bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of frequency and phonological neighbourhood density on the acquisition of past tense verbs by Finnish children
Authors: Kirjavainen, Minna , Nikolaev, Alexandre , Kidd, Evan 
Published: April 2012

AbstractThe acquisition of the past tense has received substantial attention in the psycholinguistics literature, yet most studies report data from English or closely related Indo-European languages. We report on a past tense elicitation study on 136 4–6-year-old children that were acquiring a highly inflected Finno-Ugric (Uralic) language—Finnish. The children were tested on real and novel verbs (N = 120) exhibiting (1) productive, (2) semi-productive, or (3) non-productive inflectional processes manipulated for frequency and phonological neighbourhood density (PND). We found that Finnish children are sensitive to lemma/base frequency and PND when processing inflected words, suggesting that even though children were using suffixation processes, they were also paying attention to the item level properties of the past tense verbs. This paper contributes to the growing body of research suggesting a single analogical/associative mechanism is sufficient in processing both productive (i.e., regular-like) and non-productive (i.e., irregular-like) words. We argue that seemingly rule-like elements in inflectional morphology are an emergent property of the lexicon.
Mechanisms of resistance to endocrine therapies for breast cancer
Authors: Heudel Pierre , Vilquin Paul , Tredan Olivier , Ray-Coquard Isabelle , Guastalla Jean-Paul , Treilleux Isabelle , Bachelot Thomas 
Published: April 2012

Abstract
Breast cancer is the most frequently diagnosed cancer in women and 70% of the cases are hormone-dependent. The presence of ERα is one of the most important prognostic factors predictive of response to endocrine therapy in human breast cancers. Resistance to endocrine therapies has become a major public health concern and it appears essential to understand the mechanisms underlying this phenomenon. This review provides insights into the molecular mechanisms associated with resistance to endocrine therapies and presents the different strategies currently developed in pre-clinical models to overcome this resistance.
Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture
Authors: Darbre Philippa D. 
Published: April 2012

Abstract
Growth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.
Models and mechanisms of acquired antihormone resistance in breast cancer: significant clinical progress despite limitations
Authors: Sweeney Elizabeth E. , McDaniel Russell E. , Maximov Philipp Y. , Fan Ping , Jordan V. Craig 
Published: April 2012

Abstract
Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded significant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75-1) that continue to advance our understanding of the estrogen-regulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line, in particular, has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated findings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer.
Molecular basis of pregnancy-induced breast cancer prevention
Authors: Russo Jose , Russo Irma H. 
Published: April 2012

Abstract
Reduction in breast cancer risk is associated with elevated circulating levels of human chorionic gonadotropin (hCG) during the first trimester of gestation. The knowledge that hCG also modifies the genomic signature of breast epithelial cells, from highly susceptible to refractory, to undergo neoplastic transformation, and also exerts both preventive and therapeutic effects on chemically induced mammary cancer, lead us to select this hormone for inducing chromatin remodeling in breast epithelial cells as a surrogate end point of complete differentiation and cancer prevention. We have found that chromatin remodeling is the driving force of the differences between the nulliparous and parous breast. In the parous breast, the epithelial cells have a condensed chromatin and increased reactivity with anti-H3K9me2 [di-methyl histone 3 (H3) (Lysine 9)] and H3K27me3 antibodies. This is accompanied by upregulation of noncoding RNA (ncRNA) elements including X2-inactive specific transcript (XIST) and chromatin remodeling genes, such as chromodomain helicase DNA-binding protein 2 (CHD2) and the chromobox homolog 3 (CBX3), whose products are required for controlling recruitment of protein/protein or DNA/protein interactions Another important gene upregulated in the parous breast epithelial cells is the histone-lysine N-methyltransferase or enhancer of zeste homolog 2 (EZH2), a member of the polycomb group (PcG) forming multimeric protein complexes that maintains the transcriptional repressive state of genes over successive cell generations. The fact that recent studies indicate that ncRNAs recruit PcG complexes to the locus of transcription or to sites located elsewhere in the genome cause us to postulate that the increased chromatin condensation in the parous breast has been initiated by ncRNAs, a postulate supported by the observed upregulation of several ncRNAs that included the XIST. The identification of a specific genomic signature of pregnancy has uncovered a novel tool that will serve as a surrogate biomarker for testing new chemopreventive agents and will significantly advance the field of cancer prevention. The clinical impact of this work is that it validates in an experimental system the genomic signature of prevention identified in the human parous breast and establish the bases for the use of the hormone hCG in the prevention of breast cancer, an approach that has not been fully developed until now.
Cytochrome P450-7B1 and 11β-hydroxysteroid dehydrogenase type 1 distribution in human tissues
Authors: Chalbot Sonia , Morfin Robert 
Published: April 2012

