bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG Theta and Alpha Reactivity on Opening the Eyes in the Diagnosis of Alzheimer's Disease
Authors: Fonseca Lineu C. , Tedrus Gloria M. A. S. , Fondello Marina A. , Reis Isabel N. , Fontoura Dayana S. 
Published: February 2012

The objective of this study was to evaluate the contribution of EEG theta and alpha reactivity on opening the eyes, in the diagnosis of slight and moderate Alzheimer's disease (AD). Thirty four patients with AD and a control group of 30 individuals were studied, all being assessed using a neurological evaluation, CERAD neuropsychological battery (consortium to establish a registry for Alzheimer's disease), incorporating the Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR) and a qEEG analysis of the absolute band power at rest, with the eyes both open and closed. The theta and alpha reactivity indices were calculated on opening the eyes, defined from the relationship between the absolute powers in the respective bands in the periods with the eyes open and with them closed, the quotient of the relationship between the alpha and theta indices, the alpha/theta ratio, was also calculated. Multiple regression models were used to determine the accuracy in discriminating between the AD and control groups. A regression model using only cognitive data provided an accuracy of 92.2%, whereas a regression model combining cognitive data and qEEG measurements provided an accuracy of 95.3% in the classification between AD and the controls. The variable for the qEEG was the left hemisphere alpha/theta index, since the other parameters were shown to be inferior with respect to the clinical data in the regression analysis. The integrated study of the theta and alpha reactivity indices on opening the eyes and the alpha/theta index, was shown to be a useful approach in qEEG in the evaluation of AD and should be evaluated with larger samples and with other data analysis methods, with the aim of increasing the accuracy.
Three-component cure rate model for nonproportional hazards alternative in the design of randomized clinical trials
Authors: Kim Haesook Teresa , Gray Robert 
Published: February 2012

Background Cure rate models have been extensively studied and widely used in time-to-event data in cancer clinical trials. Purpose Although cure rate models based on the generalized exponential distribution have been developed, they have not been used in the design of randomized cancer clinical trials, which instead have relied exclusively on two-component exponential cure rate model with a proportional hazards (PH) alternative. In some studies, the efficacy of the experimental treatment is expected to emerge some time after randomization. Since this does not conform to a PH alternative, such studies require a more flexible model to describe the alternative hypothesis. Methods In this article, we report the study design of a phase III clinical trial of acute myeloid leukemia using a three-component exponential cure rate model to reflect the alternative hypothesis. A newly developed power calculation program that does not require PH assumption was used. Results Using a custom-made three-component cure rate model as an alternative hypothesis, the proposed sample size was 409, compared with a sample size of 209 under the assumption of exponential distribution and 228 under the PH alternative. A simulation study was performed to present the degree of power loss when the alternative hypothesis is not appropriately specified. Limitations The power calculation program used in this study is for a single analysis and does not account for group sequential tests in phase III trials. However, the loss in power is small, and this was handled by inflating the sample size by 5%. Conclusion Misspecification of the alternative hypothesis can result in a seriously underpowered study. We report examples of clinical trials that required a custom-made alternative hypothesis to reflect a later indication of experimental treatment efficacy. The proposed three-component cure rate model could be very useful for specifying non-PH alternative.
Reduction of severe exacerbations and hospitalization-derived costs in alpha-1-antitrypsin-deficient patients treated with alpha-1-antitrypsin augmentation therapy
Authors: Barros-Tizón Juan Carlos , Torres María Luisa , Blanco Ignacio , Martínez María Teresa ,   the investigators of the rEXA study group
Published: February 2012

Objective: Severe exacerbations in alpha-1-antitrypsin (AAT)-deficient patients with chronic obstructive pulmonary disease (COPD) and/or emphysema are a major cause of hospitalization. A multicentre, observational, retrospective study was undertaken to evaluate the effect of continuous AAT augmentation therapy in reducing the incidence of exacerbations in these patients. Methods: Patients treated with Trypsone® or Prolastin® for at least 18 months were recruited if their medical records for 18 months before starting augmentation therapy were available. The number of mild and severe exacerbations in the two periods was compared and hospitalization-related costs were analysed. Results: A total of 127 patients were recruited; 75 of them experienced at least one exacerbation in the period prior to augmentation. In the treatment period, the mean number of exacerbations per patient was reduced in both the total population and the population with exacerbations (mean ± SD: 1.2 ± 1.6 versus 1.0 ± 2.2 and 2.0 ± 1.6 versus 1.4 ± 2.7, respectively; p < 0.01). The percentage of patients experiencing exacerbations was reduced in the total population (59.1% versus 44.1%; p < 0.05). In the patient subgroup of the total population who experienced a change in their number of exacerbations between the two periods, 43.7% had a reduction and 21.4% had an increase ( p < 0.01). The number of severe exacerbations diminished in 42.9% of this subgroup and increased in 12.0% ( p < 0.001). Most adverse events were nonserious or not related to treatment. Hospitalization costs savings per patient associated with treatment ranged from approximately €400 to €900 ( p < 0.05). Conclusions: Augmentation therapy with AAT concentrates was associated with a reduction in the incidence and severity of exacerbations in AAT-deficient patients, which resulted in lower hospitalization expenditures.
Quantitative modeling of chronic myeloid leukemia: insights from radiobiology
Authors: Radivoyevitch Tomas , Hlatky Lynn , Landaw Julian , Sachs Rainer K. 
Published: February 2012

AbstractMathematical models of chronic myeloid leukemia (CML) cell population dynamics are being developed to improve CML understanding and treatment. We review such models in light of relevant findings from radiobiology, emphasizing 3 points. First, the CML models almost all assert that the latency time, from CML initiation to diagnosis, is at most ∼ 10 years. Meanwhile, current radiobiologic estimates, based on Japanese atomic bomb survivor data, indicate a substantially higher maximum, suggesting longer-term relapses and extra resistance mutations. Second, different CML models assume different numbers, between 400 and 106, of normal HSCs. Radiobiologic estimates favor values > 106 for the number of normal cells (often assumed to be the HSCs) that are at risk for a CML-initiating BCR-ABL translocation. Moreover, there is some evidence for an HSC dead-band hypothesis, consistent with HSC numbers being very different across different healthy adults. Third, radiobiologists have found that sporadic (background, age-driven) chromosome translocation incidence increases with age during adulthood. BCR-ABL translocation incidence increasing with age would provide a hitherto underanalyzed contribution to observed background adult-onset CML incidence acceleration with age, and would cast some doubt on stage-number inferences from multistage carcinogenesis models in general.
RETRACTED ARTICLE: Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the inflammatory response and protects mice from sepsis
Authors: Bitto Alessandra , Minutoli Letteria , David Antonio , Irrera Natasha , Rinaldi Mariagrazia , Venuti Francesco S , Squadrito Francesco , Altavilla Domenica 
Published: February 2012

Abstract
Introduction
Cecal ligation and puncture (CLP) is an inflammatory condition that leads to multisystemic organ failure. Flavocoxid, a dual inhibitor of cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX), has been shown in vitro to possess antiinflammatory activity in lipopolysaccharide (LPS)-stimulated rat macrophages by reducing nuclear factor (NF)-κB activity and COX-2, 5-LOX and inducible nitric oxide synthase (iNOS) expression. The aim of this study was to evaluate the effects of flavocoxid in a murine model of CLP-induced polymicrobial sepsis.

Methods
C57BL/6J mice were subjected to CLP or sham operation. In a first set of experiments, an intraperitoneal injection of flavocoxid (20 mg/kg) or vehicle was administered 1 hour after surgery and repeated every 12 hours. Survival rate was monitored every 24 hours throughout 120 hours. Furthermore, additional groups of sham and CLP mice were killed 18 hours after surgical procedures for blood-sample collection and the lung and liver were collected for biomolecular, biochemical and histopathologic studies.

Results
COX-2, 5-LOX, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, extracellular-regulated-kinase 1/2 (ERK), JunN-terminal kinase (JNK), NF-κB, and β-arrestin 2 protein expression were evaluated in lung and liver with Western blot analysis. In addition, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), cytokines, and lipoxin A4 serum content were measured with an enzyme-linked immunosorbent assay (ELISA). Flavocoxid administration improved survival, reduced the expression of NF-κB, COX-2, 5-LOX, TNF-α and IL-6 and increased IL-10 production. Moreover, flavocoxid inhibited the mitogen-activated protein kinases (MAPKs) pathway, preserved β-arrestin 2 expression, reduced blood LTB4, PGE2, TNF-α and IL-6, and increased IL-10 and lipoxin A4 serum levels. The treatment with flavocoxid also protected against the histologic damage induced by CLP and reduced the myeloperoxidase (MPO) activity in the lung and liver.

