bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoreductive radiofrequency ablation in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with sunitinib or interferon‐α
Authors: Tsimafeyeu Ilya , Zart Janie S. , Chung Bin 
Published: June 2013

Objectives
To evaluate the role of cytoreductive radiofrequency ablation (cRFA) in patients with metastatic renal cell carcinoma (RCC) with small primary tumours treated with immuno‐ or targeted therapy.
To assess the efficacy of sunitinib in patients with metastatic RCC with unresected small primary tumours.
Patients and Methods
Three parallel single‐arm prospective studies were conducted. Eligibility criteria were nearly identical for all trials and included: histopathologically confirmed RCC; metastatic measurable disease; size of primary tumour <5 cm; good or intermediate prognosis according to the Memorial Sloan‐Kettering Cancer Center model; and no previous therapy.
Study 1: Patients were treated with percutaneous cRFA under computed tomography guidance followed by interferon (IFN)‐α, 9 MIU, s.c., three times per week. Study 2: Patients received cRFA followed by sunitinib in repeated 6‐week cycles of 50 mg/day orally for 4 weeks, then 2 weeks off treatment. Study 3: Patients with unresected primary RCC received sunitinib alone. The primary endpoint was progression‐free survival (PFS).
Results
Baseline patient characteristics (age, gender, histology, Eastern Cooperative Oncology Group performance status, metastatic sites, primary tumour size) were similar in all three studies.
Efficacy data for 114 evaluable patients showed an objective response rate of 8% (95% confidence interval [CI] 4.5, 10.5) for study 1, 28.9% (95% CI 15.2, 34) for study 2, and 31.6% (95% CI 20.3, 38.9) for study 3. The median (95% CI) PFS times were 9.1 (6.9, 10.2), 13.4 (9.8, 14.4) and 12.7 (11.3, 13.5) months for studies 1, 2 and 3, respectively.
Objective response rate was significantly higher and PFS significantly longer in the sunitinib trials than in study 1 (P < 0.01 all differences); no differences were found between studies 2 and 3 (objective response rate, P = 0.1; PFS, P = 0.6). Study 1 met its primary endpoint, showing that PFS was significantly longer than the expected 5 months (P = 0.02).
The median (95% CI) overall survival (OS) times were greater in study 2 (cRFA/sunitinib) and study 3 (sunitinib‐alone) than in study 1 (IFN‐α) at 27.2 (22.6, 31.8) and 22.5 (20.7, 24.3) vs 19.5 (16.3, 22.7) months, respectively. Differences were significant (study 1 vs 2, hazard ratio [HR] = 0.55; P = 0.003; study 1 vs study 3 HR = 0.6, P = 0.01). OS was significantly longer in the cRFA/sunitinib group compared with the sunitinib‐alone group (HR = 0.71; P = 0.04).
There were no unexpected toxicities of medical treatment or complications of cRFA.
Conclusions
cRFA is a safe and effective approach for select patients with metastatic RCC treated with immunotherapy.
The cRFA technique did not improve PFS in patients treated with sunitinib; cRFA probably has impact on OS in these patients. This needs to be tested in a larger trial.
Sunitinib was effective in patients with metastatic RCC with unresected small primary tumours.
The mitogen‐inducible gene‐6 is involved in regulation of cellular senescence in normal diploid fibroblasts
Authors: Xie Bushan , Zhao Lin , Chen Hao , Jin Bo , Mao Zebin , Yao Zhi 
Published: June 2013

Background informationThe mitogen‐inducible gene‐6 (Mig‐6) is a non‐kinase scaffolding adaptor protein. It has been shown that Mig‐6 may play important roles in regulating stress response, maintaining homeostasis and functioning as a tumour suppressor. In this study, we investigated the role of Mig‐6 in cellular senescence.ResultsOur results showed that Mig‐6 is up‐regulated during the senescence process. Functional analysis indicated that cells over‐expressing Mig‐6 have reduced DNA synthesis and showed the signs of senescence. Knockdown of Mig‐6 delayed the initiation of Ras‐induced cellular senescence. These results suggest that the increase of Mig‐6 expression contributes to establishment of cellular senescence. Furthermore, our results showed that Mig‐6 induction of senescence is related to its inhibition of EGF receptor (EGFR)/Erb B signalling. Subsequent analysis of the mechanism responsible for the up‐regulation of its expression showed that FOXO3A transcriptionally up‐regulates Mig‐6 expression via directly binding to the FOXO response element in Mig‐6 5′‐flanking regulatory sequences.ConclusionsMig‐6 induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts.
High variability in baseline urinary free cortisol values in patients with Cushing's disease
Authors: Petersenn S. , Newell‐Price J. , Findling J. W. , Gu F. , Maldonado M. , Sen K. , Salgado L. R. , Colao A. , Biller B. M. K. ,   Pasireotide B2305 Study Group
Published: June 2013

