100,557 research outputs found
Synergistic cytotoxic effect of l-asparaginase combined with decitabine as a demethylating agent in pediatric T-ALL, with specific epigenetic signature
No full textT-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment. Hence we treated different T-ALL cell lines with L-asparaginase and correlated different responses to the treatment with ASNS expression. Then we demonstrated that the ASNS expression was dependent on the methylation status of the promoter. Finally we showed that, despite the demethylating effect on the ASNS gene expression, the combined treatment with the demethylating agent Decitabine could synergistically improve the L-asparaginase sensitivity in those T-ALL cell lines characterized by hypermethylation of the ASNS gene. In conclusion, this preclinical study identified an unexpected synergistic activity of L-asparaginase and Decitabine in the subgroup of T-ALL with low ASNS expression due to hypermethylation of the ASNS promoter, while it did not restore sensitivity in the resistant cell lines characterized by higher ASNS expression
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Cancer mortality in Italy, 2008, and predictions for 2012
No full textAims and background. This report provides up-to-date data and statistics for cancer mortality in Italy in 2008, and predicts the figures and rates for selected cancer sites for 2012. Methods. Cancer death certifications (for 30 sites) and resident population estimates in 2008 stratified by sex and age were obtained from the World Health Organization (WHO) database (WHOSIS). Mortality rates were age-standardized on the world standard population. Results. Cancer deaths registered in Italy in 2008 were 172,783 (97,773 men and 75,010 women), corresponding to age-standardized death rates of 144.1/100,000 men and 84.3/100,000 women. The projected cancer deaths in 2012 are 178,000 (100,000 men, 78,000 women) and the corresponding rates 132,5/100,000 men and 80.5/100,000 women. The favorable trend in lung cancer mortality among men was confirmed, with rates of 37.7/100,000 in 2008 (all ages) and 33.3 for 2012. Other tobacco-related cancers also declined in men but not in women, including pancreatic cancer, whose rates tended to level off over the last 3 years. The fall in female cancer mortality rates continues to be led by favorable trends in breast cancer (16.1/100,000 in 2007 and 15.2 in 2012), intestinal cancer, stomach cancer and uterine cancer. However, the female lung cancer mortality was still rising with 7743 deaths in 2008 (9.5/100,000), and lung cancer is predicted to become the second cause of female cancer mortality by 2012 (8,500 deaths, 9.8/100,000). Conclusions. Reduced tobacco and alcohol consumption are largely responsible for the favorable trends in cancer mortality in men. Advances in treatment and management accounted for the reduced mortality from colorectal cancer, breast cancer, leukemias and a few other cancers, as well as improved diagnosis for colorectal, cervical and breast cancer. The rising epidemic of tobacco-related deaths in women indicates the need for targeted tobacco-control strategies
20-Year trends of hospitalisation among people with dementia: a region-wide retrospective cohort study from Lombardy, Italy
No full textObjectives: The aim of this study was to investigate the trends of hospitalisations among people with dementia, linking region-wide hospital and demographic health records. Study design: A retrospective cohort study was conducted using hospitalisation health records from the Lombardy region in Italy. Methods: The study included people aged =65 years with a diagnosis of dementia who were hospitalised between 2002 and 2020 in Lombardy, which is the most populated region in Italy with 10 million inhabitants. Using data on resident population, this study computed rates of hospitalisation by calendar year, age, sex and cause of hospitalisation. Results: In total, 340,144 hospitalised patients with dementia were included in the study. The rate of hospitalisation was 100.6 per 10,000 in 2002 and progressively decreased to 65.1 per 10,000 in 2020. The average age at hospitalisation in 2002 was 78.9 years for men and 81.8 years for women, which increased to 82.0 years and 84.2 years, respectively, in 2020. Respiratory diseases caused 10.4% of all hospitalisations in 2002 and grew steadily to 26.8% in 2020, becoming the leading cause of hospital admissions since 2017. Conclusions: Hospitalisation patterns for people with dementia have changed over the last 20 years, reflecting evolving epidemiological trends and the impact of healthcare policies. Region-wide administrative health record data analysis should be further utilised to explore the health needs of people with dementia and inform the planning, implementation and monitoring of effective prevention strategies in this population group
Cancer mortality in Europe, 1970-2009: an age, period, and cohort analysis
No full textThe aim of this study was to interpret long-term trends in cancer mortality. We analyzed age, period of death, and cohort of birth effects for 18 major cancer sites and all neoplasms combined in the European Union and 16 European countries over the period 1970-2009 using data from the WHO mortality database. We used a log-linear Poisson model with a likelihood penalizing function to solve the identifiability problem. The present comprehensive analysis confirms the appreciable declines of cancer mortality since the late 1980s in most European countries. For several major sites, the declines were appreciably greater for cohort effects than for period ones. This reflects - besides the inherent characteristics of the model used - a major impact of tobacco smoking on total cancer mortality, particularly in men, as the role of tobacco in mortality of subsequent generations is largely - although not totally - a cohort effect. For neoplasms largely affected by improvements in management and therapy (e.g. testis, Hodgkin lymphoma, leukemia, but also breast and colorectal cancer), a favorable period effect is evident. However, there is also a cohort effect as the advancements have been generally greater in younger generations. For several cancer sites, there were considerable differences in cohort and period effects across Europe, and particularly high age-specific estimates were observed in eastern countries
Cancer mortality trend analysis in Italy, 1980-2010, and predictions for 2015
No full textAims: To update cancer mortality statistics in Italy, analyzing 1980-2010 trends, and to predict 2015 mortality rates. Methods: World Health Organization cancer mortality and census data were extracted to calculate death rates for 30 cancer sites from 1980 to 2010. Trends were analyzed with joinpoint regression and predicted 2015 deaths rates were computed. Results: In 2010 in Italy, there were 175,046 cancer deaths (98,847 men and 76,199 women), with total mortality rates, respectively, of 138.22 and 82.6/100,000. The leading cause of cancer death in men was lung cancer (25,457 deaths, 36.2/100,000), whereas in women it was breast cancer (12,115 deaths, 15.38/100,000). Total cancer mortality in men has been decreasing since the late 1980s, with an estimated annual percentage change (EAPC) of -1.8 in 1994-2010. In women, total cancer mortality rates decreased throughout the study period, with an EAPC of -1.1 in 1992-2010. Trends in mortality were decreasing for most cancers in both sexes. Only pancreatic and lung cancer trends in women were unfavorable. Total numbers of predicted cancer deaths in Italy for 2015 increased to 102,647 men and 82,047 women; however, the predicted rates decreased in men (129.1/100,000), while remaining stable in women (82.6/100,000). Conclusions: Mortality rates for the most common cancers in Italy showed favorable trends that are likely to continue in the near future, with the exception of lung cancer mortality in women. Maintaining these trends requires continuous and improved control of tobacco, alcohol, and nutrition/overweight. Further improvements in diagnosis and treatment may also have a significant impact on cancer mortality
Handwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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