bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eps homology domain endosomal transport proteins differentially localize to the neuromuscular junction
Authors: Mate Suzanne E , Van Der Meulen Jack H , Arya Priyanka , Bhattacharyya Sohinee , Band Hamid , Hoffman Eric P 
Published: September 2012

AbstractBackgroundRecycling of endosomes is important for trafficking and maintenance of proteins at the neuromuscular junction (NMJ). We have previously shown high expression of the endocytic recycling regulator Eps15 homology domain-containing (EHD)1 proteinin theTorpedo californicaelectric organ, a model tissue for investigating a cholinergic synapse. In this study, we investigated the localization of EHD1 and its paralogs EHD2, EHD3, and EHD4 in mouse skeletal muscle, and assessed the morphological changes in EHD1−/−NMJs.MethodsLocalization of the candidate NMJ protein EHD1 was assessed by confocal microscopy analysis of whole-mount mouse skeletal muscle fibers after direct gene transfer and immunolabeling. The potential function of EHD1 was assessed by specific force measurement and α-bungarotoxin-based endplate morphology mapping in EHD1−/−mouse skeletal muscle.ResultsEndogenous EHD1 localized to primary synaptic clefts of murine NMJ, and this localization was confirmed by expression of recombinant green fluorescent protein labeled-EHD1 in murine skeletal musclein vivo.EHD1−/−mouse skeletal muscle had normal histology and NMJ morphology, and normal specific force generation during muscle contraction. The EHD 1–4 proteins showed differential localization in skeletal muscle: EHD2 to muscle vasculature, EHD3 to perisynaptic regions, and EHD4 to perinuclear regions and to primary synaptic clefts, but at lower levels than EHD1. Additionally, specific antibodies raised against mammalian EHD1-4 recognized proteins of the expected mass in theT. californicaelectric organ. Finally, we found that EHD4 expression was more abundant in EHD1−/−mouse skeletal muscle than in wild-type skeletal muscle.ConclusionEHD1 and EHD4 localize to the primary synaptic clefts of the NMJ. Lack of obvious defects in NMJ structure and muscle function in EHD1−/−muscle may be due to functional compensation by other EHD paralogs.
A holistic approach to visualizing business models for the internet of things
Authors: Sun Yunchuan , Yan Hongli , Lu Cheng , Bie Rongfang , Thomas Peter 
Published: September 2012

Abstract
The Internet of Things (IoT) promises huge potential economic benefits. However, current IoT applications are in their infancy and the full potential of possible business opportunities is yet to be discovered. To help realize these economic benefits, workable business models are required that show where opportunities exist. In this article we describe the Business DNA Model - a representation of a business model in terms of Design, Needs, and Aspirations, which greatly simplifies presentation, analysis, and design of business models. This model can be used by IoT stakeholders to generate and analyse stories, models, and projects for strategic management, business strategy, and innovation. We present one scenario - smart logistics - to illustrate how the Business DNA Model might be applied.
Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw
Authors: Gómez-Rodríguez Víctor Manuel , Rodríguez-Garay Benjamín , Barba-Gonzalez Rodrigo 
Published: September 2012

AbstractA cytological analysis of the microsporogenesis was carried out in theAgave tequilanaandA. angustifoliaspecies. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned2nmicrospores, allowed us to confirm the presence of2npollen as well as its frequency. In bothA. tequilanaandA. angustifoliatwo different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two2ncells and triads containing twoncells and one2ncell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with twoncells and one2ncell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of2npollen in the genusAgave. The genetic implications of the presence of2npollen in the genusAgaveare discussed.
Perfusion curve f (t) analysis of breast cancer by contrast-enhanced ultrasonography
Authors: Guo Liang , Liu Zhi-Gang , Han Pei-Hua , Yuan Quan , He Yu , Li Jun 
Published: September 2012