SummaryObjectiveTwenty‐four‐hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate‐to‐severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data.DesignObservational study (enrolment phase of Phase III study).MethodsPatients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30–145 nmol/24 h) were included. Mean UFC level was calculated from four 24‐h urine samples collected over 2 weeks.ResultsOver 600 24‐h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48–56). The intrapatient CV was 51% (95% CI: 44–58) for samples 1 and 2, 49% (95% CI: 43–56) for samples 3 and 4 and 54% (95% CI: 49–59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism.ConclusionsThere is intrapatient variability of approximately 50% in 24‐h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24‐h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity.
Operationalizing the Resilience of Coral Reefs in an Era of Climate Change
Authors: Mumby Peter J. , Wolff Nicholas H. , Bozec Yves‐Marie , Chollett Iliana , Halloran Paul 
Published: June 2013

AbstractEcosystem management frequently aims to manage resilience yet measuring resilience has proven difficult. Here, we quantify the ecological resilience of the largest reef in the Caribbean and map potential benefits of marine reserves under two scenarios of greenhouse gas emissions. Resilience is calculated using spatial ecological models and defined as the probability of a reef remaining in its coral‐dominated basin of attraction such that it does not flip into an alternate, algal‐dominated attractor. In practice, resilience is the probability that coral populations will maintain the ability to exhibit a recovery trend after acute disturbances such as hurricanes. The inputs required to estimate resilience are a reef's initial state, physical environment, and disturbance regime. One major driver of reef resilience is herbivory by parrotfish and recent action to protect parrotfish in Belize was found to have increased resilience 6‐fold. However, the expected benefits of parrotfish protection to future coral cover were relatively modest with only a 2‐ to 2.6‐fold improvement over a business‐as‐usual scenario, demonstrating how resilience and ecosystem states are decoupled. Global action to reduce greenhouse gas emissions had little impact on average coral state unless it was accompanied by local controls of fishing. However, combined global and local action reduced the rate of reef degradation threefold. Operationalizing resilience explicitly integrates available biophysical data and accommodates the complex interactions among ecological processes and multiple types of disturbance.
Hypertension risk: exercise is medicine* for most but not all
Authors: Loenneke Jeremy P. , Fahs Christopher A. , Abe Takashi , Rossow Lindy M. , Ozaki Hayao , Pujol Thomas J. , Bemben Michael G. 
Published: June 2013

SummaryHypertension is a risk factor for heart disease, and chronic exercise is recognized as a method for reducing resting blood pressure. Recent studies report that while exercise may benefit the majority of the population, the blood pressure adaptation is not always uniform; some individuals have an adverse blood pressure response to chronic aerobic exercise programmes. The purpose of this study was to examine the individual changes in resting blood pressure in response to exercise training regimens aimed at increasing muscle mass and strength. We have also included exercise (resistance and aerobic) in combination with blood flow restriction (BFR). Of 74 individuals, 11% had an increased risk, 16% had a decreased risk and 73% had no change in risk classification following exercise. The statistical analysis found that the group that decreased risk with exercise tended to have higher baseline levels of blood pressure. However, there were little baseline differences between the group that increased risk or the group that had no change in risk, suggesting that starting values may not necessarily determine who will see a beneficial response. In conclusion, the blood pressure adaptation to resistance training and exercise with BFR is not homogeneous with some participants increasing, decreasing or staying in the same risk category following an exercise intervention. These are important findings as they would not have been noted or discussed when looking only at the group means. Future research may identify molecular predictors so that individuals at risk for adverse events can be identified prior to exercise.
A Multiparametric Clinical and Echocardiographic Score to Risk Stratify Patients with Chronic Systolic Heart Failure: Derivation and Testing
Authors: Fontanive Paolo , Miccoli Mario , Simioniuc Anca , Angelillis Marco , Bello Vitantonio Di , Baggiani Angelo , Bongiorni Maria Grazia , Marzilli Mario , Dini Frank Lloyd 
Published: June 2013

