bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokeratin-19 and Mammaglobin Gene Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients Enrolled in North Central Cancer Treatment Group Trials, N0234/336/436/437
Authors: Reinholz Monica M. , Kitzmann Kathleen A. , Tenner Kathleen , Hillman David , Dueck Amylou C. , Hobday Timothy J. , Northfelt Donald W. , Moreno-Aspitia Alvaro , Roy Vivek , LaPlant Betsy , Allred Jake B. , Stella Philip J. , Lingle Wilma L. , Perez Edith A. 
Published: October 2011

Abstract
Purpose: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN).
Experimental Design: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan + cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched with CD45 depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized to β2-microglobulin and calibrated to healthy blood using the 2–ΔΔCq algorithm; positivity was defined as 2 or more.
Results: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05).
Conclusions: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients. Clin Cancer Res; 17(22); 7183–93. ©2011 AACR.
Gene Expression Differences between Colon and Rectum Tumors
Authors: Sanz-Pamplona Rebeca , Cordero David , Berenguer Antonio , Lejbkowicz Flavio , Rennert Hedy , Salazar Ramon , Biondo Sebastiano , Sanjuan Xavier , Pujana Miguel A. , Rozek Laura , Giordano Thomas J. , Ben-Izhak Ofer , Cohen Hector I. , Trougouboff Philip , Bejhar Jacob , Sova Yanina , Rennert Gad , Gruber Stephen B. , Moreno Victor 
Published: October 2011

Abstract
Purpose: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level.
Experimental Design: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons.
Results: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum.
Conclusions: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer. Clin Cancer Res; 17(23); 7303–12. ©2011 AACR.
Enhanced Antitumor Efficacy of Low-Dose Etoposide with Oncolytic Herpes Simplex Virus in Human Glioblastoma Stem Cell Xenografts
Authors: Cheema Tooba A. , Kanai Ryuichi , Kim Geon Woo , Wakimoto Hiroaki , Passer Brent , Rabkin Samuel D. , Martuza Robert L. 
Published: October 2011

Abstract
Purpose: Glioblastoma (GBM) inevitably recurs despite surgery, radiation, and chemotherapy. A subpopulation of tumor cells, GBM stem cells (GSC), has been implicated in this recurrence. The chemotherapeutic agent etoposide is generally reserved for treating recurrent tumors; however, its effectiveness is limited due to acute and cumulative toxicities to normal tissues. We investigate a novel combinatorial approach of low-dose etoposide with an oncolytic HSV to enhance antitumor activity and limit drug toxicity.
Experimental Design: In vitro, human GBM cell lines and GSCs were treated with etoposide alone, oncolytic herpes simplex virus (oHSV) G47Δ alone, or the combination. Cytotoxic interactions were analyzed using the Chou–Talalay method, and changes in caspase-dependent apoptosis and cell cycle were determined. In vivo, the most etoposide-resistant human GSC, BT74, was implanted intracranially and treated with either treatment alone or the combination. Analysis included effects on survival, therapy-associated adverse events, and histologic detection of apoptosis.
Results: GSCs varied in their sensitivity to etoposide by over 50-fold in vitro, whereas their sensitivity to G47Δ was similar. Combining G47Δ with low-dose etoposide was moderately synergistic in GSCs and GBM cell lines. This combination did not enhance virus replication, but significantly increased apoptosis. In vivo, the combination of a single cycle of low-dose etoposide with G47Δ significantly extended survival of mice-bearing etoposide–insensitive intracranial human GSC–derived tumors.
Conclusions: The combination of low-dose etoposide with G47Δ increases survival of mice-bearing intracranial human GSC–derived tumors without adverse side effects. These results establish this as a promising combination strategy to treat resistant and recurrent GBM. Clin Cancer Res; 17(23); 7383–93. ©2011 AACR.
Multiple Intelligences, Problem Solving, and Diversity in the General Classroom
Authors: Maker C. June , Rogers Judith A. , Nielson Aleene B. , Bauerle Patricia R. 
Published: October 2011

Classroom teaching strategies and curriculum based on the theory of multiple intelligences (Gardner, 1983), principles for differentiation to meet the needs of gifted students (Maker et) Nielson, 1996), and integration of culturally and linguistically appropriate content have been advocated for students with diverse learning needs, including gifted students and students learning English as a second language. In this study of two teachers' classrooms, pre- and postassessments were used to compare teacher's level of implementation of the DISCOVER1 approach on: problem-solving behaviors, number of students identified as gifted, problem solving by gender, and problem solving by students' language of preference. Significant relationships were found between level of implementation by teacher and positive changes in problem solving in Pablo® and math activities, mean math performance, and number of students identified as gifted on postassessment. The results indicate the value of the DISCOVER approach in general classrooms with a high proportion of Spanish-speaking or bilingual children.
A four-week walking exercise programme in patients with knee osteoarthritis improves the ability of dual-task performance: a randomized controlled trial
Authors: Hiyama Yoshinori , Yamada Minoru , Kitagawa Akira , Tei Norihiro , Okada Shuichi 
Published: October 2011

Objective: To investigate whether a four-week walking exercise programme in patients with knee osteoarthritis improves the ability of dual-task performance in older adults with knee osteoarthritis. Design: A randomized controlled trial with two groups: a walking group and a control group. Subjects: Forty older adults with knee osteoarthritis, 20 participants in each group. Intervention: The walking intervention was designed to increase the number of steps walked daily. The walking group was instructed to increase their number of steps to 3000 steps more than before the intervention. Main outcome measures: Dual-task performance was computed by an automaticity index: the walking velocity under single-task condition/under dual-task conditions × 100 (%), defined as automaticity. The nearer to 100% automaticity, the better the dual-task performance. Decrease of the Trail Making Test (TMT) performance was defined as ΔTMT. ΔTMT was calculated as the difference between times (part B–part A) as a measure of executive function. In addition, functional ability was measured by the Japanese Knee Osteoarthritis Measure. Results: The walking group improved significantly in automaticity ( P < 0.001, from 75.2 (7.6) to 86.9 (10.4), ΔTMT ( P < 0.001, from 63.4 (43.1) to 48.3 (29.6)) and Japanese Knee Osteoarthritis Measure score ( P < 0.001, from 54.4 to 51.9) compared with before the intervention, while the control group displayed no significant differences. Conclusions: We found that walking exercise improves executive function and dual-task performance.
Impaired cortical deactivation during hand movement in the relapsing phase of multiple sclerosis: a cross-sectional and longitudinal fMRI study
Authors: Pantano Patrizia , Bernardi Silvia , Tinelli Emanuele , Pontecorvo Simona , Lenzi Delia , Raz Eytan , Tona Francesca , Gasperini Claudio , Pozzilli Carlo 
Published: October 2011

Background: Little is known about the cortical activation changes during clinical relapses in multiple sclerosis (MS). Objective: To assess cross-sectional and longitudinal differences in functional magnetic resonance imaging (fMRI) cortical patterns between the relapsing and stable phases of MS. Methods: We studied 32 patients with relapsing–remitting MS with mild disability: 19 within 48 h of symptom onset of a new relapse (G1) and 13 in the stable phase, relapse-free for at least 6 months (G2). All patients underwent fMRI twice, upon entry (time 1) and 30–50 days later (time 2), during right-hand movement. Results: No between-group differences were observed in age, disability or T2 lesion load. Between-group analysis showed a significant difference in the ipsilateral precentral gyrus (IPG) activation at time 1. Activity differences in the IPG expressed reduced deactivation in G1 compared with G2. Longitudinal changes in brain activity in the IPG were significantly greater in G1 than G2. G1 patients with a slow clinical recovery ( n = 8) showed different activity at baseline and greater activity changes over time in the IPG than patients with a fast recovery ( n = 11). Conclusion: This study shows that the relapsing phase is associated with reduced brain deactivation in the IPG, which is more marked in patients with a slow clinical recovery. Increased cortical excitability associated with inflammation may determine functional modifications within the ipsilateral motor area.
A regulator’s view of comparative effectiveness research
Authors: Temple Robert 
Published: October 2011

Background ‘Comparative effectiveness’ is the current enthusiasm, and for good reason. After knowing a treatment works, the most critical question is how it compares with alternatives. Comparative studies are not commonly conducted by drug companies and they represent a significant methodological challenge. Comparative data could include evidence of overall superiority to an alternative or advantages in identifiable subsets, for example, people who do not respond to or tolerate alternatives, or members of a genetic subset and could also include convincing evidence that there is little difference between two treatments. Purpose To describe regulations, guidance, and Food and Drug Administration experience related to studies of comparative effectiveness, including approaches to showing superiority and problems encountered in showing similarity. Methods Review of Food and Drug Administration regulations and guidance and experience with showing superiority and similarity, particularly related to randomized trials and epidemiologic studies. Results Methods exist, and they have been successful for showing overall superiority of one drug over another, advantages in specific population subsets. Efforts to show true equivalence face problems of definition and very large sample sizes needed to rule out small differences. Limitations There is need for further discussion of what is meant by similarity or equivalence of two treatments. Conclusion Comparative studies are challenging because differences between effective therapies are likely to be small and can be detected reliably only in randomized trials, often large ones. Despite the difficulties, comparative trials have been successful and we clearly would like to see more of them.
Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia
Authors: Löwenberg Bob , Muus Petra , Ossenkoppele Gert , Rousselot Philippe , Cahn Jean-Yves , Ifrah Norbert , Martinelli Giovanni , Amadori Sergio , Berman Ellin , Sonneveld Pieter , Jongen-Lavrencic Mojca , Rigaudeau Sophie , Stockman Paul , Goudie Alison , Faderl Stefan , Jabbour Elias , Kantarjian Hagop 
Published: October 2011

AbstractThe primary objective of this 2-part phase 1/2 study was to determine the maximum-tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of barasertib administered as a continuous 7-day infusion every 21 days. In part B, the efficacy of barasertib was evaluated at the MTD. In part A, 32 patients were treated with barasertib 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 400 mg (n = 4), 800 mg (n = 7), 1200 mg (n = 6), and 1600 mg (n = 6). Dose-limiting toxicities (stomatitis/mucosal inflammation events) were reported in the 800 mg (n = 1), 1200 mg (n = 1), and 1600 mg (n = 2) groups. The MTD was defined as 1200 mg. In part B, 32 patients received barasertib 1200 mg. In each part of the study, 8 of 32 patients had a hematologic response according to Cheson AML criteria. The most commonly reported grade ≥ 3 events were febrile neutropenia (n = 24) and stomatitis/mucosal inflammation (n = 16). We concluded that the MTD of barasertib is 1200 mg in patients with relapsed or newly diagnosed AML. Toxicity was manageable and barasertib treatment resulted in an overall hematologic response rate of 25%. This study is registered at www.ClinicalTrials.gov as NCT00497991.
Polyphosphate is a cofactor for the activation of factor XI by thrombin
Authors: Choi Sharon H. , Smith Stephanie A. , Morrissey James H. 
Published: October 2011

AbstractFactor XI deficiency is associated with a bleeding diathesis, but factor XII deficiency is not, indicating that, in normal hemostasis, factor XI must be activated in vivo by a protease other than factor XIIa. Several groups have identified thrombin as the most likely activator of factor XI, although this reaction is slow in solution. Although certain nonphysiologic anionic polymers and surfaces have been shown to enhance factor XI activation by thrombin, the physiologic cofactor for this reaction is uncertain. Activated platelets secrete the highly anionic polymer polyphosphate, and our previous studies have shown that polyphosphate has potent procoagulant activity. We now report that polyphosphate potently accelerates factor XI activation by α-thrombin, β-thrombin, and factor XIa and that these reactions are supported by polyphosphate polymers of the size secreted by activated human platelets. We therefore propose that polyphosphate is a natural cofactor for factor XI activation in plasma that may help explain the role of factor XI in hemostasis and thrombosis.
Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model
Authors: Noth Rainer , Lange-Grumfeld Julia , Stüber Eckhard , Kruse Marie-Luise , Ellrichmann Mark , Häsler Robert , Hampe Jochen , Bewig Burkhard , Rosenstiel Philip , Schreiber Stefan , Arlt Alexander 
Published: October 2011

Abstract

Background
Hematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models.

Methods
To investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice.

Results
By assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-α expression was significantly upregulated.

Conclusions
This analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin.
Adjusting for sampling variability in sparse data: geostatistical approaches to disease mapping
Authors: Hampton Kristen H , Serre Marc L , Gesink Dionne C , Pilcher Christopher D , Miller William C 
Published: October 2011

Abstract

Background
Disease maps of crude rates from routinely collected health data indexed at a small geographical resolution pose specific statistical problems due to the sparse nature of the data. Spatial smoothers allow areas to borrow strength from neighboring regions to produce a more stable estimate of the areal value. Geostatistical smoothers are able to quantify the uncertainty in smoothed rate estimates without a high computational burden. In this paper, we introduce a uniform model extension of Bayesian Maximum Entropy (UMBME) and compare its performance to that of Poisson kriging in measures of smoothing strength and estimation accuracy as applied to simulated data and the real data example of HIV infection in North Carolina. The aim is to produce more reliable maps of disease rates in small areas to improve identification of spatial trends at the local level.

Results
In all data environments, Poisson kriging exhibited greater smoothing strength than UMBME. With the simulated data where the true latent rate of infection was known, Poisson kriging resulted in greater estimation accuracy with data that displayed low spatial autocorrelation, while UMBME provided more accurate estimators with data that displayed higher spatial autocorrelation. With the HIV data, UMBME performed slightly better than Poisson kriging in cross-validatory predictive checks, with both models performing better than the observed data model with no smoothing.

Conclusions
Smoothing methods have different advantages depending upon both internal model assumptions that affect smoothing strength and external data environments, such as spatial correlation of the observed data. Further model comparisons in different data environments are required to provide public health practitioners with guidelines needed in choosing the most appropriate smoothing method for their particular health dataset.
PAX8 Mutation Disturbing Thyroid Follicular Growth: A Case Report
Authors: Narumi Satoshi , Yoshida Akira , Muroya Koji , Asakura Yumi , Adachi Masanori , Fukuzawa Ryuji , Kameyama Kaori , Hasegawa Tomonobu 
Published: October 2011

AbstractContext:Heterozygous inactivating PAX8 mutations cause congenital hypothyroidism. Although more than 30 mutation carriers have been reported, no histological examination of the thyroid has been conducted.Objective:The objective of this study was to document the histological characteristics of the thyroid tissue harboring a PAX8 mutation.Subjects and Methods:The patient was a 40-yr-old female, whose two children had congenital hypothyroidism and an inactivating PAX8 mutation (p.K80_A84dup). She had normal thyroid function but had a thyroid nodule and received right hemithyroidectomy at age 28 yr. Mutation analyses using DNA derived from multiple sources, namely lymphocytes, nails, and laser capture microdissected thyroid samples, were performed.Results:The PAX8 mutation was detected in the lymphocytes; however, the level of the mutant allele was significantly lower than that of the wild-type allele. This finding was compatible with her somatic mosaic state. We reviewed the histology of her resected thyroid and found a characteristic lesion in the nonneoplastic tissue: dense aggregates of thyrocytes with absent or very small follicles, resembling a fetal thyroid in the late phase of development. Mutation analyses of laser capture microdissected thyroid samples revealed that the fetal-like tissue carried the PAX8 mutation, whereas surrounding morphologically normal tissue and adenoma tissue did not.Conclusions:In our case, the histology of PAX8 mutation-carrying thyroid tissue was characterized by the lack of follicular growth. Our observations provide the first evidence suggesting that the late phase of thyroid development is sensitive to the PAX8 gene dosage and can be disturbed by heterozygous inactivating PAX8 mutations.
Application of response surface methodology to study the influence of hydrothermal processing on phytochemical constituents of the Irish edible brown seaweed Himanthalia elongata
Authors: Cox Sabrina , Gupta Shilpi , Abu-Ghannam Nissreen 
Published: October 2011

Abstract
We used response surface methodology to investigate the effect of time and temperature of hydrothermal processing (blanching) on the phytochemical content, texture and colour of a semi-dried brown seaweed (Himanthalia elongata). A central composite design was employed with a hydrothermal processing time of 10–30 min and temperature of 60–90°C. Predicted models were found to be significant for total phenolic content, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, total flavonoids, total condensed tannins, texture and colour. The predicted values for each of the responses were in good agreement with experimental values. Processing time had the most significant effect on phytochemical constituents of H. elongata. An acceptable edible texture and colour of seaweed was also achieved during the blanching procedure. Thus, central composite design and response surface methodology can be used to model phytochemical content, texture and colour of H. elongata while minimising the number of experiments required. Multiple response optimisation demonstrated that the phytochemical content of H. elongata may be maximised by blanching for 20.4 min at 80.5°C.