bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinic and ambulatory heart rates in patients with ischaemic heart disease and/or chronic heart failure taking rate-limiting medications: are they interchangeable?
Authors: Javed Omar , Koo Kenneth , El-Omar Omar , Allen Stuart , Squires Alexander , El-Omar Magdi 
Published: November 2014

ABSTRACT

Background
The prognostic benefit from heart rate (HR) reduction in patients with ischaemic heart disease (IHD) and/or chronic heart failure (CHF) is now firmly established. Most decisions regarding initiation and/or dose adjustment of HR-limiting medications in such patients are based on clinic HR. Yet, this is a highly variable parameter that may not necessarily reflect HR control over the 24 h period.

Objective
To examine the level of agreement between mean clinic and mean ambulatory HRs in patients with IHD and/or CHF taking rate-limiting medications.

Methods
Prospective, observational study. Fifty patients with IHD and/or CHF who attended cardiology outpatient clinics at the Manchester Heart Centre and underwent same-day 24 h continuous ECG recording between March and October 2013 were included in the study. Mean clinic HR was compared with mean 24 h, daytime and night-time HRs. Limits-of-agreement plots were constructed to examine the relationship between the two HR measures in more detail.

Results
The mean clinic HR was numerically similar to the mean HRs of all ambulatory time periods examined. However, on Bland–Altman plots, the limits of agreement between clinic and ambulatory HR means were quite wide, with the mean clinic HR ranging between 10.93 and 13.58 bpm below and 8.4 and 18.15 bpm above the mean ambulatory HR.

Conclusions
Although numerically similar, the means of clinic and ambulatory HRs in patients with IHD and/or CHF display wide limits of agreement. As such, the two measures cannot be regarded as interchangeable.
Interobserver Agreement in Describing the Ultrasound Appearance of Adnexal Masses and in Calculating the Risk of Malignancy Using Logistic Regression Models
Authors: Sladkevicius Povilas , Valentin Lil 
Published: November 2014

Abstract
Purpose: To estimate interobserver agreement with regard to describing adnexal masses using the International Ovarian Tumor Analysis (IOTA) terminology and the risk of malignancy calculated using IOTA logistic regression models LR1 and LR2, and to elucidate what explained the largest interobserver differences in calculated risk of malignancy.
Experimental Design: One hundred and seventeen women with adnexal masses were examined with transvaginal gray scale and power Doppler ultrasound by two independent experienced sonologists who described the masses using IOTA terminology. The risk of malignancy was calculated using LR1 and LR2. A predetermined risk of malignancy cutoff of 10% indicated malignancy.
Results: There were 94 benign, four borderline, and 19 invasively malignant tumors. There was substantial variability between the two sonologists in measurement results and some variability in assessment of categorical variables (agreement 40%–98%, Kappa 0.30–0.91). Interobserver agreement when classifying tumors as benign or malignant was 84% (98/117), Kappa 0.68 for LR1, and for LR2 85% (99/117), Kappa 0.68. When using LR1 and LR2, the interobserver difference in calculated risk was ≥25 percentage units in 9% (11/117) and 12% (14/117) of tumors, respectively. Differences in assessment of wall irregularity, acoustic shadowing, color score, and color flow in papillary projections explained most of these largest differences.
Conclusions: Interobserver agreement in classifying tumors as benign or malignant using the risk of malignancy cutoff of 10% for LR1 and LR2 was good. However, because risk estimates may differ substantially between sonologists, one should be cautious with using the risk value for counseling patients about their individual risk. Clin Cancer Res; 21(3); 594–601. ©2014 AACR.
Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck
Authors: Kim Han Sang , Kwon Hyeong Ju , Jung Inkyung , Yun Mi Ran , Ahn Myung-Ju , Kang Byung Woog , Sun Jong-Mu , Kim Sung Bae , Yoon Dok-Hyun , Park Keon Uk , Lee Se-Hoon , Koh Yoon Woo , Kim Se Hun , Choi Eun Chang , Koo Dong Hoe , Sohn Jin Hee , Kim Bomi , Kwon Nak-Jung , Yun Hwan Jung , Lee Min Goo , Lee Ji Hyun , Kim Tae-Min , Kim Hye Ryun , Kim Joo Hang , Paik Soonmyung , Cho Byoung Chul 
Published: November 2014

Abstract
Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN).
Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes.
Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progression-free survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9–5.0] and 6.6 months (95% CI, 5.4–10.3). Adverse events were mostly grade 1–2. Mutations in the PI3K pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005).
Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib. Clin Cancer Res; 21(3); 544–52. ©2014 AACR.
Phase I Trial of Cyclophosphamide as an Immune Modulator for Optimizing Oncolytic Reovirus Delivery to Solid Tumors
Authors: Roulstone Victoria , Khan Khurum , Pandha Hardev S. , Rudman Sarah , Coffey Matt , Gill George M. , Melcher Alan A. , Vile Richard , Harrington Kevin J. , de Bono Johann , Spicer James 
Published: November 2014

Abstract
Purpose: Reovirus is a wild-type oncolytic virus that is ubiquitous in the environment; most patients are therefore preimmune. Therapeutic administration leads to an increase in neutralizing antireovirus antibody (NARA) titer. We hypothesized that if NARA limited reovirus antitumor activity, the effect might be attenuated by coadministration of cyclophosphamide.
Experimental design: In a phase I study, patients with advanced cancer received cyclophosphamide 3 days before intravenous reovirus serotype 3 Dearing (RT3D). The primary objective was to reduce the resulting rise in NARA titer. Cyclophosphamide dose was escalated from 25–1,000 mg/m2 through nine cohorts; we aimed to define a well-tolerated immunomodulatory dose.
Results: The combination was well tolerated in 36 patients, with grade 3/4 toxicities only seen at or above the maximum tolerated dose of cyclophosphamide, which was 800 mg/m2 combined with reovirus. Immunosuppressive effect, defined as maintaining NARA titer rise below a predefined threshold, was observed in only one patient. Furthermore, despite expected myelosuppression seen at higher cyclophosphamide doses, no changes in T-cell subsets, including Tregs, occurred with dose escalation. Viable virus was detected in association with peripheral blood mononuclear cells (PBMC) from 14% of patients 10 days after the last RT3D injection, despite high plasma NARA titer, demonstrating a potential mechanism for prolonged evasion of neutralization by reovirus.
Conclusions: Coadministration of cyclophosphamide with reovirus is safe, but does not attenuate host antiviral responses. Alternative immunomodulation approaches should be explored, but association with PBMCs may allow reovirus to persist and evade even high levels of neutralizing antibodies. Clin Cancer Res; 21(6); 1305–12. ©2014 AACR.
Identifying Rare Events in Rare Diseases
Authors: Attiyeh Edward F. , Maris John M. 
Published: November 2014

Abstract
Utilizing genomic signatures from diagnostic tumor samples to forecast clinical behavior and response to therapy has long been a goal, and we are now poised to further refine how we can identify the relatively rare patients with aggressive neuroblastoma masquerading as patients with a more benign form of the disease. Clin Cancer Res; 21(8); 1782–5. ©2014 AACR.
See related article by Oberthuer et al., p. 1904
Deciphering Traditional African Education in R.S. Petersâ€™ Education as Initiation
Authors: Ndofirepi Amasa P. 
Published: November 2014

In this theoretical paper, I examine education in traditional African societies in the context of R.S. Petersâ€™ (1966) conception of â€œEducation as Initiationâ€. Philosophers of education have developed a concern and insight into the notion of education primarily by addressing the question of conceptual analysis:Â what do we mean by education and add a justificatory question: how do we know that education is valuable? Traditional conceptions of education have viewed education as the process of initiation of new entrants into the practices of a given social group. This paper focuses special interest on the extent to which traditional African view of education is defensible within the R.S. Peterâ€™s conception of education. I draw some philosophical insights by interrogating some perspectives on indoctrination and initiation in the understanding of the notion of the aim of education.
The Relationship between Personal Mastery and Teachers’ Competencies at Schools in Indonesia
Authors: Algi Settaraming , Abdul Rahman Mohd Anuar 
Published: November 2014

The purpose of the present research is to study the relationships between indicators of personal mastery and indicators of teachers’ competencies at Junior Secondary State Bone district in Indonesia. The respondents of the research consists of all the Junior Secondary State teachers of the Bone district including 200 teachers (80 males 120 females). The obtained data was analyzed by Structural Equation Modeling (SEM). The results have indicated that there exists a significant correlation between personal mastery and teachers’ competencies at the 0.05 significance level. Further, a significant positive correlation was observed between the indicators of personal mastery (personal vision, creative tension, commitment, trust, and consciousness) and indicators of teachers’ competencies (pedagogic, professional, personality, and social).
Muslim Women in Past and Present Governmental Leadership: Case of Rulers of the Sultanate of Aceh and the Fifth President of the Republic of Indonesia
Authors: Ahyat Ita Syamtasiyah 
Published: November 2014

A Muslim woman is a woman who believes in Islam. In its historical path, Indonesia has been led by Muslim women along with the development of Islam in the Archipelago in the 17th century. A case example among others is the Sultanate of Aceh during the colonial period. During the independence period, Indonesia was also led by a Muslim woman as the fifth President of the Republic of Indonesia around the early 21st century. In these case examples of Muslim women as rulers, they received criticism during their reigns from men who viewed the matter from the perspective of Islam. This made an impact on the ongoing governance and the people. The article discusses how Muslim women leaders faced these criticisms from men who viewed the matter from the point of view of Islam and how it affected their governmental administration. Therefore, the article is expected to be able to reconstruct how Muslim women leaders face criticism from men who viewed the matter from the perspective of Islam. Research in this paper is conducted through historical method actions, preceded by source collection, selection and interpretation along with the reconstruction of the intended events, which is referred to as historiography. The study is also based on local sources, documents, and writings of related critics on the issue.
Environmental Factors and Students’ Learning Approaches: A Survey on Malaysian Polytechnics Students
Authors: Mustapha Ramlee , Mokhtar Seri Bunian , Rahman Saemah , Husain Mohd Yusof , Ahamad Bahtiar Rahayu 
Published: November 2014

Several studies have shown the impact of environmental factors on student learning approaches. Despite the importance of such studies, studies on technical learners are few. Thus, this study aimed to determine the influence of learning environment on Polytechnics students’ learning approaches in Malaysia. Learning environment plays an important role in the cognitive, effective and social domains of students because it could improve students’ learning outcomes. Learning approaches refer to the ways students deal with academic tasks that are related to learning outcomes. This study used Course Experience Questionnaire (CEQ) and Revised Two-Factor Study Process Questionnaire (RSPQ-2F) to collect the research data. Data were analyzed using AMOS Version 18. Multiple regressions were conducted to predict learning environment factors that influenced the level of students’ learning approaches. The result shows that effective teaching is a major factor that influences students' deep approach followed by the assessment, learning resources and clear objectives.
Possible Involvement of Minor Lysophospholipids in the Increase in Plasma Lysophosphatidic Acid in Acute Coronary Syndrome
Authors: Kurano Makoto , Suzuki Akiko , Inoue Asuka , Tokuhara Yasunori , Kano Kuniyuki , Matsumoto Hirotaka , Igarashi Koji , Ohkawa Ryunosuke , Nakamura Kazuhiro , Dohi Tomotaka , Miyauchi Katsumi , Daida Hiroyuki , Tsukamoto Kazuhisa , Ikeda Hitoshi , Aoki Junken , Yatomi Yutaka 
Published: November 2014

Objective—
Lysophosphatidic acids (LPA) have important roles in the field of vascular biology and are derived mainly from lysophosphatidylcholine via autotaxin. However, in our previous study, only the plasma LPA levels, and not the serum autotaxin levels, increased in patients with acute coronary syndrome (ACS). The aim of this study was to elucidate the pathway by which LPA is increased in patients with ACS.

