bluuebunny/crossref_metadata_2025_split huggingface dataset:
An exploration of counterfeit medicine surveillance strategies guided by geospatial analysis: lessons learned from counterfeit Avastin detection in the US drug supply chain
Authors: Cuomo Raphael E , Mackey Tim K 
Published: December 2014

ObjectiveTo explore healthcare policy and system improvements that would more proactively respond to future penetration of counterfeit cancer medications in the USA drug supply chain using geospatial analysis.DesignA statistical and geospatial analysis of areas that received notices from the Food and Drug Administration (FDA) about the possibility of counterfeit Avastin penetrating the US drug supply chain. Data from FDA warning notices were compared to data from 44 demographic variables available from the US Census Bureau via correlation, means testing and geospatial visualisation. Results were interpreted in light of existing literature in order to recommend improvements to surveillance of counterfeit medicines.Setting/participantsThis study analysed 791 distinct healthcare provider addresses that received FDA warning notices across 30 431 zip codes in the USA.OutcomesStatistical outputs were Pearson's correlation coefficients and t values. Geospatial outputs were cartographic visualisations. These data were used to generate the overarching study outcome, which was a recommendation for a strategy for drug safety surveillance congruent with existing literature on counterfeit medication.ResultsZip codes with greater numbers of individuals age 65+ and greater numbers of ethnic white individuals were most correlated with receipt of a counterfeit Avastin notice. Geospatial visualisations designed in conjunction with statistical analysis of demographic variables appeared more capable of suggesting areas and populations that may be at risk for undetected counterfeit Avastin penetration.ConclusionsThis study suggests that dual incorporation of statistical and geospatial analysis in surveillance of counterfeit medicine may be helpful in guiding efforts to prevent, detect and visualise counterfeit medicines penetrations in the US drug supply chain and other settings. Importantly, the information generated by these analyses could be utilised to identify at-risk populations associated with demographic characteristics. Stakeholders should explore these results as another tool to improve on counterfeit medicine surveillance.
Communication skills assessment in the final postgraduate years to established practice: a systematic review
Authors: Gillis Amy E , Morris Marie C , Ridgway Paul F 
Published: December 2014

ABSTRACT

Introduction
Communication breakdown is a factor in the majority of all instances of medical error. Despite the importance, a relative paucity of time is invested in communication skills in postgraduate curricula. Our objective is to systematically review the literature to identify the current tools used to assess communication skills in postgraduate trainees in the latter 2 years of training and in established practice.

Methods
Two reviewers independently reviewed the literature identifying communication skill assessment tools, for postgraduate trainees in the latter 2 years of training and in established practice following Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, and inclusion/exclusion criteria from January 1990 to 15 August 2014. Databases: PubMed/CINAHL/ERIC/EMBASE/PsycInfo/Psyc Articles/Cochrane.

Results
222 articles were identified; after review, 34 articles fulfilled criteria for complete evaluation; the majority (26) had a high level of evidence scoring 3 or greater on the Best Evidence Medical Education guide. 22 articles used objective structured clinical examination/standardised patient (SP)-based formats in an assessment or training capacity. Evaluation tools included author-developed questionnaires and validated tools. Nineteen articles demonstrated an educational initiative.

Conclusions
The reviewed literature is heterogeneous for objectives and measurement techniques for communication. Observed interactions, with patients or SPs, is the current favoured method of evaluation using author-developed questionnaires. The role of self-evaluation of skill level is questioned. The need for a validated assessment tool for communication skills is highlighted.
Assay Reproducibility and Interindividual Variation for 15 Serum Estrogens and Estrogen Metabolites Measured by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Fuhrman Barbara J. , Xu Xia , Falk Roni T. , Dallal Cher M. , Veenstra Timothy D. , Keefer Larry K. , Graubard Barry I. , Brinton Louise A. , Ziegler Regina G. , Gierach Gretchen L. 
Published: December 2014

