bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary therapies for labour and birth study: a randomised controlled trial of antenatal integrative medicine for pain management in labour
Authors: Levett Kate M , Smith C A , Bensoussan A , Dahlen H G 
Published: July 2016

ObjectiveTo evaluate the effect of an antenatal integrative medicine education programme in addition to usual care for nulliparous women on intrapartum epidural use.DesignOpen-label, assessor blind, randomised controlled trial.Setting2 public hospitals in Sydney, Australia.Population176 nulliparous women with low-risk pregnancies, attending hospital-based antenatal clinics.Methods and interventionThe Complementary Therapies for Labour and Birth protocol, based on the She Births and acupressure for labour and birth courses, incorporated 6 evidence-based complementary medicine techniques: acupressure, visualisation and relaxation, breathing, massage, yoga techniques, and facilitated partner support. Randomisation occurred at 24–36 weeks’ gestation, and participants attended a 2-day antenatal education programme plus standard care, or standard care alone.Main outcome measuresRate of analgesic epidural use. Secondary: onset of labour, augmentation, mode of birth, newborn outcomes.ResultsThere was a significant difference in epidural use between the 2 groups: study group (23.9%) standard care (68.7%; risk ratio (RR) 0.37 (95% CI 0.25 to 0.55), p≤0.001). The study group participants reported a reduced rate of augmentation (RR=0.54 (95% CI 0.38 to 0.77), p<0.0001); caesarean section (RR=0.52 (95% CI 0.31 to 0.87), p=0.017); length of second stage (mean difference=−0.32 (95% CI −0.64 to 0.002), p=0.05); any perineal trauma (0.88 (95% CI 0.78 to 0.98), p=0.02) and resuscitation of the newborn (RR=0.47 (95% CI 0.25 to 0.87), p≤0.015). There were no statistically significant differences found in spontaneous onset of labour, pethidine use, rate of postpartum haemorrhage, major perineal trauma (third and fourth degree tears/episiotomy), or admission to special care nursery/neonatal intensive care unit (p=0.25).ConclusionsThe Complementary Therapies for Labour and Birth study protocol significantly reduced epidural use and caesarean section. This study provides evidence for integrative medicine as an effective adjunct to antenatal education, and contributes to the body of best practice evidence.Trial registration numberACTRN12611001126909.
Evaluation of the Metasin assay for intraoperative assessment of sentinel lymph node metastases in breast cancer
Authors: Smith G J , Hodges E , Markham H , Zhang S , Cutress R I 
Published: July 2016

AimsSentinel lymph node (SLN) biopsy is the preferred surgical technique for staging the axilla in clinically node-negative breast cancer. Accurate intraoperative staging allows for the immediate performance of an axillary clearance in node-positive patients. We assessed the Metasin assay for the intraoperative analysis of SLNs in a prospective evaluation of 250 consecutive patients undergoing intraoperative SLN analysis at the Breast Unit, University Hospital, Southampton, UK.MethodsMetasin uses a quantitative reverse transcription PCR to detect two markers of metastasis: cytokeratin 19 (CK19) an epithelial marker and mammaglobin (MGB) a breast specific marker. Metasin results were compared with the results from routine paraffin block histopathology.ResultsMetasin was robust, with a failure rate of <1%, and demonstrated excellent accuracy and reproducibility. The average turnaround time for the Metasin assay was 42 min, the largest variable being the number of nodes assayed. A total of 533 SLNs were evaluated with 75 patients testing positive for MGB and/or CK19. Based on the analysis of individual SLNs, the overall concordance between Metasin and histology was 92.3% (sensitivity 88.7%, specificity 92.9%). When adjusted for tissue allocation bias, the concordance was 93.8% (sensitivity 89.8%, specificity 94.6%). In this evaluation, 57/250 patients (23%) proceeded to axillary clearance based on Metasin results and were considered spared a second operative procedure.ConclusionsMetasin has proven to be an accurate, reproducible and reliable laboratory test. The analysis time is acceptable for intraoperative use, and in comparison to routine histology demonstrates acceptable concordance, sensitivity and specificity.
β-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by ‘gastric adenocarcinoma and proximal polyposis of the stomach’ (GAPPS)
Authors: McDuffie Lucas A , Sabesan Arvind , Allgäeuer Michael , Xin Liqiang , Koh Christopher , Heller Theo , Davis Jeremy L , Raffeld Mark , Miettienen Markku , Quezado Martha , Rudloff Udo 
Published: July 2016

