bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral Simultaneous Reaming Technique With Femoral Head Allograft Implantation for Tibiocalcaneal Arthrodesis
Authors: Rigby Ryan B. , Cottom James M. 
Published: October 2012

Femoral head allograft is an accepted alternative for significant bone loss in severe hindfoot reconstruction. This is primarily because the size and shape of the graft provides not only structural support but additionally prevents significant loss of limb length. We present a case using a technique from a directly lateral approach and simultaneous preparation of the tibia and calcaneus for tibiocalcaneal arthrodesis. Acetabular resurfacing reamers were used to prepare the joint for grafting as well as sculpt the graft itself for near press fit between the tibia and calcaneus. Fixation with a lateral locking plate avoids the unnecessary decompression reaming of the graft core itself, ultimately sparing the valuable poles of the graft for increased likelihood of incorporation. Levels of Evidence: Therapeutic, Level IV, Case Study
EVA: Exome Variation Analyzer, an efficient and versatile tool for filtering strategies in medical genomics
Authors: Coutant Sophie , Cabot Chloé , Lefebvre Arnaud , Léonard Martine , Prieur-Gaston Elise , Campion Dominique , Lecroq Thierry , Dauchel Hélène 
Published: October 2012

Abstract

Background
Whole exome sequencing (WES) has become the strategy of choice to identify a coding allelic variant for a rare human monogenic disorder. This approach is a revolution in medical genetics history, impacting both fundamental research, and diagnostic methods leading to personalized medicine. A plethora of efficient algorithms has been developed to ensure the variant discovery. They generally lead to ~20,000 variations that have to be narrow down to find the potential pathogenic allelic variant(s) and the affected gene(s). For this purpose, commonly adopted procedures which implicate various filtering strategies have emerged: exclusion of common variations, type of the allelics variants, pathogenicity effect prediction, modes of inheritance and multiple individuals for exome comparison. To deal with the expansion of WES in medical genomics individual laboratories, new convivial and versatile software tools have to implement these filtering steps. Non-programmer biologists have to be autonomous combining themselves different filtering criteria and conduct a personal strategy depending on their assumptions and study design.

Results
We describe EVA (Exome Variation Analyzer), a user-friendly web-interfaced software dedicated to the filtering strategies for medical WES. Thanks to different modules, EVA (i) integrates and stores annotated exome variation data as strictly confidential to the project owner, (ii) allows to combine the main filters dealing with common variations, molecular types, inheritance mode and multiple samples, (iii) offers the browsing of annotated data and filtered results in various interactive tables, graphical visualizations and statistical charts, (iv) and finally offers export files and cross-links to external useful databases and softwares for further prioritization of the small subset of sorted candidate variations and genes. We report a demonstrative case study that allowed to identify a new candidate gene related to a rare form of Alzheimer disease.

Conclusions
EVA is developed to be a user-friendly, versatile, and efficient-filtering assisting software for WES. It constitutes a platform for data storage and for drastic screening of clinical relevant genetics variations by non-programmer geneticists. Thereby, it provides a response to new needs at the expanding era of medical genomics investigated by WES for both fundamental research and clinical diagnostics.
Important role of CCR2 in a murine model of coronary vasculitis
Authors: Martinez Hernan G , Quinones Marlon P , Jimenez Fabio , Estrada Carlos , Clark Kassandra M , Suzuki Kazuo , Miura Noriko , Ohno Naohito , Ahuja Sunil K , Ahuja Seema S 
Published: October 2012

Abstract

Background
Chemokines and their receptors play a role in the innate immune response as well as in the disruption of the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg), underlying the pathogenesis of coronary vasculitis in Kawasaki disease (KD).

Results
Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of Candida albicans water-soluble cell wall extracts (CAWS). Mechanistically, both T and B cells were required for the induction of vasculitis, a role that was directly modulated by CCR2. CAWS administration promoted mobilization of CCR2-dependent inflammatory monocytes (iMo) from the bone marrow (BM) to the periphery as well as production of IL-6. IL-6 was likely to contribute to the depletion of Treg and expansion of Th17 cells in CAWS-injected Ccr2

+/+
mice, processes that were ameliorated following the genetic inactivation of CCR2.

Conclusion
Collectively, our findings provide novel insights into the role of CCR2 in the pathogenesis of vasculitis as seen in KD and highlight novel therapeutic targets, specifically for individuals resistant to first-line treatments.
Lipopolysaccharide promotes lipid accumulation in human adventitial fibroblasts via TLR4-NF-κB pathway
Authors: Wang Jun , Si Yanfang , Wu Chen , Sun Lu , Ma Yudong , Ge Aili , Li Baomin 
Published: October 2012

Abstract

Background
Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions.

Results
In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1).

Conclusions
Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.
Functional changes in adipose tissue in a randomised controlled trial of physical activity
Authors: Sjögren Per , Sierra-Johnson Justo , Kallings Lena V , Cederholm Tommy , Kolak Maria , Halldin Mats , Brismar Kerstin , de Faire Ulf , Hellénius Mai-Lis , Fisher Rachel M 
Published: October 2012

AbstractBackgroundA sedentary lifestyle predisposes to cardiometabolic diseases. Lifestyle changes such as increased physical activity improve a range of cardiometabolic risk factors. The objective of this study was to examine whether functional changes in adipose tissue were related to these improvements.MethodsSeventy-three sedentary, overweight (mean BMI 29.9 ± 3.2 kg/m2) and abdominally obese, but otherwise healthy men and women (67.6 ± 0.5 years) from a randomised controlled trial of physical activity on prescription over a 6-month period were included (control n = 43, intervention n = 30). Detailed examinations were carried out at baseline and at follow-up, including fasting blood samples, a comprehensive questionnaire and subcutaneous adipose tissue biopsies for fatty acid composition analysis (n = 73) and quantification of mRNA expression levels of 13 candidate genes (n = 51), including adiponectin, leptin and inflammatory cytokines.ResultsAt follow-up, the intervention group had a greater increase in exercise time (+137 min/week) and a greater decrease in body fat mass (−1.5 kg) compared to the control subjects (changes of 0 min/week and −0.5 kg respectively). Circulating concentrations of adiponectin were unchanged, but those of leptin decreased significantly more in the intervention group (−1.8 vs −1.1 ng/mL for intervention vs control,P < 0.05). The w6-polyunsaturated fatty acid content, in particular linoleic acid (18:2w6), of adipose tissue increased significantly more in the intervention group, but the magnitude of the change was small (+0.17 vs +0.02 percentage points for intervention vs control,P < 0.05). Surprisingly leptin mRNA levels in adipose tissue increased in the intervention group (+107% intervention vs −20% control,P < 0.05), but changes in expression of the remaining genes did not differ between the groups.ConclusionsAfter a 6-month period of increased physical activity in overweight elderly individuals, circulating leptin concentrations decreased despite increased levels of leptin mRNA in adipose tissue. Otherwise, only minor changes occurred in adipose tissue, although several improvements in metabolic parameters accompanied the modest increase in physical activity.
Fixed points for G-contractions on uniform spaces endowed with a graph
Authors: Aghanians Aris , Fallahi Kamal , Nourouzi Kourosh 
Published: October 2012

Abstract
In this paper, we generalize some main results of (Jachymski in Proc. Am. Math. Soc. 136:1359-1373, 2008) from metric to uniform spaces endowed with an ℰ-distance and a graph using a new type of contractions by employing a class of nondecreasing functions.

MSC:47H10, 05C40.
Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation
Authors: Bullon Pedro , Cordero Mario David , Quiles José Luis , Ramirez-Tortosa Maria del Carmen , Gonzalez-Alonso Adrian , Alfonsi Simona , García-Marín Rocio , de Miguel Manuel , Battino Maurizio 
Published: October 2012

Abstract

Background
Periodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis.

Methods
Peripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy.

Results
We found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy.

