bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial
Authors: Baek Soyoung , Kim Choung-Soo , Kim Sung-Bae , Kim Yong-man , Kwon Seog-Woon , Kim YongMan , Kim HyunSoo , Lee Hyunah 
Published: November 2011

Abstract

Background
Ten cancer patients (Six renal cell carcinoma and four breast cancer patients) were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs) and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration.

Methods
Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay), NK activity and the cytokine modulation were measured.

Results
Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses.

Conclusion
Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.
Rheological non-Newtonian behaviour of ethylene glycol-based Fe2O3 nanofluids
Authors: Pastoriza-Gallego María Jose , Lugo Luis , Legido José Luis , Piñeiro Manuel M 
Published: November 2011

AbstractThe rheological behaviour of ethylene glycol-based nanofluids containing hexagonal scalenohedral-shaped α-Fe2O3 (hematite) nanoparticles at 303.15 K and particle weight concentrations up to 25% has been carried out using a cone-plate Physica MCR rheometer. The tests performed show that the studied nanofluids present non-Newtonian shear-thinning behaviour. In addition, the viscosity at a given shear rate is time dependent, i.e. the fluid is thixotropic. Finally, using strain sweep and frequency sweep tests, the storage modulus G', loss modulus G″ and damping factor were determined as a function of the frequency showing viscoelastic behaviour for all samples.
Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms
Authors: Scherbart Agnes M , Langer Julia , Bushmelev Alexey , van Berlo Damiёn , Haberzettl Petra , van Schooten Frederik-Jan , Schmidt Annette M , Rose Christine R , Schins Roel PF , Albrecht Catrin 
Published: November 2011

AbstractInhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties.NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering.All three particle types were rapidly taken up by AM. DQ12 and ufTiO2, but not fTiO2, caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-α release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2, while DQ12 exclusively triggered interleukin (IL) 1β release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcγ receptor II (FcγRII) antibody revealed that the endocytosis of fTiO2by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2was dominated by FcγIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2, ufTiO2and DQ12 relate to differences in the involvement of specific uptake mechanisms.
Basal progenitor cells in the embryonic mouse thalamus - their molecular characterization and the role of neurogenins and Pax6
Authors: Wang Lynn , Bluske Krista K , Dickel Lauren K , Nakagawa Yasushi 
Published: November 2011

Abstract

Background
The size and cell number of each brain region are influenced by the organization and behavior of neural progenitor cells during embryonic development. Recent studies on developing neocortex have revealed the presence of neural progenitor cells that divide away from the ventricular surface and undergo symmetric divisions to generate either two neurons or two progenitor cells. These 'basal' progenitor cells form the subventricular zone and are responsible for generating the majority of neocortical neurons. However, not much has been studied on similar types of progenitor cells in other brain regions.

Results
We have identified and characterized basal progenitor cells in the embryonic mouse thalamus. The progenitor domain that generates all of the cortex-projecting thalamic nuclei contained a remarkably high proportion of basally dividing cells. Fewer basal progenitor cells were found in other progenitor domains that generate non-cortex projecting nuclei. By using intracellular domain of Notch1 (NICD) as a marker for radial glial cells, we found that basally dividing cells extended outside the lateral limit of radial glial cells, indicating that, similar to the neocortex and ventral telencephalon, the thalamus has a distinct subventricular zone. Neocortical and thalamic basal progenitor cells shared expression of some molecular markers, including Insm1, Neurog1, Neurog2 and NeuroD1. Additionally, basal progenitor cells in each region also expressed exclusive markers, such as Tbr2 in the neocortex and Olig2 and Olig3 in the thalamus. In Neurog1/Neurog2 double mutant mice, the number of basally dividing progenitor cells in the thalamus was significantly reduced, which demonstrates the roles of neurogenins in the generation and/or maintenance of basal progenitor cells. In Pax6 mutant mice, the part of the thalamus that showed reduced Neurog1/2 expression also had reduced basal mitosis.

