bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tonsillar Squamous Cell Carcinoma
Authors: Miller Mia E. , Elashoff David A. , Abemayor Elliot , St. John Maie 
Published: March 2011

ObjectiveTo analyze outcomes in patients with squamous cell carcinoma (SCCA) of the tonsil from the years 1998 to 2006. To assess factors that may affect disease‐specific survival, such as patient characteristics and/or treatment modality.Study Design and SettingNational Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program.Subjects and MethodsThe SEER database was used to perform a population‐based cohort analysis for patients diagnosed with SCCA of the tonsil from 1998 to 2006. Disease‐specific survival was correlated with sex, age, ethnicity, year of diagnosis, and treatment modality in a univariate Cox proportional hazards analysis and a multiple Cox‐regression model with and without interaction effect.ResultsApplied inclusion criteria resulted in 8378 patients. Of this patient cohort, 80% were male and 85% were white. The mean patient age at diagnosis was 58.1 years. On univariate and multivariate analyses, ethnicities other than white carried a significantly higher rate of disease‐specific death (hazard ratio = 1.71, P <. 001). Each additional year of age at the time of diagnosis carried approximately a 4% increase in likelihood of disease‐specific death. With each passing year of time at diagnosis, patients carried a decreased risk of disease‐specific death (P <. 001); this value was significant in all 3 statistical models. Patients who underwent external‐beam radiation had a higher likelihood of disease‐specific survival with each passing year at time of diagnosis.ConclusionPopulation analysis based on the SEER database reveals increased disease‐specific survival from tonsillar SCCA in more recent years. This may be because of earlier diagnosis, an increase in less aggressive subtypes of SCCA, and more effective treatment modalities.
Eye movements and reading comprehension while listening to preferred and non-preferred study music
Authors: Johansson Roger , Holmqvist Kenneth , Mossberg Frans , Lindgren Magnus 
Published: March 2011

In the present study 24 university students read four different texts in four conditions: (1) while listening to music they preferred to listen to while studying; (2) while listening to music they did not prefer to listen to while studying; (3) while listening to a recording of noise from a café; and finally (4) in silence. After each text they took a reading-comprehension test. Eye movement data were recorded for all participants in all conditions. A main effect for the reading-comprehension scores revealed that the participants scored significantly lower after they had been listening to the non-preferred music while reading, compared with reading in silence. No significant effects were found between the other conditions. No significant differences between conditions were found for the traditional eye movement measures in reading (fixation duration, saccadic amplitude, regressions, and first-pass and second-pass reading time). It is suggested that this result is a consequence of participants not being aware that their reading processes are disrupted by a non-preferred musical background. They do not make the necessary changes to the processes involved in reading required to compensate for increased cognitive load. The results are discussed in relation to study/reading habits, extraversion, arousal and working memory capacity.
Efficacy of eplerenone added to renin-angiotensin blockade in elderly hypertensive patients: the Jichi-Eplerenone Treatment (JET) study
Authors: Yano Yuichiro , Hoshide Satoshi , Tamaki Noboru , Nagata Masahiko , Sasaki Kouji , Kanemaru Yoshimasa , Shimada Kazuyuki , Kario Kazuomi 
Published: March 2011

