bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple-Negative Breast Cancer
Authors: Parvani Jenny G. , Gujrati Maneesh D. , Mack Margaret A. , Schiemann William P. , Lu Zheng-Rong 
Published: April 2015

Abstract
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial–mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGFβ-mediated EMT and invasion, restore TGFβ-mediated cytostasis, and inhibit three-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden and, more importantly, significantly inhibited metastasis. In the span of 16 weeks of the experiments and observations, including primary tumor resection at week 9 and release from the treatment for 4 weeks, the mice bearing orthotopic, TGFβ-prestimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse, in comparison with untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC. Cancer Res; 75(11); 2316–25. ©2015 AACR.
Regulation of Smooth Muscle Dystrophin and Synaptopodin 2 Expression by Actin Polymerization and Vascular Injury
Authors: Turczyńska Karolina M. , Swärd Karl , Hien Tran Thi , Wohlfahrt Johan , Mattisson Ingrid Yao , Ekman Mari , Nilsson Johan , Sjögren Johan , Murugesan Vignesh , Hultgårdh-Nilsson Anna , Cidad Pilar , Hellstrand Per , Pérez-García M. Teresa , Albinsson Sebastian 
Published: April 2015

Objective—
Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype.

Approach and Results—

Mouse aortic smooth muscle cells were treated with an actin-stabilizing agent, jasplakinolide, and analyzed by microarrays. Several transcripts were upregulated including both known and previously unknown actin-regulated genes. Dystrophin and synaptopodin 2 were selected for further analysis in models of phenotypic modulation and vascular disease. These genes were highly expressed in differentiated versus synthetic smooth muscle and their expression was promoted by the transcription factors myocardin and myocardin-related transcription factor A. Furthermore, the expression of both synaptopodin 2 and dystrophin was significantly reduced in balloon-injured human arteries. Finally, using a dystrophin mutant
mdx
mouse and synaptopodin 2 knockdown, we demonstrate that these genes are involved in the regulation of smooth muscle differentiation and function.

Conclusions—
This study demonstrates novel genes that are promoted by actin polymerization, that regulate smooth muscle function, and that are deregulated in models of vascular disease. Thus, targeting actin polymerization or the genes controlled in this manner can lead to novel therapeutic options against vascular pathologies that involve phenotypic modulation of smooth muscle cells.
Safety and Efficacy of Resolute Zotarolimus-Eluting Stents Compared With Everolimus-Eluting Stents
Authors: Piccolo Raffaele , Stefanini Giulio G. , Franzone Anna , Spitzer Ernest , Blöchlinger Stefan , Heg Dik , Jüni Peter , Windecker Stephan 
Published: April 2015

Background—
Although new-generation drug-eluting stents represent the standard of care among patients undergoing percutaneous coronary intervention, there remains debate about differences in efficacy and the risk of stent thrombosis between the Resolute zotarolimus-eluting stent (R-ZES) and the everolimus-eluting stent (EES). The aim of this study was to evaluate the safety and efficacy of the R-ZES compared with EES in patients undergoing percutaneous coronary intervention.

Methods and Results—

A systematic literature search of electronic resources was performed using specific search terms until September 2014. Random-effects meta-analysis was performed comparing clinical outcomes between patients treated with R-ZES and EES up to maximum available follow-up. The primary efficacy end point was target-vessel revascularization. The primary safety end point was definite or probable stent thrombosis. Secondary safety end points were cardiac death and target-vessel myocardial infarction. Five trials were identified, including a total of 9899 patients. Compared with EES, R-ZES had similar risks of target-vessel revascularization (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.90–1.24;
P
=0.50), definite or probable stent thrombosis (RR, 1.26; 95% CI, 0.86–1.85;
P
=0.24), cardiac death (RR, 1.01; 95% CI, 0.79–1.30;
P
=0.91), and target-vessel myocardial infarction (RR, 1.10; 95% CI, 0.89–1.36;
P
=0.39). Moreover, R-ZES and EES had similar risks of late definite or probable very late stent thrombosis (RR, 1.06; 95% CI, 0.53–2.11;
P
=0.87). No evidence of significant heterogeneity was observed across trials.

Conclusions—
R-ZES and EES provide similar safety and efficacy among patients undergoing percutaneous coronary intervention.
State Management of River Dikes in Early China: New Sources on the Environmental History of the Central Yangzi Region
Authors: Lander Brian 
Published: April 2015

While it is generally believed that the agricultural colonization of the middle Yangzi wetlands began in Tang-Song times, newly discovered texts show that the early Han state administered river dikes in the region. The texts, which were written between 192 and 121 bce, calculate dike sizes in order to estimate corvée requirements for dike maintenance and discuss the area of new farmland to be created. Our picture of the early history of the Yangzi region has been distorted by the northern focus of early texts, but archaeological discoveries are correcting this bias and suggest that the conversion of the Central Yangzi lowlands to farmland began many centuries earlier than previously believed. On pense en général que la mise en valeur agricole des marais du moyen Yangzi a commencé sous les Tang et les Song. Or, des textes récemment découverts montrent que dès le début des Han l’État administrait des digues dans la région. Rédigés entre 192 et 121 avant notre ère, ces textes contiennent des calculs sur les dimensions des digues servant à évaluer les besoins en travail corvéable pour leur entretien, ainsi que des considérations sur la superficie de nouvelles terres cultivées à ouvrir. Alors que nous nous faisions une image de l’histoire ancienne du bassin du Yangzi déformée par les textes anciens, qui privilégient la Chine du Nord, les découvertes archéologiques remettent les choses en perspective et suggèrent que la mise en valeur des basses terres du moyen Yangzi a démarré de nombreux siècles plus tôt qu’on ne croyait.
Met Expectations and Satisfaction with Duration
Authors: Gregory Emily F. , Butz Arlene M. , Ghazarian Sharon R. , Gross Susan M. , Johnson Sara B. 
Published: April 2015

Background: Breastfeeding expectations predict breastfeeding duration. The extent to which expectations for duration are met remains unknown. Objectives: To evaluate prospective measures of expected breastfeeding duration, changes in expectations over time, and factors associated with meeting expectations. Methods: The Infant Feeding Practices Study II followed women from late pregnancy to 1 year postpartum. Expected breastfeeding duration was assessed 5 times. Logistic regression identified factors associated with met prenatal expectations. Subgroup analysis compared met prenatal expectations to satisfaction with breastfeeding duration. Results: One-year postpartum, 34.7% of 1802 participants had met prenatal expected breastfeeding duration, and 23.9% were still breastfeeding. Fifty-eight percent of women met expectations stated at 7 months postpartum. Modifiable risk factors associated with meeting prenatal expectations included early regular breast pump use (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.18-2.07). Return to work was negatively associated with met expectations (return by 6 weeks postpartum: OR, 0.48; 95% CI, 0.33-0.71; later return: OR, 0.73; 95% CI, 0.56-0.95). Among those who reported on satisfaction with duration (n = 1226), 40.4% were satisfied. Satisfaction was associated with meeting expectations (OR, 10.56; 95% CI, 7.67-14.55), but expectation and satisfaction measures were not equivalent. Elevated body mass index and depressive symptoms at 2 months postpartum were negatively associated with both measures. Conclusion: Most participants did not meet prenatal or postnatal expectations for breastfeeding duration and were unsatisfied with duration. However, at 12 months, more participants felt they had met their expectations and were satisfied with their breastfeeding duration than were actually breastfeeding. Therefore, women may perceive greater breastfeeding progress than suggested by Healthy People 2020 benchmarks.
Randomized Controlled Trial Comparing Orthosis Augmented by Either Stretching or Stretching and Strengthening for Stage II Tibialis Posterior Tendon Dysfunction
Authors: Houck Jeff , Neville Christopher , Tome Josh , Flemister Adolph 
Published: April 2015

Background: The value of strengthening and stretching exercises combined with orthosis treatment in a home-based program has not been evaluated. The purpose of this study was to compare the effects of augmenting orthosis treatment with either stretching or a combination of stretching and strengthening in participants with stage II tibialis posterior tendon dysfunction (TPTD). Methods: Participants included 39 patients with stage II TPTD who were recruited from a medical center and then randomly assigned to a strengthening or stretching treatment group. Excluding 3 dropouts, there were 19 participants in the strengthening group and 17 in the stretching group. The stretching treatment consisted of a prefabricated orthosis used in conjunction with stretching exercises. The strengthening treatment consisted of a prefabricated orthosis used in conjunction with the stretching and strengthening exercises. The main outcome measures were self-report (ie, Foot Function Index and Short Musculoskeletal Function Assessment) and isometric deep posterior compartment strength. Two-way analysis of variance was used to test for differences between groups at 6 and 12 weeks after starting the exercise programs. Results: Both groups significantly improved in pain and function over the 12-week trial period. The self-report measures showed minimal differences between the treatment groups. There were no differences in isometric deep posterior compartment strength. Conclusions: A moderate-intensity, home-based exercise program was minimally effective in augmenting orthosis wear alone in participants with stage II TPTD. Level of Evidence: Level I, prospective randomized study.
The development and pilot randomised controlled trial of a group education programme for promoting walking in people with intermittent claudication
Authors: Tew Garry A , Humphreys Liam , Crank Helen , Hewitt Catherine , Nawaz Shah , Al-Jundi Wissam , Trender Hazel , Michaels Jonathan , Gorely Trish 
Published: April 2015