Background Imaging the perfusion of contrast media in breast tumors may allow improved diagnosing and treating breast cancer. Purpose To compare the perfusion curve f (t) characteristics of contrast-enhanced ultrasonography in benign and malignant breast tumors. Material and Methods Patients with breast tumors ( n = 87) were evaluated with contrast-enhanced ultrasonography and the perfusion curve f (t) parameters were calculated using Sonoliver® software to compare analysis (tumor) and reference (normal) tissue areas. Differences between breast and breast tumors were assessed. Results Compared to benign tumors, malignant tumors had faster enhancement time and a shorter mean transit time (all P values < 0.05). The intensity of the signal was also greater for malignant compared with benign tumors. Conclusion Perfusion curve f (t) parameter measurements can distinguish differences in vascular flow between malignant and benign breast tumors and may provide a new quantitative indicator of breast tumor.
The Impact of Mammographic Screening on Breast Cancer Mortality in Europe: A Review of Observational Studies
Authors: Broeders Mireille , Moss Sue , Nyström Lennarth , Njor Sisse , Jonsson Håkan , Paap Ellen , Massat Nathalie , Duffy Stephen , Lynge Elsebeth , Paci Eugenio 
Published: September 2012

Objectives To assess the impact of population-based mammographic screening on breast cancer mortality in Europe, considering different methodologies and limitations of the data. Methods We conducted a systematic literature review of European trend studies ( n = 17), incidence-based mortality (IBM) studies ( n = 20) and case-control (CC) studies ( n = 8). Estimates of the reduction in breast cancer mortality for women invited versus not invited and/or for women screened versus not screened were obtained. The results of IBM studies and CC studies were each pooled using a random effects meta-analysis. Results Twelve of the 17 trend studies quantified the impact of population-based screening on breast cancer mortality. The estimated breast cancer mortality reductions ranged from 1% to 9% per year in studies reporting an annual percentage change, and from 28% to 36% in those comparing post- and prescreening periods. In the IBM studies, the pooled mortality reduction was 25% (relative risk [RR] 0.75, 95% confidence interval [CI] 0.69–0.81) among invited women and 38% (RR 0.62, 95% CI 0.56–0.69) among those actually screened. The corresponding pooled estimates from the CC studies were 31% (odds ratio [OR] 0.69, 95% CI 0.57–0.83), and 48% (OR 0.52, 95% CI 0.42–0.65) adjusted for self-selection. Conclusions Valid observational designs are those where sufficient longitudinal individual data are available, directly linking a woman's screening history to her cause of death. From such studies, the best ‘European’ estimate of breast cancer mortality reduction is 25–31% for women invited for screening, and 38–48% for women actually screened. Much of the current controversy on breast cancer screening is due to the use of inappropriate methodological approaches that are unable to capture the true effect of mammographic screening.
The Impact of Mammographic Screening on Breast Cancer Mortality in Europe: A Review of Trend Studies
Authors: Moss Sm , Nyström L , Jonsson H , Paci E , Lynge E , Njor S , Broeders M 
Published: September 2012

Objective Analysing trends in population breast cancer mortality statistics appears a simple method of estimating the effectiveness of mammographic screening programmes. We reviewed such studies of population-based screening in Europe to assess their value. Methods A literature review identified 17 papers, of which 12 provided quantitative estimates of the impact of screening. Due to differences in comparisons and outcome measures, no pooled estimate of effectiveness was calculated. Results Comparisons included breast cancer mortality before and after the introduction of screening, trends in early and late starting areas and trends in age groups affected and unaffected by screening. Studies that calculated the percentage annual change after the start of screening found reductions of 1–9% per year (1%, 2.3–2.8% and 9% for those with adequate follow-up). Of studies that compared mortality in time periods before and after introduction of screening, three single country studies all had adequate follow-up and estimated mortality reductions ranging from 28% to 36%. Limitations of studies of population mortality rates include the inability to exclude deaths in women with breast cancer diagnosed before invitation to screening, diluting any observable impact of screening, and the gradual implementation of screening in a country or region. Conclusions Although analysing population breast cancer mortality rates over time can be a first step in examining changes following the introduction of screening, this method is of limited value for assessment of screening impact. Other methods and individual data are necessary to properly quantify the effect.
False-Positive Results in Mammographic Screening for Breast Cancer in Europe: A Literature Review and Survey of Service Screening Programmes
Authors: Hofvind Solveig , Ponti Antonio , Patnick Julietta , Ascunce Nieves , Njor Sisse , Broeders Mireille , Giordano Livia , Frigerio Alfonso , Törnberg Sven 
Published: September 2012

