bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of p-STAT3 Enhances IFN-α Efficacy against Metastatic Melanoma in a Murine Model
Authors: Kong Ling-Yuan , Gelbard Alexander , Wei Jun , Reina-Ortiz Chantal , Wang Yongtao , Yang Eric C. , Hailemichael Yared , Fokt Izabela , Jayakumar Arumugam , Qiao Wei , Fuller Gregory N. , Overwijk Willem W. , Priebe Waldemar , Heimberger Amy B. 
Published: April 2010

AbstractPurpose: Melanoma is a common and deadly tumor that upon metastasis to the central nervous system has a median survival duration of &lt;6 months. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma malignancy, including immune suppression in melanoma patients. We hypothesized that WP1193, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of IFN-α against metastatic melanoma.Experimental Design: Combinational therapy of STAT3 blockade agents with IFN-α was investigated in a metastatic and an established syngeneic intracerebral murine tumor model of melanoma. The immunologic in vivo mechanisms of efficacy were investigated by T-cell and natural killer (NK) cell cytotoxic assays.Results: IFN-α immunotherapy was synergistic with WP1193 showing marked in vivo efficacy against metastatic and established intracerebral melanoma. At autopsy, it was noted that there was a decreased trend in mice with melanoma developing leptomeningeal disease treated with combinational therapy. The combinational approach enhanced both NK-mediated and T-cell–mediated antitumor cytotoxicity.Conclusions: The immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-α immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities. This combination therapy has the potential in the treatment of metastatic melanoma that is typically refractory to this type of immune therapeutic approach. Clin Cancer Res; 16(9); 2550–61. ©2010 AACR.
Autologous Bone Marrow–Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation
Authors: Nejadnik Hossein , Hui James H. , Feng Choong Erica Pei , Tai Bee-Choo , Lee Eng Hin 
Published: April 2010

Background: First-generation autologous chondrocyte implantation has limitations, and introducing new effective cell sources can improve cartilage repair. Purpose: This study was conducted to compare the clinical outcomes of patients treated with first-generation autologous chondrocyte implantation to patients treated with autologous bone marrow–derived mesenchymal stem cells (BMSCs). Study Design: Cohort study; Level of evidence, 3. Methods: Seventy-two matched (lesion site and age) patients underwent cartilage repair using chondrocytes (n = 36) or BMSCs (n = 36). Clinical outcomes were measured before operation and 3, 6, 9, 12, 18, and 24 months after operation using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package, which included questions from the Short-Form Health Survey, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Lysholm knee scale, and Tegner activity level scale. Results: There was significant improvement in the patients’ quality of life (physical and mental components of the Short Form-36 questionnaire included in the ICRS package) after cartilage repair in both groups (autologous chondrocyte implantation and BMSCs). However, there was no difference between the BMSC and the autologous chondrocyte implantation group in terms of clinical outcomes except for Physical Role Functioning, with a greater improvement over time in the BMSC group ( P = .044 for interaction effect). The IKDC subjective knee evaluation ( P = .861), Lysholm ( P = .627), and Tegner ( P = .200) scores did not show any significant difference between groups over time. However, in general, men showed significantly better improvements than women. Patients younger than 45 years of age scored significantly better than patients older than 45 years in the autologous chondrocyte implantation group, but age did not make a difference in outcomes in the BMSC group. Conclusion: Using BMSCs in cartilage repair is as effective as chondrocytes for articular cartilage repair. In addition, it required 1 less knee surgery, reduced costs, and minimized donor-site morbidity.
Is Participation Having an Impact?
Authors: Mackinnon Shauna , Stephens Sara 
Published: April 2010

• Summary: In 2005, a consortium of eight community-based organizations (CBOs) that do neighbourhood-level preventative work with families, youth and children in the inner city of Winnipeg, Canada, sought to develop indicators to measure the results of their work. Increasingly pressed by governments and other funders to produce such indicators, they believed that those generally in use missed many of the human gains that they were confident they were making with low-income, inner-city residents. They believed that their emphasis on the importance of colonization, and the need for decolonization, played an important role in their success, but that funders could not fully grasp this philosophical orientation, nor its practical implications. They approached the authors’ research institute for assistance in designing a methodology to better identify the outcomes of their efforts. • Findings: The close and collaborative working relationship between the academic researchers and the community practitioners led to the development of indicators that better reflect outcomes for participants as seen through their eyes. The purpose of this article is to describe the research design that we developed, and the manner in which we worked together to develop it; to describe some of the key themes emerging from the research, and the implications for social policy; and to reflect on the PAR framework that was used in the study. • Applications : This study, including the process, design and findings, is relevant for social workers employed as community developers in non-profit organizations; social workers on the front lines advocating for outcome measures that are sensitive to their ‘clients’ needs; social workers employed as evaluators and administrator; and social workers committed to research that contributes to building community capacity.
Sample size re-estimation in a breast cancer trial
Authors: Hade Erinn M , Jarjoura David , Lai Wei  
Published: April 2010