Abstract
Background: Interindividual differences in estrogen metabolism may partially account for differences in risks of estrogen-responsive cancers. We conducted a proof-of-performance study to assess the reproducibility of a LC/MS-MS method for measurement of 15 serum estrogens and metabolites (all 15 termed EM) in total (conjugated+unconjugated) and unconjugated forms and describe interindividual variation.
Methods: Interindividual variation in serum EM profiles was evaluated for 20 premenopausal women, 15 postmenopausal women, and 10 men. Replicate aliquots from 10 premenopausal women, 5 postmenopausal women, and 5 men were assayed eight times over 4 weeks. Components of variance were used to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC).
Results: In postmenopausal women and men, median EM concentrations were similar and substantially lower than that in premenopausal women. Within each sex/menopausal group, the sum of all EM varied 5- to 7-fold across extreme deciles. Some EM had greater variation; total estrone varied approximately 12-fold in premenopausal and postmenopausal women. Unconjugated estradiol varied 17-fold in postmenopausal women but only 5-fold in premenopausal women and men. CVs reflecting variation across replicate measures for individuals were &lt;5% for most EM, but higher in some individuals with a low EM concentration. Overall laboratory CVs for all but one EM were &lt;2% and ICCs were &gt;99% for all EM in each group.
Conclusions: The serum EM assay has excellent laboratory reproducibility. In premenopausal women, postmenopausal women, and men, interindividual variation in EM measures is substantially greater than laboratory variation.
Impact: The serum EM assay is suitable for epidemiologic application.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2649–57. ©2014 AACR.
Suitability of Circulating miRNAs as Potential Prognostic Markers in Colorectal Cancer
Authors: Ristau Jonas , Staffa Jürgen , Schrotz-King Petra , Gigic Biljana , Makar Karen W. , Hoffmeister Michael , Brenner Herrmann , Ulrich Alexis , Schneider Martin , Ulrich Cornelia M. , Habermann Nina 
Published: December 2014

Abstract
miRNAs are crucial in cellular processes and have been shown to be abnormally expressed in cancer tissue and the circulation. Circulating miRNAs may serve as a novel class of minimally invasive biomarkers for prognosis. Within a first methodologic study, we evaluated the miRNA profile kinetics in the plasma of patients with colorectal cancer after surgical tumor removal to identify potential suitability as prognostic biomarkers. This pilot study is based on the ColoCare Study, a cohort study of newly diagnosed patients with stage I–IV colorectal cancer. Colorectal cancer pre- and postsurgical blood (2–7 days after surgery) and 6 months follow-up blood from 35 patients were examined and candidate miRNAs were investigated in the plasma. miRNA levels were measured by two-step qRT-PCR. Statistical analysis was performed using log-transformed normalized CT values using SAS 9.3. Comparing pre- and postsurgical miRNA levels revealed a statistically significant decrease of nine circulating miRNAs after surgery (miR92a, miR18a, miR320a, miR106a, miR16-2, miR20a, miR223, miR17, and miR143). Analyses of plasma levels over all three time points demonstrated a statistically significant decrease from presurgery to postsurgery and re-increase from postsurgery to the six months follow-up time point of four circulating miRNAs (miR92a, miR320a, miR106a, and miR18a). We were able to show for the first time that in plasma miRNA profiles change within days after colorectal cancer surgery. Our results underscore the role of the investigated miRNAs in colorectal cancer and their potential utility as prognostic biomarkers.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2632–7. ©2014 AACR.
Usefulness of Saliva Samples for Biomarker Studies in Radiation Research
Authors: Pernot Eileen , Cardis Elisabeth , Badie Christophe 
Published: December 2014

Abstract
Salivary biomarkers have important potential to facilitate breakthroughs in epidemiologic studies, management of emergency situations, and detection and surveillance of diseases by medical staff. During the last decade, an increasing number of studies on salivary biomarkers have been published as a consequence of the impressive development of new high-throughput technologies. Here, we present a review of salivary biomarkers potentially useful in ionizing radiation (IR) research, particularly in molecular epidemiologic studies. Although several salivary biomarkers of cancer and other IR-associated diseases have been identified, few salivary biomarkers of exposure and no biomarker of susceptibility or effects specific to IR have been reported so far. Further studies are therefore needed to fully assess the potential of saliva as a source of biomarkers in the radiation research field. Although the use of saliva samples is not without drawbacks, it could represent an ideal noninvasive alternative to blood, particularly in children and in the context of large molecular epidemiology studies on the effects of low doses of IR, where, given the expected limited magnitude of effects, an extensive number of samples is required to reach statistical significance.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2673–80. ©2014 AACR.
Chemoprevention Activity of 25-Hydroxyvitamin D in the MMTV-PyMT Mouse Model of Breast Cancer
Authors: Rossdeutscher Lionel , Li Jiarong , Luco Aimée-Lee , Fadhil Ibtihal , Ochietti Benoit , Camirand Anne , Huang Dao Chao , Reinhardt Timothy A. , Muller William , Kremer Richard 
Published: December 2014

AbstractDevelopment of oncologic conditions is often accompanied by inadequate vitamin D status. The chemoprevention ability of this molecule is of high interest for breast cancer, the most common malignancy in women worldwide. Because current effective vitamin D analogues, including the naturally occurring active metabolite 1,25-dihydroxycholecalciferol (1,25(OH)2D), frequently cause hypercalcemia at pharmacologic doses, the development of safer molecules for clinical chemopreventive use is essential. This study examines whether exogenously supplied prohormone 25-hydroxycholecalciferol (25(OH)D) can delay tumor progression in vivo without hypercalcemic effects. A low vitamin D diet (25 IU/kg) in the non-immunodeficient MMTV-PyMT mouse model of metastatic breast cancer revealed a significant acceleration of mammary neoplasia compared with normal diet (1,000 IU/kg). Systemic perfusion of MMTV-PyMT mice with 25(OH)D or 1,25(OH)2D delayed tumor appearance and significantly decreased lung metastasis, and both metabolites reduced Ki-67, cyclin D1, and ErbB2 levels in tumors. Perfusion with 25(OH)D caused a 50% raise in tumor 1,25(OH)2D levels, indicating good tumor penetration and effective activation. Importantly, in contrast with 1,25(OH)2D, perfusion with 25(OH)D did not cause hypercalcemia. In vitro treatment of cultured MMTV-PyMT mammary tumor cells with 25(OH)D inhibited proliferation, confirming local activation of the prohormone in this system. This study provides an in vivo demonstration in a non-immunodeficient model of spontaneous breast cancer that exogenous 25(OH)D delays neoplasia, tumor growth, and metastasis, and that its chemoprevention efficacy is not accompanied by hypercalcemia. Cancer Prev Res; 8(2); 120–8. ©2014 AACR.
MicroRNA-150 Protects the Heart From Injury by Inhibiting Monocyte Accumulation in a Mouse Model of Acute Myocardial Infarction
Authors: Liu Zheng , Ye Ping , Wang Sihua , Wu Jie , Sun Yuan , Zhang Anchen , Ren Linyun , Cheng Chao , Huang Xiaofan , Wang Ke , Deng Peng , Wu Chuangyan , Yue Zhang , Xia Jiahong 
Published: December 2014

Background—
MicroRNAs (miRs) and inflammatory monocytes participate in many cardiac pathophysiological processes including acute myocardial infarction (AMI). Recently, we observed that miR-150 is downregulated in injured mouse plasma after AMI as well as in human infarcted monocytes. However, the precise functional role of miR-150 in response to AMI remains unknown.

Methods and Results—

In a mouse model of AMI and in human subjects with AMI, we found that miR-150 expression was reduced in monocytes. In vitro studies showed that ectopic expression of miR-150 markedly reduced monocyte migration and proinflammatory cytokine production, whereas blockade of miR-150 had opposing effects. In vivo studies showed that overexpression of miR-150 in mice resulted in improved cardiac function, reduced myocardial infarction size, inhibition of apoptosis, and reduced inflammatory Ly-6C
high
monocyte invasion levels after AMI. Wild-type mice transplanted with miR-150 null (−/−) bone marrow cells could reverse this protective effect. Mechanistic studies demonstrated that miR-150 inhibited the expression of chemokine receptor 4 (CXCR4), thereby promoting monocyte migration.

Conclusions—
Our findings indicate that miR-150 acts as a critical regulator of monocyte cell migration and production of proinflammatory cytokines, leading to cardioprotective effects against AMI-induced injury. Thus, miR-150 may be a suitable target for therapeutic intervention in the setting of ischemic heart disease.
Phenotype and Physiological Significance of the Endocardial Smooth Muscle Cells in Human Failing Hearts
Authors: Okada Hideshi , Takemura Genzou , Kanamori Hiromitsu , Tsujimoto Akiko , Goto Kazuko , Kawamura Itta , Watanabe Takatomo , Morishita Kentaro , Miyazaki Nagisa , Tanaka Toshiki , Ushikoshi Hiroaki , Kawasaki Masanori , Miyazaki Tatsuhiko , Suzui Natsuko , Nishigaki Kazuhiko , Mikami Atsushi , Ogura Shinji , Minatoguchi Shinya 
Published: December 2014

Background—
Extravascular smooth muscle cells are often observed in the endocardium of human failing hearts. Here, we characterized the phenotype of those cells and investigated their physiological significance.

Methods and Results—

We examined left ventricular biopsy specimens obtained from 44 patients with dilated cardiomyopathy and 6 nonfailing hearts. In Masson trichrome–stained histological preparations, bundles of smooth muscle cells were seen localized in the endocardium in 23 of the 44 specimens (none of the 6 controls). These cells were immunopositive for α-smooth muscle actin, type 2 smooth muscle myosin, desmin, and calponin, but were negative for embryonic smooth muscle myosin, vimentin, fibronectin, and periostin. This profile is indicative of a late differentiation (contractile) smooth muscle phenotype. Electron microscopy confirmed that phenotype, revealing the cells to contain abundant myofilaments with dense bodies but little rough endoplasmic reticulum or Golgi apparatus. In the endocardial smooth muscle–positive group, the left ventricular end-systolic volume index (73±34 versus 105±50 mL/m
2
;
P
=0.021), left ventricular peak wall stress (164±47 versus 196±43 dynes 10
3
/cm
2
;
P
=0.023), and left ventricular end-systolic meridional wall stress (97±38 versus 121±37 dynes 10
3
/cm
2
;
P
=0.036) were all significantly smaller, and the ejection fraction was larger (41±8.8 versus 33±9.3%;
P
=0.005) than in the endocardial smooth muscle–negative group. However, no histological parameters differed between the 2 groups.

Conclusions—
Endocardial smooth muscle cell bundles in hearts with dilated cardiomyopathy exhibit a mature contractile phenotype and may play a compensatory role mitigating heart failure by reducing left ventricular wall stress and systolic dysfunction.
Clinical Presentation and Outcomes of Coronary In-Stent Restenosis Across 3-Stent Generations
Authors: Magalhaes Marco A. , Minha Sa’ar , Chen Fang , Torguson Rebecca , Omar Al Fazir , Loh Joshua P. , Escarcega Ricardo O. , Lipinski Michael J. , Baker Nevin C. , Kitabata Hironori , Ota Hideaki , Suddath William O. , Satler Lowell F. , Pichard Augusto D. , Waksman Ron 
Published: December 2014

Background—
Clinical presentation of bare metal stent in-stent restenosis (ISR) in patients undergoing target lesion revascularization is well characterized and negatively affects on outcomes, whereas the presentation and outcomes of first- and second-generation drug-eluting stents (DESs) remains under-reported.

Methods and Results—

The study included 909 patients (1077 ISR lesions) distributed as follows: bare metal stent (n=388), first-generation DES (n=425), and second-generation DES (n=96), categorized into acute coronary syndrome (ACS) or non-ACS presentation mode at the time of first target lesion revascularization. ACS was further classified as myocardial infarction (MI) and unstable angina. For bare metal stent, first-generation DES and second-generation DES, ACS was the clinical presentation in 67.8%, 71.0%, and 66.7% of patients, respectively (
P
=0.470), whereas MI occurred in 10.6%, 10.1%, and 5.2% of patients, respectively (
P
=0.273). The correlates for MI as ISR presentation were current smokers (odds ratio, 3.02; 95% confidence interval [CI], 1.78–5.13;
P
<0.001), and chronic renal failure (odds ratio, 2.73; 95% CI, 1.60–4.70;
P
<0.001), with a protective trend for the second-generation DES ISR (odds ratio, 0.35; 95% CI, 0.12–1.03;
P
=0.060). ACS presentations had an independent effect on major adverse cardiac events (death, MI, and re-target lesion revascularization) at 6 months (MI versus non-ACS: adjusted hazard ratio, 4.06; 95% CI, 1.84–8.94;
P
<0.001; unstable angina versus non-ACS: adjusted hazard ratio, 1.98; 95% CI, 1.01–3.87;
P
=0.046).

Conclusions—
ISR clinical presentation is similar irrespective of stent type. MI as ISR presentation seems to be associated with patient and not device-related factors. ACS as ISR presentation has an independent effect on major adverse cardiac events, suggesting that ISR remains a hazard and should be minimized.
Mortality Among Patients With Familial Hypercholesterolemia: A Registry‐Based Study in Norway, 1992–2010
Authors: Mundal Liv , Sarancic Mirza , Ose Leiv , Iversen Per Ole , Borgan Jens‐Kristian , Veierød Marit B. , Leren Trond P. , Retterstøl Kjetil 
Published: December 2014

Background
Untreated patients with familial hypercholesterolemia are at increased risk of premature cardiovascular death. The primary aim of this study was to investigate whether this is also the case in the statin era.

Methods and Results

In this registry‐based study, 4688 male and female patients from the Unit for Cardiac and Cardiovascular Genetics (
UCCG
) Registry with verified molecular genetic diagnosis of familial hypercholesterolemia in the period 1992–2010 were linked to the Norwegian Cause of Death Registry. Standardized mortality ratios and 95%
CI
s were estimated. There were 113 deaths. Mean age of death was 61.1 years. Cardiovascular disease was the most common cause of death (46.0%), followed by cancer (30.1%). Compared with the Norwegian population, cardiovascular disease mortality was significantly higher in the
UCCG
Registry in all age groups younger than 70 years (standardized mortality ratio 2.29, 95%
CI
1.65 to 3.19 in men and women combined; standardized mortality ratio 2.00, 95%
CI
1.32 to 3.04 in men; standardized mortality ratio 3.03, 95%
CI
1.76 to 5.21 in women). No significant differences were found in all‐cause mortality or cancer mortality.

Conclusions
Despite prescription of lipid‐lowering drugs, familial hypercholesterolemia patients still had significantly increased cardiovascular disease mortality compared with the general Norwegian population.
Serum Parathyroid Hormone and 25‐Hydroxyvitamin D Concentrations and Risk of Incident Heart Failure: The Multi‐Ethnic Study of Atherosclerosis
Authors: Bansal Nisha , Zelnick Leila , Robinson‐Cohen Cassianne , Hoofnagle Andy N. , Ix Joachim H. , Lima Joao A. , Shoben Abigail B. , Peralta Carmen A. , Siscovick David S. , Kestenbaum Bryan , de Boer Ian H. 
Published: December 2014

Background

Heart failure (
HF
) is common and is associated with high mortality. We aimed to determine associations of serum parathyroid hormone (
PTH
) and 25‐hydroxyvitamin D (25[
OH
]D) with incident
HF
and left ventricular mass.

Methods and Results

Among 6459 participants in the community‐based Multi‐Ethnic Study of Atherosclerosis, all of whom were free of prevalent clinical cardiovascular disease, we measured serum concentrations of PTH and 25(OH)D at the baseline examination. In longitudinal analyses, we tested associations of PTH and 25(OH)D with incident HF events, adjudicated by a panel of physicians. In cross‐sectional analyses of a subset of 4763 participants, we tested associations of PTH and 25(OH)D with left ventricular mass, measured by cardiac magnetic resonance imaging at baseline. Multivariable Cox proportional hazard and linear regression models were adjusted for demographics, physical examination measures, comorbidity, kidney function, and other mineral metabolism markers. Mean age was 62 years and 53% of participants were female. There were 180 incident HF events over a median (interquartile range) follow‐up time of 8.46 (7.67 to 8.63) years. Compared with participants with PTH <65 pg/
mL
, PTH ≥65 pg/
mL
was associated with a 50% greater risk of incident HF (95% CI: 3% to 210%) and a 5.3 g higher left ventricular mass (95% CI: 2.6, 7.9 g). In contrast, there was no association of 25(OH)D with risk of incident HF or elevated left ventricular mass.

Conclusions

In a racially/ethnically diverse population without prevalent cardiovascular disease, higher serum
PTH
concentration was associated with increased left ventricular mass and increased risk of incident
HF
. Further studies should be pursued to determine whether
PTH
excess may be a modifiable risk factor for
HF
.