bluuebunny/crossref_metadata_2025_split huggingface dataset:
Issues in implementing prenatal screening for cystic fibrosis: results of a working conference
Authors: Haddow J.E. , Bradley L.A. , Palomaki G.E. , Doherty R.A. 
Published: May 2013

Objective To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Methods Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Results Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Conclusions Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis.
Women with false positive screening mammograms: how do they cope?
Authors: Olsson P. , Armelius K. , Nordahl G. , Lenner P. , Westman G. 
Published: May 2013

Objectives To assess the long term psychological impact on women who were recalled for further investigation after mammography screening and to find any factors that might predict coping ability in order to identify those subjects who require additional support at an earlier stage. Setting Counties of Västerbotten and Västernorrland, Sweden. Methods A prospective design was used in which 252 recalled women completed questionnaires twice—once within a week of having received the all-clear and again at follow up six months later. A group of 1104 randomly selected, screen negative women were followed up in the same way for comparison. The questionnaire included the Psychological Consequences Questionnaire (PCQ) and basic sociodemographic data. The main outcome measure was the total score on the PCQ at six months. Results Of the 252 women, 235 (93%) completed both questionnaires. In the control group, 987 (89.4%) women responded. Six months after the all-clear, recalled women were still significantly more anxious (p<0.001) than those who had been screened but not recalled. The strongest predictor of psychological distress at six months was the PCQ score at the first measurement. Other predictors were a low level of education, living in high density urban areas, and having only one child or no children at all. Widows appeared to cope better than other women. Conclusions It is possible to define a group of women with false positive results who are already at risk of coping less effectively at the time of recall. Offering these women counselling or other types of support should be considered.
Implementation of screening as a public health policy: issues in design and evaluation
Authors: Hakama M. , Pukkala E. , Söderman B. , Day N. 
Published: May 2013

Objective To propose principles of design and measures of effect for cancer screening as a public health policy. Material Finnish routine screening programme with mammography. Design Evaluation of mortality from breast cancer by before-after time trends among Finnish women, by geographical (by municipalities) comparisons, and by intention to screen at an individual level with individual controls who were cluster randomised and matched for age. Outcome measuresStandardised mortality ratios (SMRs) from breast cancer (total), SMRs from breast cancers diagnosed during the screening programme (refined), deaths prevented, prolongation of life for each breast cancer detected, for each death prevented, for each compliant woman, for each screen, and for each invitation. Relative prolongation of life—that is, time gained versus time spent. Results SMRs only at an individual level with deaths from cancers diagnosed during the screening programme and individually selected controls showed 24% protection, whereas the other SMR measures were too crude or biased because of dilution and selection. Prolongation of life varied from 15 years for each death prevented to two days for each woman screened, with approximation for the prolongation relative to time spent of 3 to 1. Conclusions A public health policy should be introduced gradually. Those not covered immediately by the policy serve as controls and they should be randomly allocated. The most relevant outcome measure is prolongation of life, and for public health purposes it should be given per unit of intervention, such as screen or invitation, and also related to the time spent for the intervention. Such gains are often small in a Western society, which implies that medicine, including research, should focus more on other aspects of life than length.
The adherence ofTrichomonas vaginalisto host ectocervical cells is influenced by lactobacilli
Authors: Phukan Niha , Parsamand Tina , Brooks Anna E S , Nguyen Tan N M , Simoes-Barbosa Augusto 
Published: May 2013

ObjectivesTrichomoniasis is a common sexually transmitted disease, and adhesion of the pathogenTrichomonas vaginalisto the host vaginal cells is the first step in establishing infection. For this to happen, the pathogen has to overcome a natural protective barrier composed mostly of lactobacilli. The objective of this study was to understand the role of lactobacilli in the adhesion ofT vaginalisto host cells.MethodsAdhesion assays were carried out by incubating vaginal epithelial cells (VECs) withT vaginalisand lactobacilli together and compared with non-lactobacilli recipient controls. By varying incubation parameters and testing several microbial isolates, the number of pathogens that adhered to the VECs was determined by flow cytometry.ResultsOverall, but with few exceptions, lactobacilli caused inhibition ofT vaginalisadhesion to a variable degree.Lactobacillus gasseriATCC 9857 and CBI3 (ambiguousLactobacillus plantarumorLactobacillus pentosus) caused the highest level of parasite adhesion inhibition and enhancement, respectively. These isolates ofLactobacilluscan profoundly alter the adhesive properties of low-adherent and high-adherent strains ofT vaginalisin a dose-dependent manner. Additionally, the effects of lactobacilli onT vaginalisadhesion are strictly contact-dependent, and surface lipoglycans ofT vaginalisare most likely not involved in this modulation of adhesion mediated by the bacteria.ConclusionsLactobacilli can modulate adhesion ofT vaginalisby significantly modifying the natural adhesive properties of variousT vaginalisstrains. This study highlights the importance of considering the role of the vaginal microbiota in the pathogenesis of trichomoniasis.
Chromatin Regulator PRC2 Is a Key Regulator of Epigenetic Plasticity in Glioblastoma
Authors: Natsume Atsushi , Ito Motokazu , Katsushima Keisuke , Ohka Fumiharu , Hatanaka Akira , Shinjo Keiko , Sato Shinya , Takahashi Satoru , Ishikawa Yuta , Takeuchi Ichiro , Shimogawa Hiroki , Uesugi Motonari , Okano Hideyuki , Kim Seung U. , Wakabayashi Toshihiko , Issa Jean-Pierre J. , Sekido Yoshitaka , Kondo Yutaka 
Published: May 2013

Abstract
Tumor cell plasticity contributes to functional and morphologic heterogeneity. To uncover the underlying mechanisms of this plasticity, we examined glioma stem-like cells (GSC) where we found that the biologic interconversion between GSCs and differentiated non-GSCs is functionally plastic and accompanied by gain or loss of polycomb repressive complex 2 (PRC2), a complex that modifies chromatin structure. PRC2 mediates lysine 27 trimethylation on histone H3 and in GSC it affected pluripotency or development-associated genes (e.g., Nanog, Wnt1, and BMP5) together with alterations in the subcellular localization of EZH2, a catalytic component of PRC2. Intriguingly, exogenous expression of EZH2-dNLS, which lacks nuclear localization sequence, impaired the repression of Nanog expression under differentiation conditions. RNA interference (RNAi)–mediated attenuation or pharmacologic inhibition of EZH2 had little to no effect on apoptosis or bromodeoxyuridine incorporation in GSCs, but it disrupted morphologic interconversion and impaired GSC integration into the brain tissue, thereby improving survival of GSC-bearing mice. Pathologic analysis of human glioma specimens revealed that the number of tumor cells with nuclear EZH2 is larger around tumor vessels and the invasive front, suggesting that nuclear EZH2 may help reprogram tumor cells in close proximity to this microenvironment. Our results indicate that epigenetic regulation by PRC2 is a key mediator of tumor cell plasticity, which is required for the adaptation of glioblastoma cells to their microenvironment. Thus, PRC2-targeted therapy may reduce tumor cell plasticity and tumor heterogeneity, offering a new paradigm for glioma treatment. Cancer Res; 73(14); 4559–70. ©2013 AACR.
Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy
Authors: Nogueira Veronique , Hay Nissim 
Published: May 2013

Abstract
Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases, including cancers. Cancer cells have increased ROS levels compared with normal cells, because of their accelerated metabolism. The high ROS levels in cancer cells, which distinguish them from normal cells, could be protumorigenic, but are also their Achilles' heel. The high ROS content in cancer cells renders them more susceptible to oxidative stress–induced cell death, and can be exploited for selective cancer therapy. In this review, we describe several potential therapeutic strategies that take advantage of ROS imbalance in cancer cells by further increasing oxidative stress, either alone or in combination with drugs that modulate certain signaling pathways. Clin Cancer Res; 19(16); 4309–14. ©2013 AACR.
Strengthening Context-Dependent Anticancer Effects on Non–Small Cell Lung Carcinoma by Inhibition of Both MET and EGFR
Authors: Zhang Yu-Wen , Staal Ben , Essenburg Curt , Lewis Steven , Kaufman Dafna , Vande Woude George F. 
Published: May 2013

