bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats
Authors: Sakr Saber A , Abo-El-Yazid Samah M 
Published: November 2011

The purpose of this work was to evaluate the effect of aqueous extract of fenugreek seeds against hepatotoxicity induced in albino rats by the anticancer drug adriamycin (ADR). Animals were given single dose of ADR (10 mg/kg body weight) and were killed after 2 and 4 weeks. Liver of ADR-treated animals showed histopathological and biochemical alterations. The histopathological changes include hepatic tissue impairment, cytoplasmic vacuolization of the hepatocytes, congestion of blood vessels, leucocytic infiltrations and fatty infiltration. Moreover, the expression of proliferating cell nuclear antigen was increased in ADR-treated rats. The liver enzymes, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were increased in the sera of treated rats. Moreover, ADR significantly increased the concentration of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatic tissue. Treating animals with ADR and aqueous extract of fenugreek (0.4 g/kg body weight) seeds led to an improvement in histological and biochemical alterations induced by ADR. The biochemical results showed that AST and ALT appeared normal together with reduction in the level of MDA (lipid peroxidation marker) and increase in SOD and CAT activities. It was concluded from this study that the aqueous extract fenugreek seeds has a beneficial impact on ADR-induced hepatotoxicity due to its antioxidant effect in albino rats.
Nonlinear behavior of PLA and lignin-based flax composites subjected to tensile loading
Authors: Rozite Liva , Varna Janis , Joffe Roberts , Pupurs Andrejs 
Published: November 2011

The effect of temperature ( T = 22°C, 30°C and 35°C) and relative humidity (RH = 34% and 66%) on mechanical behavior of natural fiber reinforced bio-based matrix composites subjected to tensile loading was investigated. Three composites were studied (a) polylactic acid (PLA) composite with 10% weight fraction of flax fibers; (b) PLA composite containing 5% viscose fibers (filaments of regenerated cellulose); (c) lignin-based composite with 30% of flax fibers. Elastic modulus, the nonlinear tensile stress–strain curves and failure were analyzed showing that all materials are temperature sensitive. The nonlinearity was analyzed studying modulus degradation as well as development of viscoelastic and viscoplastic strains. The modulus reduction in PLA-based composites starts after reaching the stress maximum and is not significant, whereas the modulus reduction in lignin-based composites starts before the maximum and it can reach 50%. With increasing RH these effects are slightly larger. The time-dependent phenomena were analyzed in short-term creep and strain recovery tests demonstrating significantly higher viscoplastic strain in lignin composites. Both viscoelastic and viscoplastic strains are larger at higher RH.
Lymphocyte Recovery After Breast Cancer Treatment and Mindfulness-Based Stress Reduction (MBSR) Therapy
Authors: Lengacher Cecile A. , Kip Kevin E. , Post-White Janice , Fitzgerald Shirley , Newton Cathy , Barta Michelle , Jacobsen Paul B. , Shelton Melissa M. , Moscoso Manolete , Johnson-Mallard Versie , Harris Eleanor , Loftus Loretta , Cox Charles , Le Nancy , Goodman Matthew , Djeu Julie , Widen Raymond H. , Bercu Barry B. , Klein Thomas W. 
Published: November 2011

