gradients that are consistent with possible porewater pressures in a deep repository. High hydraulic gradients may also quicken the determination of these parameters. Results show a decrease in hydraulic conductivity with increasing saturation pressure up to a threshold dry density, with no further change at higher dry densities. The influence of saturation pressure on measured pressure decreases with dry density until a certain value is reached. For samples with lower density, the slope of the increase is close to unity.
Slug Promotes Survival during Metastasis through Suppression of Puma-Mediated Apoptosis
Authors: Kim Seaho , Yao Jiahong , Suyama Kimita , Qian Xia , Qian Bin-Zhi , Bandyopadhyay Sanmay , Loudig Olivier , De Leon-Rodriguez Carlos , Zhou Zhen Ni , Segall Jeffrey , Macian Fernando , Norton Larry , Hazan Rachel B. 
Published: May 2014

Abstract
Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here, we show in the Polyoma Middle T mammary tumor model that N-cadherin (Cdh2) expression causes Slug (Snai2) upregulation, which in turn promotes carcinoma cell survival. Slug was dramatically upregulated in metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in carcinoma cells suppressed lung colonization by decreasing cell survival at metastatic sites, but had no effect on tumor cell invasion or extravasation. In support of this idea, Slug inhibition by shRNA sensitized tumor cells to apoptosis by DNA damage, resulting in caspase-3 and PARP cleavage. The prosurvival effect of Slug was found to be caused by direct repression of the proapoptotic gene, Puma (Bbc3), by Slug. Consistent with a pivotal role for a Slug–Puma axis in metastasis, inhibition of Puma by RNA interference in Slug-knockdown cells rescued lung colonization, whereas Puma overexpression in control tumor cells suppressed lung metastasis. The survival function of the Slug–Puma axis was confirmed in human breast cancer cells, where Slug knockdown increased Puma expression and inhibited lung colonization. This study demonstrates a pivotal role for Slug in carcinoma cell survival, implying that disruption of the Slug–Puma axis may impinge on the survival of metastatic cells. Cancer Res; 74(14); 3695–706. ©2014 AACR.
Autophagy Inhibition by Sustained Overproduction of IL6 Contributes to Arsenic Carcinogenesis
Authors: Qi Yuanlin , Zhang Mingfang , Li Hui , Frank Jacqueline A. , Dai Lu , Liu Huijuan , Zhang Zhuo , Wang Chi , Chen Gang 
Published: May 2014

Abstract
Chronic inflammation has been implicated as an etiologic factor in cancer, whereas autophagy may help preserve cancer cell survival but exert anti-inflammatory effects. How these phenomenas interact during carcinogenesis remains unclear. We explored this question in a human bronchial epithelial cell–based model of lung carcinogenesis that is mediated by subchronic exposure to arsenic. We found that sustained overexpression of the pro-inflammatory IL6 promoted arsenic-induced cell transformation by inhibiting autophagy. Conversely, strategies to enhance autophagy counteracted the effect of IL6 in the model. These findings were confirmed and extended in a mouse model of arsenic-induced lung cancer. Mechanistic investigations suggested that mTOR inhibition contributed to the activation of autophagy, whereas IL6 overexpression was sufficient to block autophagy by supporting Beclin-1/Mcl-1 interaction. Overall, our findings argued that chronic inflammatory states driven by IL6 could antagonize autophagic states that may help preserve cancer cell survival and promote malignant progression, suggesting a need to uncouple inflammation and autophagy controls to enable tumor progression. Cancer Res; 74(14); 3740–52. ©2014 AACR.
Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer
Authors: Zhao Chunyan , Qiao Yichun , Jonsson Philip , Wang Jian , Xu Li , Rouhi Pegah , Sinha Indranil , Cao Yihai , Williams Cecilia , Dahlman-Wright Karin 
Published: May 2014

