bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organizational structure and the periphery of the gene regulatory network in B-cell lymphoma
Authors: de Matos Simoes Ricardo , Tripathi Shailesh , Emmert-Streib Frank 
Published: May 2012

Abstract

Background
The physical periphery of a biological cell is mainly described by signaling pathways which are triggered by transmembrane proteins and receptors that are sentinels to control the whole gene regulatory network of a cell. However, our current knowledge about the gene regulatory mechanisms that are governed by extracellular signals is severely limited.

Results
The purpose of this paper is three fold. First, we infer a gene regulatory network from a large-scale B-cell lymphoma expression data set using the C3NET algorithm. Second, we provide a functional and structural analysis of the largest connected component of this network, revealing that this network component corresponds to the peripheral region of a cell. Third, we analyze the hierarchical organization of network components of the whole inferred B-cell gene regulatory network by introducing a new approach which exploits the variability within the data as well as the inferential characteristics of C3NET. As a result, we find a functional bisection of the network corresponding to different cellular components.

Conclusions
Overall, our study allows to highlight the peripheral gene regulatory network of B-cells and shows that it is centered around hub transmembrane proteins located at the physical periphery of the cell. In addition, we identify a variety of novel pathological transmembrane proteins such as ion channel complexes and signaling receptors in B-cell lymphoma.
Efficient subtraction of insect rRNA prior to transcriptome analysis of Wolbachia-Drosophila lateral gene transfer
Authors: Kumar Nikhil , Creasy Todd , Sun Yezhou , Flowers Melissa , Tallon Luke J , Dunning Hotopp Julie C 
Published: May 2012

Abstract

Background
Numerous methods exist for enriching bacterial or mammalian mRNA prior to transcriptome experiments. Yet there persists a need for methods to enrich for mRNA in non-mammalian animal systems. For example, insects contain many important and interesting obligate intracellular bacteria, including endosymbionts and vector-borne pathogens. Such obligate intracellular bacteria are difficult to study by traditional methods. Therefore, genomics has greatly increased our understanding of these bacteria. Efficient subtraction methods are needed for removing both bacteria and insect rRNA in these systems to enable transcriptome-based studies.

Findings
A method is described that efficiently removes >95% of insect rRNA from total RNA samples, as determined by microfluidics and transcriptome sequencing. This subtraction yielded a 6.2-fold increase in mRNA abundance. Such a host rRNA-depletion strategy, in combination with bacterial rRNA depletion, is necessary to analyze transcription of obligate intracellular bacteria. Here, transcripts were identified that arise from a lateral gene transfer of an entire Wolbachia bacterial genome into a Drosophila ananassae chromosome. In this case, an rRNA depletion strategy is preferred over polyA-based enrichment since transcripts arising from bacteria-to-animal lateral gene transfer may not be poly-adenylated.

Conclusions
This enrichment method yields a significant increase in mRNA abundance when poly-A selection is not suitable. It can be used in combination with bacterial rRNA subtraction to enable experiments to simultaneously measure bacteria and insect mRNA in vector and endosymbiont biology experiments.
Mouse strain specific gene expression differences for illumina microarray expression profiling in embryos
Authors: Kraus Petra , Xing Xing , Lim Siew Lan , Fun Max E , Sivakamasundari V , Yap Sook Peng , Lee Haixia , Karuturi R Krishna Murthy , Lufkin Thomas 
Published: May 2012

Abstract

Background
In the field of mouse genetics the advent of technologies like microarray based expression profiling dramatically increased data availability and sensitivity, yet these advanced methods are often vulnerable to the unavoidable heterogeneity of in vivo material and might therefore reflect differentially expressed genes between mouse strains of no relevance to a targeted experiment. The aim of this study was not to elaborate on the usefulness of microarray analysis in general, but to expand our knowledge regarding this potential “background noise” for the widely used Illumina microarray platform surpassing existing data which focused primarily on the adult sensory and nervous system, by analyzing patterns of gene expression at different embryonic stages using wild type strains and modern transgenic models of often non-isogenic backgrounds.

Results
Wild type embryos of 11 mouse strains commonly used in transgenic and molecular genetic studies at three developmental time points were subjected to Illumina microarray expression profiling in a strain-by-strain comparison. Our data robustly reflects known gene expression patterns during mid-gestation development. Decreasing diversity of the input tissue and/or increasing strain diversity raised the sensitivity of the array towards the genetic background. Consistent strain sensitivity of some probes was attributed to genetic polymorphisms or probe design related artifacts.