Abstract
Successive action of cytochrome P450-7B1 (CYP7B1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on 3β-hydroxysteroids such as DHEA and epiandrosterone leads to the production of cytoprotective 7β-hydroxylated derivatives. Investigation of the presence of these enzymes in human tissues could be carried out on commercially available human tissue arrays with use of antibodies specific to CYP7B1 and 11β-HSD1 for immunohistochemistry. Both enzymes were detected mainly in tissues of endodermic and ectodermic origin which are prone to undergo inflammation. As low doses of the 7β-hydroxylated derivatives of DHEA and epiandrosterone trigger the resolution of inflammation and tissue repair, CYP7B1 and 11β-HSD1 tissue contents may reflect the tissue ability for reparation after pathological conditions.
Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model
Authors: Visser Monique , Kloosterboer Helenius J. , Bennink Herjan J.T. Coelingh 
Published: April 2012

Abstract

Background: Estetrol (E4) is a pregnancy-specific estrogenic steroid hormone produced by the human fetal liver in both male and female fetuses. During pregnancy, E4 plasma values increase exponentially until parturition and decrease thereafter. The synthesis of E4 in the liver of a newborn ceases during the first weeks after birth.

Materials and methods: Here we report the effect of E4 on the initiation and growth of mammary tumors chemically induced by 7,12 dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats in two different protocols. Two prevention studies to test the effect on initiation and growth of induced tumors and one intervention study to test the effect on tumor growth were performed. In the prevention studies, the effect of oral doses of E4 over a dose range of 0.5–3.0 mg/kg was investigated. In the intervention study, oral doses of 1, 3 and 10 mg/kg E4 were used. The anti-estrogen tamoxifen (TAM) and ethinylestradiol (EE) were used as reference compounds. In all studies, a group with ovariectomized animals (OVX) was included.

Results: In the prevention studies, 2.5 mg and 3 mg/kg E4 showed a significant effect on the number and growth of induced tumors by DMBA, and the effects were comparable to those of TAM, whereas EE had no effect. In the intervention study, the effect of a high dose of E4 (10 mg/kg) on tumor number was similar to that of OVX and better than TAM and high-dose EE. The 3 mg/kg E4 had an effect comparable to high-dose EE. The treatment effects were largely due to complete regression of existing tumors.

Conclusions: The natural fetal estrogen E4 prevents tumor initiation by DMBA and inhibits the growth of existing DMBA-induced tumors.
Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications
Authors: Pasqualini Jorge R. , Chetrite Gérard S. 
Published: April 2012

Abstract
The bioformation and transformation of estrogens and other hormones in the breast tissue as a result of the activity of the various enzymes involved attract particular attention for the role they play in the development and pathogenesis of hormone-dependent breast cancer. The enzymatic process concerns the aromatase, which transforms androgens into estrogens; the sulfatase, which hydrolyzes the biologically inactive sulfates to the active hormone; the 17β-hydroxysteroid dehydrogenases, which are involved in the interconversion estradiol/estrone or testosterone/androstenedione; hydroxylases, which transform estrogens into mitotic and antimitotic derivatives; and sulfotransferases and glucuronidases, which, respectively convert into the biologically inactive sulfates and glucuronides. These enzymatic activities are more intense in the carcinoma than in the normal tissue. Concerning aromatase, the application of antiaromatase agents has been largely developed in the treatment of breast cancer patients, with very positive results. Various studies have shown that the activity levels of these enzymes and their mRNA can be involved as interesting prognostic factors for breast cancer. In conclusion, the application of new antienzymatic molecules can open attractive perspectives in the treatment of hormone-dependent breast cancer.
Interaction of dietary polyphenols with molecular signaling pathways of antiestrogen resistance: possible role in breast cancer recurrence
Authors: Aiyer Harini S. , Bouker Kerrie B. , Cook Katherine L. , Facey Caroline O.B. , Hu Rong , Schwartz Jessica L. , Shajahan Ayesha N. , Hilakivi-Clarke Leena , Clarke Robert 
Published: April 2012