Abstract
Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1–regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell–cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties. Cancer Res; 74(14); 3983–94. ©2014 AACR.
Sialic Acids Sweeten a Tumor's Life
Authors: Büll Christian , Stoel Marieke A. , den Brok Martijn H. , Adema Gosse J. 
Published: May 2014

Abstract
Over four decades ago, specific tumor characteristics were ascribed to the increased expression of sialic acid sugars on the surface of cancer cells, and this led to the definition of sialic acids as potential therapeutic targets. Recent advances in glycobiology and cancer research have defined the key processes underlying aberrant expression of sialic acids in cancer, and its consequences, more precisely. These consequences include effects on tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Collectively, these novel insights provide further rationale for the design and development of therapeutic approaches that interfere with excessively high expression of sialic acids in cancer cells. Strategies to target aberrant sialylation in cancer, however, have evolved comparatively slowly. Here, we review recent findings that emphasize the detrimental effects of hypersialylation on multiple aspects of tumor growth and behavior. We also discuss novel therapeutic strategies. Cancer Res; 74(12); 3199–204. ©2014 AACR.
A MicroRNA Cluster at 14q32 Drives Aggressive Lung Adenocarcinoma
Authors: Nadal Ernest , Zhong Jinjie , Lin Jules , Reddy Rishindra M. , Ramnath Nithya , Orringer Mark B. , Chang Andrew C. , Beer David G. , Chen Guoan 
Published: May 2014

Abstract
Purpose: To determine whether different subtypes of lung adenocarcinoma (AC) have distinct microRNA (miRNA) expression profiles, and to identify miRNAs associated with aggressive subgroups of resected lung AC.
Experimental Design: miRNA expression profile analysis was performed in 91 resected lung AC and 10 matched nonmalignant lung tissues using a PCR-based array. An independent cohort of 60 lung ACs was used for validating by quantitative PCR the top 3 prognostic miRNAs. Gene-expression data from 51 miRNA profiled tumors was used for determining transcript-specific miRNA correlations and gene-enrichment pathway analysis.
Results: Unsupervised hierarchical clustering of 356 miRNAs identified 3 major clusters of lung AC correlated with stage (P = 0.023), tumor differentiation (P &lt; 0.003), and IASLC histologic subtype of lung AC (P &lt; 0.005). Patients classified in cluster 3 had worse survival as compared with the other clusters. Eleven of 22 miRNAs associated with poor survival were encoded in a large miRNA cluster at 14q32. The top 3 prognostic 14q32 miRNAs (miR-411, miR-370, and miR-376a) were validated in an independent cohort of 60 lung AC. A significant association with cell migration and cell adhesion was found by integrating gene-expression data with miR-411, miR-370, and miR-376a expression. miR-411 knockdown significantly reduced cell migration in lung AC cell lines and this miRNA was overexpressed in tumors from patients who relapsed systemically.
Conclusions: Different morphologic subtypes of lung AC have distinct miRNA expression profiles, and 3 miRNAs encoded at 14q32 (miR-411, miR-370, and miR-376a) were associated with poor survival after lung AC resection. Clin Cancer Res; 20(12); 3107–17. ©2014 AACR.
Lysyl Oxidases Play a Causal Role in Vascular Remodeling in Clinical and Experimental Pulmonary Arterial Hypertension
Authors: Nave Alexander H. , Mižíková Ivana , Niess Gero , Steenbock Heiko , Reichenberger Frank , Talavera María L. , Veit Florian , Herold Susanne , Mayer Konstantin , Vadász István , Weissmann Norbert , Seeger Werner , Brinckmann Jürgen , Morty Rory E. 
Published: May 2014

Objective—
Pulmonary vascular remodeling, the pathological hallmark of pulmonary arterial hypertension, is attributed to proliferation, apoptosis resistance, and migration of vascular cells. A role of dysregulated matrix cross-linking and stability as a pathogenic mechanism has received little attention. We aimed to assess whether matrix cross-linking enzymes played a causal role in experimental pulmonary hypertension (PH).