AimTo evaluate possible colon involvement in the ‘gastric adenocarcinoma and proximal polyposis of the stomach’ (GAPPS) gastrointestinal polyposis syndrome.MethodsProspective clinicopathological evaluation of two GAPPS families and expression of nuclear β-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS.ResultsPatients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (p<0.01). Colonic polyps shared immunohistochemical features of fundic gland polyps and gastric cancers including increased expression of nuclear β-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of β-catenin signalling.ConclusionsSimilarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted.Clinical Trial Registration Number#09-C-0079; Results.
A Cell-Penetrating Peptide Targeting AAC-11 Specifically Induces Cancer Cells Death
Authors: Jagot-Lacoussiere Léonard , Kotula Ewa , Villoutreix Bruno O. , Bruzzoni-Giovanelli Heriberto , Poyet Jean-Luc 
Published: July 2016

Abstract
AAC-11 is an antiapoptotic protein that is upregulated in most cancer cells. Increased expression of AAC-11 confers a survival advantage when cancer cells are challenged with various stresses and contributes to tumor invasion and metastases, whereas its deregulation reduces resistance to chemotherapeutic drugs. The antiapoptotic effect of AAC-11 may be clinically relevant as its expression correlates with poor prognosis in several human cancers. Thus, inactivation of AAC-11 might constitute an attractive approach for developing cancer therapeutics. We have developed an AAC-11–derived cell-penetrating peptide, herein named RT53, mimicking in part the heptad leucine repeat region of AAC-11, which functions as a protein–protein interaction module, and that can prevent AAC-11 antiapoptotic properties. In this study, we investigated the anticancer effects of RT53. Our results indicate that RT53 selectively kills cancer cells while sparing normal cells. RT53 selectively inserts into the membranes of cancer cells, where it adopts a punctate distribution and induces membranolysis and release of danger-associated molecular pattern molecules. Systemic administration of RT53 inhibited the growth of preexisting BRAF wild-type and V600E mutant melanoma xenograft tumors through induction of apoptosis and necrosis. Toxicological studies revealed that repetitive injections of RT53 did not produce significant toxicity. Finally, RT53-killed B16F10 cells induced tumor growth inhibition in immunocompetent mice following a rechallenge with live cancer cells of the same type. Collectively, our data demonstrate that RT53 possesses tumor-inhibitory activity with no toxicity in mice, suggesting its potential as a therapeutic agent for the treatment of melanoma and probably other cancers. Cancer Res; 76(18); 5479–90. ©2016 AACR.
Identification of a Natural Killer Cell Receptor Allele That Prolongs Survival of Cytomegalovirus-Positive Glioblastoma Patients
Authors: Dominguez–Valentin Mev , Gras Navarro Andrea , Rahman Aminur Mohummad , Kumar Surendra , Retière Christèle , Ulvestad Elling , Kristensen Vessela , Lund-Johansen Morten , Lie Benedicte Alexandra , Enger Per Øyvind , Njølstad Gro , Kristoffersen Einar , Lie Stein Atle , Chekenya Martha 
Published: July 2016

Abstract
By affecting immunological presentation, the presence of cytomegalovirus in some glioblastomas may impact progression. In this study, we examined a hypothesized role for natural killer (NK) cells in impacting disease progression in this setting. We characterized 108 glioblastoma patients and 454 healthy controls for HLA-A,-B,-C, NK-cell KIR receptors, and CMV-specific antibodies and correlated these metrics with clinical parameters. Exome sequences from a large validation set of glioblastoma patients and control individuals were examined from in silico databases. We demonstrated that the KIR allele KIR2DS4*00101 was independently prognostic of prolonged survival. KIR2DS4*00101 displayed 100% concordance with cognate HLA-C1 ligands in glioblastoma patients, but not controls. In the context of both HLA-C1/C2 ligands for the KIR2DS4 receptor, patient survival was further extended. Notably, all patients carrying KIR2DS4*00101 alleles were CMV seropositive, but not control individuals, and exhibited increased NK-cell subpopulations, which expressed the cytotoxicity receptors CD16, NKG2D, and CD94/NKG2C. Finally, healthy controls exhibited a reduced risk for developing glioblastoma if they carried two KIR2DS4*00101 alleles, where protection was greatest among Caucasian individuals. Our findings suggest that KIR2DS4*00101 may offer a molecular biomarker to identify intrinsically milder forms of glioblastoma. Cancer Res; 76(18); 5326–36. ©2016 AACR.
A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells
Authors: Toriyama Seijiro , Horinaka Mano , Yasuda Shusuke , Taniguchi Tomoyuki , Aono Yuichi , Takamura Toshiya , Morioka Yukako , Miki Tsuneharu , Ukimura Osamu , Sakai Toshiyuki 
Published: July 2016

