bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence evasion by MCF-7 human breast tumor-initiating cells
Authors: Karimi-Busheri Feridoun , Rasouli-Nia Aghdass , Mackey John R , Weinfeld Michael 
Published: June 2010

Abstract
Introduction
A subpopulation of cancer cells, tumor-initiating cells, is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy. The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins, as well as a reduced propensity to undergo apoptosis or senescence.

Methods
To test this hypothesis, we isolated CD24-/low/CD44+ tumor-initiating cells (as mammospheres) from MCF-7 breast cancer cells grown in adherent monolayer culture, and carried out a comprehensive comparison of cell death and DNA damage response pathways prior to and after exposure to ionizing radiation in mammospheres and monolayer MCF-7 cells. Single and double-strand break repair was measured by single-cell gel electrophoresis. The latter was also examined by phosphorylation of histone H2AX and formation of 53BP1 and Rad51 foci. Apoptosis was quantified by flow-cytometric analysis of annexin V-binding and senescence was analyzed on the basis of cellular β-galactosidase activity. We employed the telomeric repeat amplification protocol to quantify telomerase activity. Expression of key DNA repair and cell cycle regulatory proteins was detected and quantified by western blot analysis.

Results
Our data demonstrate that in comparison to the bulk population of MCF-7 cells (predominantly CD24+/CD44+), the MCF-7 mammosphere cells benefit from a multifaceted approach to cellular protection relative to that seen in monolayer cells, including a reduced level of reactive oxygen species, a more active DNA single-strand break repair (SSBR) pathway, possibly due to a higher level of expression of the key SSBR protein, human AP endonuclease 1 (Ape1), and a significantly reduced propensity to undergo senescence as a result of increased telomerase activity and a low level of p21 protein expression. No significant difference was seen in the rates of double-strand break repair (DSBR) between the two cell types, but DSBR in mammospheres appears to by-pass the need for H2AX phosphorylation.

Conclusions
Enhanced survival of MCF-7 tumor-initiating cells in response to ionizing radiation is primarily dependent on an inherent down-regulation of the senescence pathway. Since MCF-7 cells are representative of cancer cells that do not readily undergo apoptosis, consideration of senescence pathways may play a role in targeting stem cells from such tumors.
Breast Cancer Adjuvant Chemotherapy Decisions in Older Women: The Role of Patient Preference and Interactions With Physicians
Authors: Mandelblatt Jeanne S. , Sheppard Vanessa B. , Hurria Arti , Kimmick Gretchen , Isaacs Claudine , Taylor Kathryn L. , Kornblith Alice B. , Noone Anne-Michelle , Luta Gheorghe , Tallarico Michelle , Barry William T. , Hunegs Lisa , Zon Robin , Naughton Michael , Winer Eric , Hudis Clifford , Edge Stephen B. , Cohen Harvey Jay , Muss Hyman 
Published: June 2010

Purpose Breast cancer chemotherapy decisions in patients ≥ 65 years old (older) are complex because of comorbidity, toxicity, and limited data on patient preference. We examined relationships between preferences and chemotherapy use. Methods Older women (n = 934) diagnosed with invasive (≥ 1 cm), nonmetastatic breast cancer from 2004 to 2008 were recruited from 53 cooperative group sites. Data were collected from patient interviews (87% complete), physician survey (93% complete), and charts. Logistic regression and multiple imputation methods were used to assess associations between chemotherapy and independent variables. Chemotherapy use was also evaluated according to the following two groups: indicated (estrogen receptor [ER] negative and/or node positive) and possibly indicated (ER positive and node negative). Results Mean patient age was 73 years (range, 65 to 100 years). Unadjusted chemotherapy rates were 69% in the indicated group and 16% in the possibly indicated group. Women who would choose chemotherapy for an increase in survival of ≤ 12 months had 3.9 times (95% CI, 2.4 to 6.3 times; P < .001) higher odds of receiving chemotherapy than women with lower preferences, controlling for covariates. Stronger preferences were seen when chemotherapy could be indicated (odds ratio [OR] = 7.7; 95% CI, 3.8 to 16; P < .001) than when treatment might be possibly indicated (OR = 1.9; 95% CI, 1.0 to 3.8; P = .06). Higher patient rating of provider communication was also related to chemotherapy use in the possibly indicated group (OR = 1.9 per 5-point increase in communication score; 95% CI, 1.4 to 2.8; P < .001) but not in the indicated group (P = .15). Conclusion Older women's preferences and communication with providers are important correlates of chemotherapy use, especially when benefits are more equivocal.
Phase II Window Study on Rituximab in Newly Diagnosed Pediatric Mature B-Cell Non-Hodgkin's Lymphoma and Burkitt Leukemia
Authors: Meinhardt Andrea , Burkhardt Birgit , Zimmermann Martin , Borkhardt Arndt , Kontny Udo , Klingebiel Thomas , Berthold Frank , Janka-Schaub Gritta , Klein Christoph , Kabickova Edita , Klapper Wolfram , Attarbaschi Andishe , Schrappe Martin , Reiter Alfred 
Published: June 2010

Purpose The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL. Patients and Methods Patients younger than age 19 years with CD20+ B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m2 administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had ≥ 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity. Results From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007). Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.
Quality of Nonmetastatic Colorectal Cancer Care in the Department of Veterans Affairs
Authors: Jackson George L. , Melton L. Douglas , Abbott David H. , Zullig Leah L. , Ordin Diana L. , Grambow Steven C. , Hamilton Natia S. , Zafar S. Yousuf , Gellad Ziad F. , Kelley Michael J. , Provenzale Dawn 
Published: June 2010

Purpose The Veterans Affairs (VA) healthcare system treats approximately 3% of patients with cancer in the United States each year. We measured the quality of nonmetastatic colorectal cancer (CRC) care in VA as indicated by concordance with National Comprehensive Cancer Network practice guidelines (six indicators) and timeliness of care (three indicators). Patients and Methods A retrospective medical record abstraction was done for 2,492 patients with incident stages I to III CRC diagnosed between October 1, 2003, and March 31, 2006, who underwent definitive CRC surgery. Patients were treated at one or more of 128 VA medical centers. The proportion of patients receiving guideline-concordant care and time intervals between care processes were calculated. Results More than 80% of patients had preoperative carcinoembryonic antigen determination (ie, stages II to III disease) and documented clear surgical margins (ie, stages II to III disease). Between 72% and 80% of patients had appropriate referral to a medical oncologist (ie, stages II to III disease), preoperative computed tomography scan of the abdomen and pelvis (ie, stages II to III disease), and adjuvant fluorouracil-based chemotherapy (ie, stage III disease). Less than half of patients with stages I to III CRC (43.5%) had a follow-up colonoscopy 7 to 18 months after surgery. The mean number of days between major treatment events included the following: 26.6 days (standard deviation [SD], 38.2; median, 20 days) between diagnosis and initiation of treatment (in stages II to III disease); 64.9 days (SD, 54.9; median, 50 days) between definitive surgery and start of adjuvant chemotherapy (in stages II to III disease); and 444.1 days (SD, 182.1; median, 393 days) between definitive surgery and follow-up colonoscopies (in stages I to III disease). Conclusion Although there is opportunity for improvement in the area of cancer surveillance, the VA performs well in meeting established guidelines for diagnosis and treatment of CRC.
Molecular Staging of Intracranial Ependymoma in Children and Adults
Authors: Korshunov Andrey , Witt Hendrik , Hielscher Thomas , Benner Axel , Remke Marc , Ryzhova Marina , Milde Till , Bender Sebastian , Wittmann Andrea , Schöttler Anna , Kulozik Andreas E. , Witt Olaf , von Deimling Andreas , Lichter Peter , Pfister Stefan 
Published: June 2010

Purpose The biologic behavior of intracranial ependymoma is unpredictable on the basis of current staging approaches. We aimed at the identification of recurrent genetic aberrations in ependymoma and evaluated their prognostic significance to develop a molecular staging system that could complement current classification criteria. Patients and Methods As a screening cohort, we studied a cohort of 122 patients with ependymoma before standardized therapy by using array-based comparative genomic hybridization. DNA copy-number aberrations identified as possible prognostic markers were validated in an independent cohort of 170 patients with ependymoma by fluorescence in situ hybridization analysis. Copy-number aberrations were correlated with clinical, histopathologic, and survival data. Results In the screening cohort, age at diagnosis, gain of 1q, and homozygous deletion of CDKN2A comprised the most powerful independent indicators of unfavorable prognosis. In contrast, gains of chromosomes 9, 15q, and 18 and loss of chromosome 6 were associated with excellent survival. On the basis of these findings, we developed a molecular staging system comprised of three genetic risk groups, which was then confirmed in the validation cohort. Likelihood ratio tests and multivariate Cox regression also demonstrated the clear improvement in predictive accuracy after the addition of these novel genetic markers. Conclusion Genomic aberrations in ependymomas are powerful independent markers of disease progression and survival. By adding genetic markers to established clinical and histopathologic variables, outcome prediction can potentially be improved. Because the analyses can be conducted on routine paraffin-embedded material, it will now be possible to prospectively validate these markers in multicenter clinical trials on population-based cohorts.
Potential Role of Salicylates in Type 2 Diabetes
Authors: Rumore Martha M , Kim Katelynn S 
Published: June 2010