Approach and Results—
We measured the plasma lysophospholipids species in 141 consecutive patients undergoing coronary angiography (ACS, n=38; stable angina pectoris, n=71; angiographically normal coronary arteries, n=32) using a liquid chromatography-tandem mass spectrometry analysis. Among the ACS subjects, notable increases in the 22:6 LPA, 18:2 LPA, and 20:4 LPA levels were observed. The in vitro experiments revealed that serum incubation mainly increased the 18:2 LPA level, whereas platelet activation increased the 20:4 LPA level. Minor lysophospholipids other than LPA were also elevated in ACS subjects and were well correlated with the corresponding LPA species, including 22:6 LPA. A multiple regression analysis also revealed that lysophosphatidylinositol, lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylglycerol were independent explanatory variables for several LPA species.

Conclusions—
Specific LPA species, especially long-chain unsaturated LPA, were elevated in ACS patients, along with the corresponding minor lysophospholipids. The elevation of these LPA species might be mainly caused by presently unidentified LPA-producing pathway(s). Minor lysophospholipids might be involved in the generation of LPA, especially 22:6 LPA, and in the pathogenesis of ACS.
Identification of Hospital Outliers in Bleeding Complications After Percutaneous Coronary Intervention
Authors: Hess Connie N. , Rao Sunil V. , McCoy Lisa A. , Neely Megan L. , Singh Mandeep , Spertus John A. , Krone Ronald J. , Weaver W. Douglas , Peterson Eric D. 
Published: November 2014

Background—
Post-percutaneous coronary intervention (PCI) bleeding complications are an important quality metric. We sought to characterize site-level variation in post-PCI bleeding and explore the influence of patient and procedural factors on hospital bleeding performance.

Methods and Results—

Hospital-level bleeding performance was compared pre- and postadjustment using the newly revised CathPCI Registry
®
bleeding risk model (c-index, 0.77) among 1292 National Cardiovascular Data Registry
®
hospitals performing >50 PCIs from 7/2009 to 9/2012 (n=1 984 998 procedures). Using random effects models, outlier sites were identified based on 95% confidence intervals around the hospital’s random intercept. Bleeding 72 hours post-PCI was defined as: arterial access site, retroperitoneal, gastrointestinal, or genitourinary bleeding; intracranial hemorrhage; cardiac tamponade; nonbypass surgery–related blood transfusion with preprocedure hemoglobin ≥8 g/dL; or absolute decrease in hemoglobin value ≥3 g/dL with preprocedure hemoglobin ≤16 g/dL. Overall, the median unadjusted post-PCI bleeding rate was 5.2% and varied among hospitals from 2.6% to 10.4% (5th, 95th percentiles). Center-level bleeding variation persisted after case-mix adjustment (2.8%–9.5%; 5th, 95th percentiles). Although hospitals’ observed and risk-adjusted bleeding ranks were correlated (Spearman ρ: 0.88), individual rankings shifted after risk-adjustment (median Δ rank order: ±91.5; interquartile range: 37.0, 185.5). Outlier classification changed postadjustment for 29.3%, 16.1%, and 26.5% of low-, non-, and high-outlier sites, respectively. Hospital use of bleeding avoidance strategies (bivalirudin, radial access, or vascular closure device) was associated with risk-adjusted bleeding rates.

Conclusions—
Despite adjustment for patient case-mix, there is wide variation in rates of hospital PCI-related bleeding in the United States. Opportunities may exist for best performers to share practices with other sites.
Influence of Arterial Occlusion on Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Medlin Friedrich , Amiguet Michael , Vanacker Peter , Michel Patrik 
Published: November 2014

Background and Purpose—
We aimed to assess the interaction between intravenous thrombolysis (IVT) and arterial occlusion on acute cervicocerebral computed tomographic angiography on the outcome of patients with acute ischemic stroke.

Methods—
Patients from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) registry with onset-to-door-time ≤4 hours, acute cervicocerebral computed tomographic angiography, a premorbid modified Rankin Scale ≤2, and a National Institute of Health Stroke Scale (NIHSS) >4 were selected. Patients with significant intracranial arterial obstruction (≥50%–99%) and undergoing acute endovascular treatment were excluded. An interaction analysis of IVT and initial arterial occlusion for favorable 3 months outcome (modified Rankin Scale <3) were performed with adjustment for potential confounders.

Results—

Among 654 included patients, 382 (58%) showed arterial occlusion, of whom 263 (69%) received IVT. Two hundred seventy-two showed no/minimal obstruction of whom 139 (51%) received IVT. In the adjusted interaction analysis, there was a trend in favor of the arterial occlusion group (odds ratio [OR]=3.97; 95% confidence interval [CI], 0.83–18.97;
P
=0.08). IVT (versus no IVT) was associated with better outcome in patients with occlusion (adjusted OR for favorable outcome, 3.01; 95% CI, 1.10–8.28) but not in patients with no/minimal obstruction (OR, 0.76; 95% CI, 0.21–2.74). Conversely, patients with occlusion had a similar rate of favorable outcome as no/minimal obstruction when thrombolysed (OR, 0.5; 95% CI, 0.17–1.47) but had a less favorable outcome without thrombolysis (OR, 0.13; 95% CI, 0.04–0.44).

Conclusions—
In this retrospective analysis of consecutive patients with acute ischemic stroke, there was a trend for more favorable outcomes with IVT in the setting of initial arterial occlusion than in the setting of no/minimal obstruction. Before confirmation in randomized controlled studies, this information should not influence thrombolysis decisions, however.
Risk of Thromboembolic Events in Atrial Fibrillation With Chronic Kidney Disease
Authors: Zeng Wu-Tao , Sun Xiu-Ting , Tang Kai , Mei Wei-Yi , Liu Li-Juan , Xu Qing , Cheng Yun-Jiu 
Published: November 2014

Background and Purpose—
Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular atrial fibrillation (AF). We conducted a meta-analysis to summarize all published studies to investigate the link between chronic kidney disease and risk of thromboembolic events in AF.

Methods—
We performed a literature search using MEDLINE (source PubMed, 1966 to July, 2014) and EMBASE (1980 to July 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis.

Results—

Eighteen studies involving 538 479 patients and 41 719 incident thromboembolic events were identified. From the pooled analysis, AF patients with estimated glomerular filtration rate <60 mL/min compared with those with estimated glomerular filtration rate ≥60 mL/min experienced a significantly increased risk for developing thromboembolic events (relative risk, 1.62 [95% confidence interval, 1.40–1.87;
P
<0.001]). The annual rate of thromboembolic events increased by 0.41% (95% confidence interval, 0.17%–0.65%) for a 10 mL/min decrease in renal function. Addition of renal impairment to CHADS
2
slightly improved the stroke risk stratification.

Conclusions—
Impaired renal function is an independent predictor of stroke or systemic embolism in patients with nonvalvular AF. Consideration of renal function may improve stroke risk stratification in patients with AF.
Migraine Prophylaxis, Ischemic Depolarizations, and Stroke Outcomes in Mice
Authors: Eikermann-Haerter Katharina , Lee Jeong Hyun , Yalcin Nilufer , Yu Esther S. , Daneshmand Ali , Wei Ying , Zheng Yi , Can Anil , Sengul Buse , Ferrari Michel D. , van den Maagdenberg Arn M.J.M. , Ayata Cenk 
Published: November 2014

Background and Purpose—
Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression (SD) are implicated in the pathogenesis of both migraine and stroke. Spontaneous SD waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced SD susceptibility facilitates anoxic depolarizations and peri-infarct SDs and accelerates infarct growth, suggesting that susceptibility to SD is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses SD susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome.

Methods—
We measured the cortical susceptibility to SD and ischemic depolarizations, and determined tissue and neurological outcomes after middle cerebral artery occlusion in wild-type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing.

Results—
Chronic treatment with topiramate or lamotrigine reduced the susceptibility to KCl-induced or electric stimulation-induced SDs as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes were improved. Notably, treatment with a single dose of either drug was ineffective.

Conclusions—
These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury.