bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of DNMT1 silencing on malignant phenotype and methylated gene expression in cervical cancer cells
Authors: Zhang Yi , Chen Fu-qiang , Sun Ye-hong , Zhou Shu-yan , Li Ti-yuan , Chen Rui 
Published: November 2011

Abstract

Background
DNA methylation has been widely used in classification, early diagnosis, therapy and prediction of metastasis as well as recurrence of cervical cancer. DNMT methyltransferase 1 (DNMT1), which plays a significant role in maintaining DNA methylation status and regulating the expression of tumor suppressor genes. The aim of this research was to investigate the relationship between DNMT1 and abnormal methylation of tumor suppressor genes and malignant phenotype in cervical cancer.

Methods
Levels of DNMT1 mRNA and protein were detected using qPCR and Western blot, respectively. Cell proliferation was analyzed by MTT and apoptosis was performed by Annexin V-FITC/PI double staining flow cytometry, respectively. MeDIP-qPCR and qPCR were performed to measure demethylation status and mRNA re-expression level of 7 tumor-suppressor genes (CCNA1, CHFR, FHIT, PAX1, PTEN, SFRP4, TSLC1) in Hela and Siha cells after silencing DNMT1.

Results
The average expression levels of DNMT1 mRNA and protein in Hela and Siha cells were decreased significantly compared with control group. The flow cytometry and MTT results showed that Hela and Siha cells apoptosis rates and cell viabilities were 19.4 ± 2.90%, 25.7 ± 3.92% as well as 86.7 ± 3.12%, 84.16 ± 2.67% respectively 48 h after transfection (P < 0.01). Furthermore, the promoter methylation of five tumor suppressor genes was decreased with the increased mRNA expression after silencing DNMT1, whereas there were no significant changes in PTEN and FHIT genes in Hela cells, and CHFR and FHIT genes in Siha cells.

Conclusions
Our experimental results demonstrate that methylation status of DNMT1 can influence several important tumor suppressor genes activity in cervical tumorigenesis and may have the potential to become an effective target for treatment of cervical cancer.
Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study
Authors: Kim Soo Hyun , Jung Seung Eun , Oh Sang Hoon , Park Kyu Nam , Youn Chun Song 
Published: November 2011

Abstract

Background
Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department.

Methods
We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient.

Results
A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001).

Conclusions
The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations.
Effectiveness of Australian youth suicide prevention initiatives
Authors: Page Andrew , Taylor Richard , Gunnell David , Carter Greg , Morrell Stephen , Martin Graham 
Published: November 2011

BackgroundAfter an epidemic rise in Australian young male suicide rates over the 1970s to 1990s, the period following the implementation of the original National Youth Suicide Prevention Strategy (NYSPS) in 1995 saw substantial declines in suicide in young men.AimsTo investigate whether areas with locally targeted suicide prevention activity implemented after 1995 experienced lower rates of young adult suicide, compared with areas without such activity.MethodLocalities with or without identified suicide prevention activity were compared during the period of the NYSPS implementation (1995–1998) and a period subsequent to implementation (1999–2002) to establish whether annual average suicide rates were lower and declined more quickly in areas with suicide prevention activity over the period 1995–2002.ResultsMale suicide rates were lower in areas with targeted suicide prevention activity (and higher levels of funding) compared with areas receiving no activity both during (RR = 0.89, 95% CI 0.80–0.99,P= 0.030) and after (RR = 0.86, 95% CI 0.77–0.96,P= 0.009) implementation, with rates declining faster in areas with targeted activity than in those without (13%v.10% decline). However, these differences were reduced and were no longer statistically significant following adjustment for sociodemographic variables. There was no difference in female suicide rates between areas with or without targeted suicide prevention activity.ConclusionsThere was little discernible impact on suicide rates in areas receiving locally targeted suicide prevention activities in the period following the NYSPS.
Impact of positive images of a person with intellectual disability on attitudes: randomised controlled trial
Authors: Varughese Sabu John , Mendes Vania , Luty Jason 
Published: November 2011