Objective: To review the evidence base supporting the use of salicylates for glucose level control in patients with type 2 diabetes and provide a comprehensive review of available information describing the potential role of salicylates and, in particular, salsalate, for glucose control in type 2 diabetes prevention and treatment. DATA SOURCES: A literature search using MEDLINE (1966–March 2010), PubMed, and Google Scholar was conducted using the search terms salicylates, salicylic acid, aspirin, salsalate, acetytsalicylic acid, insulin, glucose, glycemic control, diabetes, hyperglycemia, and nuclear factor. The bibliographies of identified articles were reviewed for additional citations. Study Selection and Data Extraction: All relevant English-language information on the pharmacology, efficacy, and safety of salicylates for glucose control related to insulin resistance or diabetes prevention were reviewed. Preclinical data, clinical trials, and case reports were identified, evaluated, and included in this systematic review. Data Synthesis: Treatment of inflammation may be a potential novel strategy in prevention and treatment of type 2 diabetes, in which the body is resistant to the effects of insulin. Previous and recent studies reveal a possible relationship between inflammation and obesity. The chronic activation of the immune system due to low-grade inflammation was found in several studies to be associated with obesity, and this, in turn, can promote development of insulin resistance and impaired glucose tolerance. Administration of salicylates was shown over a century ago to lower glucose levels in patients with diabetes. Many in vitro and in vivo pharmacologic studies have demonstrated a glucose-lowering effect of salicylates. Salicylates, especially salsalate, were found in several clinical studies and case reports to be potential agents for diabetes treatment with a favorable safety profile. Although these studies had inherent limitations, such as small numbers of patients and short duration, the vast majority showed significant glucose-lowering effects. A large randomized trial, the National Institute of Diabetes and Digestive and Kidney Diseases–sponsored Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D) trial, recently concluded that salsalate lowers hemoglobin A1c levels and improves glycemic control in patients with type 2 diabetes. Conclusions: Salicylates, especially salsalate, appear to be a promising treatment option for prevention or treatment of diabetes by lowering glucose levels. More extensive studies are needed to confirm the mechanisms involved and whether the effects are sustainable with continued administration of these agents. Further studies are warranted.
Probable Hypoglycemic Adverse Drug Reaction Associated with Prickly Pear Cactus, Glipizide, and Metformin in a Patient with Type 2 Diabetes Mellitus
Authors: Sobieraj Diana M , Freyer Craig W 
Published: June 2010

Objective: To report a case of an adverse drug reaction (ADR) in a patient with type 2 diabetes mellitus taking prickly pear cactus (PPC), glipizide, and metformin. Case Summary: A 58-year-old Mexican male with type 2 diabetes mellitus being treated with metformin 1000 mg twice daily and extended-release glipizide 10 mg daily was referred to the pharmacist for medication education. He denied taking herbal supplements or experiencing hypoglycemia. Two hemoglobin A1c values (6.8% and 6.7%) obtained over the past year demonstrated glycemic control, which was supported by his reported fasting blood glucose readings of 113–132 mg/dL. One month later, the patient reported 4 hypoglycemic events with blood glucose readings of 49–68 mg/dL, which resulted in discontinuation of glipizide. One month later, the patient denied any further hypoglycemia. During medication reconciliation he reported consuming crude PPC pads daily for 2 months for glucose control. Discussion: Literature suggests that PPC has an effect on lowering blood glucose levels in patients with type 2 diabetes mellitus, although few identified data describe ADRs from combining PPC with other agents used in treating type 2 diabetes mellitus. A literature search of MEDLINE (through December 2009) using the search terms diabetes mellitus, prickly pear cactus, nopal, opuntia, metformin, glipizide, glyburide, glimepiride, and sulfonylurea revealed no case reports of the described ADR. One case report describing the blood glucose–lowering effect of PPC in a patient concurrently taking oral antihyperglycemics documented an episode of hypoglycemia, although the Naranjo probability scale was not applied. One patient survey discovered the most common drug-herbal interaction in the given population to be between PPC and antihyperglycemic agents, resulting in hypoglycemia. In our case, use of the Naranjo probability scale suggests the ADR to be probable. The mechanism may be due to the additive glucose lowering of the 3 agents consumed concurrently by the patient. Conclusions: Patients with type 2 diabetes mellitus should be routinely counseled about the use of herbal products to minimize the risk of ADRs.
Impact on Siblings of Children With Intellectual Disability: The Role of Child Behavior Problems
Authors: Neece Cameron L. , Blacher Jan , Baker Bruce L. 
Published: June 2010