Abstract
Breast cancer is the most common cancer diagnosed in women and its global incidence is rising rapidly. Adjuvant hormonal therapy, with antiestrogens (AE) such as tamoxifen and fulvestrant, is highly effective in the treatment of estrogen receptor-positive (ER+) breast cancers and is largely responsible for the increase in survival rates seen in the past four decades. However, nearly 50% of women with ER+ cancer display de novo or acquired resistance to AE therapies. Potential molecular mechanisms driving the resistance phenotype are beginning to be elucidated, allowing further development of more effective therapeutic and preventive strategies to reduce the overall mortality due to breast cancer. Over 70% of breast cancer survivors surveyed report increasing their comsumption of fruits, vegetables, and natural product supplements upon diagnosis. These are rich sources of dietary polyphenols (PPs) that can interact with cell-signaling pathways involved in the development of AE resistance. However, research on mechanisms by which these agents may affect AE resistance and whether PP intake can significantly change breast cancer recurrence is limited. We summarize the available data on the effects of PPs on breast cancer recurrence and the interactions of these compounds with some of the signaling pathways hypothesized to drive cell death and survival involved in the development of AE resistance in breast cancer.
Barriers to Medication Adherence in HIV-Infected Children and Youth Based on Self- and Caregiver Report
Authors: Buchanan Ashley L. , Montepiedra Grace , Sirois Patricia A. , Kammerer Betsy , Garvie Patricia A. , Storm Deborah S. , Nichols Sharon L. 
Published: April 2012

OBJECTIVE:
Nonadherence to antiretroviral therapy among children/youth with HIV often is associated with disease progression. This study examined the agreement between child and caregiver perceptions of barriers to adherence and factors associated with these barriers.

METHODS:
Children/youth with perinatally acquired HIV and their parents/caregivers (n = 120 dyads) completed a questionnaire about 19 potential barriers to adherence to the child’s antiretroviral therapy regimen. Agreement between the 2 reports was measured via the kappa statistic. Factors associated with the barriers were assessed by using multiple logistic regression.

RESULTS:
Of the 120 children, 55% were African American, 54% were boys, and the average age was 12.8 years. The most frequently reported barrier by either the caregiver or youth was “forgot.” There were varying degrees of agreement between child and caregiver on the following barriers: “forgot,” “taste,” “child was away from home,” “child refused,” and “child felt good.” Children who knew their HIV status were more likely to report logistical barriers, such as scheduling issues. Children with a biological parent as their caregiver were more likely to report regimen or fear of disclosure as a barrier.

CONCLUSIONS:
Lack of agreement was observed for more than half of the studied barriers, indicating discrepancies between children’s and caregivers’ perceptions of factors that influence medication-taking. The findings suggest a need for interventions that involve both child and caregiver in the tasks of remembering when to administer the child’s medications, sustaining adherence, and appropriately transitioning medication responsibility to the youth.
Magnesium Use in Asthma Pharmacotherapy: A Pediatric Emergency Research Canada Study
Authors: Schuh Suzanne , Zemek Roger , Plint Amy , Black Karen J. L. , Freedman Stephen , Porter Robert , Gouin Serge , Hernandez Alexandra , Johnson David W. 
Published: April 2012

OBJECTIVES:
To examine the use of intravenous magnesium in Canadian pediatric emergency departments (EDs) in children requiring hospitalization for acute asthma and association of administration of frequent albuterol/ipratropium and timely corticosteroids with hospitalization.

METHODS:
Retrospective medical record review at 6 EDs of otherwise healthy children 2 to 17 years of age with acute asthma. Data were extracted on history, disease severity, and timing of ED stabilization treatments with inhaled albuterol, ipratropium, corticosteroids, and magnesium. Primary outcome was the proportion of hospitalized children given magnesium in the ED. Secondary outcome was the ED use of “intensive therapy” in hospitalized children, defined as 3 albuterol inhalations with ipratropium and corticosteroids within 1 hour of triage.

RESULTS:
A total of 19 (12.3%) of 154 hospitalized children received magnesium (95% confidence interval 7.1, 17.5) versus 2 of 962 discharged patients. Children given magnesium were more likely to have been previously admitted to ICU (odds ratio [OR] 11.2), hospitalized within the past year (OR 3.8), received corticosteroids before arrival (OR 4.0), presented with severe exacerbation (OR 6.1), and to have been treated at 1 particular center (OR 14.9). Forty-two (53%) of 90 hospitalized children were not given “intensive therapy.” Children receiving “intensive therapy” were more likely to present with severe disease to EDs by using asthma guidelines (ORs 8.9, 3.0). Differences in the frequencies of all stabilization treatments were significant across centers.

CONCLUSIONS:
Magnesium is used infrequently in Canadian pediatric EDs in acute asthma requiring hospitalization. Many of these children also do not receive frequent albuterol and ipratropium, or early corticosteroids. Significant variability in the use of these interventions was detected.
Automated Primary Care Screening in Pediatric Waiting Rooms
Authors: Anand Vibha , Carroll Aaron E. , Downs Stephen M. 
Published: April 2012

BACKGROUND AND OBJECTIVE:
Implementing US Preventive Services Task Force and American Academy of Pediatrics preventive service guidelines within the short duration of a visit is difficult because identifying which of a large number of guidelines apply to a particular patient is impractical. Clinical decision support system integrated with electronic medical records offer a good strategy for implementing screening in waiting rooms. Our objective was to determine rates of positive risk screens during typical well-care visits among children and adolescents in a primary care setting.

METHODS:
Child Health Improvement through Computer Automation (CHICA) is a pediatric clinical decision support system developed by our research group. CHICA encodes clinical guidelines as medical logic modules to generate scanable paper forms: the patient screening form to collect structured data from patient families in the waiting room and the physician worksheet to provide physician assessments at each visit. By using visit as a unit of analysis from CHICA’s database, we have determined positive risk screen rates in our population.

RESULTS:
From a cohort of 16 963 patients, 408 601 questions were asked in 31 843 visits. Of the questions asked, 362 363 (89%) had a response. Of those, 39 176 (11%) identified positive risk screens in both the younger children and the adolescent age groups.

CONCLUSIONS:
By automating the process of screening and alerting the physician to those who screened positive, we have significantly decreased the burden of identifying relevant guidelines and screening of patient families in our clinics.
Birth Asphyxia: A Major Cause of Early Neonatal Mortality in a Tanzanian Rural Hospital
Authors: Ersdal Hege Langli , Mduma Estomih , Svensen Erling , Perlman Jeffrey 
Published: April 2012

OBJECTIVE:
Early neonatal mortality within the first 24 hours contributes substantially to overall neonatal mortality rates. The definition of birth asphyxia (BA) is imprecise, and reliable cause-specific mortality data are limited; thus the estimated proportion of BA-related deaths globally remains questionable. The objective was to determine the presumed causes of neonatal death within the first 24 hours in a rural hospital in Northern Tanzania.

METHODS:
This is a prospective descriptive observational study conducted in the delivery room and adjacent neonatal area. Research assistants were trained to observe and record events related to labor, neonatal resuscitation, and 24-hour postnatal course. BA was defined as failure to initiate spontaneous respirations and/or 5-minute Apgar score &lt;7, prematurity as gestational age &lt;36 weeks, and low birth weight (LBW) as birth weight &lt;3rd centile for gestational age. Data were analyzed with χ2 and Student’s t tests.

RESULTS:
Over 1 year, 4720 infants were born and evaluated. Of these, 256 were admitted to the neonatal area. Forty-nine infants died secondary to BA (61%), prematurity (18%), LBW (8%), infection (2%), congenital abnormalities (8%), and unclear reason (2%). The 5-minute Apgar score was ≥7 in 50% of the infants who died secondary to BA.

CONCLUSIONS:
Most cases of early neonatal mortality were related to BA, and prematurity and LBW are additional important considerations. Reducing perinatal mortality requires a multifaceted approach with attention to issues related to BA, potential complications of prematurity, and LBW. The 5-minute Apgar score is a poor surrogate of BA.
Noncontact probing method for estimation of ferroelectric properties of PbTiO3-based films for microelectromechanical systems
Authors: Ehara Yoshitaka , Utsugi Satoru , Nakajima Mitsumasa , Chentir Mohamed-Tahar , Yamada Tomoaki , Iijima Takashi , Nishida Ken , Yamamoto Takashi , Funakubo Hiroshi 
Published: April 2012

Abstract
Decision Making in Gingival Recession Treatment: Scientific Evidence and Clinical Experience
Authors: Rasperini Giulio , Acunzo Raffaele , Limiroli Enrico 
Published: April 2012

Focused Clinical Question: What are the key considerations for selecting the best surgical approach in mucogingival plastic surgery?Summary: Treatment of gingival recession has become an important therapeutic issue due to the increasing number of cosmetic requests from patients. The dual goals of mucogingival treatment include complete root coverage, up to the cemento‐enamel junction, and blending of tissue color between the treated area and non‐treated adjacent tissues. Even though the connective tissue graft is commonly considered the “gold standard” for treatment of recession defects, it may not always be the best surgical option for every case.Conclusions: Under non‐experimental conditions, all root coverage procedures may be effective in terms of complete root coverage and excellent esthetics. Careful analyses of patient‐ and defect‐related factors, however, are key considerations prior to selecting an appropriate surgical technique.