Objectives: This randomized controlled trial was conducted to examine immune recovery following breast cancer (BC) therapy and evaluate the effect of mindfulness-based stress reduction therapy (MBSR) on immune recovery with emphasis on lymphocyte subsets, T cell activation, and production of T-helper 1 (Th1; interferon [IFN]-γ) and T-helper 2 (Th2; interleukin-4 [IL-4]) cytokines. Method: Participants who completed the study consisted of 82 patients diagnosed with Stage 0–III BC, who received lumpectomy and adjuvant radiation ± chemotherapy. Patients were randomized into an MBSR(BC) intervention program or a control (usual care) group. Immune cell measures were assessed at baseline and within 2 weeks after the 6-week intervention. The numbers and percentages of lymphocyte subsets, activated T cells, and Th1 and Th2 cells in peripheral blood samples were determined by immunostaining and flow cytometry. Results: Immune subset recovery after cancer treatment showed positive associations with time since treatment completion. The B and natural killer (NK) cells were more susceptible than T cells in being suppressed by cancer treatment. Women who received MBSR(BC) had T cells more readily activated by the mitogen phytohemagglutinin (PHA) and an increase in the Th1/Th2 ratio. Activation was also higher for the MBSR(BC) group if <12 weeks from the end of treatment and women in MBSR(BC) <12 weeks had higher T cell count for CD4+. Conclusion: MBSR(BC) promotes a more rapid recovery of functional T cells capable of being activated by a mitogen with the Th1 phenotype, whereas substantial recovery of B and NK cells after completion of cancer treatment appears to occur independent of stress-reducing interventions.
Psychological Stress and Cytokine Production in Multiple Sclerosis
Authors: Sorenson Matthew , Janusek Linda , Mathews Herbert 
Published: November 2011

Objective: Psychological variables such as perceived stress appear to play a role in symptom onset or disease exacerbation in multiple sclerosis (MS). The authors sought to determine if perceived stress is indeed associated with the expression of pro-inflammatory cytokines and disease symptoms in individuals with MS. To do so, the authors examined the relationships among disease symptomatology, perceived stress, and cytokine production from peripheral blood mononuclear cells in 42 outpatients with MS and 36 normative controls. Method: The authors drew peripheral blood from all subjects prior to the completion of a series of psychological instruments. The authors measured stress using the Perceived Stress scale and negative mood with the Profile of Mood States. Disease symptoms were measured using the Multiple Sclerosis Symptom Checklist. Cytokine production was induced separately by lipopolysaccharide and a combination of phytohemagglutinin and phorbol-12-myristate-13-acetate. Results: In MS subjects, the induced production of interleukin (IL)-6 and IL-10 positively correlated with psychological stress, mood disturbance, and disease symptomatology. In contrast, psychological stress in control subjects significantly correlated with level of tumor necrosis factor-alpha (TNF-α), and mood disturbance correlated with levels of TNF-α and interferon-gamma. As well, compared to controls, MS subjects exhibited a significant fourfold increase in the production of IL-12. Conclusion: There is, in those with MS, a pattern of IL-6 and IL-10 production that correlates significantly with perceived stress and disease symptomatology.
Pain and Inflammation in Women With Early-Stage Breast Cancer Prior to Induction of Chemotherapy
Authors: Starkweather Angela R. , Lyon Debra E. , Schubert Christine M. 
Published: November 2011

Context: Pain is a commonly experienced and distressing symptom in women with breast cancer (BCA), and recent evidence suggests that immune activation may be associated with pain and other co-occurring symptoms. However, no studies to date have explored the relationships among perceived pain and biomarkers of inflammation in women with early-stage BCA during the initial course of treatment. Objectives: The purpose of this research study was to examine the relationships among pro- and anti-inflammatory biomarkers and the presence of pain and other symptoms (anxiety, depression, fatigue, and sleep disorder) prior to induction of chemotherapy. Method: This was a secondary analysis of data that measured perceived symptoms, including the presence of pain and pain interference, and plasma levels of pro- and anti-inflammatory cytokines and C-reactive protein (CRP) in women with early-stage BCA ( N = 32) at 1 month postsurgery but prior to induction of chemotherapy. Results: Women experiencing pain had significantly higher levels of CRP ( p < .01), interleukin (IL) 13 ( p < .02), and IL-7 ( p < .02) and more pain interference ( p < .01), depression ( p < .01), and sleep disturbance ( p < .01) compared to women reporting no pain. Conclusion: The presence of pain during the initial course of treatment in women with early-stage BCA was associated with significantly higher levels of CRP, IL-7, and IL-13, suggesting a potential role of immune activation in perceived pain. Further research to examine the precise effects of these biological factors in modulating pain is needed. Perceived pain was also associated with multiple co-occurring symptoms, and this finding has important implications for symptom management.
A functional variant in the core promoter of the CD95 cell death receptor gene predicts prognosis in acute promyelocytic leukemia
Authors: Sunter Nicola J. , Scott Kathryn , Hills Robert , Grimwade David , Taylor Sheila , Worrillow Lisa J. , Fordham Sarah E. , Forster Victoria J. , Jackson Graham , Bomken Simon , Jones Gail , Allan James M. 
Published: November 2011