Although echo Doppler and biomarkers are the most common examinations performed worldwide in heart failure (HF), they are rarely considered in risk scores. In outpatients with chronic HF and left ventricular ejection fraction (LVEF) ≤45%, data on clinical status, echo Doppler variables, aminoterminal pro‐type B natriuretic peptide (NT‐proBNP), estimated glomerular filtration rate (eGFR), and drug therapies were combined to build up a multiparametric score. We randomly selected 250 patients to produce a derivation cohort and 388 patients were used as a testing cohort. Follow‐up lasted 29 ± 23 months. The univariable predictors that entered into the multivariable Cox model were as follows: furosemide daily dose >25 mg, inability to tolerate angiotensin converting enzyme (ACE) inhibitors, inability to tolerate β‐blockers, age >75 years, New York Heart Association (NYHA) >2, eGFR<60 mL/min, NT‐proBNP plasma levels above the median, tricuspid plane systolic excursion (TAPSE) ≤14 mm, LV end‐diastolic volume index (LVEDVi) >96 mL/m2, moderate‐to‐severe mitral regurgitation (MR) and LVEF <30%. The scores of prognostic factors were obtained with the respective odds ratio divided by the lower odd ratio: 4 points for furosemide dose, 3 points for age, NT‐proBNP, LVEDVi, TAPSE, 2 points for inability to tolerate β‐blockers, inability to tolerate ACE inhibitors, NYHA, eGFR<60 mL/min, moderate‐to‐severe MR, 1 point for LVEF. The multiparametric score predicted all‐cause mortality either in the derivation cohort (68.4% sensitivity, 79.5% specificity, area under the curve [AUC] 78.7%) or in the testing cohort (73.7% sensitivity, 71.3% specificity, AUC 77.2%). All‐cause mortality significantly increased with increasing score both in the derivation and in the testing cohort (P < 0.0001). In conclusion, this multiparametric score is able to predict mortality in chronic systolic HF.
Emerging Role of Three‐Dimensional Speckle Tracking Strain for Accurate Quantification of Left Ventricular Dyssynchrony
Authors: Tanaka Hidekazu , Tatsumi Kazuhiro , Matsumoto Kensuke , Kawai Hiroya , Hirata Ken‐ichi 
Published: June 2013

A case was 53‐year‐old female with dilated‐phase hypertrophic cardiomyopathy. She was classified as New York Heart Association functional class III heart failure despite receiving optimal medical therapy. The electrocardiogram taken showed intraventricular conduction delay with a QRS width of 194 msec. The left ventricular (LV) end‐diastolic and systolic volumes, and ejection fraction (EF) were 101 mL, 68 mL, and 32%, respectively. The patient showed no significant mechanical LV dyssynchrony as evidenced by two‐dimensional (2D) speckle tracking radial strain, which is defined as the time difference between anterior‐septum and posterior wall, of 105 msec (<130 msec). Three‐dimensional (3D) speckle tracking radial strain was performed for more detailed LV mechanical dyssynchrony analysis. An especially important finding for 3D speckle tracking radial strain analysis was that the average time‐to‐peak strain of 5 septum segments at 3 different LV levels (basal‐anterior‐septum, basal‐septum, mid‐anterior‐septum, mid‐septum, apical‐septum) was significantly shorter than that of 5 posterolateral segments at 3 different LV levels (basal‐posterior, basal‐lateral, mid‐posterior, mid‐lateral, apical‐lateral). This time difference between septum and posterolateral wall was 216 msec (204 msec vs. 420 msec), which was considered to indicate significant LV mechanical dyssynchrony (≥130 msec). 12 months after cardiac resynchronization therapy (CRT), EF had improved to 47%, while end‐systolic and diastolic volumes had decreased to 88 mL and 47 mL, respectively, so that the patient was classified as a responder. In conclusions, a newly developed 3D speckle tracking strain can provide a comprehensive evaluation of “true” LV mechanical dyssynchrony from pyramidal 3D data sets acquired in the same beat, thus yielding more accurate information than previously possible with the 2D speckle tracking system.
Second and third year oral health and dental student perceptions of future professional work
Authors: Tan A. S. , Anderson V. R. , Foster Page L. A. 
Published: June 2013

AbstractObjectivesTo explore and compare the ways dental and oral health students characterise their future professional work (FPW) at the end of their second and third professional years.Materials and methodsQuestionnaires were given to a cohort group of 48 dental students and 31 oral health students at the end of their second and third professional years at the University of Otago. Students' characterisations of their FPW were identified using an inductive approach, and the emphasis on each characterisation was confirmed using a ‘weighted’ table.ResultsDental student response rates were 92% (in 2010) and 85% (in 2011); and oral health student response rates were 100% (in 2011) and 97% (in 2011). Students characterised their FPW in ten broad ways: in reference to treatment‐related concerns, patient‐related concerns, oral health promotion, oral health education, disease prevention and monitoring, communication, teamwork, maintaining an ideal clinical environment, maintaining a sense of self and improving quality of life. In both years, dental students emphasised treatment‐related concerns as central to their FPW and dealing with patient‐related concerns as a primary source of difficulty. Oral health students emphasised oral health promotion, oral health education, disease prevention and monitoring and restorative tasks as central to their FPW and dealing with patient‐related concerns as a primary source of difficulty.ConclusionStudents' broad perceptions of their FPW changed little as they progressed through their programmes; however, their responses suggested the need for greater attention within their programmes to patient management and teamwork.
Effects of background light conditions on thermoperiodic eclosion rhythm of onion fly Delia antiqua
Authors: Watari Yasuhiko , Tanaka Kazuhiro 
Published: June 2013

AbstractTo elucidate the effects of light on thermoperiodic regulation of adult eclosion rhythm in the onion fly, Delia antiqua, the responses to two thermoperiods, 29°C (12 h):21°C (12 h) and 25.5°C (12 h):24.5°C (12 h), with different amplitude and same average temperature, were examined in continuous darkness (DD) and continuous light (LL). Irrespective of the temperature step between warm phase (W) and cool phase (C), temperature cycles effectively entrained the adult eclosion rhythm in both DD and LL. Eclosion peaks, however, varied with light conditions and temperature step between W and C. It advanced by approximately 2–3 h in DD than in LL and at smaller temperature step. Background light conditions and temperature step also affect the amplitude of eclosion rhythm. It became lower in LL than in DD and at smaller temperature steps. On transfer to constant temperature (25°C), eclosion rhythm was elicited earliest in the pupae at 8°C temperature step in DD and latest in those at 1°C temperature step in LL. Pupae at 1°C temperature step in DD and at 8°C temperature step in LL demonstrated intermediate responses, but the eclosion rhythm was elicited 1 day earlier in the former than in the latter. This might be ascribed to the interaction between background light and temperature step under thermoperiodic conditions. The results suggest that continuous light and a smaller temperature step weaken the coupling strength between eclosion rhythm and thermoperiod, but the light effect is stronger than the temperature step effect.
Bridging the Gap: Humanitarian Protection and the Convergence of Laws in Europe
Authors: Dean Meryll 
Published: June 2013

AbstractThis article uses the thematic of humanitarian protection to examine the convergence of laws in Europe. It considers the heterogeneous architecture of the Refugee Convention and European Convention on Human Rights then analyses the homogenous framework of the EU's Common Asylum System and, in particular, the Qualification Directive. It argues that in an area where international, regional and national laws intersect, convergence needs to be underpinned by Member States adopting a common interpretative methodology that has international law at its core. Article 15 of the Qualification Directive (QD) is used to illustrate how this can be achieved. The article adds to the growing literature on the convergence of laws in Europe and illustrates the importance of adopting a common interpretative methodology. It suggests a paradigm for protection regimes around the world and a methodology that could be transplanted to other areas of law involving the intersection of international, regional and national laws.
Distal hindlimb kinematics of gallopingThoroughbred racehorses on dirt and synthetic racetrack surfaces
Authors: Symons J. E. , Garcia T. C. , Stover S. M. 
Published: June 2013

SummaryReasons for performing studyThe effect of racetrack surface (dirt or synthetic) on distal hindlimb kinematics of racehorses running at competition speeds is not known.ObjectivesTo compare distal hindlimb and hoof kinematics during stance of breezing (unrestrained gallop) racehorses between dirt and synthetic surfaces.Study designTwo‐dimensional kinematic video analysis of 5Thoroughbred racehorses galloping at high speeds (12–17 m/s) on a dirt racetrack and a synthetic racetrack.MethodsThe positions of kinematic markers applied to the left hindlimb were recorded at 500 Hz. Position, velocity and acceleration of joint angles and hoof translation during stance were calculated in the sagittal plane. Peak translational and angular kinematic values were compared between the dirt and synthetic race surfaces using mixed model analyses of covariance.ResultsMaximum and heel‐strike metatarsophalangeal (fetlock) angles were greater (P<0.05) on the dirt surface than on the synthetic surface. Maximum fetlock angle occurred earlier during stance on the dirt surface (P<0.05). Greater horizontal displacement of the heel during slide occurred on the dirt surface (P<0.05).ConclusionsDuring high‐speed gallop, hindlimb fetlock hyperextension and horizontal hoof slide are greater on a dirt surface than on a synthetic surface. Synthetic race surfaces may mitigate risk of injury to hindlimb fetlock structures by reducing fetlock hyperextension and associated strains in fetlock support structures. Differences in hoof slide may contribute to different distal hindlimb kinematics between surfaces.
Latent myostatin has significant activity and this activity is controlled more efficiently by WFIKKN1 than by WFIKKN2
Authors: Szláma György , Trexler Mária , Patthy László 
Published: June 2013

Myostatin, a negative regulator of skeletal muscle growth, is produced from myostatin precursor by multiple steps of proteolytic processing. After cleavage by a furin‐type protease, the propeptide and growth factor domains remain associated, forming a noncovalent complex, the latent myostatin complex. Mature myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases. Here, we show that, in reporter assays, latent myostatin preparations have significant myostatin activity, as the noncovalent complex dissociates at an appreciable rate, and both mature and semilatent myostatin (a complex in which the dimeric growth factor domain interacts with only one molecule of myostatin propeptide) bind to myostatin receptor. The interaction of myostatin receptor with semilatent myostatin is efficiently blocked by WAP, Kazal, immunoglobulin, Kunitz and NTR domain‐containing protein 1 or growth and differentiation factor‐associated serum protein 2 (WFIKKN1), a large extracellular multidomain protein that binds both mature myostatin and myostatin propeptide [Kondás et al. (2008) J Biol Chem 283, 23677–23684]. Interestingly, the paralogous protein WAP, Kazal, immunoglobulin, Kunitz and NTR domain‐containing protein 2 or growth and differentiation factor‐associated serum protein 1 (WFIKKN2) was less efficient than WFIKKN1 as an antagonist of the interactions of myostatin receptor with semilatent myostatin. Our studies have shown that this difference is attributable to the fact that only WFIKKN1 has affinity for the propeptide domain, and this interaction increases its potency in suppressing the receptor‐binding activity of semilatent myostatin. As the interaction of WFIKKN1 with various forms of myostatin permits tighter control of myostatin activity until myostatin is liberated from latent myostatin by bone morphogenetic protein 1/tolloid proteases, WFIKKN1 may have greater potential as an antimyostatic agent than WFIKKN2.Structured digital abstract

Furin cleaves Promyostatin by protease assay (View interaction)

myostatin binds to PRO by surface plasmon resonance (View interaction)

BMP-1 cleaves Promyostatin by protease assay (View interaction)

ACR IIB physically interacts with Latent Myostatin by surface plasmon resonance (View interaction)

Promyostatin and Promyostatin bind by comigration in gel electrophoresis (View interaction)

WFIKKN1 binds to Latent Myostatin by pull down (View interaction)

ACR IIB binds to Mature Myostatin by surface plasmon resonance (View Interaction: 1, 2, 3)

WFIKKN1 binds to Myostatin Prodomain by surface plasmon resonance (View Interaction: 1, 2, 3)