bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eribulin Mesylate: Mechanism of Action of a Unique Microtubule-Targeting Agent
Authors: Dybdal-Hargreaves Nicholas F. , Risinger April L. , Mooberry Susan L. 
Published: April 2015

Abstract
Eribulin mesylate (eribulin), an analogue of the marine natural product halichondrin B, is a microtubule-depolymerizing drug that has utility in the treatment of patients with breast cancer. Clinical trial results have demonstrated that eribulin treatment provides a survival advantage to patients with metastatic or locally advanced breast cancer previously treated with an anthracycline and a taxane. Furthermore, a pooled analysis of two pivotal phase III trials has demonstrated that eribulin also improves overall survival in several patient subgroups, including in women with HER2-negative disease and triple-negative breast cancer. This review covers the preclinical research that led to the clinical testing and approval of eribulin, as well as subsequent research that was prompted by distinct and unexpected effects of eribulin in the clinic. Initial studies with halichondrin B demonstrated unique effects on tubulin binding that resulted in distinct microtubule-dependent events and antitumor actions. Consistent with the actions of the natural product, eribulin has potent microtubule-depolymerizing activities and properties that distinguish it from other microtubule-targeting agents. Here, we review new results that further differentiate the effects of eribulin from other agents on peripheral nerves, angiogenesis, vascular remodeling, and epithelial-to-mesenchymal transition. Together, these data highlight the distinct properties of eribulin and begin to delineate the mechanisms behind the increased survival benefit provided by eribulin for patients. Clin Cancer Res; 21(11); 2445–52. ©2015 AACR.
Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas
Authors: Lee Misu , Wiedemann Tobias , Gross Claudia , Leinhäuser Ines , Roncaroli Federico , Braren Rickmer , Pellegata Natalia S. 
Published: April 2015

Abstract
Purpose: Novel therapeutic approaches are needed to improve the postoperative management of residual nonfunctioning pituitary adenomas (NFPA), given their high relapse rate. Here, we evaluated the antitumor efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in the only available model of spontaneous NFPAs (MENX rats).
Experimental Design: Organotypic cultures of rat primary NFPAs were incubated with NVP-BEZ235 and assessed for cell viability, proliferation, apoptosis, and PI3K/mTOR inhibition. NVP-BEZ235, or placebo, was administered to MENX rats and tumor response was monitored noninvasively by diffusion weighted-magnetic resonance imaging (DW-MRI). Following treatment, tumor tissues were investigated for cell proliferation, apoptosis, and PI3K/mTOR inhibition. Genes mediating the cytotoxic activity of NVP-BEZ235 were identified by gene-expression profiling. Among them, Defb1, encoding beta-defensin 1, was further studied for its role in pituitary cells and in human pancreatic neuroendocrine tumor (NET) cells.
Results: NVP-BEZ235 showed antiproliferative and pro-cell death activities against NFPAs both in vitro and in vivo, and the response to the drug correlated with inhibition of the PI3K pathway. DW-MRI identified early functional changes (decreased cellularity) in the adenomas before their size was affected and emerged as a useful modality to assess therapy response. The cytotoxic effect of PI3K/mTOR blockade in NFPA was mediated by several genes, including Defb1. NVP-BEZ235 treatment induced Defb1 expression in NFPAs in vitro and in vivo, and in pancreatic NET cells. High Defb1 levels sensitized NET cells to PI3K/mTOR inhibition.
Conclusions: Our findings provide rationale for clinical investigation of PI3K/mTOR inhibition in NFPAs and identify novel effectors of PI3K-mediated neuroendocrine cell survival. Clin Cancer Res; 21(14); 3204–15. ©2015 AACR.
Cellular Cholesterol Accumulation Facilitates Ubiquitination and Lysosomal Degradation of Cell Surface–Resident ABCA1
Authors: Mizuno Tadahaya , Hayashi Hisamitsu , Kusuhara Hiroyuki 
Published: April 2015

Objective—
By excreting cellular cholesterol to apolipoprotein A-I, ATP-binding cassette transporter A1 (ABCA1) mediates the biogenesis of high-density lipoprotein in hepatocytes and prevents foam cell formation from macrophages. We recently showed that cell surface–resident ABCA1 (csABCA1) undergoes ubiquitination and later lysosomal degradation through the endosomal sorting complex required for transport system. Herein, we investigated the relevance of this degradation pathway to the turnover of csABCA1 in hypercholesterolemia.