Objective To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. Methods A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). Results The estimated cumulative risk of a false-positive screening result in women aged 50–69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. Conclusion The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.
Communicating the Balance Sheet in Breast Cancer Screening
Authors: Giordano Livia , Cogo Carla , Patnick Julietta , Paci Eugenio 
Published: September 2012

Objective Despite the difficulties, there is a moral responsibility to provide the public with the best estimates of benefits and harms of breast cancer screening. Methods In this paper we review the issues in communication of benefits and harms of medical interventions and discuss these in terms of the principles of the balance sheet proposed in this supplement. Results The balance sheet can be seen as a tool to convey estimates based on the best available evidence and addressed to a readership wider than just potential screening participants. It reflects a re-assessment of screening efficacy, showing again that screening is effective and brings more benefits than harms. It can be viewed as an opportunity to re-affirm some basic principles of good evidence-based communication. Further research is needed to improve communication strategy, to assess the impact of this communication on women's awareness and to evaluate its utility in the informed decision-making process. Conclusion The balance sheet could be a starting point for a broader vision of informed decision-making in screening, which should also recognize the role played by ‘non-numerical’ factors on women's choice of participating in breast cancer screening.
Mammographic Screening Programmes in Europe: Organization, Coverage and Participation
Authors: Giordano Livia , Von Karsa Lawrence , Tomatis Mariano , Majek Ondrej , De Wolf Chris , Lancucki Lesz , Hofvind Solveig , Nystrom Lennarth , Segnan Nereo , Ponti Antonio 
Published: September 2012

Objectives To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. Methods We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse ( EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. Results The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50–69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4–88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9–115.2%) only 48.2% (range 28.4–92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. Conclusions The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.
Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study
Authors: Szulc P , Hofbauer L C , Rauner M , Goettsch C , Chapurlat R , Schoppet M 
Published: September 2012

ObjectiveTo assess the association between abdominal aortic calcification (AAC) and serum levels of myostatin, a negative regulator of skeletal muscle mass, which has been implicated in the development of atherosclerotic lesions in mice.Design and patientsWe assessed AAC semiquantitatively from the lateral spine scans obtained using dual energy X-ray absorptiometry in 1071 men aged 20–87 years. Serum myostatin levels were measured by an immunoassay that detects all myostatin forms.ResultsTotal myostatin serum levels did not differ between men with or without self-reported ischemic heart disease, hypertension, or diabetes mellitus. Total serum myostatin levels were higher in men with higher serum calcium levels and lower in men with higher serum concentrations of highly sensitive C-reactive protein. Men with AAC had lower myostatin levels compared with men without AAC. Prevalence of AAC (AAC score >0) was lower in the highest myostatin quartile compared with the three lower quartiles (P<0.05). After adjustment for confounders, odds of AAC (AAC score >0) were lower (OR=0.62; 95% confidence interval (95% CI), 0.45–0.85; P<0.005) for the fourth myostatin quartile vs the three lower quartiles combined. In the sub-analysis of 745 men aged ≥60 years, the results were similar: AAC prevalence was lower in the highest myostatin quartile compared with the three lower quartiles combined (OR=0.54; 95% CI, 0.38–0.78; P<0.001).ConclusionsIn older men, total myostatin serum levels are inversely correlated with AAC. Further studies are needed to investigate mechanisms underlying this association and to assess utility of myostatin as a cardiovascular marker.
Prevalence of thoracic vertebral fractures in hospitalized elderly patients with heart failure
Authors: Mazziotti G , Baracca M , Doga M , Porcelli T , Vescovi P P , Giustina A 
Published: September 2012

ObjectiveHeart failure (HF) has been associated with increased risk of fragility fractures. Indeed, most literature data on fractures were based on an historical and clinical approach focused on the identification of peripheral fractures, whereas the risk of vertebral fractures in this clinical setting is still unclear.DesignCross-sectional study.AimTo evaluate the prevalence and determinants of radiological thoracic vertebral fractures in patients with HF.MethodsThe study includes 1031 elderly hospitalized patients (491 females and 540 males; median age, 75 years; range, 65–90; 430 patients with HF) who were evaluated for the presence of thoracic vertebral fractures by quantitative morphometric analysis, using chest X-ray routinely performed in the diagnostic work-up of HF.ResultsVertebral fractures were found in 166 patients (16.1%), the prevalence being significantly higher in patients with HF as compared with those without HF, both in females (30.9 vs 15.8%; P<0.001) and in males (16.4 vs 7.4%; P=0.001). The association between HF and vertebral fractures remained statistically significant (odds ratio, 2.14; 95% CI, 1.25–3.66; P=0.01) even after adjustment for age, sex, loop diuretic therapy, anticoagulant therapy, proton pump therapy, coexistent chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, and chronic liver diseases. In patients with HF, vertebral fractures were positively correlated with female sex, duration of HF, ischemic heart disease, cigarette smoking, and treatment with anti-osteoporotic drugs, and inversely correlated with left ventricular ejection fraction.ConclusionsHospitalized patients suffering from HF are at higher risk of vertebral fractures than patients without HF in the same clinical context.
Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism
Authors: Vos Xander G , Endert Erik , Tijssen Jan G P , Wiersinga Wilmar M 
Published: September 2012

BackgroundGenetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated.ObjectiveTo test the hypothesis that subjects with susceptibility genotypes develop more severe Graves' hyperthyroidism at a younger age and after less exposure to environmental factors, with attention to gender differences.Study designA prospective observational multicenter study in 205 adult Caucasian patients with untreated first episode of Graves' hyperthyroidism.MethodsEvaluation of genotypes (HLA DRB1*03, DQA1*05, DQB1*02; CTLA4 49A/G, CT60 A/G; PTPN22 C/T) in relation to phenotypes (age, sex, severity (clinical, biochemical, and immunological)) of hyperthyroidism and environmental factors (smoking, stress questionnaires).ResultsG-alleles in CTLA4 single nucleotide polymorphisms were dose-dependently associated with younger age at the time of diagnosis and less exposure to daily hassles. In gender-specific analysis, this association is enhanced in men and attenuated in women. Males (but not females) in HLA linkage disequilibrium had more severe (biochemical and immunological) hyperthyroidism and a tendency to younger age at diagnosis, compared with those not in linkage disequilibrium.ConclusionGraves' hyperthyroidism occurs at a younger age with less exposure to environmental factors in subjects carrying susceptibility genotypes. The impact of genotypes seems to be greater in males than in females.
Pretreatment Neutrophil-to-Lymphocyte Ratio in Metastatic Castration-Resistant Prostate Cancer Patients Treated With Ketoconazole: Association with Outcome and Predictive Nomogram
Authors: Keizman Daniel , Gottfried Maya , Ish-Shalom Maya , Maimon Natalie , Peer Avivit , Neumann Avivit , Rosenbaum Eli , Kovel Svetlana , Pili Roberto , Sinibaldi Victoria , Carducci Michael A. , Hammers Hans , Eisenberger Mario A. , Sella Avishay 
Published: September 2012

Abstract

Background.
The neutrophil-to-lymphocyte ratio (NLR), an inflammation marker, is prognostic in several cancers. We assessed the association between the pretreatment NLR and outcome of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with the CYP17 inhibitor ketoconazole.

Methods.
This was an international, retrospective study of 156 mCRPC patients treated with ketoconazole. The independent effect of the pretreatment NLR and factors associated with treatment outcome were determined by multivariate analysis.

Results.
Seventy-eight patients (50%) had a ≥50% decline in prostate-specific antigen (PSA). The median progression-free survival (PFS) time was 8 months. Excluded from the analysis were 23 patients without available data on their NLR and those with a recent health event or treatment associated with a blood count change. Sixty-two patients (47%) had a pretreatment NLR &gt;3. Risk factors associated with the PFS outcome were a pretreatment NLR &gt;3 and PSA doubling time (PSADT) &lt;3 months and a prior response to a gonadotropin-releasing hormone agonist of &lt;24 months or to an antiandrogen of &lt;6 months. The number of risk factors was used to form a predictive nomogram by patient categorization into favorable (zero or one factor), intermediate (two factors), and poor (three or four factors) risk groups.

Conclusions.
In mCRPC patients treated with ketoconazole, the pretreatment NLR and PSADT, and prior response to androgen-deprivation therapy, may be associated with the PFS time and used to form a risk stratification predictive nomogram.