Abstract
The prognosis of muscle-invasive bladder cancer with metastasis is poor. There have been no therapeutic improvements for many years, and an innovative therapy for muscle-invasive bladder cancer has been awaited to replace the conventional cytotoxic chemotherapy. Here, we show a candidate method for the treatment of bladder cancer. The combined treatment with a novel histone deacetylase (HDAC) inhibitor, OBP-801, and celecoxib synergistically inhibited cell growth and markedly induced apoptosis through the caspase-dependent pathway in high-grade bladder cancer cells. Furthermore, the combined treatment induced expression of death receptor 5 (DR5). We identified that knockdown of DR5 by small interfering RNA (siRNA) significantly suppressed apoptosis by the combined treatment. Therefore, we conjectured that the apoptosis induced by OBP-801 and celecoxib is at least partially dependent on DR5. However, it was interesting that the combined treatment drastically suppressed expression of DR5 ligand, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). These data suggest that there is no involvement of TRAIL in the induction of apoptosis by the combination, regardless of the dependence of DR5. Moreover, xenograft studies using human bladder cancer cells showed that the combined therapy suppressed tumor growth by upregulating expressions of DR5 and Bim. The inhibition of tumor growth was significantly more potent than that of each agent alone, without significant weight loss. This combination therapy provided a greater benefit than monotherapy in vitro and in vivo. These data show that the combination therapy with OBP-801 and celecoxib is a potential novel therapeutic strategy for patients with muscle-invasive bladder cancer. Mol Cancer Ther; 15(9); 2066–75. ©2016 AACR.
Bilateral Internal Thoracic Artery Configuration for Coronary Artery Bypass Surgery
Authors: Glineur David , Boodhwani Munir , Hanet Claude , de Kerchove Laurent , Navarra Emiliano , Astarci Parla , Noirhomme Philippe , El Khoury Gebrine 
Published: July 2016

Background—
Bilateral internal thoracic arteries (BITA) have demonstrated superior patency and improved survival in patients undergoing coronary artery bypass grafting. However, the optimal configuration for BITA utilization and its effect on long-term outcome remains uncertain.

Methods and Results—

We randomly assigned 304 patients undergoing coronary artery bypass grafting using BITA to either in situ or Y grafting configurations. The primary end point was 3-year angiographic patency. Secondary end points included major adverse cardiac and cerebrovascular events (ie, death from any cause, stroke, myocardial infarction, or repeat revascularization) at 7 years. More coronary targets were able to be revascularized using internal thoracic arteries in patients randomized to Y grafting versus in situ group (3.2±0.8 versus 2.4±0.5 arteries/patient;
P
<0.01). The primary end point did not show significant differences in graft patency between groups. Secondary end points occurred more frequently in the in situ group (
P
=0.03), with 7-year rates of 34±10% in the in situ and 25±12% in the Y grafting groups, driven largely by a higher incidence of repeat revascularization in the in situ group (14±4.5% versus 7.4±3.2% at 7 years;
P
=0.009). There were no significant differences in hospital mortality or morbidity or in late survival, myocardial infarction, or stroke between groups.

Conclusions—
Three-year systematic angiographic follow-up revealed no significant difference in graft patency between the 2 BITA configurations. However, compared with in situ configuration, the use of BITA in a Y grafting configuration results in lower rates of major adverse cardiovascular and cerebrovascular events at 7 years.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01666366.
National Survey of UK Consultant Surgeons’ Opinions on Surgeon-Specific Mortality Data in Cardiothoracic Surgery
Authors: Jarral Omar A. , Baig Kamran , Pettengell Christopher , Uppal Rakesh , Taggart David P. , Darzi Ara , Westaby Stephen , Athanasiou Thanos 
Published: July 2016

Background—
In the United Kingdom, cardiothoracic surgeons have led the outcome reporting revolution seen over the last 20 years. The objective of this survey was to assess cardiothoracic surgeons’ opinions on the topic, with the aim of guiding future debate and policy making for all subspecialties.