Background During the recruitment phase of a randomized breast cancer trial, investigating the time to recurrence, we found a strong suggestion that the failure probabilities used at the design stage were too high. Since most of the methodological research involving sample size re-estimation has focused on normal or binary outcomes, we developed a method which preserves blinding to re-estimate sample size in our time to event trial. Purpose A mistakenly high estimate of the failure rate at the design stage may reduce the power unacceptably for a clinically important hazard ratio. We describe an ongoing trial and an application of a sample size re-estimation method that combines current trial data with prior trial data or assumes a parametric model to re-estimate failure probabilities in a blinded fashion. Methods Using our current blinded trial data and additional information from prior studies, we re-estimate the failure probabilities to be used in sample size re-calculation. We employ bootstrap re-sampling to quantify uncertainty in the re-estimated sample sizes. Results At the time of re-estimation data from 278 patients were available, averaging 1.2 years of follow up. Using either method, we estimated a sample size increase of zero for the hazard ratio because the estimated failure probabilities at the time of re-estimation differed little from what was expected. We show that our method of blinded sample size re-estimation preserves the type I error rate. We show that when the initial guess of the failure probabilities are correct, the median increase in sample size is zero. Limitations Either some prior knowledge of an appropriate survival distribution shape or prior data is needed for re-estimation. Conclusions In trials when the accrual period is lengthy, blinded sample size re-estimation near the end of the planned accrual period should be considered. In our examples, when assumptions about failure probabilities and HRs are correct the methods usually do not increase sample size or otherwise increase it by very little. Clinical Trials 2010; 7: 219. http://ctj.sagepub.com
Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches
Authors: Winkler Ingrid G. , Barbier Valérie , Wadley Robert , Zannettino Andrew C. W. , Williams Sharon , Lévesque Jean-Pierre 
Published: April 2010

Abstract
Hematopoietic stem cell (HSC) niches have been reported at the endosteum or adjacent to bone marrow (BM) vasculature. To investigate functional attributes of these niches, mice were perfused with Hoechst 33342 (Ho) in vivo before BM cell collection in presence of pump inhibitors and antibody stained. We report that the position of phenotypic HSCs, multipotent and myeloid progenitors relative to blood flow, follows a hierarchy reflecting differentiation stage, whereas mesenchymal stromal cells are perivascular. Furthermore, during granulocyte colony-stimulating factor–induced mobilization, HSCs migrated closer to blood flow, whereas stromal cells did not. Interestingly, phenotypic Lin−Sca1+KIT+CD41−CD48−CD150+ HSCs segregated into 2 groups (Honeg or Homed), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and long-term bromodeoxyuridine label retention were enriched in Honeg HSCs, whereas Homed HSCs cycled more frequently and only reconstituted a single host. This suggests that the most potent HSC niches are enriched in locally secreted factors and low oxygen tension due to negligible blood flow. Importantly, blood perfusion of niches correlates better with HSC function than absolute distance from vasculature. This technique enables prospective isolation of serially reconstituting HSCs distinct from other less potent HSCs of the same phenotype, based on the in vivo niche in which they reside.
Inhibition of NKG2D expression in NK cells by cytokines secreted in response to human cytomegalovirus infection
Authors: Muntasell Aura , Magri Giuliana , Pende Daniela , Angulo Ana , López-Botet Miguel 
Published: April 2010

AbstractThe NKG2D receptor activates natural killer (NK) cell cytotoxicity and cytokine production on recognition of self-molecules induced by cellular stress under different conditions such as viral infections. The importance of NKG2D in the immune response to human cytomegalovirus (HCMV) is supported by the identification of several viral molecules that prevent the expression of NKG2D ligands by infected cells. In this study we report that, paradoxically, a significant, selective, and transient reduction of NKG2D expression on NK cells is detected during HCMV infection of peripheral blood mononuclear cells if needed. Antagonizing type I interferon (IFN), interleukin-12 (IL-12), and IFNγ prevented HCMV-induced down-regulation of surface NKG2D. Moreover, treatment of purified NK cells with recombinant IFNβ1 and IL-12 mimicked the effect, supporting a direct role of these cytokines in regulating NKG2D surface expression in NK cells. The loss of NKG2D expression selectively impaired NK-cell cytotoxicity against cells expressing NKG2D ligands but preserved the response triggered through other activating receptors. These results support that down-regulation of NKG2D expression on NK cells by cytokines with a key role in antiviral immune response may constitute a physiologic mechanism to control NK-cell reactivity against normal cells expressing NKG2D ligands in the context of inflammatory responses to viral infections.
Using multiple household food inventories to measure food availability in the home over 30 days: a pilot study
Authors: Sisk Cheree , Sharkey Joseph R , McIntosh William A , Anding Jenna 
Published: April 2010

AbstractBackgroundThe consumption of foods, especially by children, may be determined by the types of foods that are available in the home. Because most studies use a single point of data collection to determine the types of foods in the home, which can miss the change in availability when resources are not available, the primary objective of this study was to determine the extent to which the weekly availability of household food items changed over one month by 1) developing the methodology for the direct observation of the presence and amount of food items in the home; 2) conducting five in-home household food inventories over a thirty-day period in a small convenience sample; and 3) determining the frequency that food items were present in the participating households.MethodsAfter the development and pre-testing of the 251-item home observation guide that used direct observation to determine the presence and amount of food items in the home (refrigerator, freezer, pantry, elsewhere), two trained researchers recruited a convenience sample of 9 households (44.4% minority); administered a baseline questionnaire (personal info, shopping habits, food resources, and food security); and conducted 5 in-home assessments (7-day interval) over a 30-day period. Each in-home assessment included food-related activities since the last assessment, and an observational survey of types and amounts of foods present.ResultsComplete data were collected from all 9 women (32.8 y ± 6.0; 3 married; 4 ± 1.6 adults/children in household; 4 received food assistance; and 6 had very low food security) and their households. Weekly grocery purchases (place, amount, and purpose) varied from once (n = 1) to every week (n = 5); 4 used fast food 2-3 times/wk for 4 weeks. The weekly presence and amounts of fresh and processed fruits and vegetables and dairy varied.ConclusionsThe feasibility of conducting multiple in-home assessments was confirmed with 100% retention of participants through 5 in-home assessments, which paid particular attention to the intra-monthly changes in household availability in type and amount of foods. This study contributes to research on home food availability by identifying the importance of multiple measures, presence of certain foods in the home, and the feasibility of comprehensive in-home assessments.
Development of the Japanese version of the Pediatric Quality of Life Inventory™ Brain Tumor Module
Authors: Sato Iori , Higuchi Akiko , Yanagisawa Takaaki , Mukasa Akitake , Ida Kohmei , Sawamura Yutaka , Sugiyama Kazuhiko , Saito Nobuhito , Kumabe Toshihiro , Terasaki Mizuhiko , Nishikawa Ryo , Ishida Yasushi , Kamibeppu Kiyoko 
Published: April 2010

Abstract

Background
The Pediatric Quality of Life Inventory™ (PedsQL™) is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL™ Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL™ Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents.

Methods
Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children.

Results
Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70) except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95). Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents). Evaluation of known-groups validity confirmed that the Cognitive Problems scale was sensitive for developmental impairment, the Movement and Balance scale for infratentorial tumors or paresis, and the Nausea scale for a patient currently undergoing chemotherapy. Convergent and discriminant validity with the PedsQL™ Generic Core Scales and State-Trait Anxiety Inventory for children were acceptable.

Conclusions
The Japanese version of the PedsQL™ Brain Tumor Module is suitable for assessing health-related quality of life in children with brain tumors in clinical trials and research studies.
Polarized light based scheme to monitor column performance in a continuous foam fractionation column
Authors: Swamy Janakiraman N , Crofcheck Czarena L , Mengüç MP 
Published: April 2010

Abstract

Background
A polarized light scattering technique was used to monitor the performance of a continuously operated foam fractionation process. The S
11 and S
12 parameters, elements of the light scattering matrix, combined together (S
11
+S
12) have been correlated with the bubble size and liquid content for the case of a freely draining foam. The performance of a foam fractionation column is known to have a strong dependence on the bubble size distribution and liquid hold up in foam. In this study the enrichment is used as a metric, representative of foam properties and column performance, and correlated to the S
11
+S
12 parameter.

Results
Three different superficial gas velocities (6.9, 7.5, and 10.6 cm/min) and four different pH values (4.8, 5.5, 6.5, and 7.5) are tested for the foam fractionation of a dilute solution of bovine serum albumin (0.1 mg/ml). As a result, at scattering angle of 125° the magnitude of S
11
+S
12 is higher as the pH increases. When the bubble sizes are small with a larger liquid content, the foam is strongly back scattering resulting in lower values of S
11
+S
12 (at 125°) at pH = 4.8. The light scattering data and the enrichment values are measured over a period of 90 minutes and correlated using a linear model. The predictive power of the model was found to be statistically significant.

Conclusion
The time average S
11
+S
12 shows a direct proportionality with the enrichment value, indicating that polarized light should be a valuable technique for monitoring foam fractionation columns. Additional knowledge of the nature of dependence between foam properties and S
11
+S
12 combined with models relating the enrichment to the bubble size and liquid hold up is needed to develop an accurate diagnostics tool for monitoring enrichment utilizing S
11
+S
12 measurements.
Ion transport regulation by P2Y receptors, protein kinase C and phosphatidylinositol 3-kinase within the semicircular canal duct epithelium
Authors: Pondugula Satyanarayana R , Raveendran Nithya N , Marcus Daniel C 
Published: April 2010

Abstract

Background
The ionic composition of the luminal fluid in the vestibular labyrinth is maintained within tight limits by the many types of epithelial cells bounding the lumen. Regulatory mechanisms include systemic, paracrine and autocrine hormones along with their associated intracellular signal pathways. The epithelium lining the semicircular canal duct (SCCD) is a tissue that is known to absorb sodium and calcium and to secrete chloride.

Findings
Transport function was assessed by measurements of short circuit current (I

sc
) and gene transcript expression was evaluated by microarray. Neither ATP nor UTP (100 microM) on the apical side of the epithelium had any effect on I

sc
. By contrast, basolateral ATP transiently increased I

sc
and transepithelial resistance dropped significantly after basolateral ATP and UTP. P2Y2 was the sole UTP-sensitive purinergic receptor expressed. I

sc
was reduced by 42%, 50% and 63% after knockdown of α-ENaC, stimulation of PKC and inhibition of PI3-K, while the latter two increased the transepithelial resistance. PKCdelta, PKCgamma and PI3-K were found to be expressed.

Conclusions
These observations demonstrate that ion transport by the SCCD is regulated by P2Y2 purinergic receptors on the basolateral membrane that may respond to systemic or local agonists, such as ATP and/or UTP. The sodium absorption from endolymph mediated by ENaC in SCCD is regulated by signal pathways that include the kinases PKC and PI3-K. These three newly-identified regulatory components may prove to be valuable drug targets in the control of pathologic vestibular conditions involving dysfunction of transport homeostasis in the ear, such as Meniere's disease.
Effects of childhood body size on breast cancer tumour characteristics
Authors: Li Jingmei , Humphreys Keith , Eriksson Louise , Czene Kamila , Liu Jianjun , Hall Per 
Published: April 2010

Abstract
Introduction
Although a role of childhood body size in postmenopausal breast cancer risk has been established, less is known about its influence on tumour characteristics.

Methods
We studied the relationships between childhood body size and tumour characteristics in a Swedish population-based case-control study consisting of 2,818 breast cancer cases and 3,111 controls. Our classification of childhood body size was derived from a nine-level somatotype. Relative risks were estimated by odds ratios with 95% confidence intervals, derived from fitting unconditional logistic regression models. Association between somatotype at age 7 and tumour characteristics were evaluated in a case-only analysis where P values for heterogeneity were obtained by performing one degree of freedom trend tests.

Results
A large somatotype at age 7 was found to be associated with decreased postmenopausal breast cancer risk. Although strongly associated with other risk factors such as age of menarche, adult body mass index and mammographic density, somatotype at age 7 remained a significant protective factor (odds ratio (OR) comparing large to lean somatotype at age 7 = 0.73, 95% confidence interval (CI) = 0.58-0.91, P trend = 0.004) after adjustment. The significant protective effect was observed within all subgroups defined by estrogen receptor (ER) and progesterone receptor (PR) status, with a stronger effect for ER-negative (0.40, 95% CI = 0.21-0.75, P trend = 0.002), than for ER-positive (0.80, 95% CI = 0.62-1.05, P trend = 0.062), tumours (P heterogeneity = 0.046). Somatotype at age 7 was not associated with tumour size, histology, grade or the presence or absence of metastatic nodes.

Conclusions
Greater body size at age 7 is associated with a decreased risk of postmenopausal breast cancer, and the associated protective effect is stronger for the ER-negative breast cancer subtype than for the ER-positive subtype.