Conclusions
Flavocoxid protects mice from sepsis, suggesting that this dual inhibitor may represent a promising approach in such a life-threatening condition.
Three strategies to stabilise nearly monodispersed silver nanoparticles in aqueous solution
Authors: Stevenson Amadeus PZ , Blanco Bea Duani , Civit Sergi , Antoranz Contera Sonia , Iglesias Cerveto Alberto , Trigueros Sonia 
Published: February 2012

Abstract
Silver nanoparticles are extensively used due to their chemical and physical properties and promising applications in areas such as medicine and electronics. Controlled synthesis of silver nanoparticles remains a major challenge due to the difficulty in producing long-term stable particles of the same size and shape in aqueous solution. To address this problem, we examine three strategies to stabilise aqueous solutions of 15 nm citrate-reduced silver nanoparticles using organic polymeric capping, bimetallic core-shell and bimetallic alloying. Our results show that these strategies drastically improve nanoparticle stability by distinct mechanisms. Additionally, we report a new role of polymer functionalisation in preventing further uncontrolled nanoparticle growth. For bimetallic nanoparticles, we attribute the presence of a higher valence metal on the surface of the nanoparticle as one of the key factors for improving their long-term stability. Stable silver-based nanoparticles, free of organic solvents, will have great potential for accelerating further environmental and nanotoxicity studies.

PACS: 81.07.-b; 81.16.Be; 82.70.Dd.
Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells
Authors: Grassi Rici Rose Eli , Alcântara Dayane , Fratini Paula , Wenceslau Cristiane Valverde , Ambrósio Carlos Eduardo , Miglino Maria Angelica , Maria Durvanei Augusto 
Published: February 2012

AbstractBackgroundThe bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry.ResultsWe evaluated the regenerative potential ofin vitrotreatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53.ConclusionWe propose that rhBMP-2 has great therapeutic potential in bone marrow cells by serving as a tumor suppressor to increase p53 and the pro-apoptotic proteins Bad and Bax, as well as by increasing the activity of phosphorylated caspase 3.Study designCanine bone marrow mesenchymal stem cells associated with rhBMP2 in canine osteosarcoma treatment: "in vitro" study
Family model of HIV care and treatment: a retrospective study in Kenya
Authors: Lewis Kulzer Jayne , Penner Jeremy A , Marima Reson , Oyaro Patrick , Oyanga Arbogast O , Shade Starley B , Blat Cinthia C , Nyabiage Lennah , Mwachari Christina W , Muttai Hellen C , Bukusi Elizabeth A , Cohen Craig R 
Published: February 2012

BackgroundNyanza Province, Kenya, had the highest HIV prevalence in the country at 14.9% in 2007, more than twice the national HIV prevalence of 7.1%. Only 16% of HIV‐infected adults in the country accurately knew their HIV status. Targeted strategies to reach and test individuals are urgently needed to curb the HIV epidemic. The family unit is one important portal.MethodsA family model of care was designed to build on the strengths of Kenyan families. Providers use a family information table (FIT) to guide index patients through the steps of identifying family members at HIV risk, address disclosure, facilitate family testing, and work to enrol HIV‐positive members and to prevent new infections. Comprehensive family‐centred clinical services are built around these steps. To assess the approach, a retrospective study of patients receiving HIV care between September 2007 and September 2009 at Lumumba Health Centre in Kisumu was conducted. A random sample of FITs was examined to assess family reach.ResultsThrough the family model of care, for each index patient, approximately 2.5 family members at risk were identified and 1.6 family members were tested. The approach was instrumental in reaching children; 61% of family members identified and tested were children. The approach also led to identifying and enrolling a high proportion of HIV‐ positive partners among those tested: 71% and 89%, respectively.ConclusionsThe family model of care is a feasible approach to broaden HIV case detection and service reach. The approach can be adapted for the local context and should continue to utilize index patient linkages, FIT adaption, and innovative methods to package services for families in a manner that builds on family support and enhances patient care and prevention efforts. Further efforts are needed to increase family member engagement.
Patient Selection for Oncology Phase I Trials: A Multi-Institutional Study of Prognostic Factors
Authors: Olmos David , A'Hern Roger P. , Marsoni Silvia , Morales Rafael , Gomez-Roca Carlos , Verweij Jaap , Voest Emile E. , Schöffski Patrick , Ang Joo Ern , Penel Nicolas , Schellens Jan H. , del Conte Gianluca , Brunetto Andre T. , Evans T.R. Jeffry , Wilson Richard , Gallerani Elisa , Plummer Ruth , Tabernero Josep , Soria Jean-Charles , Kaye Stan B. 
Published: February 2012

Purpose The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials. Patients and Methods Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis. Results The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality. Conclusion Patient selection using any of these prognostic scores will reduce non–drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.
Isolated Tumor Cells in Regional Lymph Nodes as Relapse Predictors in Stage I and II Colorectal Cancer
Authors: Mescoli Claudia , Albertoni Laura , Pucciarelli Salvatore , Giacomelli Luciano , Russo Valentina M. , Fassan Matteo , Nitti Donato , Rugge Massimo 
Published: February 2012

PurposeLymph node (LN) involvement is the most important prognostic factor in colorectal cancer (CRC), and pN-positive status identifies patients who require adjuvant chemotherapy. Approximately 15% to 20% of patients without nodal metastases (pN0) develop recurrent disease. In this study, we tested the prognostic significance of isolated tumor cells (ITCs) in LNs of patients with pN0 CRC (stages I and II).Patients and MethodsITCs in LNs regional to CRC were assessed in 312 consecutive patients with pN0 CRC who were followed up clinically and/or endoscopically for at least 6 months after surgery (mean, 67 months; median, 64 months; range, 8 to 102 months). LNs were dissected from gross surgical specimens according to a standardized protocol (with a mean of 17 LNs per patient; range, five to 107 LNs). In all, 5,313 pN0 LNs were collected and assessed by using cytokeratin immunostaining in two serial histology sections from each LN, which amounting to a total of 10,626 specimens. The correlation between ITC status and cancer recurrence was tested by using univariate and multivariate statistics.ResultsITCs were documented in 185 of 312 patients (59%). CRC relapsed in 31 of 312 patients (10%), and 25 of 31 recurrences (81%) were documented among ITC-positive patients. CRC recurrence rates among ITC-positive and ITC-negative patients were 14% (25 of 185 patients) and 4.7% (six of 127 patients), respectively. In both univariate and multivariate analyses, ITC status was the only variable significantly associated with cancer relapse (Cox model; hazard ratio, 3.00; 95% CI, 1.23 to 7.32; P = .013).ConclusionIn patients with pN0 CRC, cancer relapse was significantly associated with ITCs in regional LNs. ITCs should be considered among the clinicobiologic variables that identify high-risk patients who can benefit from adjuvant chemotherapy.
Using tri-axial acceleration data to identify behavioral modes of free-ranging animals: general concepts and tools illustrated for griffon vultures
Authors: Nathan Ran , Spiegel Orr , Fortmann-Roe Scott , Harel Roi , Wikelski Martin , Getz Wayne M. 
Published: February 2012

Summary
Integrating biomechanics, behavior and ecology requires a mechanistic understanding of the processes producing the movement of animals. This calls for contemporaneous biomechanical, behavioral and environmental data along movement pathways. A recently formulated unifying movement ecology paradigm facilitates the integration of existing biomechanics, optimality, cognitive and random paradigms for studying movement. We focus on the use of tri-axial acceleration (ACC) data to identify behavioral modes of GPS-tracked free-ranging wild animals and demonstrate its application to study the movements of griffon vultures (Gyps fulvus, Hablizl 1783). In particular, we explore a selection of nonlinear and decision tree methods that include support vector machines, classification and regression trees, random forest methods and artificial neural networks and compare them with linear discriminant analysis (LDA) as a baseline for classifying behavioral modes. Using a dataset of 1035 ground-truthed ACC segments, we found that all methods can accurately classify behavior (80–90%) and, as expected, all nonlinear methods outperformed LDA. We also illustrate how ACC-identified behavioral modes provide the means to examine how vulture flight is affected by environmental factors, hence facilitating the integration of behavioral, biomechanical and ecological data. Our analysis of just over three-quarters of a million GPS and ACC measurements obtained from 43 free-ranging vultures across 9783 vulture-days suggests that their annual breeding schedule might be selected primarily in response to seasonal conditions favoring rising-air columns (thermals) and that rare long-range forays of up to 1750 km from the home range are performed despite potentially heavy energetic costs and a low rate of food intake, presumably to explore new breeding, social and long-term resource location opportunities.