The aim of this study was to develop and pilot a group education programme for promoting walking in people with intermittent claudication. Patient focus groups ( n=24) and literature reviews were conducted to inform the development of the education programme, which involves a three-hour group-based education workshop and follow-up telephone support. A pilot study was subsequently conducted in which 23 new patients (Rutherford category 1–3) were randomly assigned to usual care (control) or usual care plus the education programme. Outcomes were assessed at baseline and six weeks including daily steps (tri-axial accelerometer), walking capacity (six-minute walk test and Gardner treadmill test), and quality of life (Intermittent Claudication Questionnaire [ICQ]). Exit interviews were conducted to assess the acceptability and usefulness of the programme. Compared with controls, the intervention group had superior walking capacity and quality of life at six weeks. Mean differences in six-minute walk distance, treadmill maximum walking distance and ICQ score were 44.9 m (95% confidence interval [CI], 6.9 to 82.9), 173 m (95% CI, 23 to 322), and −10.6 (95% CI, −18.9 to −2.3), respectively. The daily step count did not differ between groups. The exit interviews indicated that participants valued attending the programme, that it gave them a greater understanding of their condition, and that they had been walking more for exercise since attending. The results suggest that the education programme is feasible, acceptable, and potentially useful for improving walking capacity and quality of life. A fully-powered trial exploring clinical and cost effectiveness is needed. TRIAL REGISTRATION NUMBER: ISRCTN06733130 ( http://www.controlled-trials.com ).
Management of Crohn's disease – are guidelines transferred to clinical practice?
Authors: Klag Thomas , Stange Eduard F. , Wehkamp Jan 
Published: April 2015

BackgroundManagement of Crohn's disease (CD) is a clinical challenge. In terms of an evidence‐based approach, clinical guidelines help to deal with this challenge. However, little is known about guideline adherence concerning the management of CD in Germany.ObjectiveTo survey German gastroenterologists with regards to their guideline adherence in daily clinical care.MethodA web‐based national survey was conducted among German gastroenterologists.ResultsA total of 175 inflammatory bowel disease (IBD) practitioners responded to the survey. Overall, in the different clinical situations covered in the questionnaire guideline adherence is good. However, the 5‐aminosalicylic acid (5‐ASA) prescribing habits represent a striking exception. About 10–36% use 5‐ASA as mono‐therapy in CD, depending on the clinical scenario. Predominantly it is used in mild CD and in colonic involvement. To maintain a surgically achieved remission, therapeutic decisions broadly rely on individual approaches with azathioprine and 5‐ASA being used by about 30% of the respondents. Cessation of smoking as a “therapeutic” strategy of maintenance therapy is used by only half of the surveyed physicians.ConclusionAmongst German IBD practitioners, the guideline adherence is good overall. Reflecting ongoing uncertainty about the efficacy of mesalazine, its use in Crohn's disease is still heterogeneous.
Visceral pain perception in patients with irritable bowel syndrome and healthy volunteers is affected by the MRI scanner environment
Authors: Wong Reuben K , Van Oudenhove Lukas , Li Xinhua , Cao Yang , Ho Khek Yu , Wilder‐Smith Clive H 
Published: April 2015

BackgroundThe MRI scanner environment induces marked psychological effects, but specific effects on pain perception and processing are unknown and relevant to all brain imaging studies.Objectives and methodsWe performed visceral and somatic quantitative sensory and pain testing and studied endogenous pain modulation by heterotopic stimulation outside and inside the functional MRI scanner in 11 healthy controls and 13 patients with irritable bowel syndrome.ResultsRectal pain intensity (VAS 0–100) during identical distension pressures increased from 39 (95% confidence interval: 35–42) outside the scanner to 53 (43–63) inside the scanner in irritable bowel syndrome, and from 42 (31–52) to 49 (39–58), respectively, in controls (ANOVA for scanner effect: p  = 0.006, group effect: p  = 0.92). The difference in rectal pain outside versus inside correlated significantly with stress (r  = −0.76, p  = 0.006), anxiety (r  = −0.68, p  = 0.02) and depression scores (r  = −0.67, p  = 0.02) in controls, but not in irritable bowel syndrome patients, who a priori had significantly higher stress and anxiety scores. ANOVA analysis showed trends for effect of the scanner environment and subject group on endogenous pain modulation (p  = 0.09 and p  = 0.1, respectively), but not on somatic pain (p  > 0.3).ConclusionThe scanner environment significantly increased visceral, but not somatic, pain perception in irritable bowel syndrome patients and healthy controls in a protocol specifically aimed at investigating visceral pain. Psychological factors, including anxiety and stress, are the likely underlying causes, whereas classic endogenous pain modulation pathways activated by heterotopic stimulation play a lesser role. These results are highly relevant to a wide range of imaging applications and need to be taken into account in future pain research. Further controlled studies are indicated to clarify these findings.
The association between Helicobacter pylori infection and inflammatory bowel disease based on meta‐analysis
Authors: Rokkas T , Gisbert JP , Niv Y , O’Morain C 
Published: April 2015