AbstractThe impact on everyday life for siblings of children with intellectual disability or typical development was examined. Participants were families of children with intellectual disability (n  =  39) or typical development (n  =  75). Child behavior problems and sibling impact were assessed at child ages 5, 6, 7, and 8. Results indicate that siblings of children with intellectual disability were consistently reported by mothers and fathers to be more negatively impacted compared to siblings of typically developing children. When child behavior problems were accounted for, however, there was no longer a significant relationship between child intellectual status and sibling impact. For both intellectual disability and typical development groups, cross-lagged panel analyses indicate that early child behavior problems lead to increased sibling negative impact over time.
Factorial Validity of the Supports Intensity Scale (SIS)
Authors: Kuppens Sofie , Bossaert Goele , Buntinx Wil , Molleman Catherin , Van den Abbeele Ann , Maes Bea 
Published: June 2010

Abstract
The Supports Intensity Scale (SIS) was developed to provide information on the support needs of persons with intellectual disability. Our aim here was to evaluate the factorial validity of the SIS in a sample of 14,862 persons with intellectual disability. The structure of the instrument as promulgated by the developers was tested and its stability evaluated across gender, age, disability complexity, and disability severity groups. Confirmatory factor analysis supported the originally proposed subscale structure. The six-factor structure yielded strict factorial invariance across gender, age, and disability complexity, whereas invariance of factor configuration was merely established across disability severity groups. Possible explanations and implications of these findings are discussed.
Mandala as telematic design
Authors: A Huh Jung 
Published: June 2010

This study starts from the premise that mandala is a design of the Cosmos and consciousness. mandala is a contracted and systematically designed cosmic space and represents high-level spirituality at the same time. The work of designing mandala is an experience with a sacred world as
itself and constitutes a process of self-discipline. In other words, mandala is to ritualize the world of Buddhism beyond a design context and visualize religious experience through a specific object. Therefore, it serves as a medium that gets both producers and audiences to experience the
sacred world. In this way, mandala is present as an experiencing design and a behaving medium.
This study aims to identify the archetype of empirical and synthetic design by analyzing mandala as an integrated icon for which the Cosmos and human beings or consciousness and matter meet each
other. Spatial structuralization is considered most important in the icon of mandala. The space in mandala is the place where consciousness joins reality, which represents the state of enlightenment. Many multi-dimensional Buddhas coexist in the space, and they are arranged in harmony and
in order. This visual structure allows mandala to play the role of interactive medium.
In the iconic shapes of mandala symbolizing a sacred world, major elements include a circle, square, semicircle, triangle and the numbers of 8 and 4. The respective shapes are matched to white, yellow,
red and black, and the five different senses are connected to one another. The five senses are symbolic of earth, water, fire, wind and void which constitute the universe, and again they remain connected to five different parts of the body of a disciplinant drawing mandala: liver, kidney,
spleen, lungs and heart. Those organs are associated with five Buddhas and in turn connected through the boundless space of the universe. By analyzing such a composite structure of mandala, this study tries to appreciate its in-depth meaning as an integrated design.
Virtual sites performance and materialization
Authors: Matthews Linda 
Published: June 2010

The imagistic promotion of the iconic city form is increasingly achieved by the deployment of the CCTV webcam system. This not only presents new material to mediate people's engagement with this space, but also offers new ways to materialize its actual three-dimensional form.
Recent
design-based research conducted at the University of Technology, Sydney, shows that the function of the CCTV Internet cameras can be extended and adapted to provide a type of engagement with urban environments that subverts its more representational role and converts it into one that is qualitative
and experiential. The article will discuss how the performative aspects offered by this virtual environment can be productively employed by the Internet user to not only create a new type of engagement with public space, but also, ultimately, to curate this space.
The article will also
reveal how the strategic deployment of recently developed non-proprietary software can be used to intervene within the operational logic of the Internet camera to exploit its potential for use as a design tool. By the strategic recruitment of this software, raw virtual qualitative data from
webcam images are processed to generate a formal response to civic space. This type of intervention, which utilizes the two-dimensional image as a platform for intervention within three-dimensional space, asks the designer to relinquish the techniques traditionally used to generate urban form
and instead to capitalize upon the opportunities for material intervention offered by the spatial ambiguity of virtual and real-time environments. The exploration of the distortional optical properties associated with contemporary camera technology begins to suggest the development of a range
of new techniques for design intervention that will continue to evolve in direct relationship to the technology they exploit.
This article will therefore discuss how the utilization of the interactive potential of the CCTV system can produce a new understanding of urban space that replaces
any symbolic role for form with the affect of form. This range of unprecedented techniques can be seen to offer a new paradigm for material intervention within both virtual and urban space.