1,721,399 research outputs found
Evaluating the number of stages in development of squamous cell and adenocarcinomas across cancer sites using human population-based cancer modeling.
No full textBACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site
Programmed chemotherapy for patients with metastatic unresectable gastric cancer.
Full text linkBACKGROUND: Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. CONCLUSIONS/SIGNIFICANCE: This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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Information Technology Applications in Construction and Oil and Gas Projects Management Performance – Future Vision
No full textAbstract
In recent years more and more construction projects used information technology applications to support execution and management tasks. However, construction companies in the world and accordingly in UAE still wrestle with information technology applications in construction (ITC) and how they could be effectively applied on their specific projects. One main reason for this struggle is that an account about how ITC have been used in the past or could be used in the future is missing. This research aims to provide new impetus to UAE's growth and competitiveness in construction engineering and management areas.
The paper presents some areas that ITC could be applied in oil & gas construction sector of UAE. It offers practitioners such an account of the application areas of ITC technologies including the purposes for which these technologies have been applied. The paper qualitatively aggregates the results of more than 200 papers to show how ITC have been applied to address different projects challenges. The paper presents samples of key practical areas for simulation modelling applications in construction industry that are proposed by author for oil & gas projects. The main finding of this analysis is that ITC could play significant role in controlling key indicators of oil & gas construction projects performance including, but not limited to, schedule, cost, safety, quality, team work, and scope management. It could help project managers solving critical concerns such as claim analysis, cash-flow optimization, resources optimization, camp management, and many others.
Keyword: Oil & Gas, construction, UAE, information technology, project performance, IT
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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Targeting Interleukin-1 Signaling to Remodel the Tumor Microenvironment in Pancreatic Cancer
No full textPancreatic ductal adenocarcinoma (PDAC) remains a major therapeutic challenge due to its innate and acquired resistance to chemotherapy, immunotherapy, and targeted treatment approaches. More so than any other tumor type, PDAC tumor cells interact extensively with CAFs, the predominant cellular component of the PDAC stroma, to shape the TME and influence therapeutic resistance and foster disease progression. We and others have identified interleukin-1 (IL-1) as a critical factor that polarizes CAFs to a pro-tumorigenic, inflammatory phenotype. Herein, we comprehensively characterize the IL-1-dependent interactions that lead to an activated CAF phenotype, resulting in their release of cytokines and growth factors that sustain oncogenic signaling pathways within neoplastic cells and simultaneously promote the immunosuppressive phenotype characteristic of PDAC tumors. Further, we investigate the synergistic effects of IL-1 receptor inhibition with chemotherapy and/or immunotherapy using syngeneic and orthotopic mouse models of PDAC. These results expand our understanding of the phenomenon of stromal-mediated therapeutic resistance and offer valuable preclinical data on the potential use of IL-1 pathway inhibitors as a strategy to enhance the response to chemotherapy/immunotherapy and improve outcomes in PDAC via the disruption of inflammatory tumor-stromal-immune crosstalk.</p
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DUOX2-Mediated Host-Microbiome Interactions in Health and Disease
No full textThe gut epithelium regulates host-microbiome dynamics through mechanisms that include the release of reactive oxygen species by NADPH oxidases. Dual oxidase 2 (DUOX2) is an antimicrobial NADPH oxidase that catalyzes the production of hydrogen peroxide. Dysregulation of DUOX2 activity, either via loss-of-function mutations or overexpression, has been associated with pathologies involving chronic inflammation, dysbiosis, and epithelial barrier defects, such as inflammatory bowel disease (IBD) and associated cancers. DUOX2 is consistently altered in IBD patients, even before the onset of disease, and this alteration is associated with dysbiosis. However, the role of DUOX2 in driving IBD or associated cancers is not known.Here, we aimed to elucidate the functional consequences of DUOX2 activity and interrogate the underlying mechanisms by which it promotes pathology. We also explored potential regulators of DUOX2 activity that could be leveraged for therapeutic applications. Given DUOX2's role in maintaining homeostasis, we simultaneously investigated the systemic consequences of losing DUOX2 activity in the gut. Our findings reveal that chronic DUOX2 activity promotes colonic tumors (chapter 2) and is linked to epithelial barrier defects seen early in IBD (chapter 3). We also identified the microbial metabolite butyrate and HDAC inhibitors as regulators of DUOX2, highlighting the potential of microbiome and metabolome-targeting approaches in IBD therapeutics (Chapter 3). Lastly, our work reveals a novel role for intestinal-specific DUOX2 in protecting against metabolic syndrome (chapter 4). Overall, this thesis elucidates the dual role of DUOX2 in both disease progression and maintenance of homeostasis, emphasizing its potential as a target for therapeutic strategies.</p
5-Methylcytosine hydroxylation-mediated LINE-1 hypomethylation: a novel mechanism of proto-oncogenes activation in colorectal cancer?
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