BackgroundIn humans there are epidemiological data suggesting a protective effect of Helicobacter pylori (H. pylori) infection against the development of autoimmune diseases and in addition, there are laboratory data illustrating H. pylori 's ability to induce immune tolerance and limit inflammatory responses. Thus, numerous observational studies have examined the association between H. pylori infection and inflammatory bowel disease (IBD) with various results.ObjectiveWe performed a meta‐analysis of available studies to better define the association of H. pylori infection and IBD.MethodsMedical literature searches for human studies were performed through September 2014, using suitable keywords. In each study the risk ratio (RR) of H. pylor i infection in IBD patients vs controls was calculated and pooled estimates were obtained using fixed‐ or random‐effects models as appropriate. Heterogeneity between studies was evaluated using Cochran Q test and I2 statistics, whereas the likelihood of publication bias was assessed by constructing funnel plots.ResultsThirty‐three studies were eligible for meta‐analysis, including 4400 IBD patients and 4763 controls. Overall 26.5% of IBD patients were positive for H. pylori infection, compared to 44.7% of individuals in the control group. There was significant heterogeneity in the included studies (Q  = 137.2, df (Q) =32, I2   = 77%, p  < 0.001) and therefore the random‐effects model of meta‐analysis was used. The obtained pool RR estimation was 0.62 (95% confidence interval (CI) 0.55–0.71, test for overall effect Z  = –7.04, p  < 0.001). There was no evidence of publication bias.ConclusionThe results of this meta‐analysis showed a significant negative association between H. pylori infection and IBD that supports a possible protective benefit of H. pylori infection against the development of IBD.
Inflammatory bowel disease‐specific pregnancy knowledge of gastroenterologists against general practitioners and obstetricians
Authors: Kashkooli Soleiman B , Andrews Jane M , Roberts Matthew B , Selinger Christian P , Leong Rupert W 
Published: April 2015

BackgroundPatients with inflammatory bowel disease (IBD) tend to have smaller family sizes. Health care professionals (HCPs) may inadvertently provide inaccurate advice to patients resulting in voluntary childlessness or unfavourable pregnancy outcomes.ObjectiveThe study aims to objectively measure IBD‐specific pregnancy‐related knowledge of general practitioners (GPs) and obstetricians/gynaecologists (OB/GYNs) in comparison with gastroenterologists (GEs) using the validated Crohn's and Colitis Pregnancy Knowledge (CCPKnow) questionnaire.MethodsGPs, OB/GYNs and GEs in two Australian states completed the CCPKnow (range 0–17) and demographic questionnaires. The CCPKnow addresses issues pertaining to conception, IBD inheritance, risk of congenital abnormalities, medication use in the peri‐conceptual period, pregnancy and breastfeeding, and mode of delivery.ResultsIn total, 337 HCPs responded. GPs (n  = 188/2086) and OB/GYNs (n  = 94/228) had significantly lower knowledge than GEs (n  = 55/165) for the composite CCPKnow (medians 11, 13 and 17, respectively, p  < 0.001), and almost all domains. GEs were the only group to attain a median CCPKnow score in the top category (14–17). More than 70% of GPs and OB/GYNs expressed discomfort with initiation of IBD medications around conception/pregnancy. GPs (43.6%) and OB/GYNs (45.7%) perceived thiopurine use to be unsafe during pregnancy and to cause serious harm to the baby.ConclusionsOur study demonstrates that GPs and OB/GYNs have inadequate and variable IBD‐specific pregnancy‐related knowledge including use of IBD medications. These results support the need for GEs’ prime role in a team‐based management for IBD patients who are pregnant or planning pregnancy.
Hereditary systemic immunoglobulin light-chain amyloidosis
Authors: Benson Merrill D. , Liepnieks Juris J. , Kluve-Beckerman Barbara 
Published: April 2015

Key PointsProtein and DNA analyses reveal that mutation in the immunoglobulin κ light-chain constant region gene may cause hereditary amyloidosis. Sequencing of immunoglobulin light-chain constant region genes is indicated for patients with AL amyloidosis and no evidence of a plasma cell dyscrasia.