Conclusion
Our study provides an extensive reference list of gene expression profiling background noise of value to anyone in the field of developmental biology and transgenic research performing microarray expression profiling with the widely used Illumina microarray platform. Probes identified as strain specific background noise further allow for microarray expression profiling on its own to be a valuable tool for establishing genealogies of mouse inbred strains.
Reconstruction of scalp defects with the radial forearm free flap
Authors: Sweeny Larissa , Eby Brendan , Magnuson J Scott , Carroll William R , Rosenthal Eben L 
Published: May 2012

AbstractBackgroundAdvanced and recurrent cutaneous squamous cell carcinoma of the scalp and forehead require aggressive surgical excision often resulting in complex defects requiring reconstruction. This study evaluates various microvascular free flap reconstructions in this patient population, including the rarely utilized radial forearm free flap.Patients and methodsA retrospective review of patients undergoing free flap surgeries (n = 47) of the scalp between 1997 and 2011 were included. Patients were divided primarily into two cohorts: a new primary lesion (n = 21) or recurrence (n = 26). Factors examined include patient demographics, indication for surgery, defect, type of flap used, complications (major and minor), and outcomes.ResultsThe patients were primarily male (n = 34), with a mean age of 67 years (25–91). A total of 58 microvascular free flap reconstructions were performed (radial forearm free flap: n = 28, latissimus dorsi: n = 20, rectus abdominis: n = 9, scapula: n = 1). Following reconstruction with a radial forearm free flap, duration of hospitalization was shorter (P= 0.04) and complications rates were similar (P= 0.46). Donor site selection correlated with defect area (P< 0.001), but not with the extent of skull defect (P= 0.70). Larger defect areas correlated with higher complications rates (P= 0.03) and longer hospitalization (P= 0.003). Patients were more likely to require multiple reconstructions if referred for a recurrent lesions (P= 0.01) or received prior radiation therapy (P= 0.02).ConclusionAdvanced and recurrent malignancies of the scalp are aggressive and challenging to treat. The radial forearm free flap is an underutilized free flap in the reconstruction of complex scalp defects.
Metabolic syndrome in central Brazil: prevalence and correlates in the adult population
Authors: Dutra Eliane Said , de Carvalho Kênia MaraBaiocchi , Miyazaki Édina , Hamann Edgar Merchán- , Ito Marina Kiyomi 
Published: May 2012

Abstract

Background
The prevalence of metabolic syndrome (MetS) has increased in developing countries in recent decades. This syndrome, a clustering of metabolic abnormalities, has been correlated to various socioeconomic and behavioral variables. We investigated the prevalence and prevalence ratios (PR) of MetS and related factors in an adult population of the Federal District (FD) of Brazil, which is located in the central region of the country.

Methods
A cross-sectional, population-based study conducted in 2007, with 2130 adults (aged 18 years or older) in the FD of Brazil. Metabolic syndrome was defined according to the recently harmonized criteria. The prevalence of MetS and PR were estimated for each sex according to the diagnostic components and the overall contribution of the selected correlates.

Results
The overall prevalence of MetS was 32.0% (95%CI: 28.9–35.2), with no gender difference. The single component with the greatest contribution to the diagnosis of MetS was hypertension in men (PR 5.10, 95%CI: 3.17–8.22) and high waist circumference in women (PR 5.02, 95%CI: 3.77–6.69). The prevalence of MetS increased significantly and progressively with age and excess weight. In women, higher education was protective against MetS (PR 0.66, 95%CI: 0.49–0.89) compared to 8 or less years of education. There was no association between the prevalence of MetS and behavioral variables studied.

Conclusions
This study provides comprehensive and alarming data about the prevalence of MetS among the adult population of Brazil’s FD. The results suggest that reducing education inequalities may be an important public policy goal to improve health outcomes, especially among women.
Expansion of hematopoietic stem cells for transplantation: current perspectives
Authors: Schuster Jessica A , Stupnikov Maria R , Ma Gina , Liao Wenbin , Lai Raymond , Ma Yupo , Aguila Jerell R 
Published: May 2012

Abstract
Hematopoietic stem cells (HSCs) are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The expansion of HSCs has remained an important goal to develop advanced cell therapies for bone marrow transplantation and many blood disorders. Over the last several decades, there have been numerous attempts to expand HSCs in vitro using purified growth factors that are known to regulate HSCs. However, these attempts have been met with limited success for clinical applications. New developments in the HSC expansion field coupled with gene therapy and stem cell transplant should encourage progression in attractive treatment options for many disorders including hematologic conditions, immunodeficiencies, and genetic disorders.
Elevated levels of fibrinogen-derived endogenous citrullinated peptides in synovial fluid of rheumatoid arthritis patients
Authors: Raijmakers Reinout , van Beers Joyce JBC , El-Azzouny Mahmoud , Visser Natasja FC , Božič Borut , Pruijn Ger JM , Heck Albert JR 
Published: May 2012

Abstract
Introduction
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints and the presence of autoantibodies directed against proteins containing the non-standard arginine-derived amino acid citrulline. The protein fibrinogen, which has an essential role in blood clotting, is one of the most prominent citrullinated autoantigens in RA, particularly because it can be found in the inflamed tissue of affected joints. Here, we set out to analyze the presence of citrullinated endogenous peptides in the synovial fluid of RA and arthritic control patients.

Methods
Endogenous peptides were isolated from the synovial fluid of RA patients and controls by filtration and solid phase extraction. The peptides were identified and quantified using high-resolution liquid chromatography-mass spectrometry.

Results
Our data reveal that the synovial fluid of RA patients contains soluble endogenous peptides, derived from fibrinogen, containing significant amounts of citrulline residues and, in some cases, also phosphorylated serine. Several citrullinated peptides are found to be more abundantly present in the synovial fluid of RA patients compared to patients suffering from other inflammatory diseases affecting the joints.

Conclusions
The increased presence of citrullinated peptides in RA patients points toward a possible specific role of these peptides in the immune response at the basis of the recognition of citrullinated peptides and proteins by RA patient autoantibodies.
Body mass index influences the response to infliximab in ankylosing spondylitis
Authors: Ottaviani Sébastien , Allanore Yannick , Tubach Florence , Forien Marine , Gardette Anaïs , Pasquet Blandine , Palazzo Elisabeth , Meunier Marine , Hayem Gilles , Job-Deslandre Chantal , Kahan André , Meyer Olivier , Dieudé Philippe 
Published: May 2012

Abstract
Introduction
The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients.

Methods
In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression.

Results
Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06).

Conclusions
This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.
High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study
Authors: Arts Elke , Fransen Jaap , Lemmers Heidi , Stalenhoef Anton , Joosten Leo , van Riel Piet , Popa Calin D 
Published: May 2012

Abstract
Introduction
Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity.

Methods
Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.

Results
HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186).

Conclusions
Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.
Predictors of outcome in myxoedema coma: a study from a tertiary care centre
Authors: Dutta Pinaki , Bhansali Anil , Masoodi Shriq Rashid , Bhadada Sanjay , Sharma Navneet , Rajput Rajesh 
Published: May 2012

Abstract
Background
With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients.

Methods
Twenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (IV) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise.

Results
Twenty-three patients (20 women; 87%) of 59.5 ± 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving IV thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome.

Conclusion
L-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model.
Early symptoms of bone and soft tissue sarcomas: could they be diagnosed earlier?
Authors: George A , Grimer R 
Published: May 2012

INTRODUCTION Delays in diagnosis are common for patients with bone and soft tissue sarcoma (STS) despite guidance produced by the National Institute for Health and Clinical Excellence. This study set out to identify early symptoms experienced by patients and reasons for delays in making a definitive diagnosis. METHODS Retrospective interviews were carried out with 107 patients (66 with an STS and 41 with a bone sarcoma) presenting to a specialist centre. Symptoms were determined prior to definitive diagnosis and the occurrence of patient and doctor delays in reaching specialist care. RESULTS The median patient delay was 1 month while the median doctor delay was 3.2 months from first symptoms to diagnosis for all sarcomas. Forty-nine patients with STS (74%) presented initially to their general practitioner with at least one guideline feature to prompt urgent referral. Only 2 patients (4%), however, were referred directly to a sarcoma unit, with 21 (43%) referred to secondary care for investigation. Patients with a lump increasing in size exhibited longer patient delays while doctor delay was shorter for deep lumps. Thirty-six patients with a bone sarcoma (88%) presented initially with symptoms to prompt further investigation. Nevertheless, significant delays (3.9 months) were seen in reaching specialist care. Only 4 patients (10%) were referred directly to a sarcoma unit at first presentation, with 21 (54%) referred for further investigation elsewhere. CONCLUSIONS It is evident that awareness and referral of sarcomas remain poor. We suggest specific amendments to current guidelines and clearer referral pathways for patients. Furthermore, the need for robust education strategies is indicated, predominantly among healthcare professionals.
Ectopic Expression of TIM-3 in Lung Cancers
Authors: Zhuang Xuewei , Zhang Xiaoning , Xia Xiyan , Zhang Cuijuan , Liang Xiaohong , Gao Lifen , Zhang Xin , Ma Chunhong 
Published: May 2012

Abstract
T-cell immunoglobulin– and mucin domain-3–containing molecule 3 (TIM-3) is a membrane protein expressed in various kinds of immune cells and plays a pivotal role in immune regulation. Recently, TIM-3 was reported to be expressed aberrantly in melanoma cells, contributing to the low adhesion ability of tumor cells and promoting the survival of melanoma cells. We investigated TIM-3 expression in non–small cell lung cancers (NSCLCs), and further analyzed whether the aberrant expression of TIM-3 is related to the prognosis for patients with lung cancer. Tumor tissue samples from 30 patients with NSCLC were involved. Results of immunohistochemical analysis showed that TIM-3 stained positive on tumor cells in 86.7% (26/30) patients with primary NSCLC. The TIM-3 expression in NSCLC tumor cells was correlated with histologic type and pathologic T classification of the disease (P &lt; .05). More importantly, patients with TIM-3–positive tumor cells had a significantly shorter survival time than those with TIM-3–negative tumors. Multivariate analysis demonstrated the significant role of TIM-3 expression in tumor cells as an independent prognostic factor for patients with NSCLC (relative risk, 4.481; 95% confidence interval, 1.790–11.22; P = .0005). Our results suggest that the ectopic expression of TIM-3 in tumor cells may be a potential, independent prognostic factor for patients with NSCLC.