bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent Radiotherapy and Ipilimumab Immunotherapy for Patients with Melanoma
Authors: Barker Christopher A. , Postow Michael A. , Khan Shaheer A. , Beal Kathryn , Parhar Preeti K. , Yamada Yoshiya , Lee Nancy Y. , Wolchok Jedd D. 
Published: July 2013

AbstractIpilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records of patients treated with ipilimumab and radiotherapy for melanoma at our institution between 2005 and 2011. The review included details of treatment, response, adverse events (AE), and overall survival (OS). Twenty-nine patients underwent 33 courses of non-brain radiotherapy between their first and last dose of ipilimumab. Immune-related AEs (ir-AEs) were observed in 43% of patients receiving ipilimumab at 10 mg/kg and in 22% of patients receiving 3 mg/kg; the frequency of ir-AEs was not significantly different compared with previous studies of ipilimumab alone. Radiotherapy-related AEs were significantly more common in patients receiving higher doses of radiation. Palliation of symptoms was reported by 77% of patients after radiotherapy. Median OS was 9 and 39 months in patients receiving radiotherapy during induction and maintenance with ipilimumab, respectively. In this retrospective study, concurrent ipilimumab and radiotherapy was neither associated with higher than expected rates of AEs nor did it abrogate palliative effects of radiotherapy or survival benefits of ipilimumab. Further studies to prospectively explore the efficacy of this therapeutic combination are warranted. Cancer Immunol Res; 1(2); 92–98. ©2013 AACR.
Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors
Authors: Chow Wing Sun , Xu Aimin , Woo Yu Cho , Tso Annette W.K. , Cheung Stephen C.W. , Fong Carol H.Y. , Tse Hung Fat , Chau Ming Tak , Cheung Bernard M.Y. , Lam Karen S.L. 
Published: July 2013

Objective—
Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects.

Approach and Results—

The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (
r
=0.32;
P
<0.001), but not in men (
r
=0.06;
P
=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (
P
=0.039), together with age (
P
<0.001) and hypertension (
P
=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted
R
2
=35.8%;
P
<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (
P
=0.01).

Conclusions—
The present study is the first demonstration that elevated serum FGF21 levels are associated with carotid atherosclerosis in humans, independent of established risk factors including adverse lipid profiles and C-reactive protein. The role of FGF21 as a biomarker or therapeutic target of atherosclerotic diseases warrants further investigation.
Risk Prediction Models for Mortality in Ambulatory Patients With Heart Failure
Authors: Alba Ana C. , Agoritsas Thomas , Jankowski Milosz , Courvoisier Delphine , Walter Stephen D. , Guyatt Gordon H. , Ross Heather J. 
Published: July 2013

Background—
Optimal management of heart failure requires accurate assessment of prognosis. Many prognostic models are available. Our objective was to identify studies that evaluate the use of risk prediction models for mortality in ambulatory patients with heart failure and describe their performance and clinical applicability.

Methods and Results—

We searched for studies in Medline, Embase, and CINAHL in May 2012. Two reviewers selected citations including patients with heart failure and reporting on model performance in derivation or validation cohorts. We abstracted data related to population, outcomes, study quality, model discrimination, and calibration. Of the 9952 studies reviewed, we included 34 studies testing 20 models. Only 5 models were validated in independent cohorts: the Heart Failure Survival Score, the Seattle Heart Failure Model, the PACE (incorporating peripheral vascular disease, age, creatinine, and ejection fraction) risk score, a model by Frankenstein et al, and the SHOCKED predictors. The Heart Failure Survival Score was validated in 8 cohorts (2240 patients), showing poor-to-modest discrimination (
c
-statistic, 0.56–0.79), being lower in more recent cohorts. The Seattle Heart Failure Model was validated in 14 cohorts (16 057 patients), describing poor-to-acceptable discrimination (0.63–0.81), remaining relatively stable over time. Both models reported adequate calibration, although overestimating survival in specific populations. The other 3 models were validated in a cohort each, reporting poor-to-modest discrimination (0.66–0.74). Among the remaining 15 models, 6 were validated by bootstrapping (
c
-statistic, 0.74–0.85); the rest were not validated.

Conclusions—
Externally validated heart failure models showed inconsistent performance. The Heart Failure Survival Score and Seattle Heart Failure Model demonstrated modest discrimination and questionable calibration. A new model derived from contemporary patient cohorts may be required for improved prognostic performance.
Predicting Clinical Outcomes After Thrombolysis Using the iScore
Authors: Saposnik Gustavo , Reeves Mathew J. , Johnston S. Claiborne , Bath Philip M.W. , Ovbiagele Bruce 
Published: July 2013

Background and Purpose—
The ischemic stroke risk score (iScore) is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. Our goal was to determine the ability of the iScore to estimate clinical outcomes after intravenous thrombolysis tissue-type plasminogen activator (tPA) in the Virtual International Stroke Trials Archive (VISTA).

Methods—

We applied the iScore (
www.sorcan.ca/iscore
) to patients with an acute ischemic stroke within the VISTA collaboration to examine the effect of tPA. We explored the association between the iScore (<200 and ≥200) and the primary outcome of favorable outcome at 3 months defined as a modified Rankin scale score of 0 to 2. Secondary outcomes included death at 3 months, catastrophic outcomes (modified Rankin scale, 4–6), and Barthel index >90 at 3 months.

Results—

Among 7140 patients with an acute ischemic stroke, 2732 (38.5%) received tPA and 711 (10%) had an iScore ≥200. Overall, tPA treatment was associated with a significant improvement in the primary outcome among patients with an iScore <200 (38.9% non-tPA versus 47.5% tPA;
P
<0.001) but was not associated with a favorable outcome among patients with an iScore ≥200 (5.5% non-tPA versus 7.6% tPA;
P
=0.45). In the multivariable analysis after adjusting for age, baseline National Institutes of Health Stroke Scale, and onset-to-treatment time, there was a significant interaction between tPA administration and iScore; tPA administration was associated with 47% higher odds of a favorable outcome at 3 months among patients with an iScore <200 (odds ratio, 1.47; 95% confidence interval, 1.30–1.67), whereas the association between tPA and favorable outcome among those with an iScore ≥200 remained nonsignificant (odds ratio, 0.80; 95% confidence interval, 0.45–1.42). A similar pattern of benefit with tPA among patients with an iScore <200, but not ≥200, was observed for secondary outcomes including death.

Conclusions—
The iScore is a useful and validated tool that helps clinicians estimate stroke outcomes. In stroke patients participating in VISTA, an iScore <200 was associated with better outcomes at 3 months after tPA.
Effects of Intensive and Moderate Public Education on Knowledge of Early Stroke Symptoms Among a Japanese Population
Authors: Morimoto Akiko , Miyamatsu Naomi , Okamura Tomonori , Nakayama Hirofumi , Toyoda Kazunori , Suzuki Kazuo , Toyota Akihiro , Hata Takashi , Yamaguchi Takenori 
Published: July 2013

Background and Purpose—
To assess the effects of intensive and moderate public education on knowledge of early stroke symptoms among a general Japanese population.

Methods—
Information on early stroke symptoms was distributed by leaflet 12× and by booklet twice in an intensive intervention area >22 months, and by leaflet and booklet once each in a moderate intervention area. No distribution occurred in the control area. Before and after the intervention, a mailed survey was conducted in the 3 areas. A total of 2734 individuals, aged 40 to 74 years, who did not select all 5 correct symptoms of stroke in the preintervention survey were eligible for our analysis.

Results—

The numbers of correct answers selected about stroke symptoms did not differ significantly among the 3 areas in the preintervention survey (
P
=0.156). In the postintervention survey, the proportions of participants who selected sudden 1-sided numbness or weakness (94.2% in the intensive intervention area, 88.3% in the moderate intervention area, and 89.2% in the control area;
P
<0.001) and sudden severe headache (76.8%, 70.1%, and 70.4%, respectively;
P
<0.001) differed significantly among the 3 areas. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for correctly choosing all 5 symptoms were 1.35 (1.07–1.71) in the intensive intervention area and 0.96 (0.74–1.24) in the moderate intervention area compared with the control area.

Conclusions—
Our findings suggest that frequent distribution of leaflets and booklets significantly improved the short-term knowledge of community residents about early symptoms of stroke.
New Appearance of Extraischemic Microbleeds on T2*-Weighted Magnetic Resonance Imaging 24 Hours After Tissue-type Plasminogen Activator Administration
Authors: Kimura Kazumi , Aoki Junya , Shibazaki Kensaku , Saji Naoki , Uemura Junichi , Sakamoto Yuki 
Published: July 2013

Background and Purpose—
It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs.

Methods—
Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis.

Results—

A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213];
P
=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%;
P
=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68–54.279;
P
=0.0046).

Conclusions—
New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.
Cerebral Atherosclerosis Is Associated With Cystic Infarcts and Microinfarcts but Not Alzheimer Pathologic Changes
Authors: Zheng Ling , Vinters Harry V. , Mack Wendy J. , Zarow Chris , Ellis William G. , Chui Helena C. 
Published: July 2013

Background and Purpose—
Some studies have reported associations between intracranial atherosclerosis and Alzheimer disease pathology. We aimed to correlate severity of cerebral atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy with neurofibrillary tangles, neuritic plaques, and cerebral infarcts.

Methods—
This autopsy study (n=163) was drawn from a longitudinal study of subcortical ischemic vascular disease, Alzheimer disease, and normal aging. Multivariable logistic regression models were used to test associations among the 3 forms of cerebrovascular disease and the presence of ischemic and neurodegenerative brain lesions. Apolipoprotein E genotype was included as a covariate in these multivariable models.

Results—
Cerebral atherosclerosis was positively associated with microinfarcts (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2–4.4) and cystic infarcts (OR, 2.0; 95% CI, 1.0–4.2) but not Alzheimer disease pathology. Arteriolosclerosis showed a positive correlation with lacunar infarcts (OR, 2.0; 95% CI, 1.0–4.2) but not Alzheimer disease pathology. Cerebral amyloid angiopathy was inversely associated with lacunar infarcts (OR, 0.6; 95% CI, 0.41–1.1), but positively associated with Braak and Braak stage (OR, 1.5; 95% CI, 1.1–2.1) and Consortium to Establish a Registry for Alzheimer Disease plaque score (OR, 1.5; 95% CI, 1.1–2.2).

Conclusions—
Microinfarcts, which have been correlated with severity of cognitive impairment, were most strongly associated with atherosclerosis. Possible pathogenetic mechanisms include artery-to-artery emboli, especially microemboli that may include atheroemboli or platelet-fibrin emboli. Arteriolosclerosis was positively, whereas cerebral amyloid angiopathy was negatively correlated with lacunar infarcts, which might prove helpful in clinical differentiation of arteriolosclerotic from cerebral amyloid angiopathy–related vascular brain injury.
Localized Increase of Chemokines in the Lumen of Human Cerebral Aneurysms
Authors: Chalouhi Nohra , Points Lauren , Pierce Gary L. , Ballas Zuhair , Jabbour Pascal , Hasan David 
Published: July 2013

Background and Purpose—
Inflammation may play an important role in the formation and rupture of cerebral aneurysms. Chemokines act as chemoattractants for leukocytes directing them toward sites of tissue inflammation. The purpose of this study was to determine whether chemokines and chemoattractant cytokines were increased in the lumen of human cerebral aneurysms.

Methods—
The concentrations of chemokines and other inflammatory molecules in blood samples drawn from the lumen of human cerebral aneurysms of 16 consecutive patients (harboring 18 aneurysms) were compared with blood samples from the femoral arteries of the same patients. Three aneurysms had ruptured.

Results—
The mean plasma concentration of regulated on activation, normal T cell expressed and secreted (RANTES), monokine-induced-by-γ-interferon (MIG), interferon-γ-induced protein-10 (IP-10), eotaxin, interleukin (IL) 8, and IL17 was significantly higher in samples taken from cerebral aneurysms compared with femoral arteries. In contrast, plasma concentrations of all remaining inflammatory molecules (except IL6) that were tested did not differ between cerebral aneurysms and femoral arteries. For unruptured aneurysms, there was a significantly higher mean plasma concentration of monocyte chemoattractant protein-1 as well as RANTES, MIG, IP-10, eotaxin, IL8, and IL17 in samples obtained from cerebral aneurysms.

Conclusions—
High plasma concentrations of chemokines (monocyte chemoattractant protein-1, RANTES, MIG, IP-10, and eotaxin) and chemoattractant cytokines (IL8 and IL17) were found in the lumen of human cerebral aneurysms. These findings suggest that there may be an active recruitment of inflammatory cells into the aneurysm wall that may be exploited therapeutically.
Morphological and Functional Assessment of Carotid Plaques Have Similar Predictive Accuracy for Coronary Artery Disease
Authors: Toutouzas Konstantinos , Benetos Georgios , Drakopoulou Maria , Michelongona Archontoula , Nikolaou Charalampia , Masoura Constantina , Stathogiannis Konstantinos , Aggeli Constantina , Tsiamis Eleftherios , Siores Elias , Stefanadis Christodoulos 
Published: July 2013

Background and Purpose—
Microwave radiometry allows noninvasive in vivo measuring of internal temperature of tissues reflecting inflammation. In the present study, we evaluated the predictive accuracy of this method for the diagnosis of coronary artery disease (CAD).

Methods—

Consecutive patients (n=287) scheduled for coronary angiography were included in the study. In carotid arteries of both groups, the following measurements were performed: (1) intima-media thickness (IMT
max
) and (2) temperature measurements by microwave radiometry (Δ
T
max
). C-statistic and net reclassification improvement were used to compare the prediction ability of the markers IMT
max
and Δ
T
max
for the presence of CAD and multivessel CAD.

Results—

Of 287 patients, 239 had stenoses ≥50% (CAD group), and 48 did not have significant stenoses (NO-CAD group). Δ
T
max
was an independent predictor for the presence of CAD and multivessel CAD, showing similar predictive accuracy to intima-media thickness, as assessed by c-statistic and net reclassification improvement.

Conclusions—
Local inflammatory activation, as detected by microwave radiometry, has similar predictive accuracy to intima-media thickness for the presence and extent of CAD.
Support for Traditional Female Roles across 32 Countries: Female Labour Market Participation, Policy Models and Gender Differences
Authors: André Stéfanie , André Stéfanie , Gesthuizen Maurice , André Stéfanie , Gesthuizen Maurice , Scheepers Peer 
Published: July 2013

Abstract
In this research we study support for traditional female roles. We test individual and contextual explanations for differences in support for traditional female roles within and across 32 countries. Higher educated, employed people and those who do not adhere to a religion are least supportive. The higher the female labour market participation, the less traditional the average citizen is: this contextual effect is stronger for women than for men. Governmental child care expenditure does not affect average levels of support for traditional female roles. Yet, we do find a significant drop in traditional attitudes for men, when governments spend more on child care. This shows the importance of including the possibility of differences in contextual effects for men and women.
Who Joins Trade Unions? Testing New Sociological Explanations
Authors: Kollmeyer Christopher 
Published: July 2013

Abstract
Why do some workers join trade unions and others do not? This article attempts to shed new light on this question by considering how certain behavioural and attitudinal differences among workers shape their propensities to join trade unions. In particular, it is hypothesized that variations in civic and political engagement, as well political and cultural values, are important but overlooked determinants of trade union membership. This hypothesis is tested with data on 12 affluent democracies from the World Value Survey. Results from binary logistic regression models indicate that individual-level variation in trade union participation positively correlates with civic and political participation, with left-leaning political views, but not with post-materialist values. The article concludes by discussing the research’s limitations and its implications for issues surrounding organized labour’s changing fortunes.
Moments of Millennium: Three Fictionalisations of Revelation 20 in Relation to Zoroastrian Eschatology
Authors: Mollett Margaret 
Published: July 2013

Abstract
While the Millennium as described in Revelation 20 is the penultimate terminus in the premillennial dispensational end-time scheme, not much attention has been given by scholars or commentators to its precise nature. Scant mention is made of the nature of human life during this period. Claiming fidelity to absolute literalism, yet lavish in artistic license, three authors have recently plotted fictional accounts of what they imagine will happen after Christ returns to earth to reign for 1000 years. These novels are 1000. . .a Novel of the Millennium by Salem Kirban, Kingdom Come by LaHaye and Jerry Jenkins and Thunder in Paradise: Satan’s Last Storm by Jonathan Cash. This article seeks to draw out a correlation between these animated accounts and the text of Revelation 20, and in a step further, to examine their apparent resemblances to ancient Iranian texts in the post-exilic period.
Status Update: The Many Faces of Intertextuality in New Testament Study
Authors: McKay Niall 
Published: July 2013

Abstract
In recent years the language of intertextuality has surfaced in many approaches to biblical interpretation. These approaches often rest on divergent and sometimes contradictory assumptions about the nature of texts. A survey of the use of intertextuality in New Testament Studies provides a snapshot of the battle lines which divide biblical scholarship today. As intertextuality is explored, the interpretive limits of historical, literary and ideological approaches are brought into focus. Concluding this survey, I argue that further productive interpretation will depend on an honest confrontation with the contradictory textual assumptions held within biblical scholarship and theology more generally.
Leafhoppers (Homoptera: Cicadellidae) that probe human skin: A review of the world literature and nineteen new records, from Panama
Authors: Núñez Edwin Domínguez , Aiello Annette 
Published: July 2013

We review the world literature on leafhoppers (Cicadellidae) that have probed human skin, update the names presented in those published reports, and sort out which are original accounts and which are citations of previous reports (Table 1). We add 19 new records, representing five subfamilies, and at least 13 genera, all from Panama (Table 2). We speculate as to why these normally phytophagous insects sometimes probe human skin, and provide insight into the possible evolutionary consequences of this behavior.