Abstract
Up to 15% of acute promyelocytic leukemia (APL) patients fail to achieve or maintain remission. We investigated a common G > A polymorphism at position −1377 (rs2234767) in the core promoter of the CD95 cell death receptor gene in 708 subjects with acute myeloid leukemia, including 231 patients with APL. Compared with the GG genotype, carrier status for the −1377A variant was associated with a significantly worse prognosis in APL patients. Carriers were more likely to fail remission induction (odds ratio = 4.22; 95% confidence interval, 1.41-12.6, P = .01), were more likely to die during the first 8 weeks of remission induction therapy (hazard ratio = 7.26; 95% confidence interval, 2.39-22.9, P = .0005), and had a significantly worse 5-year overall survival (odds ratio = 2.14; 95% confidence interval, 1.10-4.15, P = .03). The −1377A variant destroys a binding site for the SP1 transcriptional regulator and is associated with lower transcriptional activity of the CD95 promoter. Identifying patients at high risk of life-threatening events, such as remission induction failure, is a high priority in APL, especially because such events represent a major cause of death despite the introduction of differentiation therapy.
Correlated mutations via regularized multinomial regression
Authors: Sreekumar Janardanan , ter Braak Cajo JF , van Ham Roeland CHJ , van Dijk Aalt DJ 
Published: November 2011

Abstract

Background
In addition to sequence conservation, protein multiple sequence alignments contain evolutionary signal in the form of correlated variation among amino acid positions. This signal indicates positions in the sequence that influence each other, and can be applied for the prediction of intra- or intermolecular contacts. Although various approaches exist for the detection of such correlated mutations, in general these methods utilize only pairwise correlations. Hence, they tend to conflate direct and indirect dependencies.

Results
We propose RMRCM, a method for Regularized Multinomial Regression in order to obtain Correlated Mutations from protein multiple sequence alignments. Importantly, our method is not restricted to pairwise (column-column) comparisons only, but takes into account the network nature of relationships between protein residues in order to predict residue-residue contacts. The use of regularization ensures that the number of predicted links between columns in the multiple sequence alignment remains limited, preventing overprediction. Using simulated datasets we analyzed the performance of our approach in predicting residue-residue contacts, and studied how it is influenced by various types of noise. For various biological datasets, validation with protein structure data indicates a good performance of the proposed algorithm for the prediction of residue-residue contacts, in comparison to previous results. RMRCM can also be applied to predict interactions (in addition to only predicting interaction sites or contact sites), as demonstrated by predicting PDZ-peptide interactions.

Conclusions
A novel method is presented, which uses regularized multinomial regression in order to obtain correlated mutations from protein multiple sequence alignments.

Availability
R-code of our implementation is available via http://www.ab.wur.nl/rmrcm
Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility
Authors: Wang Wenqi , Liu Yang , Liao Kan 
Published: November 2011

AbstractBackgroundCell migration plays an important role in many physiological and pathological processes, including immune cell chemotaxis and cancer metastasis. It is a coordinated process that involves dynamic changes in the actin cytoskeleton and its interplay with focal adhesions. At the leading edge of a migrating cell, it is the re-arrangement of actin and its attachment to focal adhesions that generates the driving force necessary for movement. However, the mechanisms involved in the attachment of actin filaments to focal adhesions are still not fully understood.ResultsSignaling by the FAK-Src complex plays a crucial role in regulating the formation of protein complexes at focal adhesions to which the actin filaments are attached. Cortactin, an F-actin associated protein and a substrate of Src kinase, was found to interact with FAK through its SH3 domain and the C-terminal proline-rich regions of FAK. We found that the autophosphorylation of Tyr397in FAK, which is necessary for FAK activation, was not required for the interaction with cortactin, but was essential for the tyrosine phosphorylation of the associated cortactin. At focal adhesions, cortactin was phosphorylated at tyrosine residues known to be phosphorylated by Src. The tyrosine phosphorylation of cortactin and its ability to associate with the actin cytoskeleton were required in tandem for the regulation of cell motility. Cell motility could be inhibited by truncating the N-terminal F-actin binding domains of cortactin or by blocking tyrosine phosphorylation (Y421/466/475/482F mutation). In addition, the mutant cortactin phosphorylation mimic (Y421/466/475/482E) had a reduced ability to interact with FAK and promoted cell motility. The promotion of cell motility by the cortactin phosphorylation mimic could also be inhibited by truncating its N-terminal F-actin binding domains.ConclusionsOur results suggest that cortactin acts as a bridging molecule between actin filaments and focal adhesions. The cortactin N-terminus associates with F-actin, while its C-terminus interacts with focal adhesions. The tyrosine phosphorylation of cortactin by the FAK-Src complex modulates its interaction with FAK and increases its turnover at focal adhesions to promote cell motility.
Transcriptional signatures of regulatory and toxic responses to benzo-[a]-pyrene exposure
Authors: Michaelson Jacob J , Trump Saskia , Rudzok Susanne , Gräbsch Carolin , Madureira Danielle J , Dautel Franziska , Mai Juliane , Attinger Sabine , Schirmer Kristin , von Bergen Martin , Lehmann Irina , Beyer Andreas 
Published: November 2011

Abstract

Background
Small molecule ligands often have multiple effects on the transcriptional program of a cell: they trigger a receptor specific response and additional, indirect responses ("side effects"). Distinguishing those responses is important for understanding side effects of drugs and for elucidating molecular mechanisms of toxic chemicals.

Results
We explored this problem by exposing cells to the environmental contaminant benzo-[a]-pyrene (B[a]P). B[a]P exposure activates the aryl hydrocarbon receptor (Ahr) and causes toxic stress resulting in transcriptional changes that are not regulated through Ahr. We sought to distinguish these two types of responses based on a time course of expression changes measured after B[a]P exposure. Using Random Forest machine learning we classified 81 primary Ahr responders and 1,308 genes regulated as side effects. Subsequent weighted clustering gave further insight into the connection between expression pattern, mode of regulation, and biological function. Finally, the accuracy of the predictions was supported through extensive experimental validation.

Conclusion
Using a combination of machine learning followed by extensive experimental validation, we have further expanded the known catalog of genes regulated by the environmentally sensitive transcription factor Ahr. More broadly, this study presents a strategy for distinguishing receptor-dependent responses and side effects based on expression time courses.
Global assessment of genomic variation in cattle by genome resequencing and high-throughput genotyping
Authors: Zhan Bujie , Fadista João , Thomsen Bo , Hedegaard Jakob , Panitz Frank , Bendixen Christian 
Published: November 2011

Abstract

Background
Integration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations. This requires an accurate identification of the different types of variation in individual genomes.

Results
We report the integration of the whole genome sequence of a single Holstein Friesian bull with data from single nucleotide polymorphism (SNP) and comparative genomic hybridization (CGH) array technologies to determine a comprehensive spectrum of genomic variation. The performance of resequencing SNP detection was assessed by combining SNPs that were identified to be either in identity by descent (IBD) or in copy number variation (CNV) with results from SNP array genotyping. Coding insertions and deletions (indels) were found to be enriched for size in multiples of 3 and were located near the N- and C-termini of proteins. For larger indels, a combination of split-read and read-pair approaches proved to be complementary in finding different signatures. CNVs were identified on the basis of the depth of sequenced reads, and by using SNP and CGH arrays.

Conclusions
Our results provide high resolution mapping of diverse classes of genomic variation in an individual bovine genome and demonstrate that structural variation surpasses sequence variation as the main component of genomic variability. Better accuracy of SNP detection was achieved with little loss of sensitivity when algorithms that implemented mapping quality were used. IBD regions were found to be instrumental for calculating resequencing SNP accuracy, while SNP detection within CNVs tended to be less reliable. CNV discovery was affected dramatically by platform resolution and coverage biases. The combined data for this study showed that at a moderate level of sequencing coverage, an ensemble of platforms and tools can be applied together to maximize the accurate detection of sequence and structural variants.
Assessment of effectiveness measures in patients with schizophrenia initiated on risperidone long-acting therapy: the SOURCE study results
Authors: Macfadden Wayne , DeSouza Cherilyn , Crivera Concetta , Kozma Chris M , Dirani Riad D , Mao Lian , Rodriguez Stephen C 
Published: November 2011

Abstract

Background
To evaluate effectiveness outcomes in a real-world setting in patients with schizophrenia initiating risperidone long-acting therapy (RLAT).

Methods
This was a 24-month, multicenter, prospective, longitudinal, observational study in patients with schizophrenia who were initiated on RLAT. Physicians could change treatment during the study as clinically warranted. Data were collected at baseline and subsequently every 3 months up to 24 months. Effectiveness outcomes included changes in illness severity as measured by Clinical Global Impression-Severity (CGI-S) scale; functional scores as measured by Personal and Social Performance (PSP) scale, Global Assessment of Functioning (GAF), and Strauss-Carpenter Levels of Functioning (LOF); and health status (Medical Outcomes Survey Short Form-36 [SF-36]). Life-table methodology was used to estimate the cumulative probability of relapse over time. Adverse events were evaluated for safety.

Results
532 patients were enrolled in the study; 209 (39.3%) completed the 24-month study and 305 (57.3%) had at least 12 months of follow-up data. The mean (SD) age of patients was 42.3 (12.8) years. Most patients were male (66.4%) and either Caucasian (60.3%) or African American (23.7%). All changes in CGI-S from baseline at each subsequent 3-month follow-up visit were statistically significant (p < .0001), indicating improvement in disease severity. Improvements were also noted for the PSP, GAF, and total LOF, indicating improvement in daily functioning and health outcome.

Conclusions
Patients with schizophrenia who were initiated on RLAT demonstrated improvements in measures of effectiveness within 3 months, which persisted over 24 months.

Trial Registration
ClinicalTrials.gov: NCT00246194
Reproductive morbidity among Iranian women; issues often inappropriately addressed in health seeking behaviors
Authors: Tehrani Fahimeh Ramezani , Simbar Masoumeh , Abedini Mehrandokht 
Published: November 2011

AbstractBackgroundReproductive morbidity has a huge impact on the health and quality of life of women. We aimed to determine the prevalence of reproductive morbidities and the health seeking behavior of a nationally representative sample of Iranian urban women.MethodsA sample of 1252 women, aged 18-45 years, was selected using the multi stage, stratified probability sampling procedure. Data were collected through interviews and physical, gynecological and ultrasonographic examinations.ResultsReproductive tract infection (RTIs), pelvic organ prolapse (POP) and menstrual dysfunction were the three main groups of morbidities with a prevalence of 37.6%, 41.4% and 30.1%., respectively. Our study demonstrated that 35.1, 34.5 and 9.6 percent of women experienced one, two or these reproductive organ disorders mentioned, respectively, while 20.6 percent of participants had none of these disorders. Findings also showed that the majority of women who suffered from reproductive morbidities (on average two out of three) had not sought appropriate care for these except for infertility.ConclusionsReproductive health morbidities impose a large burden among Iranian women and have negative impact on their reproductive health and wellbeing.