Conclusions
Our current study establishes the existence of a unique and significant population of basal progenitor cells in the thalamus and their dependence on neurogenins and Pax6. These progenitor cells may have important roles in enhancing the generation of neurons within the thalamus and may also be critical for generating neuronal diversity in this complex brain region.
Identifying cancer biomarkers by network-constrained support vector machines
Authors: Chen Li , Xuan Jianhua , Riggins Rebecca B , Clarke Robert , Wang Yue 
Published: November 2011

Abstract

Background
One of the major goals in gene and protein expression profiling of cancer is to identify biomarkers and build classification models for prediction of disease prognosis or treatment response. Many traditional statistical methods, based on microarray gene expression data alone and individual genes' discriminatory power, often fail to identify biologically meaningful biomarkers thus resulting in poor prediction performance across data sets. Nonetheless, the variables in multivariable classifiers should synergistically interact to produce more effective classifiers than individual biomarkers.

Results
We developed an integrated approach, namely network-constrained support vector machine (netSVM), for cancer biomarker identification with an improved prediction performance. The netSVM approach is specifically designed for network biomarker identification by integrating gene expression data and protein-protein interaction data. We first evaluated the effectiveness of netSVM using simulation studies, demonstrating its improved performance over state-of-the-art network-based methods and gene-based methods for network biomarker identification. We then applied the netSVM approach to two breast cancer data sets to identify prognostic signatures for prediction of breast cancer metastasis. The experimental results show that: (1) network biomarkers identified by netSVM are highly enriched in biological pathways associated with cancer progression; (2) prediction performance is much improved when tested across different data sets. Specifically, many genes related to apoptosis, cell cycle, and cell proliferation, which are hallmark signatures of breast cancer metastasis, were identified by the netSVM approach. More importantly, several novel hub genes, biologically important with many interactions in PPI network but often showing little change in expression as compared with their downstream genes, were also identified as network biomarkers; the genes were enriched in signaling pathways such as TGF-beta signaling pathway, MAPK signaling pathway, and JAK-STAT signaling pathway. These signaling pathways may provide new insight to the underlying mechanism of breast cancer metastasis.

Conclusions
We have developed a network-based approach for cancer biomarker identification, netSVM, resulting in an improved prediction performance with network biomarkers. We have applied the netSVM approach to breast cancer gene expression data to predict metastasis in patients. Network biomarkers identified by netSVM reveal potential signaling pathways associated with breast cancer metastasis, and help improve the prediction performance across independent data sets.
Preventing progression to first-episode psychosis in early initial prodromal states
Authors: Bechdolf A. , Wagner M. , Ruhrmann S. , Harrigan S. , Putzfeld V. , Pukrop R. , Brockhaus-Dumke A. , Berning J. , Janssen B. , Decker P. , Bottlender R. , Maurer K. , Möller H.-J. , Gaebel W. , Häfner H. , Maier W. , Klosterkötter J. 
Published: November 2011

BackgroundYoung people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred.AimsTo investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive–behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS.MethodA randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up.ResultsA total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019).ConclusionsIntegrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.
Modeling and analysis of the migration of HTO and237Np in a fractured granite core at the Äspö hard rock laboratory
Authors: Park Chung-Kyang , Kienzler Bernhard , Vejmelka Peter , Jeong Jong-Tae 
Published: November 2011

AbstractMigration characteristics of HTO and237Np were analyzed through experiments performed with a fractured granite core in the Chemlab2 probe at the Äspö hard rock laboratory in Sweden. These experimental data covered the elution of HTO and237Np as well as information of retained actinides onto the fracture surfaces. The flow field was simulated with a two-dimensional variable aperture channel model. The mass transport process was described with a random-walk method. Three types of basic migration processes were considered: advection, sorption and matrix diffusion. By a combination of these processes, specific effects of each process on transport were evaluated. The retardation of the neptunium were analysed quantitatively by the model. The results were compared to the experimental findings in terms of the elution curves and of distribution patterns on the fracture surface. The elution curves of HTO were used to determine the hydraulic propert ies in the fractured core such as the extent of a dispersion effect according to the flow rates. After termination of the migration test, the rock core was opened, and the retained radioactivities onto the fracture surfaces were measured to investigate an extend of237Np retardation and the retardation mechanism. A retardation factor was obtained by comparing the simulated results to the distribution of sorbed tracers along the flow path. The validity of sorption data from batch tests was also discussed for estimating migration of sorbing tracers.
The Influence of Induction Therapy for Kidney Transplantation after a Non-Renal Transplant
Authors: Cassuto James R. , Levine Matthew H. , Reese Peter P. , Bloom Roy D. , Goral Simin , Naji Ali , Abt Peter L. 
Published: November 2011

Summary

Background and objectives
Non-renal transplant recipients who subsequently develop ESRD and undergo kidney transplantation are medically and immunologically complex due to comorbidities, high cumulative exposure to immunosuppressants, and sensitization to alloantigen from the prior transplant. Although prior non-renal transplant recipients are one of the fastest growing segments of the kidney wait list, minimal data exist to guide the use of antibody induction therapy (IT+) at the time of kidney after lung (KALu), heart (KAH), and liver (KALi) transplant.

Design, setting, participants, & measurements
This retrospective cohort study used national registry data to examine IT use and survival after kidney transplantation. Separate multivariate Cox regression models were constructed to assess patient survival for IT+ and IT− KALu (n=232), KAH (n=588), and KALi (n=736) recipients.

Results
Use of IT increased during the study period. The percentage of patients considered highly sensitized (panel reactive antibody ≥20%) was not statistically significant between IT+ and IT− groups. IT+ was not associated with improvement in 1- and 10-year patient survival for KALu (P=0.20 and P=0.22, respectively) or for KAH (P=0.90 and P=0.14, respectively). However, IT+ among KALi was associated with inferior patient survival at 1 and 10 years (P=0.04 and P=0.02, respectively).

Conclusions
Use of IT for kidney transplantation among prior non-renal transplant recipients may not offer a survival advantage in KALu or KAH. However, due to limited power, these findings should be interpreted cautiously. IT+ was associated with inferior outcomes for KALi. Use of IT should be judicially reconsidered in this complex group of recipients.
Improving Ascertainment of Sudden Cardiac Death in Patients with End Stage Renal Disease
Authors: Pun Patrick H. , Herzog Charles A. , Middleton John P. 
Published: November 2011

SummaryBackground and objectivesData collected by the US Renal Data System (USRDS) identify sudden cardiac death (SCD) as the leading cause of death among hemodialysis patients. However, evidence suggests that clinical events captured on the USRDS death notification form may be inaccurate. A new method for classifying SCD was recently developed to enhance the accuracy of SCD classification. This study examined the performance characteristics of this refined definition using a cohort of hemodialysis patients who experienced a witnessed SCD as the reference standard.Design, setting, participants, & measurementsThis is a retrospective cohort study of 363 patients who experienced a witnessed SCD in US Gambro (DaVita) outpatient dialysis clinics. Sensitivity of SCD defined by death notification forms and SCD defined using additional administrative sources was compared. Clinical data recorded near time of death were also examined.ResultsExisting USRDS death notification forms reported 70.8% of witnessed SCD as “cardiac arrest/cause unknown” or “arrhythmia.” The refined definition significantly improved identification to 83.8% of witnessed SCD events (P<0.001). Verified SCD cases that were not identified by either definition were more likely to be reported on the death notification form as death due to myocardial infarction, hyperkalemia, sepsis, malignancy, or unknown cause.ConclusionsCompared with the death notification form alone, the refined SCD definition significantly improves the sensitivity of reporting of witnessed SCD occurring within outpatient hemodialysis clinics. More accurate reporting of cardiac events by clinicians and refinements to existing death notification forms may further improve recognition and understanding of SCD.
Serum Fibroblast Growth Factor-23 and Risk of Incident Chronic Kidney Disease in Older Community-Dwelling Women
Authors: Semba Richard D. , Fink Jeffrey C. , Sun Kai , Cappola Anne R. , Dalal Mansi , Crasto Candace , Ferrucci Luigi , Fried Linda P. 
Published: November 2011

Summary

Background and objectives
Elevated circulating fibroblast growth factor 23 (FGF23) predicts progression of CKD, but it is unknown whether circulating FGF23 independently predicts incident CKD. This study aimed to determine whether circulating FGF23 predicts incident CKD in community-dwelling women.

Design, setting, participants, & measurements
This study examined the relationship of intact serum FGF23, 1,25-dihydroxyvitamin D3 (1,25[OH]2D), 25-hydroxyvitamin D (25[OH]D), parathyroid hormone, calcium, and phosphate with prevalent and incident CKD in 701 disabled women, ≥65 years of age, from the Women’s Health and Aging Study I in Baltimore, Maryland, from 1993 to 1997. Incident CKD was defined as a low estimated GFR (eGFR) <60 ml/min per 1.73 m2 only, low eGFR <60 ml/min per 1.73 m2 and a ≥25% decline in eGFR from baseline, and an increase in serum creatinine (≥0.4 mg/dl) at follow-up.

Results
At baseline, 381 women (54.3%) had stage 3 CKD. Of 307 women without CKD at baseline, 63 (20.5%) developed stage 3 CKD over 24 months of follow-up. After excluding prevalent cases of CKD, FGF23 (per 1 SD increase) was associated with incident stage 3 CKD (hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.06, 2.16; P=0.02), low and declining eGFR (HR, 3.69; 95% CI, 1.68, 8.11; P=0.001), and increase in serum creatinine (HR, 5.35; 95% CI, 1.27, 22.54; P=0.02) in respective multivariable Cox proportional hazards models adjusting for baseline eGFR, age, race, phosphate, 1,25-dihydroxyvitamin D3, parathyroid hormone, and other potential confounders.

Conclusions
Elevated FGF23 is an independent risk factor for incident CKD in older, disabled, community-dwelling women.
Mapping Patient-Specific Functional Scale (PSFS) Items to the International Classification of Functioning, Disability and Health (ICF)
Authors: Fairbairn Kate , May Kate , Yang Yvonne , Balasundar Sharan , Hefford Cheryl , Abbott J. Haxby 
Published: November 2011

Background
The International Classification of Functioning, Disability and Health (ICF) provides a common framework for clinical outcome measurement. Because the Patient-Specific Functional Scale (PSFS) is widely used for documenting change over time in individual patients receiving musculoskeletal physical therapy, investigation of the extent to which PSFS items reflect the ICF is needed.

Objective
The study objective was to investigate the extent to which patient-generated PSFS items reflect ICF domains.

Design
This investigation was an observational content validity study.

Methods
A total of 2,911 PSFS items from 1,050 files for patients with musculoskeletal disorders were analyzed. The data were from a random sample of participants in the Otago Outcome Measures Project at 4 clinics of the School of Physiotherapy, University of Otago, situated in 3 New Zealand cities. Patient-nominated PSFS items were categorized and mapped with thematic analysis techniques to ICF components, chapters, and categories. Subgroup analyses were conducted for body region of injury and age ranges.

Results
All (100%) of the analyzed items could be mapped to the ICF. Most patient-nominated items mapped to the activity component (80.0%), some items mapped to the participation component (7.7%), other items were related to impairment (7.4%), and the fourth group contained items that overlapped the activity and participation components (4.9%). Similar results were found for each of the 5 body regions and across age ranges in subgroup analyses.

Limitations
These results are limited to individual patients seeking musculoskeletal physical therapy. Patient-generated PSFS items were investigated.

Conclusions
The ICF activity component was most commonly represented by patient-nominated PSFS items, the participation component was moderately represented, and impairment was least represented. Hence, the PSFS would complement impairment-based clinical outcome measures.