Approach and Results—
All 5 lysyl oxidases were detected in concentric and plexiform vascular lesions of patients with idiopathic pulmonary arterial hypertension. Lox, LoxL1, LoxL2, and LoxL4 expression was elevated in lungs of patients with idiopathic pulmonary arterial hypertension, whereas LoxL2 and LoxL3 expression was elevated in laser-capture microdissected vascular lesions. Lox expression was hypoxia-responsive in pulmonary artery smooth muscle cells and adventitial fibroblasts, whereas LoxL1 and LoxL2 expression was hypoxia-responsive in adventitial fibroblasts. Lox expression was increased in lungs from hypoxia-exposed mice and in lungs and pulmonary artery smooth muscle cells of monocrotaline-treated rats, which developed PH. Pulmonary hypertensive mice exhibited increased muscularization and perturbed matrix structures in vessel walls of small pulmonary arteries. Hypoxia exposure led to increased collagen cross-linking, by dihydroxylysinonorleucine and hydroxylysinonorleucine cross-links. Administration of the lysyl oxidase inhibitor β-aminopropionitrile attenuated the effect of hypoxia, limiting perturbations to right ventricular systolic pressure, right ventricular hypertrophy, and vessel muscularization and normalizing collagen cross-linking and vessel matrix architecture.

Conclusions—
Lysyl oxidases are dysregulated in clinical and experimental PH. Lysyl oxidases play a causal role in experimental PH and represent a candidate therapeutic target. Our proof-of-principle study demonstrated that modulation of lung matrix cross-linking can affect pulmonary vascular remodeling associated with PH.
Resting Ventricular–Vascular Function and Exercise Capacity in Heart Failure With Preserved Ejection Fraction
Authors: Mohammed Selma F. , Borlaug Barry A. , McNulty Steven , Lewis Gregory D. , Lin Grace , Zakeri Rosita , Semigran Marc J. , LeWinter Martin , Hernandez Adrian F. , Braunwald Eugene , Redfield Margaret M. 
Published: May 2014

Background—
Exercise intolerance is a hallmark of heart failure, but factors associated with impaired exercise capacity in heart failure with preserved ejection fraction are unclear. We hypothesized that in heart failure with preserved ejection fraction, the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption.

Methods and Results—

Subjects with heart failure with preserved ejection fraction enrolled in the PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure (RELAX) clinical trial (n=216) underwent baseline Doppler echocardiography, cardiopulmonary exercise testing, and cardiac MRI. RELAX participants were elderly (median age 69 years) and 48% were women. Ejection fraction (60%) and stroke volume (77 mL) were normal, while diastolic dysfunction (medial
E
/
e
′, 16; deceleration time, 185 ms; left atrial volume, 44 mL/m
2
) and increased arterial load (arterial elastance, 1.51 mm Hg/mL) were evident. Peak oxygen consumption was reduced (11.7 mLkg
−1
min
−1
, 1141 mL/min) and age, sex, body mass index, hemoglobin, and chronotropic response collectively explained 64% of the variance in raw peak oxygen consumption (mL/min). After adjustment for these variables, left ventricular structure (diastolic dimension [1.5%,
P
=0.008] and left ventricular mass [1.6%,
P
=0.008]), resting stroke volume (2.0%,
P
=0.002), left ventricular diastolic dysfunction (deceleration time [0.9%,
P
=0.03] and
E
/
e
′ [1.4%,
P
=0.009]), and arterial function (arterial elastance [2.1%,
P
=0.002] and systemic arterial compliance [1.5%,
P
=0.007]), each explained only a small additional portion of the variance in peak oxygen consumption.

Conclusions—
In heart failure with preserved ejection fraction, potentially modifiable factors (obesity, anemia, and chronotropic incompetence) are strongly associated with exercise capacity, whereas resting measures of ventricular and vascular structure and function are not.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00763867
Circadian Variation in Vascular Function and Regenerative Capacity in Healthy Humans
Authors: Mheid Ibhar Al , Corrigan Frank , Shirazi Farheen , Veledar Emir , Li Qunna , Alexander Wayne R. , Taylor W. Robert , Waller Edmund K. , Quyyumi Arshed A. 
Published: May 2014

Background

Progenitor cells (
PC
s) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of
PC
s requires intact nitric oxide (
NO
) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24‐hour variation of
PC
s and their inter‐relation with vascular function remain unknown. We investigated the circadian variation of
PC
s and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (
CVE
s).

Methods and Results

In 15 healthy subjects (9 men, 37±16 years), circulating
PC
s and vascular function were measured at 8
am
, noon, 4
pm
, 8
pm
, midnight, 4
am
(only
PC
s counts), and 8
am
the following day. Circulating
PC
s were enumerated as mononuclear cells (
MNC
s;
CD
45
med
) that express
CD
34 as well as
CD
133, and their activity was assessed as the number of colonies formed by culturing
MNC
s. Vascular function was evaluated by measurement of endothelium‐dependent, flow‐mediated vasodilation (
FMD
) of the brachial artery and tonometry‐derived indices of arterial stiffness. Higher
CD
34
+
and
CD
34
+
/
CD
133
+
cell counts were observed at 8
pm
than any other time of the day (
P
‐
ANOVA
=0.038 and <0.001; respectively) and were lowest at 8
am
.
PC
colony formation was highest at midnight (
P
‐
ANOVA
=0.045) and lowest in the morning hours.
FMD
was highest at midnight and lowest at 8
am
and 8
pm
, and systemic arterial stiffness was greatest at 8
am
and lowest at 4
pm
and midnight (
P
‐
ANOVA
=0.03 and 0.01; respectively).

Conclusion

A robust circadian variation in
PC
counts and vascular function occurs in healthy humans and both exhibit an unfavorable profile in the morning hours that parallels the preponderance of
CVE
s at these times. Whether these changes are precipitated by awakening and time‐dependent physical activity or governed by the endogenous circadian clock needs to be further investigated.
Methodology for a Community-Based Stroke Preparedness Intervention
Authors: Boden-Albala Bernadette , Edwards Dorothy F. , St. Clair Shauna , Wing Jeffrey J. , Fernandez Stephen , Gibbons M. Chris , Hsia Amie W. , Morgenstern Lewis B. , Kidwell Chelsea S. 
Published: May 2014

Background and Purpose—
Acute stroke education has focused on stroke symptom recognition. Lack of education about stroke preparedness and appropriate actions may prevent people from seeking immediate care. Few interventions have rigorously evaluated preparedness strategies in multiethnic community settings.

Methods—
The Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities (ASPIRE) project is a multilevel program using a community-engaged approach to stroke preparedness targeted to underserved black communities in the District of Columbia. This intervention aimed to decrease acute stroke presentation times and increase intravenous tissue-type plasminogen activator utilization for acute ischemic stroke.

Results—
Phase 1 included (1) enhancement of focus of emergency medical services on acute stroke; (2) hospital collaborations to implement and enrich acute stroke protocols and transition District of Columbia hospitals toward primary stroke center certification; and (3) preintervention acute stroke patient data collection in all 7 acute care District of Columbia hospitals. A community advisory committee, focus groups, and surveys identified perceptions of barriers to emergency stroke care. Phase 2 included a pilot intervention and subsequent citywide intervention rollout. A total of 531 community interventions were conducted, reaching >10 256 participants; 3289 intervention evaluations were performed, and 19 000 preparedness bracelets and 14 000 stroke warning magnets were distributed. Phase 3 included an evaluation of emergency medical services and hospital processes for acute stroke care and a year-long postintervention acute stroke data collection period to assess changes in intravenous tissue-type plasminogen utilization.

Conclusions—
We report the methods, feasibility, and preintervention data collection efforts of the ASPIRE intervention.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00724555.