Aims and methodTackling discrimination, stigma and inequalities in mental health is a major UK government objective yet people with intellectual disability (also known as learning disability in UK health services) continue to suffer serious stigma and discrimination. We examine the effect of viewing pictures of a person with intellectual disability on stigmatised attitudes. The 20-point Attitude to Mental Illness Questionnaire (AMIQ) was used to assess stigmatised attitudes. Members of the general public were randomised to complete the questionnaire having looked at a good (attractive) or bad (unattractive) photograph of a person with intellectual disability.ResultsQuestionnaires were received from 187 participants (response rate 74%). The mean AMIQ stigma score for the bad photo group was 1.3 (s.e. = 0.3, median 1, interquartile range (IQR) = 0–3,n= 82). The mean AMIQ score for the good photo group was 2.8 (s.e. = 0.3, median 3, IQR = 1–5,n= 105). The difference in AMIQ stigma score was highly significant (two-sidedP= 0.0001, median difference 2, Mann–WhitneyU-test).Clinical implicationsLooking at a good (attractive) picture of a person with intellectual disability significantly reduces reported stigmatised attitudes, whereas a bad (unattractive) picture has no effect.
Probability and loss: two sides of the risk assessment coin
Authors: Large Matthew M. , Nielssen Olav B. 
Published: November 2011

SummaryRisk assessment has been widely adopted in mental health settings in the hope of preventing harms such as violence to others and suicide. However, risk assessment in its current form is mainly concerned with the probability of adverse events, and does not address the other component of risk – the extent of the resulting loss. Although assessments of the probability of future harm based on actuarial instruments are generally more accurate than the categorisations made by clinicians, actuarial instruments are of little assistance in clinical decision-making because there is no instrument that can estimate the probability of all the harms associated with mental illness, or estimate the extent of the resulting losses. The inability of instruments to distinguish between the risk of common but less serious harms and comparatively rare catastrophic events is a particular limitation of the value of risk categorisations. We should admit that our ability to assess risk is severely limited, and make clinical decisions in a similar way to those in other areas of medicine – by informed consideration of the potential consequences of treatment and non-treatment.
Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study
Authors: Bliss Judith M. , Kilburn Lucy S. , Coleman Robert E. , Forbes John F. , Coates Alan S. , Jones Stephen E. , Jassem Jacek , Delozier Thierry , Andersen Jørn , Paridaens Robert , van de Velde Cornelis J.H. , Lønning Per E. , Morden James , Reise Justine , Cisar Laura , Menschik Thomas , Coombes R. Charles 
Published: November 2011

Purpose Intergroup Exemestane Study (IES), an investigator-led study in 4,724 postmenopausal patients with early-stage breast cancer has demonstrated clinically important benefits from switching adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane. Now, with longer follow-up, a large number of non–breast cancer–related events have been reported. Exploratory analyses describe breast cancer–free survival (BCFS) and explore incidence and patterns of the different competing events. Patients and Methods Patients who were disease-free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years of adjuvant endocrine therapy. At this planned analysis, the median follow-up was 91 months. Principal analysis focuses on 4,052 patients with estrogen receptor (ER) –positive and 547 with ER-unknown tumors. Results In all, 930 BCFS events have been reported (exemestane, 423; tamoxifen, 507), giving an unadjusted hazard ratio (HR) of 0.81 (95% CI, 0.71 to 0.92; P = .001) in favor of exemestane in the ER-positive/ER unknown group. Analysis partitioned at 2.5 years after random assignment showed that the on-treatment benefit of switching to exemestane (HR, 0.60; 95% CI, 0.48 to 0.75; P < .001) was not lost post-treatment, but that there was no additional gain once treatment had ceased (HR, 0.94; 95% CI, 0.80 to 1.10; P = .60). Improvement in overall survival was demonstrated, with 352 deaths in the exemestane group versus 405 deaths in the tamoxifen group (HR, 0.86; 95% CI, 0.75 to 0.99; P = .04). Of these, 222 were reported as intercurrent deaths (exemestane, 107; tamoxifen, 115). Conclusion The protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival.
Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry
Authors: Kurian Allison W. , Gong Gail D. , John Esther M. , Johnston David A. , Felberg Anna , West Dee W. , Miron Alexander , Andrulis Irene L. , Hopper John L. , Knight Julia A. , Ozcelik Hilmi , Dite Gillian S. , Apicella Carmel , Southey Melissa C. , Whittemore Alice S. 
Published: November 2011

Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.
Generation of a genetically encoded marker of rod photoreceptor outer segment growth and renewal
Authors: Willoughby John J. , Jensen Abbie M. 
Published: November 2011

Summary
Vertebrate photoreceptors are specialized light sensing neurons. The photoreceptor outer segment is a highly modified cilium where photons of light are transduced into a chemical and electrical signal. The outer segment has the typical cilary axoneme but, in addition, it has a large number of densely packed, stacked, intramembranous discs. The molecular and cellular mechanisms that contribute to vertebrate photoreceptor outer segment morphogenesis are still largely unknown. Unlike typical cilia, the outer segment is continuously regenerated or renewed throughout the life of the animal through the combined process of distal outer segment shedding and proximal outer segment growth. The process of outer segment renewal was discovered over forty years ago, but we still lack an understanding of how photoreceptors renew their outer segments and few, if any, molecular mechanisms that regulate outer segment growth or shedding have been described. Our lack of progress in understanding how photoreceptors renew their outer segments has been hampered by the difficulty in measuring rates of renewal. We have created a new method that uses heat-shock induction of a fluorescent protein that can be used to rapidly measure outer segment growth rates. We describe this method, the stable transgenic line we created, and the growth rates observed in larval and adult rod photoreceptors using this new method. This new method will allow us to begin to define the genetic and molecular mechanisms that regulate rod outer segment renewal, a crucial aspect of photoreceptor function and, possibly, viability.
Effect of ageing and pulmonary inflammation on the incidence and number of cross-bridging structures in pneumothorax patients
Authors: Sasaki Tomoaki , Takahashi Koji , Aburano Tamio 
Published: November 2011

Background There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. Purpose To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. Material and Methods Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. Results Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross-bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. Conclusion Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations.
Evaluation of cartilage surface injuries using 3D-double echo steady state (3D-DESS): Effect of changing flip angle from 40° to 90°
Authors: Moriya Susumu , Miki Yukio , Kanagaki Mitsunori , Yamamoto Akira , Okudaira Shuzo , Nakamura Shinichiro , Yokobayashi Tsuneo , Ishikawa Mitsunori 
Published: November 2011

Background In magnetic resonance imaging (MRI) with 3D-double-echo steady-state (3D-DESS) sequences, the cartilage-synovial fluid contrast is reported to be better with a flip angle of 90° than with the conventional flip angle of 40°, and the detection rate of knee cartilage injury may be improved. Purpose To compare the diagnostic performance and certainty of diagnosis with 3D-DESS images made using two flip angle settings, 40° and 90°, for knee cartilage surface lesions of Grade 2 or above confirmed by arthroscopy. Material and Methods Images were obtained with 3D-DESS flip angles of 40° and 90° at 1.0T in 13 consecutive patients (2 men, 11 women, age range 18–68 years) evaluated for superficial cartilage injury by arthroscopy. Two radiologists classified the presence or absence of cartilage damage of ≥Grade 2 as ‘positive ( p)’ or ‘negative ( n)’, respectively. The rate of agreement with arthroscopic diagnosis was then examined, and the diagnostic performance compared. Diagnostic confidence was assessed scoring the presence or absence of cartilage damage into three categories: 3 = can diagnose with absolute confidence; 2 = can diagnose with a level of certainty as probably present or probably absent; and 1 = cannot make a diagnosis. Results In a comparison of the rate of agreement between diagnosis by 3D-DESS images and arthroscopy, the rate of agreement was significantly higher and diagnostic performance was better in 90° images for the medial femoral condyle only. Diagnostic confidence was significantly better with 90° flip angle images than with 40° flip angle images for all six cartilage surfaces. Conclusion In evaluating knee cartilage surface lesions with 3D-DESS sequences, a flip angle setting of 90° is more effective than the conventional setting of 40°.
Longitudinal predictors of adherence to annual follow-up in a lung cancer screening programme
Authors: Wildstein Kimberly A , Faustini Yolanda , Yip Rowena , Henschke Claudia I , Ostroff Jamie S 
Published: November 2011