Abstract
The MET and EGFR receptor tyrosine kinases (RTK) are often coexpressed and may cross-talk in driving the development and progression of non–small cell lung carcinoma (NSCLC). In addition, MET amplification is an alternative resistance mechanism for escaping EGFR-targeted therapy. To assess the benefits of combined targeting of MET and EGFR for treating NSCLCs, we investigated the activities of these two RTK pathways in NSCLC cell lines and evaluated their responses to SGX523 and erlotinib, the small-molecule kinase inhibitors of MET and EGFR, respectively. We showed that MET interacts with and cross-activates EGFR in MET-amplified or -overexpressed cells. The inhibition of both MET and EGFR results in maximal suppression of downstream signaling and of cell proliferation when their ligands are present. Furthermore, we showed that SGX523 plus erlotinib strengthens anticancer activity in vivo in a cellular context–dependent manner. The combination led to the regression of H1993 tumors by enhancing the suppression of proliferation and inducing apoptosis, whereas H1373 tumor growth was significantly reduced by the combination via suppression of proliferation without inducing apoptosis. SGX523 alone was sufficient to achieve near-complete regression of EBC-1 tumors; its combination with erlotinib strongly inhibited the viability of a population of insensitive cells emerging from an SGX523-treated EBC-1 tumor recurrence. Our data suggest that inhibition of both MET and EGFR can enhance anticancer effects against NSCLCs in a context-dependent manner and thus provide a strong rationale for combining MET and EGFR inhibitors in treating NSCLCs. Mol Cancer Ther; 12(8); 1429–41. ©2013 AACR.
Pharmacologic Activation of PKM2 Slows Lung Tumor Xenograft Growth
Authors: Parnell K. Mark , Foulks Jason M. , Nix Rebecca N. , Clifford Adrianne , Bullough Jeremy , Luo Bai , Senina Anna , Vollmer David , Liu Jihua , McCarthy Virgil , Xu Yong , Saunders Michael , Liu Xiao-Hui , Pearce Scott , Wright Kevin , O'Reilly Marc , McCullar Michael V. , Ho Koc-Kan , Kanner Steven B. 
Published: May 2013

Abstract
Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small-molecule PKM2 activators. The compounds exhibited low nanomolar activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of multiple lung cancer cell lines when serine was absent from the cell culture media. In addition, PKM2 activators inhibited the growth of an aggressive lung adenocarcinoma xenograft. These findings show that PKM2 activation by small molecules influences the growth of cancer cells in vitro and in vivo, and suggest that such compounds may augment cancer therapies. Mol Cancer Ther; 12(8); 1453–60. ©2013 AACR.
Preclinical Evaluation of Transcriptional Targeting Strategy for Human Hepatocellular Carcinoma in an Orthotopic Xenograft Mouse Model
Authors: Sia Kian Chuan , Huynh Hung , Chung Alexander Yaw Fui , Ooi London Lucien Peng Jin , Lim Kiat Hon , Hui Kam Man , Lam Paula Yeng Po 
Published: May 2013

Abstract
Gene regulation of many key cell-cycle players in S-, G2 phase, and mitosis results from transcriptional repression in their respective promoter regions during the G0 and G1 phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle–dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma. Mol Cancer Ther; 12(8); 1651–64. ©2013 AACR.
The Ancient Blue Oak Woodlands of California: Longevity and Hydroclimatic History
Authors: Stahle D. W. , Griffin R. D. , Meko D. M. , Therrell M. D. , Edmondson J. R. , Cleaveland M. K. , Stahle L. N. , Burnette D. J. , Abatzoglou J. T. , Redmond K. T. , Dettinger M. D. , Cayan D. R. 
Published: May 2013

AbstractAncient blue oak trees are still widespread across the foothills of the Coast Ranges, Cascades, and Sierra Nevada in California. The most extensive tracts of intact old-growth blue oak woodland appear to survive on rugged and remote terrain in the southern Coast Ranges and on the foothills west and southwest of Mt. Lassen. In the authors' sampling of old-growth stands, most blue oak appear to have recruited to the canopy in the middle to late nineteenth century. The oldest living blue oak tree sampled was over 459 years old, and several dead blue oak logs had over 500 annual rings. Precipitation sensitive tree-ring chronologies up to 700 years long have been developed from old blue oak trees and logs. Annual ring-width chronologies of blue oak are strongly correlated with cool season precipitation totals, streamflow in the major rivers of California, and the estuarine water quality of San Francisco Bay. A new network of 36 blue oak chronologies records spatial anomalies in growth that arise from latitudinal changes in the mean storm track and location of landfalling atmospheric rivers. These long, climate-sensitive blue oak chronologies have been used to reconstruct hydroclimatic history in California and will help to better understand and manage water resources. The environmental history embedded in blue oak growth chronologies may help justify efforts to conserve these authentic old-growth native woodlands.
Facial Lesions Negatively Impact Affect Display
Authors: Godoy Andres , Ishii Masaru , Dey Jacob , Boahene Kofi D. O. , Byrne Patrick J. , Ishii Lisa E. 
Published: May 2013