Methods and Results—

A questionnaire was developed using interviews with experts in the field. In January 2015, the survey was sent out to all consultant cardiothoracic surgeons in the United Kingdom (n=361). Logistic regression, bivariate correlation, and the χ
2
test were used to assess whether there was a relationship between answers and demographic variables. Free-text responses were analyzed using the grounded theory approach. The response rate was 73% (n=264). The majority of respondents (58.1% oppose, 34.1% favor, and 7.8% neither) oppose the public release of surgeon-specific mortality data and associate it with several adverse consequences. These include risk-averse behavior, gaming of data, and misinterpretation of data by the public. Despite this, the majority overwhelmingly supports publication of team-based measures of outcome. The free-text responses suggest that this is because most believe that quality of care is multifactorial and not represented by an individual’s mortality rate.

Conclusions—
There is evident opposition to surgeon-specific mortality data among UK cardiothoracic surgeons who associate this with several unintended consequences. Policy makers should refine their strategy behind publication of surgeon-specific mortality data and possibly consider shift toward team-based results for which there will be the required support. Stakeholder feedback and inclusive strategy should be completed before introducing major initiatives to avoid unforeseen consequences and disagreements.
Effects of Quercetin on Blood Pressure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Serban Maria‐Corina , Sahebkar Amirhossein , Zanchetti Alberto , Mikhailidis Dimitri P. , Howard George , Antal Diana , Andrica Florina , Ahmed Ali , Aronow Wilbert S. , Muntner Paul , Lip Gregory Y. H. , Graham Ian , Wong Nathan , Rysz Jacek , Banach Maciej ,   for the Lipid and Blood Pressure Meta‐analysis Collaboration (LBPMC) Group
Published: July 2016

Background

Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (
BP
) has not been conclusive. We assessed the impact of quercetin on
BP
through a systematic review and meta‐analysis of available randomized controlled trials.

Methods and Results

We searched
PUBMED
, Cochrane Library, Scopus, and
EMBASE
up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on
BP
. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I
2
statistic. Effect size was expressed as weighted mean difference (
WMD
) and 95%
CI
. Overall, the impact of quercetin on
BP
was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic
BP
(
WMD
: −3.04 mm Hg, 95%
CI
: −5.75, −0.33,
P
=0.028) and diastolic
BP
(
WMD
: −2.63 mm Hg, 95%
CI
: −3.26, −2.01,
P
<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic
BP
and diastolic
BP
‐reducing effect in randomized controlled trials with doses ≥500 mg/day (
WMD
: −4.45 mm Hg, 95%
CI
: −7.70, −1.21,
P
=0.007 and −2.98 mm Hg, 95%
CI
: −3.64, −2.31,
P
<0.001, respectively), and lack of a significant effect for doses <500 mg/day (
WMD
: −1.59 mm Hg, 95%
CI
: −4.44, 1.25,
P
=0.273 and −0.24 mm Hg, 95%
CI
: −2.00, 1.52,
P
=0.788, respectively), but indirect comparison tests failed to significant differences between doses.

Conclusions

The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of
BP
, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.
Prevalence of Eligibility Criteria for the Systolic Blood Pressure Intervention Trial in US Adults Among Excluded Groups: Age <50 Years, Diabetes Mellitus, or a History of Stroke
Authors: Bress Adam P. , Tanner Rikki M. , Hess Rachel , Gidding Samuel S. , Colantonio Lisandro D. , Shimbo Daichi , Muntner Paul 
Published: July 2016

Background

Adults <50 years old, with diabetes mellitus, or a history of stroke were not enrolled in the Systolic Blood Pressure Intervention Trial (
SPRINT
). Estimating the size and characteristics of these excluded groups who meet the other
SPRINT
eligibility criteria may provide information on the potential impact of providers extending the
SPRINT
findings to these populations.

