bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lidocaine 10% spray to the cervix reduces pain during intrauterine device insertion: a double-blind randomised controlled trial
Authors: Aksoy Hüseyin , Aksoy Ülkü , Ozyurt Sezin , Açmaz Gökhan , Babayigit Mustafa 
Published: March 2015

ObjectiveFear of pain during intrauterine device (IUD) insertion can be a barrier to widespread use of this safe and highly effective contraceptive method. Our objective was to determine the effectiveness of topical 10% lidocaine spray for pain control during IUD insertion.MethodsA total of 200 subjects with the request for IUD insertion were included in the study. The patients were randomly divided into two groups: lidocaine spray (n=100) and placebo (n=100). The pain experienced during the procedure was measured immediately after insertion by a standard Visual Analogue Scale (VAS) administered by a separate researcher with maintenance of allocation concealment.ResultsThe mean pain score during the procedure was 1.01±1.20 in the lidocaine spray group and 3.23±1.60 in the placebo spray group (p<0.001). Lidocaine spray treatment significantly lowered the overall procedural pain score compared with placebo.ConclusionsSignificant pain reduction during IUD insertion can be achieved by using 10% lidocaine spray alone. Lidocaine spray can be accepted as a non-invasive, easy to apply and more comfortable local anaesthetic method for IUD insertion.Trial registration numberNCT02020551.
p53 Family Members Regulate Phenotypic Response to Aurora Kinase A Inhibition in Triple-Negative Breast Cancer
Authors: Tentler John J. , Ionkina Anastasia A. , Tan Aik Choon , Newton Timothy P. , Pitts Todd M. , Glogowska Magdalena J. , Kabos Peter , Sartorius Carol A. , Sullivan Kelly D. , Espinosa Joaquin M. , Eckhardt S. Gail , Diamond Jennifer R. 
Published: March 2015

Abstract
Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel effective targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family of transcriptional regulators, commonly mutated in TNBC, in determining the phenotypic response to the AurA inhibitor alisertib (MLN8237). Alisertib exhibited potent antiproliferative and proapoptotic activity in a subset of TNBC models. The induction of apoptosis in response to alisertib exposure was dependent on p53 and p73 activity. In the absence of functional p53 or p73, there was a shift in the phenotypic response following alisertib exposure from apoptosis to cellular senescence. In addition, senescence was observed in patient-derived tumor xenografts with acquired resistance to alisertib treatment. AurA inhibitors are a promising class of novel therapeutics in TNBC. The role of p53 and p73 in mediating the phenotypic response to antimitotic agents in TNBC may be harnessed to develop an effective biomarker selection strategy in this difficult to target disease. Mol Cancer Ther; 14(5); 1117–29. ©2015 AACR.
Anti–miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation
Authors: Wagenaar Timothy R. , Zabludoff Sonya , Ahn Sung-Min , Allerson Charles , Arlt Heike , Baffa Raffaele , Cao Hui , Davis Scott , Garcia-Echeverria Carlos , Gaur Rajula , Huang Shih-Min A. , Jiang Lan , Kim Deokhoon , Metz-Weidmann Christiane , Pavlicek Adam , Pollard Jack , Reeves Jason , Rocnik Jennifer L. , Scheidler Sabine , Shi Chaomei , Sun Fangxian , Tolstykh Tatiana , Weber William , Winter Christopher , Yu Eunsil , Yu Qunyan , Zheng Gang , Wiederschain Dmitri 
Published: March 2015

Abstract
Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti–miR-21, but not with a mismatch control anti-miRNA, resulted in significant derepression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis, and necrosis was noted in anti–miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21 suppression, global gene expression profiling was performed on anti–miR-21-treated liver cancer cells, which revealed striking enrichment in miR-21 target genes and deregulation of multiple growth-promoting pathways. Finally, in vivo dependency on miR-21 was observed in two separate HCC tumor xenograft models. In summary, these data establish a clear role for miR-21 in the maintenance of tumorigenic phenotype in HCC in vitro and in vivo.
Implications: miR-21 is important for the maintenance of the tumorigenic phenotype of HCC and represents a target for pharmacologic intervention. Mol Cancer Res; 13(6); 1009–21. ©2015 AACR.
Perfect Storm
Authors: Alcántara Carmela , Muntner Paul , Edmondson Donald , Safford Monika M. , Redmond Nicole , Colantonio Lisandro D. , Davidson Karina W. 
Published: March 2015

Background—
Depression and stress have each been found to be associated with poor prognosis in patients with coronary heart disease. A recently offered psychosocial perfect storm conceptual model hypothesizes amplified risk will occur in those with concurrent stress and depressive symptoms. We tested this hypothesis in a large sample of US adults with coronary heart disease.

Methods and Results—
Participants included 4487 adults with coronary heart disease from the REasons for Geographic and Racial Differences in Stroke study, a prospective cohort study of 30 239 black and white adults. We conducted Cox proportional hazards regression with the composite outcome of myocardial infarction or death and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1% reported concurrent high stress and high depressive symptoms at baseline. During a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of follow-up, participants with concurrent high stress and high depressive symptoms had increased risk for myocardial infarction or death (adjusted hazard ratio, 1.48 [95% confidence interval, 1.08–2.02]) relative to those with low stress and low depressive symptoms. Those with low stress and high depressive symptoms (hazard ratio, 0.92 [95% confidence interval, 0.66–1.28]) or high stress and low depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57–1.29]) were not at increased risk. The association on myocardial infarction or death was not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95% confidence interval, 0.65–1.22]).

Conclusions—
Our results provide initial support for a psychosocial perfect storm conceptual model; the confluence of depressive symptoms and stress on medical prognosis in adults with coronary heart disease may be particularly destructive in the shorter term.
Decision-Making for Destination Therapy Left Ventricular Assist Devices
Authors: McIlvennan Colleen K. , Jones Jacqueline , Allen Larry A. , Lindenfeld JoAnn , Swetz Keith M. , Nowels Carolyn , Matlock Daniel D. 
Published: March 2015

Background—
Implanting centers often require the identification of a dedicated caregiver before destination therapy left ventricular assist device (DT LVAD) implantation; however, the caregiver experience surrounding this difficult decision is relatively unexplored.

Methods and Results—
From October 2012 through July 2013, we conducted semistructured, in-depth interviews with caregivers of patients considering DT LVAD. Data were analyzed using a mixed inductive and deductive approach. We interviewed 17 caregivers: 10 caregivers of patients living with DT LVAD, 6 caregivers of patients who had died with DT LVAD, and 1 caregiver of a patient who had declined DT LVAD. The themes identified, which could also be considered dialectical tensions, are broadly interpreted under 3 domains mapping to decision context, process, and outcome: (1) the stark decision context, with tension between hope and reality; (2) the challenging decision process, with tension between wanting loved ones to live and wanting to respect loved ones’ wishes; and (3) the downstream decision outcome, with tension between gratitude and burden.

Conclusions—
Decision-making surrounding DT LVAD should incorporate decision support for patients and caregivers. This should include a focus on caregiver burden and the predictable tensions that caregivers experience.
Impaired Right Ventricular Hemodynamics Indicate Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome
Authors: Gopal Deepa M. , Santhanakrishnan Rajalakshmi , Wang Yi‐Chih , Ayalon Nir , Donohue Courtney , Rahban Youssef , Perez Alejandro J. , Downing Jill , Liang Chang‐seng , Gokce Noyan , Colucci Wilson S. , Ho Jennifer E. 
Published: March 2015

Background
Metabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease.

Methods and Results

A total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m
2
), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time (
PAAT
) and ejection time. Pulmonary artery systolic pressure was estimated from
PAAT
using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter
PAAT
, shorter ejection time, and larger pulmonary artery diameter compared with controls (
P
<0.05 for all). Estimated pulmonary artery systolic pressure based on
PAAT
was 42±12 mm Hg in participants with MetS compared with 32±9 and 32±10 mm Hg in obese and nonobese controls (
P
for
ANOVA
<0.0001). After adjustment for age, sex, hypertension, diabetes, body mass index, and triglycerides, MetS remained associated with a 20‐ms–shorter
PAAT
(β=−20.4, SE=6.5,
P
=0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea.

Conclusions

MetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter
PAAT
and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.
PHASES Score for Prediction of Intracranial Aneurysm Growth
Authors: Backes Daan , Vergouwen Mervyn D.I. , Tiel Groenestege Andreas T. , Bor A. Stijntje E. , Velthuis Birgitta K. , Greving Jacoba P. , Algra Ale , Wermer Marieke J.H. , van Walderveen Marianne A.A. , terBrugge Karel G. , Agid Ronit , Rinkel Gabriel J.E. 
Published: March 2015

Background and Purpose—
Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth.

Methods—
In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles.

Results—
We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5–10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22–1.43). With the lowest quartile of the PHASES score (0–1) as reference, hazard ratios were for the second (PHASES 2–3) 1.07 (95% CI, 0.49–2.32), the third (PHASES 4) 2.29 (95% CI, 1.05–4.95), and the fourth quartile (PHASES 5–14) 2.85 (95% CI, 1.43–5.67).

Conclusions—
Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.
Feel between the Lines: Implied Emotion in Sentence Comprehension
Authors: Lai Vicky Tzuyin , Willems Roel M. , Hagoort Peter 
Published: March 2015

AbstractThis study investigated the brain regions for the comprehension of implied emotion in sentences. Participants read negative sentences without negative words, for example, “The boy fell asleep and never woke up again,” and their neutral counterparts “The boy stood up and grabbed his bag.” This kind of negative sentence allows us to examine implied emotion derived at the sentence level, without associative emotion coming from word retrieval. We found that implied emotion in sentences, relative to neutral sentences, led to activation in some emotion-related areas, including the medial prefrontal cortex, the amygdala, and the insula, as well as certain language-related areas, including the inferior frontal gyrus, which has been implicated in combinatorial processing. These results suggest that the emotional network involved in implied emotion is intricately related to the network for combinatorial processing in language, supporting the view that sentence meaning is more than simply concatenating the meanings of its lexical building blocks.
The TIGGE Project and Its Achievements
Authors: Swinbank Richard , Kyouda Masayuki , Buchanan Piers , Froude Lizzie , Hamill Thomas M. , Hewson Tim D. , Keller Julia H. , Matsueda Mio , Methven John , Pappenberger Florian , Scheuerer Michael , Titley Helen A. , Wilson Laurence , Yamaguchi Munehiko 
Published: March 2015

Abstract
The International Grand Global Ensemble (TIGGE) was a major component of The Observing System Research and Predictability Experiment (THORPEX) research program, whose aim is to accelerate improvements in forecasting high-impact weather. By providing ensemble prediction data from leading operational forecast centers, TIGGE has enhanced collaboration between the research and operational meteorological communities and enabled research studies on a wide range of topics.
The paper covers the objective evaluation of the TIGGE data. For a range of forecast parameters, it is shown to be beneficial to combine ensembles from several data providers in a multimodel grand ensemble. Alternative methods to correct systematic errors, including the use of reforecast data, are also discussed.
TIGGE data have been used for a range of research studies on predictability and dynamical processes. Tropical cyclones are the most destructive weather systems in the world and are a focus of multimodel ensemble research. Their extratropical transition also has a major impact on the skill of midlatitude forecasts. We also review how TIGGE has added to our understanding of the dynamics of extratropical cyclones and storm tracks.
Although TIGGE is a research project, it has proved invaluable for the development of products for future operational forecasting. Examples include the forecasting of tropical cyclone tracks, heavy rainfall, strong winds, and flood prediction through coupling hydrological models to ensembles.
Finally, the paper considers the legacy of TIGGE. We discuss the priorities and key issues in predictability and ensemble forecasting, including the new opportunities of convective-scale ensembles, links with ensemble data assimilation methods, and extension of the range of useful forecast skill.
Mapping TRMM TMPA into Average Recurrence Interval for Monitoring Extreme Precipitation Events
Authors: Zhou Yaping , Lau William K. M. , Huffman George J. 
Published: March 2015

AbstractA prototype online extreme precipitation monitoring system is developed from the TRMM TMPA near-real-time precipitation product. The system utilizes estimated equivalent average recurrence interval (ARI) for up-to-date precipitation accumulations from the past 1, 2, 3, 5, 7, and 10 days to locate locally severe events. The mapping of precipitation accumulations into ARI is based on local statistics fitted into generalized extreme value (GEV) distribution functions. Initial evaluation shows that the system captures historic extreme precipitation events quite well. The system provides additional rarity information for ongoing precipitation events based on local climatology that could be used by the general public and decision makers for various hazard management applications. Limitations of the TRMM ARI due to short record length and data accuracy are assessed through comparison with long-term high-resolution gauge-based rainfall datasets from the NOAA Climate Prediction Center and the Asian Precipitation–Highly-Resolved Observational Data Integration Toward Evaluation of Water Resources (APHRODITE) project. TMPA-based extreme climatology captures extreme distribution patterns from gauge data, but a strong tendency to overestimate from TMPA over regimes of complex orography exists.
Retrograde Wiring of Collateral Channels of the Heart in Chronic Total Occlusions
Authors: Khand Aleem , Patel Bilal , Palmer Nicholas , Jones Julia , Andron Mohammed , Perry Raph , Mehrotra Sanjay , Mitsudo Kazuaki 
Published: March 2015

Aim: To conduct a systematic review and meta-analysis on retrograde wiring in chronic total occlusions (CTOs) with focus on its safety and feasibility. Methods and Results: We searched publications from 1990 to December 2013 in PubMed, Ovid, EMBASE, and the Cochrane database inserting a number of terms relating to the collateral circulation of the heart in CTOs. A total of 18 case series (n range17-462) with a total of 2280 CTO revascularization attempts fulfilled criteria for a study of retrograde wiring of collateral channels in CTOs. There were no randomized studies comparing a primary antegrade with a primary retrograde approach. Procedural CTO revascularization rates ranged from 67% to 90.6% with a large proportion having previously failed an “antegrade” approach. The septal perforator collaterals and epicardial channels were used in 73.2% (n = 1670) and 21.7% (n = 495) of cases. Although collateral/coronary perforation was not infrequent (n = 90, 5%), serious acute complications were uncommon; in the combined population 18 cases of cardiac tamponade (0.8%) and 3 deaths (0.1%). Septal perforating wiring (79.3%) was significantly more likely to be successful compared to epicardial coronary artery wiring (72.5%) when chosen by the operator as a route of retrograde access to the CTO body (relative risk 1.11 [95% confidence interval: 1.02-1.20; P = .013]). Conclusion: Successful retrograde wiring of collateral channels in selected patients undertaken by “CTO dedicated” operators can significantly enhance the chances of revascularization of complex CTOs with a low risk of acute serious complications. Septal perforator channels are significantly more likely to be successfully retrogradely wired compared to epicardial vessels when either is selected, by reference to their anatomical suitability by the operator, as a route of access.
Potential Advantages of a Single-Port, Operator-Controlled Flexible Endoscope System for Transoral Surgery of the Larynx
Authors: Friedrich Daniel T. , Scheithauer Marc O. , Greve Jens , Duvvuri Uma , Sommer Fabian , Hoffmann Thomas K. , Schuler Patrick J. 
Published: March 2015

Introduction: Transoral surgery of the larynx is commonly performed with a rigid laryngoscope, a microscope, and a laser. We investigated the potential utility of a flexible, single-port, robot-assisted and physician-controlled endoscopic system to enable easy, transoral surgical access to the larynx. Methods: Transoral laryngeal surgery was performed in human cadavers (n = 4) using the Flex System and compatible flexible instruments. Anatomical landmarks were identified, and mock surgical procedures were performed. Results: Standard laryngeal surgical procedures were completed successfully in a human cadaver model. The built-in HD digital camera enabled high-quality visualization of the larynx. Epiglottectomy, as well as posterior cordectomy, were performed by laser and radio-frequency resection. The flexible design of the compatible tools enabled a nontraumatic approach. Conclusion: The Flex System has the potential to improve surgical access to the larynx, especially in patients with challenging anatomy. The associated flexible instruments enabled completion of surgical procedures in the larynx in a human cadaveric model. Further clinical studies, as well as the development of supplemental technology and tools, are recommended for future clinical applications.
The growing role of evaluation in parliaments: holding governments accountable?
Authors: Speer Sandra , Pattyn Valérie , De Peuter Bart 
Published: March 2015

To date, the role of evaluation in parliaments has hardly been analyzed. This is a surprise as members of parliament are stakeholders par excellence, who could have an interest in evaluation. But do they? Through a systematic analysis of written questions and interrogations in Germany and Flanders we investigate MPs’ attention to evaluations. The following aspects are analyzed, from a comparative perspective: the content of questions on evaluation, the political profile of the MPs posing the questions, the share of questions on evaluation, and the distribution of questions over political parties, policy areas and over time. Points for practitioners The role and use of evaluation in the democratic process might be enhanced. On the one side members of parliament might wish to be better informed on evaluation methods as well as on possibilities for using evaluation results for accountability and learning purposes. On the other side evaluators might strive for strengthening the demand for evaluation in the policy-making process and not only public administration.