ObjectiveTo evaluate the impact of facial lesions on affect display in patients as compared with individuals without lesions.Study DesignProspective randomized controlled experiment.SettingAcademic tertiary referral center.Subjects and MethodsForty‐five normal observers viewed photographs of normal faces in repose and faces with lesions in repose. Observers classified the affect display of the patients and the normals using a survey containing choices of primary emotions and personal attributes. Latent class analysis was used to find the unmeasured or “latent” classes. Latent class regression was used to determine the impact of lesion size and location on class membership. Finally, lesion classes and normal classes were checked for differences.ResultsLatent class analysis identified 4 independent latent classes for faces with lesions. The normal data were best fit by 3 latent classes. As a group, faces with lesions were most likely to be classified as either negative‐sad or negative‐angry, accounting for a combined probability of 44%. This was in contrast to the normal group, where 62% were classified as positive and only 13.9% as negative. Size and location significantly affected negative class membership. There were significant differences in the lesion classes as compared with the normal classes.ConclusionFaces with lesions were reported to display different affect in repose than normal faces in repose. The classification of the lesion faces was dependent on lesion size and location. These findings provide the first objective evidence of the affect display penalty caused by facial lesions.
Body Mass Index, Immune Status, and Virological Control in HIV-Infected Men Who Have Sex with Men
Authors: Blashill Aaron J. , Mayer Kenneth H. , Crane Heidi M. , Grasso Chris , Safren Steven A. 
Published: May 2013

Background and Aims: Prior cross-sectional studies have found inconsistent relationships between body mass index (BMI) and disease progression in HIV-infected individuals. Methods: Cross-sectional and longitudinal analyses were conducted on data from a sample of 864 HIV-infected men who have sex with men (MSM) obtained from a large, nationally distributed HIV clinical cohort. Results: Of the 864 HIV-infected MSM, 394 (46%) were of normal weight, 363 (42%) were overweight, and 107 (12%) were obese at baseline. The baseline CD4 count was 493 (standard error [SE] = 9), with viral load (log10) = 2.4 (SE = .04), and 561 (65%) were virologically suppressed. Over time, controlling for viral load, highly active antiretroviral therapy (HAART) adherence, age, and race/ethnicity, overweight and obese HIV-infected men possessed higher CD4 counts than that of normal weight HIV-infected men. Further, overweight and obese men possessed lower viral loads than that of normal weight HIV-infected men. Conclusions: For HIV-infected MSM, in this longitudinal cohort study, possessing a heavier than normal BMI is longitudinally associated with improved immunological health.
Interrelationship of alcohol misuse, HIV sexual risk and HIV screening uptake among emergency department patients
Authors: Trillo Alexis D , Merchant Roland C , Baird Janette R , Ladd George T , Liu Tao , Nirenberg Ted D 
Published: May 2013

Abstract

Background
Emergency department (ED) patients comprise a high-risk population for alcohol misuse and sexual risk for HIV. In order to design future interventions to increase HIV screening uptake, we examined the interrelationship among alcohol misuse, sexual risk for HIV and HIV screening uptake among these patients.

Methods
A random sample of 18-64-year-old English- or Spanish-speaking patients at two EDs during July-August 2009 completed a self-administered questionnaire about their alcohol use using the Alcohol Use Questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), and the HIV Sexual Risk Questionnaire. Study participants were offered a rapid HIV test after completing the questionnaires. Binging (≥ five drinks/occasion for men, ≥ four drinks for women) was assessed and sex-specific alcohol misuse severity levels (low-risk, harmful, hazardous, dependence) were calculated using AUDIT scores. Analyses were limited to participants who had sexual intercourse in the past 12 months. Multivariable logistic regression was used to assess the associations between HIV screening uptake and (1) alcohol misuse, (2) sexual risk for HIV, and (3) the intersection of HIV sexual risk and alcohol misuse. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were estimated. All models were adjusted for patient demographic characteristics and separate models for men and women were constructed.

Results
Of 524 participants (55.0% female), 58.4% identified as white, non-Hispanic, and 72% reported previous HIV testing. Approximately 75% of participants reported drinking alcohol within the past 30 days and 74.5% of men and 59.6% of women reported binge drinking. A relationship was found between reported sexual risk for HIV and alcohol use among men (AOR 3.31 [CI 1.51-7.24]) and women (AOR 2.78 [CI 1.48-5.23]). Women who reported binge drinking were more likely to have higher reported sexual risk for HIV (AOR 2.55 [CI 1.40-4.64]) compared to women who do not report binge drinking. HIV screening uptake was not higher among those with greater alcohol misuse and sexual risk among men or women.

Conclusions
The apparent disconnection between HIV screening uptake and alcohol misuse and sexual risk for HIV among ED patients in this study is concerning. Brief interventions emphasizing these associations should be evaluated to reduce alcohol misuse and sexual risk and increase the uptake of ED HIV screening.