Objective To examine rates and factors associated with adherence to annual repeat lung cancer screening in two cohorts. Participants and methods The self-pay cohort ( n = 2083) was individuals aged 40 years and older with no prior cancer and a smoking history. Participants had to obtain a prescription from their doctor for the low dose, computerized tomography scan (CT), and were responsible for payment of $300 as these CT scans are not typically covered by insurance. The no-pay cohort ( n = 1304) was individuals aged 60 and older with a smoking history, and no prior cancer. The initial and one year repeat CT were provided free of charge. Rates of adherence for each cohort were analyzed by demographic variables, smoking history, family history of lung cancer, smoking status (former/current), perceived risk and worry of getting lung cancer and baseline screening CT. Results Adherence to annual follow-up was lower for the self-pay than for the no-pay cohort (62% vs. 88%). Both the self-pay and no-pay cohorts had higher adherence rates among Caucasians and those who had a college degree. A greater perceived risk of getting lung cancer increased adherence among the self-pay cohort. Non-calcified nodules found on baseline CT increased the adherence for the self-pay cohort, but decreased the adherence for the no-pay cohort. Conclusions These findings should be used in developing educational materials and targeted retention strategies to increase adherence with repeat lung cancer screening.
Minor influence of self-selection bias on the effectiveness of breast cancer screening in case-control studies in the Netherlands
Authors: Paap Ellen , Verbeek André , Puliti Donella , Broeders Mireille , Paci Eugenio 
Published: November 2011

Background Self-selection bias is considered to be a problem when evaluating the effectiveness of breast cancer service screening in case-control studies. Objective Using the incidence-based mortality method (IBM), a correction factor for the potential influence of self-selection can be derived from a group of non-screened women and a group of not-invited women. Methods Breast cancer patients, diagnosed in 1990–1995 and between the ages of 50 to 70, were selected from the Netherlands Cancer Registry and five screening regions in the Netherlands. Person-years were calculated for non-screened and not-invited women by using population data available on the number of women invited, the number of women screened and the total population. Incidence-based breast cancer mortality rates according to screening status were calculated for the five screening regions. Results Between 1990–1995, 15,541 patients were diagnosed with breast cancer. An analysis of ten-year follow-up after diagnosis resulted in 3903 breast cancer deaths, of which 2631 were not-invited and 345 were non-screened. Poisson regression analysis showed heterogeneity between the regions with a range of IBM ratios from 0.64 (95% CI: 0.46–0.90) to 1.08 (95% CI: 0.82–1.43). Conclusions Heterogeneity between the regions stresses the importance of a country- and/or region-specific estimate of self-selection. Adjusting for self-selection bias in the regional case-control studies would not change the breast cancer mortality reduction in three regions and would result in an even larger effect in two regions. Looking at the range of IBM ratios the overall influence of self-selection in the Netherlands is minor.
Primary care strategies to improve childhood immunisation uptake in developed countries: systematic review
Authors: Williams Nia , Woodward Helen , Majeed Azeem , Saxena Sonia 
Published: November 2011

Objectives To conduct a systematic review of strategies to optimize immunisation uptake within preschool children in developed countries. Design Systematic review. Setting Developed countries Participants Preschool children who were due, or overdue, one or more of their routine primary immunisations. Main outcome measures Increase in the proportion of the target population up to date with standard recommended universal vaccinations. Results Forty-six studies were included for analysis, published between 1980 and 2009. Twenty-six studies were randomized controlled trials, 11 were before and after trials, and nine were controlled intervention trials. Parental reminders showed a statistically significant increase in immunisation rates in 34% of included intervention arms. These effects were reported with both generic and specific reminders and with all methods of reminders and recall. Strategies aimed at immunisation providers were also shown to improve immunisation rates with a median change in immunisation rates of 7% when reminders were used, 8% when educational programmes were used and 19% when feedback programmes were used. Conclusion General practitioners are uniquely positioned to influence parental decisions on childhood immunisation. A variety of strategies studied in primary care settings have been shown to improve immunisation rates, including parental and healthcare provider reminders.