bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and methods for a randomized clinical trial treating comorbid obesity and major depressive disorder
Authors: Schneider Kristin L , Bodenlos Jamie S , Ma Yunsheng , Olendzki Barbara , Oleski Jessica , Merriam Philip , Crawford Sybil , Ockene Ira S , Pagoto Sherry L 
Published: September 2008

Abstract

Background
Obesity is often comorbid with depression and individuals with this comorbidity fare worse in behavioral weight loss treatment. Treating depression directly prior to behavioral weight loss treatment might bolster weight loss outcomes in this population, but this has not yet been tested in a randomized clinical trial.

Methods and design
This randomized clinical trial will examine whether behavior therapy for depression administered prior to standard weight loss treatment produces greater weight loss than standard weight loss treatment alone. Obese women with major depressive disorder (N = 174) will be recruited from primary care clinics and the community and randomly assigned to one of the two treatment conditions. Treatment will last 2 years, and will include a 6-month intensive treatment phase followed by an 18-month maintenance phase. Follow-up assessment will occur at 6-months and 1- and 2 years following randomization. The primary outcome is weight loss. The study was designed to provide 90% power for detecting a weight change difference between conditions of 3.1 kg (standard deviation of 5.5 kg) at 1-year assuming a 25% rate of loss to follow-up. Secondary outcomes include depression, physical activity, dietary intake, psychosocial variables and cardiovascular risk factors. Potential mediators (e.g., adherence, depression, physical activity and caloric intake) of the intervention effect on weight change will also be examined.

Discussion
Treating depression before administering intensive health behavior interventions could potentially boost the impact on both mental and physical health outcomes.

Trial registration
NCT00572520
Factors associated with adolescent cigarette smoking in Greece: Results from a cross sectional study (GYTS Study)
Authors: Rachiotis George , Muula Adamson S , Rudatsikira Emmanuel , Siziya Seter , Kyrlesi Athina , Gourgoulianis Konstantinos , Hadjichristodoulou Christos 
Published: September 2008

Abstract

Background
Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study.

Methods
A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004–2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal.

Results
6141 adolescents (51.5% males and 48.5% females) participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08–3.08), parental smoking (OR: 2.59; 95% CI: 1.45–5.89), and having pocket money ≥ 16 Euros (OR: 2.64; 95% CI: 1.19–5.98).

Conclusion
Male gender, parental smoking, and having pocket-money ≥ 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.
Molecular analysis of chondrocytes cultured in agarose in response to dynamic compression
Authors: Bougault Carole , Paumier Anne , Aubert-Foucher Elisabeth , Mallein-Gerin Frédéric 
Published: September 2008

Abstract

Background
Articular cartilage is exposed to high mechanical loads under normal physiological conditions and articular chondrocytes regulate the composition of cartilaginous matrix, in response to mechanical signals. However, the intracellular pathways involved in mechanotransduction are still being defined. Using the well-characterized chondrocyte/agarose model system and dynamic compression, we report protocols for preparing and characterizing constructs of murine chondrocytes and agarose, and analyzing the effect of compression on steady-state level of mRNA by RT-PCR, gene transcription by gene reporter assay, and phosphorylation state of signalling molecules by Western-blotting. The mouse model is of particular interest because of the availability of a large choice of bio-molecular tools suitable to study it, as well as genetically modified mice.