Conclusion
Results from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontitis.
RNA polymerase I-driven reverse genetics system for enterovirus 71 and its implications for vaccine production
Authors: Meng Tao , Kiener Tanja K , Kwang Jimmy 
Published: October 2012

Abstract

Background
Enterovirus 71 (EV71) is a virus that causes from mild hand, foot and mouth disease (HFMD) to severe neurological complications and deaths in infants and young children. Effective antiviral agents and vaccines against EV71 are not available. However, Vero cell-based chemically inactivated EV71 vaccines could be developed soon based on the success of inactivated polio vaccine. Like poliovirus, EV71 has a positive single-stranded RNA genome of about 7400 nucleotides which contains a single open reading frame (ORF) flanked by conserved and untranslated regions at both the 5′ and 3′ ends.

Results
The universal amplification of the full length genome of EV71 regardless of its genetic diversity, and the subsequent construction of a human RNA polymerase I-driven reverse genetics (RG) system to produce pure virus stocks in Vero cell within 10 days were described. The rescued viruses were characterized by DNA sequencing, cytopathic effect (CPE) and indirect fluorescent assay (IFA) in comparison with the wild-type viruses. Moreover, the rescued viruses grew to high titers and retained the same immunogenicity as the wild-type viruses.

Conclusion
We have established a simplified method to rescue RG EV71 virus from diverse clinical isolates with detailed genetic information and to prepare virus stocks in only 10 days. This method could accelerate EV71 vaccine development.
Association between genetic mutations and the development of autoimmune thyroiditis in patients with chronic hepatitis C treated with interferon alpha
Authors: Krupińska Janina , Urbanowicz Waldemar , Kaczmarczyk Mariusz , Kulig Grzegorz , Sowińska-Przepiera Elżbieta , Andrysiak-Mamos Elżbieta , Syrenicz Anhelli 
Published: October 2012

Abstract

Background
Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFN-alpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA-4C (−318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene.

Methods
The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFN-alpha therapy, group 2 contained 9 patients with AT with the onset prior to IFN-alpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFN-alpha therapy.

Results
The frequency of C1858Tand C(−318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism.

Conclusions
No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFN-alpha therapy and the presence of polymorphisms within CTLA-4 C(−318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene.
Greenhouse gas emission reductions as a motivator of e85 purchases across market segments
Authors: Marra Adrienne E , Jensen Kimberly L , Clark Christopher D , English Burton C , Toliver Dustin K 
Published: October 2012

Abstract

Background
Climate change has become a concern of both policy makers and consumers. Transportation constitutes a key source of greenhouse gas (GHG) emissions; hence, alternative transportation fuels with reduced GHG emissions are of increasing interest as a potential strategy for decreasing emissions. However, consumer views on achieving emission reductions through the use of alternative fuels have not been widely studied. Understanding consumer preferences related to alternative fuels is relevant as new fuel options become available.

Methods
This study uses a two-step cluster analysis of opinion variables to segment consumers into four market segments (Potential activists, Environmentals, Neutrals, and National interests). Cluster profiles are examined based on demographics and opinion variables related to concerns about national security, food versus fuel, perceived effects of personal actions, perceived effects of other's actions, and environmental issues. Willingness to pay (WTP) for reductions in GHG emissions through purchases of ethanol blends is estimated via conjoint analysis from a national survey.

Results
Estimates reveal that WTP varies in significance and magnitude across the four segments. In particular, the Environmentals market cluster is the only cluster consistently willing to pay a premium for emission reductions.

Conclusions
Market opinion clusters play a significant role in WTP for emission reductions through purchases of E85. Results suggest the existence of a potential niche market consisting of consumers with strong environmental concerns who are willing to pay a premium for renewable fuels in order to reduce GHG emissions.
Designed plasmonic nanocatalysts for the reduction of eosin Y: absorption and fluorescence study
Authors: Komalam Abha , Muraleegharan Lekha Girija , Subburaj Suganthi , Suseela Suji , Babu Aswathy , George Sony 
Published: October 2012

Abstract
In this work, we report a one-step green synthesis of gold nanoparticles (AuNPs) by microwave irradiation using nontoxic and biodegradable polysaccharide chitosan as a reducing and stabilizing agent. The interaction between gold nanoparticles with the amine group of chitosan was confirmed by Fourier transform infrared spectroscopy analysis, and the stability of the nanoparticle is ascertained by zeta potential measurements. Transmission electron microscopy photograph and dynamic light scattering measurements confirmed the average size of gold nanoparticles as 25 nm. The ability of the synthesised gold nanoparticles as a catalyst for the reduction of eosin dye in the presence of NaBH4 was monitored by means of spectrofluorometry and spectrophotometry. It is found that the NaBH4-induced reduction of eosin is enhanced in the presence of AuNPs even without a catalyst. Time-resolved fluorescence decay studies also confirmed the reduction of eosin in the presence of AuNPs.
Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation
Authors: Terrier Benjamin , Derian Nicolas , Schoindre Yoland , Chaara Wahiba , Geri Guillaume , Zahr Noël , Mariampillai Kubéraka , Rosenzwajg Michelle , Carpentier Wassila , Musset Lucile , Piette Jean-Charles , Six Adrien , Klatzmann David , Saadoun David , Patrice Cacoub , Costedoat-Chalumeau Nathalie 
Published: October 2012

Abstract

Introduction

Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown.

Methods

In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100 000 IU of cholecalciferol per week for 4 weeks, followed by 100 000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D.

Results

Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period.

Conclusions

This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials.
Effectiveness and molecular interactions of the clinically active mTORC1 inhibitor everolimus in combination with tamoxifen or letrozole in vitro and in vivo
Authors: Martin Lesley-Ann , Pancholi Sunil , Farmer Ian , Guest Stephanie , Ribas Ricardo , Weigel Marion T , Thornhill Allan M , Ghazoui Zara , A'Hern Roger , Evans Dean B , Lane Heidi A , Johnston Stephen R , Dowsett Mitch 
Published: October 2012

Abstract
Introduction
Strategies to improve the efficacy of endocrine agents in breast cancer (BC) therapy and to delay the onset of resistance include concomitant targeting of the estrogen receptor alpha (ER) and the mammalian target of rapamycin complex 1 (mTORC1), which regulate cell-cycle progression and are supported by recent clinical results.

Methods
BC cell lines expressing aromatase (AROM) and modeling endocrine-sensitive (MCF7-AROM1) and human epidermal growth factor receptor 2 (HER2)-dependent de novo resistant disease (BT474-AROM3) and long-term estrogen-deprived (LTED) MCF7 cells that had acquired resistance associated with HER2 overexpression were treated in vitro and as subcutaneous xenografts with everolimus (RAD001-mTORC1 inhibitor), in combination with tamoxifen or letrozole. End points included proliferation, cell-cycle arrest, cell signaling, and effects on ER-mediated transactivation.

Results
Everolimus caused a concentration-dependent decrease in proliferation in all cell lines, which was associated with reductions in S6 phosphorylation. Everolimus plus letrozole or tamoxifen enhanced the antiproliferative effect and G1-accumulation compared with monotherapy, as well as increased phosphorylation (Ser10) and nuclear accumulation of p27 and pronounced dephosphorylation of Rb. Sensitivity was greatest to everolimus in the LTED cells but was reduced by added estrogen. Increased pAKT occurred in all circumstances with everolimus and, in the BT474 and LTED cells, was associated with increased pHER3. Decreased ER transactivation suggested that the effectiveness of everolimus might be partly related to interrupting cross-talk between growth-factor signaling and ER. In MCF7-AROM1 xenografts, letrozole plus everolimus showed a trend toward enhanced tumor regression, versus the single agents. In BT474-AROM3 xenografts, everolimus alone was equally effective at reducing tumor volume as were the combination therapies.

Conclusions
The results provide mechanistic support for recent positive clinical data on the combination of everolimus and endocrine therapy, as well as data on potential routes of escape via enhanced HER2/3 signaling. This merits investigation for further improvements in treatment efficacy.