Methods and Results

We analyzed the National Health and Nutrition Examination Survey 2003–2012 (n=25 076) to estimate the percentage and characteristics of
US
adults ≥20 years in 3 populations (age <50 years, diabetes mellitus, or history of stroke) excluded from
SPRINT
who otherwise meet the trial eligibility criteria: age ≥50 years, systolic blood pressure (
SBP
) 130–180 mm Hg, high cardiovascular disease risk, and not having trial exclusion criteria. Overall, 1.0% (95%
CI
0.8–1.3) of
US
adults age <50 years, 25.4% (95%
CI
23.4–27.6) with diabetes mellitus, and 19.0% (95%
CI
16.0–22.4) with history of stroke met the other
SPRINT
eligibility criteria. Among
US
adults with
SBP
≥130 mm Hg, other
SPRINT
eligibility criteria were met by 7.5% (95%
CI
6.1–9.2) of those age <50 years, 32.9% (95%
CI
30.5–35.4) with diabetes mellitus, and 23.0% (95%
CI
19.4–27.0) with history of stroke. Among
US
adults meeting the other
SPRINT
eligibility criteria, antihypertensive medication was being taken by 31.0% (95%
CI
23.9–41.3) of those <50 years, 63.0% (95%
CI
58.2–67.6) with diabetes mellitus, and 68.9% (95%
CI
59.4–77.1) with a history of stroke.

Conclusions

A substantial percentage of
US
adults with diabetes mellitus or history of stroke and a small percentage <50 years old meet the other
SPRINT
eligibility criteria.
Glycogen Synthase Kinase 3β Inhibition Improves Myocardial Angiogenesis and Perfusion in a Swine Model of Metabolic Syndrome
Authors: Potz Brittany A. , Sabe Ashraf A. , Elmadhun Nassrene Y. , Clements Richard T. , Robich Michael P. , Sodha Neel R. , Sellke Frank W. 
Published: July 2016

Background
Inhibition of glycogen synthase kinase 3β (GSK‐3β) has been reported to be cardioprotective during stressful conditions.

Methods and Results
Pigs were fed a high‐fat diet for 4 weeks to develop metabolic syndrome, then underwent placement of an ameroid constrictor to their left circumflex artery to induce chronic myocardial ischemia. Two weeks later, animals received either: no drug (high cholesterol control group [HCC]) or a GSK‐3β inhibitor (GSK‐3β inhibited group [GSK‐3βI]), which were continued for 5 weeks, followed by myocardial tissue harvest. Coronary blood flow and vessel density were significantly increased in the GSK‐3βI group compared to the HCC group. Expression levels of the following proteins were greater in the GSK‐3βI group compared to the HCC group: vascular endothelial growth factor receptor 1 , vascular endothelial cadherin, γ‐catenin, β‐catenin, protein kinase B, phosphorylated forkhead box O1, and superoxide dismutase 2.

Conclusions
In the setting of metabolic syndrome, inhibition of GSK‐3β increases blood flow and vessel density in chronically ischemic myocardium. We identified several angiogenic, cell survival, and differentiation pathways that include β‐catenin signaling and AKT/FOXO1, through which GSK‐3β appears to improve vessel density and blood flow. These results may provide a potential mechanism for medical therapy of patients suffering from coronary artery disease and metabolic syndrome.
They Protect Our Homeland but Neglect Our Community
Authors: Metcalfe Christi , Wolfe Scott E. , Gertz Evelyn , Gertz Marc 
Published: July 2016

Objectives: Terrorism is becoming a priority among police agencies in many Western democracies. Scholars argue that increasing homeland security responsibilities can erode police–community relations, in that people perceive the police as neglecting local crime problems for homeland security concerns. Methods: Using Israel as a case study, we evaluate, through path analyses, whether Israeli Jews who perceive that the Israeli National Police (INP) values homeland security more than its crime responsibilities have lower evaluations of police legitimacy and, in turn, are less willing to cooperate with the police. Results: The findings demonstrate that those who believe the INP neglects its crime responsibilities for homeland security view the police as less legitimate, and lower evaluations of police legitimacy decrease willingness to cooperate. The overall indirect effect of perceived neglect on cooperation is not significant. Conclusions: Based on the findings, it is clear that perceptions of what the police ought to be doing influence legitimacy evaluations, even when controlling for key antecedents of legitimacy. The implications of these findings for policing terrorism and legitimacy studies are discussed.