Introduction: We assessed the additional effects of eplerenone to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on 24-h blood pressure (BP) level, fibrinolytic activity, and cardiovascular protection in elderly (>60 years) hypertensive patients. Materials and methods: In total, 20 patients (mean age 74 years, 25% men), whose BP was uncontrolled despite the use of anti-hypertensive drugs including ACEIs or ARBs (average 2.4 drugs), received eplerenone once daily (mean 37.5 mg) for 24 weeks. Results: Eplerenone treatment significantly reduced mean 24-h systolic/diastolic BP levels (143/80 mmHg to 132/74 mmHg, both p < 0.002). The reduction of 24-h systolic BP levels, especially night-time BP, was significantly associated with the reduction of atrial natriuretic peptide and brain natriuretic peptide levels (all p < 0.05). Furthermore, after eplerenone treatment, the mean plasminogen activator inhibitor-1 antigen level was significantly reduced (35 ng/ml to 25 ng/ml, p < 0.05), and the median level of plasma procollagen type III aminoterminal peptide and the urinary albumin excretion rate were also significantly reduced (0.8 U/ml to 0.6 U/ml, p < 0.003 and 53 mg/g·Cr to 23 mg/g·Cr, p < 0.05, respectively). During the intervention, eplerenone treatment was well tolerated with no reports of hyperkalaemia or hypotension. Conclusions: Addition of eplerenone to ACEIs or ARBs in elderly hypertensive patients offers significant benefits in terms of 24-h BP levels, fibrinolysis, and cardiovascular protection.
A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression
Authors: Farrell John J. , Sherva Richard M. , Chen Zhi-yi , Luo Hong-yuan , Chu Benjamin F. , Ha Shau Yin , Li Chi Kong , Lee Anselm C. W. , Li Rever C. H. , Li Chi Keung , Yuen Hui Leung , So Jason C. C. , Ma Edmond S. K. , Chan Li Chong , Chan Vivian , Sebastiani Paola , Farrer Lindsay A. , Baldwin Clinton T. , Steinberg Martin H. , Chui David H. K. 
Published: March 2011

Abstract
Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.
A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease
Authors: Bagnara Davide , Kaufman Matthew S. , Calissano Carlo , Marsilio Sonia , Patten Piers E. M. , Simone Rita , Chum Philip , Yan Xiao-Jie , Allen Steven L. , Kolitz Jonathan E. , Baskar Sivasubramanian , Rader Christoph , Mellstedt Hakan , Rabbani Hodjattallah , Lee Annette , Gregersen Peter K. , Rai Kanti R. , Chiorazzi Nicholas 
Published: March 2011

AbstractChronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity.
Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome
Authors: Li Jian , Zhang Wei , Jiao Li , Duan Ming-Hui , Guan Hong-Zhi , Zhu Wei-Guo , Tian Zhuang , Zhou Dao-Bin 
Published: March 2011

Abstract
POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome.
Novel computational analysis of protein binding array data identifies direct targets of Nkx2.2 in the pancreas
Authors: Hill Jonathon T , Anderson Keith R , Mastracci Teresa L , Kaestner Klaus H , Sussel Lori 
Published: March 2011

Abstract

Background
The creation of a complete genome-wide map of transcription factor binding sites is essential for understanding gene regulatory networks in vivo. However, current prediction methods generally rely on statistical models that imperfectly model transcription factor binding. Generation of new prediction methods that are based on protein binding data, but do not rely on these models may improve prediction sensitivity and specificity.

Results
We propose a method for predicting transcription factor binding sites in the genome by directly mapping data generated from protein binding microarrays (PBM) to the genome and calculating a moving average of several overlapping octamers. Using this unique algorithm, we predicted binding sites for the essential pancreatic islet transcription factor Nkx2.2 in the mouse genome and confirmed >90% of the tested sites by EMSA and ChIP. Scores generated from this method more accurately predicted relative binding affinity than PWM based methods. We have also identified an alternative core sequence recognized by the Nkx2.2 homeodomain. Furthermore, we have shown that this method correctly identified binding sites in the promoters of two critical pancreatic islet β-cell genes, NeuroD1 and insulin2, that were not predicted by traditional methods. Finally, we show evidence that the algorithm can also be applied to predict binding sites for the nuclear receptor Hnf4α.

Conclusions
PBM-mapping is an accurate method for predicting Nkx2.2 binding sites and may be widely applicable for the creation of genome-wide maps of transcription factor binding sites.
Carbon monoxide prevents hepatic mitochondrial membrane permeabilization
Authors: Queiroga Cláudia SF , Almeida Ana S , Alves Paula M , Brenner Catherine , Vieira Helena LA 
Published: March 2011

Abstract

Background
Low concentrations of carbon monoxide (CO) protect hepatocytes against apoptosis and confers cytoprotection in several models of liver. Mitochondria are key organelles in cell death control via their membrane permeabilization and the release of pro-apoptotic factors.

