bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships between computer-extracted mammographic texture pattern features and BRCA1/2mutation status: a cross-sectional study
Authors: Gierach Gretchen L , Li Hui , Loud Jennifer T , Greene Mark H , Chow Catherine K , Lan Li , Prindiville Sheila A , Eng-Wong Jennifer , Soballe Peter W , Giambartolomei Claudia , Mai Phuong L , Galbo Claudia E , Nichols Kathryn , Calzone Kathleen A , Olopade Olufunmilayo I , Gail Mitchell H , Giger Maryellen L 
Published: August 2014

Abstract
Introduction
Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers.

Methods
We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject’s digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject’s belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model’s discriminatory capacity.

Results
In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density.

Conclusions
Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.
Genome-wide DNA methylation profiles in progression to in situand invasive carcinoma of the breast with impact on gene transcription and prognosis
Authors: Fleischer Thomas , Frigessi Arnoldo , Johnson Kevin C , Edvardsen Hege , Touleimat Nizar , Klajic Jovana , Riis Margit LH , Haakensen Vilde D , Wärnberg Fredrik , Naume Bjørn , Helland Åslaug , Børresen-Dale Anne-Lise , Tost Jörg , Christensen Brock C , Kristensen Vessela N 
Published: August 2014

Abstract
Background
Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development.

Results
We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma.

Conclusions
This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.
Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy?
Authors: van Baarsen Lisa GM , Lebre Maria C , van der Coelen Dennis , Aarrass Saïda , Tang Man W , Ramwadhdoebe Tamara H , Gerlag Daniëlle M , Tak Paul P 
Published: August 2014

Abstract
Introduction
Accumulating evidence suggests an important role for interleukin 17 (IL-17) in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Accordingly, clinical trials aimed at blocking IL-17 have been initiated, but clinical results between patients and across different diseases have been highly variable. The objective was to determine the variability in expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the synovia of patients with arthritis.

Methods
Synovial biopsies were obtained from patients with RA (n = 11), PsA (n = 15) and inflammatory osteoarthritis (OA, n = 14). For comparison, synovia from noninflamed knee joints (n = 7) obtained from controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. We used confocal microscopy to determine which cells in the synovium express IL-17A and IL-17F, double-staining with CD4, CD8, CD15, CD68, CD163, CD31, von Willebrand factor, peripheral lymph node address in, lymphatic vessel endothelial hyaluronan receptor 1, mast cell tryptase and retinoic acid receptor-related orphan receptor γt (RORγt).

Results
IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly expressed in synovial tissues of all patient groups. Whereas IL-17RA was present mostly in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant (P < 0.05) increase of only IL-17A in arthritis patients compared to noninflamed control tissues. The expression of IL-17A, IL-17F and their receptors was similar in the different patient groups, but highly variable between individual patients. CD4+ and CD8+ cells coexpressed IL-17A, and few cells coexpressed IL-17F. IL-17A and IL-17F were not expressed by CD15+ neutrophils. Mast cells were only occasionally positive for IL-17A or IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in macrophages, as well as in blood vessels and lymphatics. This staining probably reflects receptor-bound cytokine staining. Many infiltrated cells were positive for the transcription factor RORγt. Colocalisation between RORγt and IL-17A and IL-17F indicates local IL-17 production.

Conclusions
Increased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients; it is also observed in inflammatory OA. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patients.
Online social sports networks as crime facilitators
Authors: Stottelaar Bas , Senden Jeroen , Montoya Lorena 
Published: August 2014

Abstract
Emerging technologies such as broadband services and mobile and wireless technologies create not only benefits for the community but also risks (Choo, Smith, McCusker 78: iii, 2007). The implications of these developments should be evaluated to make any necessary changes to policing, policy and legislation. This study investigates the risk of disclosure of confidential information via online public exercise routes. The study identified in particular whether a) people inadvertently disclose their home address more often indirectly via online sports tracking networks than directly via other means and whether b) gender and age play a role in this disclosure. In addition, an analysis of the temporal characteristics of runs was performed to establish the window of opportunity for a home burglary and whether running is temporally predictable by hour of day or day of week. A total of 513 RunKeeper users were selected from the Dutch cities of Enschede and Nijmegen. 231 runners (45.03%) were located via RunKeeper and 122 (23.78%) via other Internet (i.e. non-social sports network) sources. It was found that a statistical difference exists between the indirect and direct disclosure of addresses; more runners disclose their home address via online sports tracking networks than via other sources. Furthermore, it was found that age played a role in the direct disclosure of addresses but not in the indirect disclosure. Older users more often disclosed their home address directly than younger ones. Conversely, gender plays a role in the indirect disclosure but not in the direct disclosure. Men more often disclosed their home address indirectly than women. Regarding temporal characteristics, it was found that the window of opportunity for a burglary is approximately 1 hour. Furthermore, the ‘within subject’ analysis suggests that the starting hour of the run is the most predictable temporal characteristic, followed by the duration of the run and the day of the week. This research ultimately shows the extent to which the unique combination of spatial and temporal information available in online sports tracking networks can enable criminals to predict where a potential target lives and when he or she will be out running.
Brief Communication: Patient Satisfaction with the Use of Tablet Computers: A Pilot Study in Two Outpatient Home Dialysis Clinics
Authors: Schick-Makaroff Kara , Molzahn Anita 
Published: August 2014

Background: Electronic capture of patients' reports of their health is significant in clinical nephrology research because health-related quality of life (HRQOL) for patients with end-stage renal disease is compromised and assessment by patients of their HRQOL in practice is relatively uncommon. Objective: The purpose of this study was to evaluate patient satisfaction with and time involved in administering HRQOL and symptom assessment measures using tablet computers in two outpatient home dialysis clinics. Design: A cross-sectional observational study design was employed. Setting: The study was conducted in two home dialysis clinics. Patients: Fifty-six patients participated in the study; 35 males (63%) and 21 females (37%) with a mean age of 66 ± 12 (36–90 years old) were included. Forty-nine participants were on peritoneal dialysis (87%), 6 on home hemodialysis (11%), and 1 on nocturnal home hemodialysis (2%). Measurements: Measures included the Kidney Disease Quality of Life-36 (KDQOL-36), the Edmonton Symptom Assessment Scale (ESAS) and Participant's Level of Satisfaction in Using a Tablet Computer. Methods: Using a tablet computer, participants completed the three measures. Descriptive statistics and bivariate correlations were calculated. Results: Participants' satisfaction with use of the tablet computer was high; 66% were “very satisfied”, 7% “satisfied”, 2% “slightly satisfied”, and 18% “neutral”. On the 7-point Likert-type scale, the mean satisfaction score was 5.11 (SD = 1.6). Mean time to complete the measures was: Level of Satisfaction 1.15 minutes (SD = 0.41), ESAS 2.55 minutes (SD = 1.04), and KDQOL 9.56 minutes (SD = 2.03); the mean time to complete all three instruments was 13.19 minutes (SD = 2.42). There were no significant correlations between level of satisfaction and age, gender, HRQOL, time taken to complete surveys, computer experience, or comfort with technology. Comfort with technology and computer experience were highly correlated, r = .7, p (one-tailed) < 0.01. Limitations: Limitations include lack of generalizability because of a small self-selected sample of relatively healthy patients and a lack of psychometric testing on the measure of satisfaction. Conclusions: Participants were satisfied with the platform and the time involved for completion of instruments was modest. Routine use of HRQOL measures for clinical purposes may be facilitated through use of tablet computers.
Is it Ethical to Prescribe Generic Immunosuppressive Drugs to Renal Transplant Patients?
Authors: Allard Julie , Fortin Marie-Chantal 
Published: August 2014

Purpose of the review: This review was conducted to determine the ethical acceptability of prescribing generic immunosuppressive drugs to renal transplant patients. Sources of information: The literature search was conducted using Pubmed and Google Scholar. Findings: The use of generic immunosuppressive drugs (ISDs) in transplantation is a controversial topic. There is a consensus among transplant societies that clinical data is lacking and that caution should be exercised. The reluctance to use generic ISDs in organ transplantation is partly related to the fact that most are “critical dose drugs”, and that either low dosing or overdosing could have serious adverse consequences for both patients and society (i.e., the loss of scarce organs). In this paper, we examine the various ethical issues involved such as distributive justice, physician duties, risks versus benefits, conflict of interest, informed consent, and logistical and economic issues. Limitations: Our analysis was limited by the paucity of clinical data on generic ISDs and the absence of health economics studies to quantify the benefits of prescribing generic ISDs. Implications: Our study led us to conclude that it would be ethical to prescribe generic ISDs provided certain conditions were met. These include regulatory safeguards to minimize the risks of substitution; education of patients; and further clinical and health economics studies to better inform clinicians, patients and society of the risks and costs related to drug substitution.
Improvement of cardiac function by placenta-derived mesenchymal stem cells does not require permanent engraftment and is independent of the insulin signaling pathway
Authors: Passipieri Juliana A , Kasai-Brunswick Tais H , Suhett Grazielle , Martins Andreza B , Brasil Guilherme V , Campos Dilza B , Rocha Nazareth N , Ramos Isalira P , Mello Debora B , Rodrigues Deivid C , Christie Beatriz B , Silva-Mendes Bernardo J , Balduíno Alex , Sá Renato M , Lopes Laudelino M , Goldenberg Regina C , Campos de Carvalho Antonio C , Carvalho Adriana B 
Published: August 2014

Abstract
Introduction
The objective of this work was to evaluate the efficacy of placenta-derived mesenchymal stem cell (MSC) therapy in a mouse model of myocardial infarction (MI). Since MSCs can be obtained from two different regions of the human term placenta (chorionic plate or villi), cells obtained from both these regions were compared so that the best candidate for cell therapy could be selected.

Methods
For the in vitro studies, chorionic plate MSCs (cp-MSCs) and chorionic villi MSCs (cv-MSCs) were extensively characterized for their genetic stability, clonogenic and differentiation potential, gene expression, and immunophenotype. For the in vivo studies, C57Bl/6 mice were submitted to MI and, after 21 days, received weekly intramyocardial injections of cp-MSCs for 3 weeks. Cells were also stably transduced with a viral construct expressing luciferase, under the control of the murine stem cell virus (MSCV) promoter, and were used in a bioluminescence assay. The expression of genes associated with the insulin signaling pathway was analyzed in the cardiac tissue from cp-MSCs and placebo groups.

Results
Morphology, differentiation, immunophenotype, and proliferation were quite similar between these cells. However, cp-MSCs had a greater clonogenic potential and higher expression of genes related to cell cycle progression and genome stability. Therefore, we considered that the chorionic plate was preferable to the chorionic villi for the isolation of MSCs. Sixty days after MI, cell-treated mice had a significant increase in ejection fraction and a reduction in end-systolic volume. This improvement was not caused by a reduction in infarct size. In addition, tracking of cp-MSCs transduced with luciferase revealed that cells remained in the heart for 4 days after the first injection but that the survival period was reduced after the second and third injections. Quantitative reverse transcription-polymerase chain reaction revealed similar expression of genes involved in the insulin signaling pathway when comparing cell-treated and placebo groups.

Conclusions
Improvement of cardiac function by cp-MSCs did not require permanent engraftment and was not mediated by the insulin signaling pathway.
Characterization of GAB1 Expression Over the Menstrual Cycle in Women With and Without Polycystic Ovarian Syndrome Provides a New Insight Into Its Pathophysiology
Authors: Roemer K. L. , Young S. L. , Savaris R. F. 
Published: August 2014

Context:
In a previous microarray analysis, GRB2-associated binding protein 1 (GAB1), a docking protein closely related to the insulin receptor substrate, was down-regulated in endometrium of women with polycystic ovary syndrome (PCOS).

Objective:
The objective of the study was to characterize the cyclic expression of endometrial GAB1 in vivo in normal women and those with PCOS as well as investigate the possible mechanisms of endometrial regulation of GAB1 expression and action in vitro.

Design:
This was an experimental and case-control study.

Setting:
The study was conducted at a tertiary university hospital.

Patients:
Normal proven fertile women (controls; n = 31) and women with PCOS (cases; n = 26) participated in the study.

Interventions:
Interventions included timed endometrial biopsies at different phases of the menstrual cycle. Ishikawa cells were cultured with β-estradiol (E2), medroxyprogesterone acetate, and E2 + medroxyprogesterone acetate. Transfection of small interfering RNA for GAB1 in Ishikawa cells incubated with or without insulin.

Main Outcome Measures:
GAB1 mRNA expression in Ishikawa cells and in endometrium of cases and controls was measured. Protein expression of phosphorylated MAPK by Western blot was also measured. Immunohistochemical localization and expression of phosphorylated GAB1 in endometrium was also measured, using a digital histological score.

Results:
In endometrial tissue, GAB1 mRNA was reduced in the proliferative phase of PCOS women, compared with controls (P = .003; ANOVA). When all the phases of the menstrual cycle were grouped, GAB1 protein expression was reduced in endometrium of PCOS women (P &lt; .0001; Student t test). E2 increases GAB1 mRNA expression in Ishikawa cells (P = .001; ANOVA). Phosphorylated MAPK is reduced in cells transfected with small interfering RNA for GAB1 (P = .008; ANOVA) and incubated with insulin.

Conclusions:
GAB1 mRNA expression is positively modulated by E2. Endometrial GAB1 protein and mRNA expression are reduced in women with PCOS, suggesting that the endometrium of PCOS women have a defect in insulin signaling due to GAB1 down-regulation.
Metal-free Reductive Cyclization and Isomerization of Sulfanyl-1,6-diynes Using Sodium Borohydride
Authors: Ito Yukiteru , Yoshimatsu Mitsuhiro 
Published: August 2014

Abstract
In this study, we demonstrated the metal-free reductive cyclization of sulfanyl-1,6-diynes with sodium borohydride in ethanol in the presence of diazabicyclo[5.4.0]undec-7-ene. 1,6-Diynes 1 and 5a–5h bearing hydrogen or phenyl as the R2 group afforded pyrroles 2 and 6a–6e in high yields without any side reaction products such as enynyl sulfides. 1,6-Diyne (R2 = Et) produced both pyrrole and enynyl sulfides; however, the use of cesium fluoride succeeded in the selective formation of pyrrole 6f.
Preparation of Highly Dispersed Pt Nanoparticles Supported on Zeolite-templated Carbon and Catalytic Application in Hydrogenation Reaction
Authors: Jiang Chuanxia , Hara Kenji , Namba Kotaro , Kobayashi Hirokazu , Ittisanronnachai Somlak , Nishihara Hirotomo , Kyotani Takashi , Fukuoka Atsushi 
Published: August 2014

Abstract
Zeolite-templated carbon (ZTC) was utilized to prepare Pt nanoparticles as a support by using a simple impregnation method. The choice of a cationic Pt precursor led to the formation of highly and uniformly dispersed Pt nanoparticles on ZTC, which afforded high conversion in the catalytic hydrogenation of phenylacetylene.
Electrodeposition Study on a Single-crystal Titanium Dioxide Electrode: Platinum on a Niobium-doped Titanium Dioxide(110) Electrode
Authors: Takakusagi Satoru , Ogawa Takafumi , Uehara Hiromitsu , Ariga Hiroko , Shimizu Ken-ichi , Asakura Kiyotaka 
Published: August 2014

Abstract
Pt was successfully electrodeposited on a Nb-doped TiO2(110) electrode from a solution of 1 mM K2[PtCl4] and 50 mM H2SO4 using single-pulse chronoamperometry. The morphology of the deposited Pt nanoparticles was sensitive to the deposition potential and holding time. A novel method for the preparation of metal particles on a single-crystal TiO2 surface in a controlled manner has been proposed.