Results
Chondrocytes cultured in agarose for one week were surrounded by a newly synthesized pericellular matrix, as revealed by immunohistochemistry prior to compression experiments. This observation indicates that this model system is suitable to study the role of matrix molecules and trans-membrane receptors in cellular responsiveness to mechanical stress. The chondrocyte/agarose constructs were then submitted to dynamic compression with FX-4000C™ Flexercell® Compression Plus™ System (Flexcell). After clearing proteins off agarose, Western-blotting analysis showed transient activation of Mitogen-activated protein kinases (MAPK) in response to dynamic compression. After assessment by capillary electrophoresis of the quality of RNA extracted from agarose, steady-state levels of mRNA expression was measured by real time PCR. We observed an up-regulation of cFos and cJun mRNA levels as a response to compression, in accordance with the mechanosensitive character observed for these two genes in other studies using cartilage explants submitted to compression. To explore further the biological response of mouse chondrocytes to the dynamic compression at the transcriptional level, we also developed an approach for monitoring changes in gene transcription in agarose culture by using reporter promoter constructs. A decrease in promoter activity of the gene coding for type II procollagen, the most abundant protein in cartilage, was observed in response to dynamic loading.

Conclusion
The protocols developed here offer the possibility to perform an integrated analysis of the molecular mechanisms of mechanotransduction in chondrocytes, at the gene and protein level.
In vivo effects of Pain Relieving Plaster on closed soft tissue injury in rabbit ears
Authors: Wang Yong-Zhi , Guo Chun-Yu , Zhong Hong-Gang , Zhang Wan-Nian , Wang De-Long , Wang Xuan , Dong Fu-Hui 
Published: September 2008

AbstractBackgroundSoft tissue injury imposes major public health burdens worldwide. The positive effect of China's Tibetan medicine and theLamiophlomis rotata-based herbal Pain Relieving Plaster (PRP) on healing closed soft tissue injury (CSTI) has been reported. The herbs contained in Plaster are also referred as 'blood-activating and stasis-dispelling' in herbal medicine. The formula of the plaster contains four China's Tibetan medical herbs, includingLamiophlomis rotata,Oxytropis falcate Bunge,Curcuma longa Linn, andMyricaria bracteata. Two of these herbs (Lamiophlomis rotate;Curcuma longa Linn) are commonly used in different formulae of Chinese medicine. The objective of this study is to use an interdisciplinary approach to test the hypothesis that the formula and its components influence the process of CSTI.MethodsIn vivo models have been established in 30 rabbit ear pinnae and studied for: (1) blood flow velocity (BFV) which was affected by pressure of 21.2 kg/cm2 for 30 second over the local rabbit ear tissue; (2) edema formation of the closed soft tissue injury; (3) in vivo local temperature change.ResultsThe results of in vivo studies indicated that CSTI significantly increased the velocity of blood flow and increased edema formation within the control group. The PRP extracts for 5 hours significantly slowed down the BFV of CSTI in rabbit ears, markedly decreased the elevated edema level from the 3rd to the 5th day.ConclusionThe ingredients contained in the formula have positive effects in healing CSTI and further study is worth exploring.
Marine metagenomics: strategies for the discovery of novel enzymes with biotechnological applications from marine environments
Authors: Kennedy Jonathan , Marchesi Julian R , Dobson Alan DW 
Published: September 2008

Abstract
Metagenomic based strategies have previously been successfully employed as powerful tools to isolate and identify enzymes with novel biocatalytic activities from the unculturable component of microbial communities from various terrestrial environmental niches. Both sequence based and function based screening approaches have been employed to identify genes encoding novel biocatalytic activities and metabolic pathways from metagenomic libraries. While much of the focus to date has centred on terrestrial based microbial ecosystems, it is clear that the marine environment has enormous microbial biodiversity that remains largely unstudied. Marine microbes are both extremely abundant and diverse; the environments they occupy likewise consist of very diverse niches. As culture-dependent methods have thus far resulted in the isolation of only a tiny percentage of the marine microbiota the application of metagenomic strategies holds great potential to study and exploit the enormous microbial biodiversity which is present within these marine environments.
Use of the viral 2A peptide for bicistronic expression in transgenic mice
Authors: Trichas Georgios , Begbie Jo , Srinivas Shankar 
Published: September 2008

Abstract

Background

Transgenic animals are widely used in biomedical research and biotechnology. Multicistronic constructs, in which several proteins are encoded by a single messenger RNA, are commonly used in genetically engineered animals. This is currently done by using an internal ribosomal entry site to separate the different coding regions. 2A peptides result in the co-translational 'cleavage' of proteins and are an attractive alternative to the internal ribosomal entry site. They are more reliable than the internal ribosomal entry site and lead to expression of multiple cistrons at equimolar levels. They work in a wide variety of eukaryotic cells, but to date have not been demonstrated to function in transgenic mice in an inheritable manner.

Results

To test 2A function in transgenic mice and uncover any possible toxicity of widespread expression of the 2A peptide, we made a bicistronic reporter construct containing the coding sequence for a membrane localised red fluorescent protein (Myr-TdTomato) and a nuclear localised green fluorescent protein (H2B-GFP), separated by a 2A sequence. When this reporter is transfected into HeLa cells, the two fluorescent proteins correctly localise to mutually exclusive cellular compartments, demonstrating that the bicistronic construct is a reliable readout of 2A function. The two fluorescent proteins also correctly localise when the reporter is electroporated into chick neural tube cells. We made two independent transgenic mouse lines that express the bicistronic reporter ubiquitously. For both lines, transgenic mice are born in Mendelian frequencies and are found to be healthy and fertile. Myr-TdTomato and H2B-GFP segregate to mutually exclusive cellular compartments in all tissues examined from a broad range of developmental stages, ranging from embryo to adult. One transgenic line shows X-linked inheritance of the transgene and mosaic expression in females but uniform expression in males, indicating that the transgene has integrated into the X chromosome in this line.

Conclusion

The 2A peptide efficiently mediates co-translational cleavage in transgenic mice in which it has been inherited through the germ-line. Mice expressing it ubiquitously throughout development and into adulthood appear normal. It is therefore a viable tool for use in genetically engineered mice and represents a superior alternative to the widely used internal ribosomal entry site.
Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism
Authors: Semmler Alexander , Hermann Sven , Mormann Florian , Weberpals Marc , Paxian Stephan A , Okulla Thorsten , Schäfers Michael , Kummer Markus P , Klockgether Thomas , Heneka Michael T 
Published: September 2008

Abstract

Background
Septic encephalopathy is a severe brain dysfunction caused by systemic inflammation in the absence of direct brain infection. Changes in cerebral blood flow, release of inflammatory molecules and metabolic alterations contribute to neuronal dysfunction and cell death.

Methods
To investigate the relation of electrophysiological, metabolic and morphological changes caused by SE, we simultaneously assessed systemic circulation, regional cerebral blood flow and cortical electroencephalography in rats exposed to bacterial lipopolysaccharide. Additionally, cerebral glucose uptake, astro- and microglial activation as well as changes of inflammatory gene transcription were examined by small animal PET using [18F]FDG, immunohistochemistry, and real time PCR.

Results
While the systemic hemodynamic did not change significantly, regional cerebral blood flow was decreased in the cortex paralleled by a decrease of alpha activity of the electroencephalography. Cerebral glucose uptake was reduced in all analyzed neocortical areas, but preserved in the caudate nucleus, the hippocampus and the thalamus. Sepsis enhanced the transcription of several pro- and anti-inflammatory cytokines and chemokines including tumor necrosis factor alpha, interleukin-1 beta, transforming growth factor beta, and monocot chemoattractant protein 1 in the cerebrum. Regional analysis of different brain regions revealed an increase in ED1-positive microglia in the cortex, while total and neuronal cell counts decreased in the cortex and the hippocampus.

Conclusion
Together, the present study highlights the complexity of sepsis induced early impairment of neuronal metabolism and activity. Since our model uses techniques that determine parameters relevant to the clinical setting, it might be a useful tool to develop brain specific therapeutic strategies for human septic encephalopathy.
A high confidence, manually validated human blood plasma protein reference set
Authors: Schenk Susann , Schoenhals Gary J , de Souza Gustavo , Mann Matthias 
Published: September 2008

Abstract

Background
The immense diagnostic potential of human plasma has prompted great interest and effort in cataloging its contents, exemplified by the Human Proteome Organization (HUPO) Plasma Proteome Project (PPP) pilot project. Due to challenges in obtaining a reliable blood plasma protein list, HUPO later re-analysed their own original dataset with a more stringent statistical treatment that resulted in a much reduced list of high confidence (at least 95%) proteins compared with their original findings. In order to facilitate the discovery of novel biomarkers in the future and to realize the full diagnostic potential of blood plasma, we feel that there is still a need for an ultra-high confidence reference list (at least 99% confidence) of blood plasma proteins.

Methods
To address the complexity and dynamic protein concentration range of the plasma proteome, we employed a linear ion-trap-Fourier transform (LTQ-FT) and a linear ion trap-Orbitrap (LTQ-Orbitrap) for mass spectrometry (MS) analysis. Both instruments allow the measurement of peptide masses in the low ppm range. Furthermore, we employed a statistical score that allows database peptide identification searching using the products of two consecutive stages of tandem mass spectrometry (MS3). The combination of MS3 with very high mass accuracy in the parent peptide allows peptide identification with orders of magnitude more confidence than that typically achieved.

Results
Herein we established a high confidence set of 697 blood plasma proteins and achieved a high 'average sequence coverage' of more than 14 peptides per protein and a median of 6 peptides per protein. All proteins annotated as belonging to the immunoglobulin family as well as all hypothetical proteins whose peptides completely matched immunoglobulin sequences were excluded from this protein list. We also compared the results of using two high-end MS instruments as well as the use of various peptide and protein separation approaches. Furthermore, we characterized the plasma proteins using cellular localization information, as well as comparing our list of proteins to data from other sources, including the HUPO PPP dataset.

Conclusion
Superior instrumentation combined with rigorous validation criteria gave rise to a set of 697 plasma proteins in which we have very high confidence, demonstrated by an exceptionally low false peptide identification rate of 0.29%.
Identification of genes down-regulated during lung cancer progression: A cDNA array study
Authors: Campioni Mara , Ambrogi Vincenzo , Pompeo Eugenio , Citro Gennaro , Castelli Mauro , Spugnini Enrico P , Gatti Antonio , Cardelli Pierluigi , Lorenzon Laura , Baldi Alfonso , Mineo Tommaso C 
Published: September 2008

Abstract

Background
Lung cancer remains a major health challenge in the world. Survival for patients with stage I disease ranges between 40–70%. This suggests that a significant proportion of patients with stage I NSCLC may actually be under-staged.

Methods
In order to identify genes relevant for lung cancer development, we carried out cDNA array experiments employing 64 consecutive patients (58 men and 6 women) with a median age of 58 years and stage 1 or stage 2 non-small-cell lung cancer (NSCLC).

Results
Basic cDNA array data identified 14 genes as differentially regulated in the two groups. Quantitative RT-PCR analysis confirmed an effective different transcriptional regulation of 8 out of 14 genes analyzed. The products of these genes belong to different functional protein types, such as extra-cellular matrix proteins and proteases (Decorin and MMP11), genes involved in DNA repair (XRCC1), regulator of angiogenesis (VEGF), cell cycle regulators (Cyclin D1) and tumor-suppressor genes (Semaphorin 3B, WNT-5A and retinoblastoma-related Rb2/p130). Some previously described differences in expression patterns were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of some genes during lung cancer progression.

Conclusion
Comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results.
Association of elevated transcript levels of interferon-inducible chemokines with disease activity and organ damage in systemic lupus erythematosus patients
Authors: Fu Qiong , Chen Xiaoqing , Cui Huijuan , Guo Yanzhi , Chen Jing , Shen Nan , Bao Chunde 
Published: September 2008

Abstract
Introduction
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with a heterogeneous course and varying degrees of severity and organ damage; thus, there is increasing interest in identifying biomarkers for SLE. In this study we correlated the combined expression level of multiple interferon-inducible chemokines with disease activity, degree of organ damage and clinical features in SLE, and we investigated their roles as biomarkers.

Methods
Peripheral blood cells obtained from 67 patients with SLE patients, 20 patients with rheumatoid arthritis (RA) and 23 healthy donors were subjected to real-time PCR in order to measure the transcriptional levels of seven interferon-inducible chemokines (RANTES, MCP-1, CCL19, MIG, IP-10, CXCL11, and IL-8). The data were used to calculate a chemokine score for each participant, after which comparisons were performed between various groups of SLE patients and control individuals.

Results
Chemokine scores were significantly elevated in SLE patients versus RA patients and healthy donors (P = 0.012 and P = 0.002, respectively). Chemokine scores were correlated positively with SLE Disease Activity Index 2000 scores (P = 0.005) and negatively with C3 levels (P < 0.001). Compared with patients without lupus nephritis and those with inactive lupus nephritis, chemokine scores were elevated in patients with active lupus nephritis, especially when their daily prednisone dosage was under 30 mg (P = 0.002 and P = 0.014, respectively). Elevated chemokine scores were also associated with the presence of cumulative organ damage (Systemic Lupus International Collaborating Clinics/American Society of Rheumatology Damage Index ≥ 1; P = 0.010) and the occurrence of anti-Sm or anti-RNP autoantibodies (both P = 0.021).

Conclusions
The combined transcription level of interferon-inducible chemokines in peripheral blood leucocytes is closely associated with disease activity, degree of organ damage, and specific autoantibody patterns in SLE. The chemokine score may serve as a new biomarker for active and severe disease in SLE.
Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning
Authors: Sorror Mohamed L. , Storer Barry E. , Sandmaier Brenda M. , Maris Michael , Shizuru Judith , Maziarz Richard , Agura Edward , Chauncey Thomas R. , Pulsipher Michael A. , McSweeney Peter A. , Wade James C. , Bruno Benedetto , Langston Amelia , Radich Jerald , Niederwieser Dietger , Blume Karl G. , Storb Rainer , Maloney David G. 
Published: September 2008

Purpose We reported encouraging early results of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in 64 patients who had advanced chronic lymphocytic leukemia (CLL). Here, we have extended the follow-up to a median of 5 years and have included data on an additional 18 patients. Patients and Methods Eighty-two patients, age 42 to 72 years, who had fludarabine-refractory CLL were conditioned with 2 Gy total-body irradiation alone or combined with fludarabine followed by HCT from related (n = 52) or unrelated (n = 30) donors. Results Complete remission (CR) and partial remission were achieved in 55% and 15% of patients, respectively. Higher CR rates were noted after unrelated HCT (67% v 48%). The 5-year incidences of nonrelapse mortality (NRM), progression/relapse, overall survival, and progression-free survival were 23%, 38%, 50%, and 39%, respectively. Among 25 patients initially reported in CR, 8% relapsed and 8% died as a result of NRM, whereas 84% have remained alive and in CR. Among 14 responding patients who were tested and who had molecular eradication of their disease, two died as a result of NRM, two relapsed, and 10 have remained negative. At 5 years, 76% of living patients were entirely well, whereas 24% continued to receive immunosuppression for chronic graft-versus-host disease; the median performance status in each group was 100% and 90%, respectively. Lymphadenopathy ≥ 5 cm, but not cytogenetic abnormalities at HCT, predicted relapse. In a risk-stratification model, patients who had lymphadenopathy less than 5 cm and no comorbidities had a 5-year OS of 71%. Conclusion Nonmyeloablative HCT resulted in a median survival of 5 years for patients who had fludarabine-refractory CLL with sustained remissions and in the continued resolution of chronic graft-versus-host disease in surviving patients.