Approach and Results—
Immunoprecipitation and cell surface-biotinylation studies with HepG2 cells and mouse peritoneal macrophages showed that the ubiquitination level and degradation of csABCA1 were facilitated by treatment with a liver X receptor (LXR) agonist and acetylated low-density lipoprotein. The effects of an LXR agonist and acetylated low-density lipoprotein on the degradation of csABCA1 were repressed completely by treatment with bafilomycin, an inhibitor of lysosomal degradation, and by depletion of tumor susceptibility gene 101, a major component of endosomal sorting complex required for transport-I. RNAi analysis indicated that LXRβ inhibited the accelerated lysosomal degradation of csABCA1 by the LXR agonist, regardless of its transcriptional activity. Cell surface coimmunoprecipitation with COS1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that LXRβ interacted with csABCA1 and inhibited the ubiquitination of csABCA1. Immunoprecipitates with anti-ABCA1 antibodies from the liver plasma membranes showed less LXRβ and a higher ubiquitination level of ABCA1 in high-fat diet–fed mice than in normal chow-fed mice.

Conclusions—
Under conditions of high cellular cholesterol content, csABCA1 became susceptible to ubiquitination by dissociation of LXRβ from csABCA1, which facilitated the lysosomal degradation of csABCA1 through the endosomal sorting complex required for transport system.
Depressive Symptoms in Younger Women and Men With Acute Myocardial Infarction: Insights From the VIRGO Study
Authors: Smolderen Kim G. , Strait Kelly M. , Dreyer Rachel P. , D'Onofrio Gail , Zhou Shengfan , Lichtman Judith H. , Geda Mary , Bueno Héctor , Beltrame John , Safdar Basmah , Krumholz Harlan M. , Spertus John A. 
Published: April 2015

Background

Depression was recently recognized as a risk factor for adverse medical outcomes in patients with acute myocardial infarction (
AMI
). The degree to which depression is present among younger patients with an AMI, the patient profile associated with being a young
AMI
patient with depressive symptoms, and whether relevant sex differences exist are currently unknown.

Methods and Results

The Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study enrolled 3572 patients with
AMI
(67.1% women; 2:1 ratio for women to men) between 2008 and 2012 (at 103 hospitals in the United States, 24 in Spain, and 3 in Australia). Information about lifetime history of depression and depressive symptoms experienced over the past 2 weeks (Patient Health Questionnaire; a cutoff score ≥10 was used for depression screening) was collected during index
AMI
admission. Information on demographics, socioeconomic status, cardiovascular risk,
AMI
severity, perceived stress (14‐item Perceived Stress Scale), and health status (Seattle Angina Questionnaire, EuroQoL 5D) was obtained through interviews and chart abstraction. Nearly half (48%) of the women reported a lifetime history of depression versus 1 in 4 in men (24%;
P
<0.0001). At the time of admission for AMI, more women than men experienced depressive symptoms (39% versus 22%,
P
<0.0001; adjusted odds ratio 1.64; 95%
CI
1.36 to 1.98). Patients with more depressive symptoms had higher levels of stress and worse quality of life (
P
<0.001). Depressive symptoms were more prevalent among patients with lower socioeconomic profiles (eg, lower education, uninsured) and with more cardiovascular risk factors (eg, diabetes, smoking).

Conclusions

A high rate of lifetime history of depression and depressive symptoms at the time of an
AMI
was observed among younger women compared with men. Depressive symptoms affected those with more vulnerable socioeconomic and clinical profiles.
Disparities in Cardiovascular Research Output and Citations From 52 African Countries: A Time‐Trend, Bibliometric Analysis (1999–2008)
Authors: Bloomfield Gerald S. , Baldridge Abigail , Agarwal Anubha , Huffman Mark D. , Colantonio Lisandro D. , Bahiru Ehete , Ajay Vamadevan S. , Prabhakaran Poornima , Lewison Grant , Prabhakaran Dorairaj 
Published: April 2015

Background
Cardiovascular research output and citations of publications from Africa have historically been low yet may be increasing. However, data from the continent are limited.

Methods and Results

To evaluate the cardiovascular research output and citations from 52 African countries between 1999 and 2008, we created a bibliometric filter to capture cardiovascular research articles published in the
Web of Knowledge
based on specialist journals and title words. Two coauthors with expertise in cardiovascular medicine tested and refined this filter to achieve >90% precision and recall. We matched retrieved records with their associated citation reports and calculated the running 5‐year citation count postpublication, including the year of publication. Publications from Africa were identified by author addresses. South Africa published 872 cardiovascular research papers, Egypt 393, Tunisia 264, and Nigeria 192 between 1999 and 2008. The number of publications increased over the time period for a small number of countries (range 0.1 to 4.8 more publications per year by fractional count). Most countries' citations were low (<50), but citations were greatest for South Africa (7063), Egypt (2557), Tunisia (903), and Nigeria (540). The same countries had the greatest annual increase in 5‐year citation index values: 65 (95%
CI
: 30, 99) for South Africa, 46 (34, 58) for Egypt, 22 (15, 28) for Tunisia, and 8 (2, 14) for Nigeria. The burden of cardiovascular disease had a weak and inconsistent relationship to cardiovascular publications (
r
2
=0.07,
P
=0.05). Greater gross domestic product was associated with more cardiovascular publications in 2008 (
r
2
=0.53,
P
<0.0001).

Conclusions
The increases in cardiovascular research outputs from Africa are concentrated in a few countries. The reasons for regional differences in research outputs require further investigation, particularly relative to competing disease burdens. Higher prioritization of cardiovascular research funding from African countries is warranted.
Simple quantitation for potential serum disease biomarker peptides, primarily identified by a peptidomics approach in the serum with hypertensive disorders of pregnancy
Authors: Hamamura Kensuke , Nonaka Daisuke , Ishikawa Hitoshi , Banzai Michio , Yanagida Mitsuaki , Nojima Michio , Yoshida Koyo , Lee Lyang-Ja , Tanaka Kenji , Takamori Kenji , Takeda Satoru , Araki Yoshihiko 
Published: April 2015

Background We previously reported peptide candidates of disease biomarkers for pregnancy-induced hypertension syndrome using a novel peptidomic analytical method, BLOTCHIP®-MS. The aim of this study was to establish a sandwich enzyme-linked immunosorbent assay system for quantitation of such peptides and to validate their usefulness as disease biomarkers of pregnancy-induced hypertension syndrome including gestational hypertension/pre-eclampsia. Methods We focused on three peptide fragments, kininogen-1439–456 (PDA039), kininogen-1438–456 (PDA044) and cysteinyl α2-HS-glycoprotein341–367 (PDA071). Using polyclonal antibodies specific for each peptide, suitable conditions for the sandwich enzyme-linked immunosorbent assay system were investigated. The quantitative enzyme-linked immunosorbent assay values were confirmed by quantitative matrix assisted laser desorption/ionization time-of-flight MS analyses. Using the established enzyme-linked immunosorbent assay systems, serum samples from gestational hypertension/pre-eclampsia patients and paired serum samples from healthy pregnant females were analysed. Results The optimum sandwich enzyme-linked immunosorbent assay conditions for PDA039/044 quantitation were developed. Quantitation of PDA071 by enzyme-linked immunosorbent assay failed, presumably due to issues with polyclonal antibody specificity for the native peptide. Bland–Altman plots showed a satisfactory correlation between the serum PDA039/044 concentration by enzyme-linked immunosorbent assay and that by quantitative MS analysis. Although the PDA044 concentration showed no significant change during pregnancy, including gestational hypertension/pre-eclampsia patients, the serum PDA039 concentration was significantly increased ( P < 0.0001) in the patients. Conclusions The simple quantitation technology for PDA039 by enzyme-linked immunosorbent assay was established for the first time. PDA039 confirmed its clinical utility as a disease biomarker for gestational hypertension/pre-eclampsia by the enzyme-linked immunosorbent assay system using clinical samples. The information provided from the present study would be a new valuable addition in the field of gestational hypertension/pre-eclampsia research.
Highly sensitive reversed-phase high-performance liquid chromatography assay for the detection of Tamm–Horsfall protein in human urine
Authors: Akimoto Masaru , Hokazono Eisaku , Ota Eri , Tateishi Takiko , Kayamori Yuzo 
Published: April 2015

Background Tamm–Horsfall protein (also known as uromodulin) is the most abundant urinary protein in healthy individuals. Since initially characterized by Tamm and Horsfall, the amount of urinary excretion and structural mutations of Tamm–Horsfall protein is associated with kidney diseases. However, currently available assays for Tamm–Horsfall protein, which are mainly enzyme-linked immunosorbent assay-based, suffer from poor reproducibility and might give false negative results. Methods We developed a novel, quantitative assay for Tamm–Horsfall protein using reversed-phase high-performance liquid chromatography. A precipitation pretreatment avoided urine matrix interference and excessive sample dilution. High-performance liquid chromatography optimization based on polarity allowed excellent separation of Tamm–Horsfall protein from other major urine components. Results Our method exhibited high precision (based on the relative standard deviations of intraday [≤2.77%] and interday [≤5.35%] repetitions). The Tamm–Horsfall protein recovery rate was 100.0–104.2%. The mean Tamm–Horsfall protein concentration in 25 healthy individuals was 31.6 ± 18.8 mg/g creatinine. There was a strong correlation between data obtained by high-performance liquid chromatography and enzyme-linked immunosorbent assay ( r = 0.906), but enzyme-linked immunosorbent assay values tended to be lower than high-performance liquid chromatography values at low Tamm–Horsfall protein concentrations. Conclusions The high sensitivity and reproducibility of our Tamm–Horsfall protein assay will reduce the number of false negative results of the sample compared with enzyme-linked immunosorbent assay. Moreover, our method is superior to other high-performance liquid chromatography methods, and a simple protocol will facilitate further research on the physiological role of Tamm–Horsfall protein.
An evaluation of the reliability of the food label literacy questionnaire in Russian
Authors: Gurevich Konstantin G , Reynolds Jesse , Bifulco Lauren , Doughty Kimberly , Njike Valentine , Katz David L 
Published: April 2015

Objective: School-based nutrition education can promote the development of skills, such as food label reading, that can contribute to making healthier food choices. The purpose of this study was to assess the reliability of a Russian language version of the previously validated Food Label Literacy for Applied Nutrition Knowledge (FLLANK) questionnaire and also to evaluate the impact of school-based nutrition education programmes on nutrition knowledge and food label–reading skills in Russian adolescents and young adults. Methods: Two nutrition education study programmes were administered to two separate groups of students – at a middle school ( n = 23) and a university ( n = 17). The study programmes consisted of a single 2-hour classroom session and emphasised basic nutrition and food components. The FLLANK questionnaire was administered to both groups of students before and after the intervention to assess change in food label–reading skills. Cronbach’s α was calculated for the post-test scores to assess the instrument’s internal consistency. Results: Middle school students increased their mean FLLANK scores from 54% to 95% ( p < .01). University students increased their scores from 46% to 91% ( p < .01). In the school group only, there was an interaction between time and gender, with boys improving significantly more than girls ( p < .05). The Cronbach’s α estimates were low for both groups: −.15 and .03 for school and university, respectively. Conclusion: Food label literacy improved among Russian adolescents and young adults after the implementation of nutrition education curricula. The translated version of the FLLANK retained its utility for capturing change in food label literacy, but performed very poorly with regard to internal consistency. Additional research with larger sample size and variance of scores to assess reliability is needed.
Nice to your heart: A pilot community-based intervention to improve heart health behaviours in urban residents
Authors: Carter Stephanie R , Walker Alia , Abdul-Latif Safiyah , Maurer Laurie , Masunungure Daniel , Tedaldi Ellen , Patterson Freda 
Published: April 2015

Objective: Efforts to improve cardiovascular health among adult African American populations, particularly through organised physical activity, have met with limited success. This study pilot-tested a novel soul line dancing and nutrition education programme ( Nice to Your Heart) that was designed and implemented as part of an academic community-based collaboration. Design: Eight, 2-hour sessions were delivered to 38 eligible and consenting participants. Each session included 60 minutes of soul line dancing and up to 30 minutes of nutrition education. Methods: The outcomes of programme attendance including days physically active and fruit and vegetable consumption in the last week, as well as blood pressure, were assessed. Results: In all, 58% of the sample ( N = 13) attended five or more sessions, with women and those not currently employed more likely to achieve high attendance. Improvements in days active in the last week ( t = −8.69, p < .01) and fruit consumption ( t = −0.03, p = .04) were observed. Conclusion: These data show that this culturally sensitive programme of soul line dancing and nutrition education was well received and had positive indications for improved cardiovascular health in a high-risk group. A fully controlled trial is warranted to determine programme effectiveness.
Evaluation of interictal autonomic function during attack and remission periods in cluster headaches
Authors: Altiokka Ozlem , Mutluay Belgin , Koksal Ayhan , Ciftci-Kavaklioglu Beyza , Ozturk Musa , Altunkaynak Yavuz , Baybas Sevim , Soysal Aysun 
Published: April 2015

Objective To investigate which part of the autonomic system is mainly involved and assess the sensitivity of face sympathetic skin response in cluster headache. Material and methods The study sample consisted of 19 drug-free cluster headache patients (16 males, three females) and 19 healthy volunteers. Demographic features and pain characteristics were thoroughly identified. Dysautonomic symptoms were evaluated during attack and remission periods of cluster headache patients. Orthostatic hypotension, R-R interval variation and sympathetic skin responses obtained from the face and four extremities were evaluated and the sensitivity of face sympathetic skin responses was assessed in contrast to extremity sympathetic skin responses. Results All sympathetic skin responses of face and extremities could be obtained during attack and remission periods. On the symptomatic side, mean latency of face sympathetic skin responses was longer compared to the asymptomatic side and controls (p = 0.02, p = 0.004). There were no differences in latency or amplitude of extremity sympathetic skin responses between symptomatic and asymptomatic sides and controls. No significant relationship was determined between sympathetic skin responses, R-R interval variation, orthostatic hypotension and cluster headache clinical features. Conclusion Sympathetic hypoactivity of the face seems to predominate the pathophysiology of cluster headache. Face sympathetic skin responses might be more sensitive compared to extremity sympathetic skin response in demonstrating dysautonomic symptoms in cluster headache patients.
Models for estimating projections for disease prevalence and burden: a systematic review focusing on chronic obstructive pulmonary disease
Authors: McLean Susannah , Barbour Victoria , Wild Sarah , Simpson Colin , Sheikh Aziz 
Published: April 2015

Objective Epidemiological models for estimating the prevalence and burden of disease inform health policy and service planning decisions. Our aim was to describe the challenges in evaluating such models using the example of epidemiological models for chronic obstructive pulmonary disease (COPD). Methods Two reviewers searched Medline, Embase, CAB Abstracts and World Health Organization (WHO) Databases from 1980 to November 2013 for epidemiological models of COPD prevalence and burden. Two reviewers extracted data and assessed the quality of the studies. We then undertook a descriptive and narrative synthesis of data. Results We identified 22 models employing a variety of techniques to calculate the prevalence and/or burden of COPD. Models calculated prevalence and/or mortality or other facet of disease burden using demographics and risk factors or trends, Markov-type modelling and microsimulation modelling. The six models which scored highly on the quality framework were: the Peabody model, which generated estimates of COPD prevalence; the WHO DISMOD II model which produced burden estimates in terms of disability adjusted life years with COPD and life years lost to COPD; the Atsou model which gave the life expectancy gains of individual smokers who quit smoking and associated costs; two Dutch COPD models which produced estimates of mortality and health care costs related to COPD; and the Pichon–Riviere model which gave the costs and cost effectiveness of smoking quit programmes. Conclusions The field of chronic disease modelling is burgeoning. As a result, policy makers need to understand how to interpret epidemiological models and their data sources.