Results
Herein, we show that CO prevents mitochondrial membrane permeabilization (MMP) in liver isolated mitochondria. Direct and indirect approaches were used to evaluate MMP inhibition by CO: mitochondrial swelling, mitochondrial depolarization and inner membrane permeabilization. Additionally, CO increases mitochondrial reactive oxygen species (ROS) generation, and their scavenging, by ß-carotene addition, decreases CO protection, which reveals the key role of ROS. Interestingly, cytochrome c oxidase transiently responds to low concentrations of CO by decreasing its activity in the first 5 min, later on there is an increase of cytochrome c oxidase activity, which were detected up to 30 min.

Conclusion
CO directly prevents mitochondrial membrane permeabilization, which might be implicated in the hepatic apoptosis inhibition by this gaseoustransmitter.
ChIP-chip versus ChIP-seq: Lessons for experimental design and data analysis
Authors: Ho Joshua WK , Bishop Eric , Karchenko Peter V , Nègre Nicolas , White Kevin P , Park Peter J 
Published: March 2011

Abstract

Background
Chromatin immunoprecipitation (ChIP) followed by microarray hybridization (ChIP-chip) or high-throughput sequencing (ChIP-seq) allows genome-wide discovery of protein-DNA interactions such as transcription factor bindings and histone modifications. Previous reports only compared a small number of profiles, and little has been done to compare histone modification profiles generated by the two technologies or to assess the impact of input DNA libraries in ChIP-seq analysis. Here, we performed a systematic analysis of a modENCODE dataset consisting of 31 pairs of ChIP-chip/ChIP-seq profiles of the coactivator CBP, RNA polymerase II (RNA PolII), and six histone modifications across four developmental stages of Drosophila melanogaster.

Results
Both technologies produce highly reproducible profiles within each platform, ChIP-seq generally produces profiles with a better signal-to-noise ratio, and allows detection of more peaks and narrower peaks. The set of peaks identified by the two technologies can be significantly different, but the extent to which they differ varies depending on the factor and the analysis algorithm. Importantly, we found that there is a significant variation among multiple sequencing profiles of input DNA libraries and that this variation most likely arises from both differences in experimental condition and sequencing depth. We further show that using an inappropriate input DNA profile can impact the average signal profiles around genomic features and peak calling results, highlighting the importance of having high quality input DNA data for normalization in ChIP-seq analysis.

Conclusions
Our findings highlight the biases present in each of the platforms, show the variability that can arise from both technology and analysis methods, and emphasize the importance of obtaining high quality and deeply sequenced input DNA libraries for ChIP-seq analysis.
Transcriptional profiling identifies differentially expressed genes in developing turkey skeletal muscle
Authors: Sporer Kelly RB , Tempelman Robert J , Ernst Catherine W , Reed Kent M , Velleman Sandra G , Strasburg Gale M 
Published: March 2011

Abstract

Background
Skeletal muscle growth and development from embryo to adult consists of a series of carefully regulated changes in gene expression. Understanding these developmental changes in agriculturally important species is essential to the production of high quality meat products. For example, consumer demand for lean, inexpensive meat products has driven the turkey industry to unprecedented production through intensive genetic selection. However, achievements of increased body weight and muscle mass have been countered by an increased incidence of myopathies and meat quality defects. In a previous study, we developed and validated a turkey skeletal muscle-specific microarray as a tool for functional genomics studies. The goals of the current study were to utilize this microarray to elucidate functional pathways of genes responsible for key events in turkey skeletal muscle development and to compare differences in gene expression between two genetic lines of turkeys. To achieve these goals, skeletal muscle samples were collected at three critical stages in muscle development: 18d embryo (hyperplasia), 1d post-hatch (shift from myoblast-mediated growth to satellite cell-modulated growth by hypertrophy), and 16wk (market age) from two genetic lines: a randombred control line (RBC2) maintained without selection pressure, and a line (F) selected from the RBC2 line for increased 16wk body weight. Array hybridizations were performed in two experiments: Experiment 1 directly compared the developmental stages within genetic line, while Experiment 2 directly compared the two lines within each developmental stage.

Results
A total of 3474 genes were differentially expressed (false discovery rate; FDR < 0.001) by overall effect of development, while 16 genes were differentially expressed (FDR < 0.10) by overall effect of genetic line. Ingenuity Pathways Analysis was used to group annotated genes into networks, functions, and canonical pathways. The expression of 28 genes involved in extracellular matrix regulation, cell death/apoptosis, and calcium signaling/muscle function, as well as genes with miscellaneous function was confirmed by qPCR.

Conclusions
The current study identified gene pathways and uncovered novel genes important in turkey muscle growth and development. Future experiments will focus further on several of these candidate genes and the expression and mechanism of action of their protein products.
Proteomic assessment of a cell model of spinal muscular atrophy
Authors: Wu Chia-Yen , Whye Dosh , Glazewski Lisa , Choe Leila , Kerr Douglas , Lee Kelvin H , Mason Robert W , Wang Wenlan 
Published: March 2011

Abstract

Background
Deletion or mutation(s) of the survival motor neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), a neuromuscular disease characterized by spinal motor neuron death and muscle paralysis. Complete loss of the SMN protein is embryonically lethal, yet reduced levels of this protein result in selective death of motor neurons. Why motor neurons are specifically targeted by SMN deficiency remains to be determined. In this study, embryonic stem (ES) cells derived from a severe SMA mouse model were differentiated into motor neurons in vitro by addition of retinoic acid and sonic hedgehog agonist. Proteomic and western blot analyses were used to probe protein expression alterations in this cell-culture model of SMA that could be relevant to the disease.

Results
When ES cells were primed with Noggin/fibroblast growth factors (bFGF and FGF-8) in a more robust neural differentiation medium for 2 days before differentiation induction, the efficiency of in vitro motor neuron differentiation was improved from ~25% to ~50%. The differentiated ES cells expressed a pan-neuronal marker (neurofilament) and motor neuron markers (Hb9, Islet-1, and ChAT). Even though SMN-deficient ES cells had marked reduced levels of SMN (~20% of that in control ES cells), the morphology and differentiation efficiency for these cells are comparable to those for control samples. However, proteomics in conjunction with western blot analyses revealed 6 down-regulated and 14 up-regulated proteins with most of them involved in energy metabolism, cell stress-response, protein degradation, and cytoskeleton stability. Some of these activated cellular pathways showed specificity for either undifferentiated or differentiated cells. Increased p21 protein expression indicated that SMA ES cells were responding to cellular stress. Up-regulation of p21 was confirmed in spinal cord tissues from the same SMA mouse model from which the ES cells were derived.

Conclusion
SMN-deficient ES cells provide a cell-culture model for SMA. SMN deficiency activates cellular stress pathways, causing a dysregulation of energy metabolism, protein degradation, and cytoskeleton stability.
Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol
Authors: van Norden Anouk GW , de Laat Karlijn F , Gons Rob AR , van Uden Inge WM , van Dijk Ewoud J , van Oudheusden Lucas JB , Esselink Rianne AJ , Bloem Bastiaan R , van Engelen Baziel GM , Zwarts Machiel J , Tendolkar Indira , Olde-Rikkert Marcel G , van der Vlugt Maureen J , Zwiers Marcel P , Norris David G , de Leeuw Frank-Erik 
Published: March 2011

Abstract

Background
Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated.

Methods/Design
The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI.

Discussion
The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism.