bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medullary thyroid carcinoma and 2q37 deletion in a patient with nevoid basal cell carcinoma syndrome: Clinical description and genetic analysis
Authors: Coca–Pelaz Andrés , Llorente–Pendás Jose Luis , García–Martínez Jorge , Vivanco–Allende Blanca , Balbín Milagros , Suárez Carlos , Hermsen Mario 
Published: February 2012

AbstractBackgroundNevoid basal cell carcinoma syndrome (NBCCS) is a rare, inheritable, multisystem disorder characterized by numerous basal cell carcinomas (BCCs), maxillary keratocyst, and musculoskeletal malformations. Occasionally, it is associated with malignancies like rhabdomyoma, melanoma, and sinonasal undifferentiated carcinoma, to name a few.MethodsA patient presented with NBCCS with a medullary thyroid carcinoma. Clinical, surgical details, and germline genetic analysis are herein described.ResultsA 32‐year‐old woman was referred to our department with suspicion of medullary thyroid carcinoma, which was confirmed by histopathological examination. The patient was diagnosed as also having NBCCS. Germline mutation analysis indicated wild‐type genes PTCH1 and RET. DNA copy number analysis by high resolution microarray comparative genomic hybridization (CGH) revealed a small interstitial loss at chromosomal band 2q37.3.ConclusionTo our knowledge, this is the first described patient with NBCCS carrying a medullary thyroid carcinoma and a 2q37 deletion, which confirms that this syndrome can be associated with many different malignancies. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: A prospective study
Authors: Paleri Vinidh , Carding Paul , Chatterjee Sanjoy , Kelly Charles , Wilson Janet Ann , Welch Andrew , Drinnan Michael 
Published: February 2012

AbstractBackgroundThe voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown.MethodsWe conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time‐points.ResultsOf 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time‐point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures.ConclusionTo the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self‐reported voice quality, even in the long term. © 2012 Wiley Periodicals, Inc. Head Neck, 2012
Small‐molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma
Authors: Boro Aleksandar , Prêtre Kathya , Rechfeld Florian , Thalhammer Verena , Oesch Susanne , Wachtel Marco , Schäfer Beat W. , Niggli Felix K. 
Published: February 2012

AbstractEwing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well‐characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read‐out system, we screened a small‐molecule compound library enriched for FDA‐approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit‐list of nine well‐known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes.
Cytotoxicity of new duplex drugs linking 3′‐C‐ethynylcytidine and 5‐fluor‐2′‐deoxyuridine against human melanoma cells
Authors: Schott Sarah , Niessner Heike , Sinnberg Tobias , Venturelli Sascha , Berger Alexander , Ikenberg Kristian , Villanueva Jessie , Meier Friedegund , Garbe Claus , Busch Christian 
Published: February 2012

AbstractMelanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2′‐Deoxy‐5‐fluorouridylyl‐(3′‐5′)‐3′‐C‐ethynylcytidine [5‐FdU(3′‐5′)ECyd] and 3′‐C‐ethynylcytidinylyl‐(5′→1‐O)‐2‐O‐octadecyl‐sn‐glycerylyl‐(3‐O→5′)‐2′‐deoxy‐5‐fluorouridine [ECyd‐lipid‐5‐FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5‐FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient‐derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real‐time)‐proliferation assays demonstrated that 5‐FdU(3′‐5′)ECyd and ECyd‐lipid‐5‐FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range. Cytotoxicity was conducted by induction of DNA cleavage indicating apoptotic cells. Chicken embryotoxicity demonstrated that the duplex drugs were less toxic than 5‐FdU at 0.01 μM. In vivo the duplex drug 5‐FdU(3′‐5′)ECyd was efficacious in the murine LOX IMVI melanoma xenograph model on administration of 11.2 mg/kg/injection every fourth day. Both duplex drugs are promising novel cytostatic agents for the treatment of malignant melanoma meriting clinical evaluation.
What proportion of lung cancer in never‐smokers can be attributed to known risk factors?
Authors: Sisti Julia , Boffetta Paolo 
Published: February 2012

AbstractThough tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancer in never‐smokers attributable to previously identified risk factors in North America, Europe and China, using population‐based estimates of exposure prevalence and estimates of relative risk derived from recently published meta‐analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40 to 19.93%. Because of differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never‐smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never‐smokers and highlight the need for further research in this area, particularly in Europe and North America.
Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake
Authors: Sun Xin , Nair Jagadeesan , Linseisen Jakob , Owen Robert W. , Bartsch Helmut 
Published: February 2012

AbstractA diet high in linoleic acid (an ω‐6 PUFA) increased the formation of miscoding etheno (ε) ‐ DNA adducts in WBC‐DNA of women, but not in men (Nair et al., Cancer Epidemiol Biomark Prev 1997;6:597‐601). This gender specificity could result from an interaction between ω‐6 PUFA intake and estrogen catabolism, via redox‐cycling of 4‐hydroxyestradiol (4‐OH‐E2) and subsequent lipid peroxidation (LPO). In this study, we investigated whether in premenopausal women LPO‐derived adducts in WBC‐DNA are affected by serum concentration of 2‐ and 4‐hydroxyestradiol metabolites and by fatty acid intake. DNA extracted from buffy coat and plasma samples, both blindly coded from healthy women (N = 124, median age 40 year) participating in the EPIC‐Heidelberg cohort study were analyzed. Three LPO‐derived exocyclic DNA adducts, εdA, εdC and M1dG were quantified by immuno‐enriched 32P‐postlabelling and estradiol metabolites by ultra‐sensitive GC‐mass spectrometry. Mean M1dG levels in WBC‐DNA were distinctly higher than those of εdA and εdC, and all were positively and significantly interrelated. Serum levels of 4‐OH‐E2, but not of 2‐OH‐E2, metabolites were positively related to etheno DNA adduct formation. Positive correlations existed between M1dG levels and linoleic acid intake or the ratios of dietary linoleic acid/oleic acid and PUFA/MUFA. Aerobic incubation of 4‐OH‐E2, arachidonic acid and calf thymus DNA yielded two to threefold higher etheno DNA adduct levels when compared with assays containing 2‐OH‐E2 instead. In conclusion, this study is the first to compare M1dG and etheno‐DNA adducts and serum estradiol metabolites in human samples in the same subjects. Our results support a novel mechanistic link between estradiol catabolism, dietary ω‐6 fatty acid intake and LPO‐induced DNA damage supported by an in vitro model. Similar studies in human breast epithelial tissue and on amplification of DNA‐damage in breast cancer patients are in progress.
Human papillomavirus types in 115,789 HPV‐positive women: A meta‐analysis from cervical infection to cancer
Authors: Guan Peng , Howell‐Jones Rebecca , Li Ni , Bruni Laia , de Sanjosé Silvia , Franceschi Silvia , Clifford Gary M. 
Published: February 2012

AbstractGenotyping may improve risk stratification of high‐risk (HR) human papillomavirus (HPV)‐positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta‐analysis of cross‐sectional HR HPV‐type distribution in 115,789 HPV‐positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low‐grade squamous intraepithelial lesions (LSIL) and 6,616 high‐grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR‐based studies worldwide. No strong differences in HPV‐type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20–28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV‐positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV‐based screening programs.
Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold
Authors: Xia Yang , Mei Fang , Duan Yongli , Gao Ying , Xiong Zhuo , Zhang Ting , Zhang Hongquan 
Published: February 2012

AbstractTo investigate the potential application of bone marrow stromal cells (BMSCs) and an injectable sodium alginate/gelatin scaffold for bone tissue engineering (BTE). The phenotype of osteogenic BMSCs was examined by mineralized nodules formation and type I collagen expression. Cell proliferation was evaluated by MTT assay. The biocompatibility of scaffold and osteogenic cells were examined by hematoxylin and eosin (H&E) staining. Ectopic bone formation as well as closure of rabbit calvarial critical‐sized defects following scaffold‐cell implantation were analyzed by histological examination and computed tomography (CT) scanning. Spindle‐shaped osteogenic cells of high purity were derived from BMSCs. The osteogenic cells and sodium alginate/gelatin (2:3) scaffold presented fine biocompatibility following cross‐linking with 0.6% of CaCl2. After implantation, the scaffold‐cell construct promoted both ectopic bone formation and bone healing in the rabbit calvarial critical‐sized defect model. Our data demonstrated that the sodium alginate/gelatin scaffold could be a suitable biomaterial for bone engineering, and the scaffold‐osteogenic cells construct is a promising alternative approach for the bone healing process. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Porous crosslinked poly(ε‐caprolactone fumarate)/nanohydroxyapatite composites for bone tissue engineering
Authors: Farokhi M. , Sharifi S. , Shafieyan Y. , Bagher Z. , Mottaghitalab F. , Hatampoor A. , Imani M. , Shokrgozar M.A. 
Published: February 2012

AbstractPorous nanocomposites based on poly(ε‐caprolactone fumarate) (PCLF) resin matrix; N‐vinyl pyrrolidone (NVP) as a reactive diluents and nanohydroxyapatite (nHA) filler were developed for bone tissue engineering applications. Nanocomposite scaffolds with three different contents of nHA [5, 10, and 20 (w/w %)] were prepared by thermal crosslinking of PCLF followed by particulate leaching and characterized in terms of mechanical properties (cyclic loading) and in vitro cell‐material interaction by MTT assay and alkaline phosphatase activity measurements. Five osteoblastic cell lines were used to investigate the ability of the nanocomposites to support cell attachment, spreading, and proliferation after 3, 7, and 14 days. By adding the nHA filler phase, elastic modulus of the nanocomposites increased significantly. Scaffolds showed comparable biocompatibility to neat nHA particles, commercial bone graft (Bio‐Oss) and tissue culture polystyrene as control groups. According to the results it can be concluded that these scaffolds are potential candidates for bone substitution because of their mechanical strength and bioactivity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Collagen scaffolds derived from fresh water fish origin and their biocompatibility
Authors: Pati Falguni , Datta Pallab , Adhikari Basudam , Dhara Santanu , Ghosh Kuntal , Mohapatra Pradeep Kumar Das 
Published: February 2012

AbstractCollagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost‐effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self‐assembly owing to its amphiphilic nature and were subsequently cross‐linked.In vitrodegradation study revealed higher stability of the cross‐linked scaffolds with only ∼50% reduction of mass in 30 days, while the uncross‐linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.
Tonicity enhancer binding protein (TonEBP) and hypoxia-inducible factor (HIF) coordinate heat shock protein 70 (Hsp70) expression in hypoxic nucleus pulposus cells: Role of Hsp70 in HIF-1α degradation
Authors: Gogate Shilpa S , Fujita Nobuyuki , Skubutyte Renata , Shapiro Irving M , Risbud Makarand V 
Published: February 2012

Abstract
The objective of our study was to examine the regulation of hypoxic expression of heat shock protein 70 (Hsp70) in nucleus pulposus cells and to determine if Hsp70 promoted hypoxia-inducible factor (HIF)-1α degradation. Rat nucleus pulposus cells were maintained in culture in either 21% or 1% oxygen. To determine the regulation of Hsp70 expression by tonicity enhancer binding protein (TonEBP) and HIF-1/2, loss-of-function and gain-of-function experiments and mutational analysis of the Hsp70 promoter were performed. Hypoxia increased Hsp70 expression in nucleus pulposus cells. Noteworthy, hypoxia increased TonEBP transactivation and mutation of TonE motifs blocked hypoxic induction of the Hsp70 promoter. In contrast, mutation of hypoxia response element (HRE) motifs coupled with loss-of-function experiments suggested that HIF-1 and HIF-2 suppressed Hsp70 promoter activity and transcription. Interestingly, HIF-α interferes with TonEBP function and suppresses the inductive effect of TonEBP on the Hsp70 promoter. In terms of Hsp70 function, when treated with Hsp70 transcriptional inhibitor, KNK437, there was an increase in HIF-1α protein stability and transcriptional activity. Likewise, when Hsp70 was overexpressed, the stability of HIF-1α and its transcriptional activity decreased. Hsp70 interacted with HIF-1α under hypoxic conditions and evidenced increased binding when treated with MG132, a proteasomal inhibitor. These results suggest that Hsp70 may promote HIF-1α degradation through the proteasomal pathway in nucleus pulposus cells. In hypoxic and hyperosmolar nucleus pulposus cells, Hsp70, TonEBP, and HIFs form a regulatory loop. We propose that the positive regulation by TonEBP and negative regulation of Hsp70 by HIF-1 and HIF-2 may serve to maintain Hsp70 levels in these cells, whereas Hsp70 may function in controlling HIF-1α homeostasis. © 2012 American Society for Bone and Mineral Research.
Influence of forest structure on density and nest success of mature forest birds in managed landscapes
Authors: Bakermans Marja H. , Rodewald Amanda D. , Vitz Andrew C. 
Published: February 2012

AbstractManaging for forest wildlife requires attention not only to quantity but quality of forests within the landscape. We examined the extent to which local structural attributes and landscape context of forest stands explained variation in density and reproductive success of mature forest birds across 12 sites in southeast Ohio, USA, 2004–2006. Results suggest that several structural characteristics influenced bird–habitat relationships in our study. Densities of 3 songbird species (i.e., ovenbird [Seiurus aurocapilla], cerulean warbler [Setophaga cerulea], and scarlet tanager [Piranga olivacea]) were positively related to canopy openness, which is usually a function of canopy gaps. Habitat attributes described by ground litter, understory density, and canopy height were positively associated with densities of ground (i.e., worm‐eating warbler [Helmitheros vermivorum]), or shrub nesting species (i.e., Kentucky and hooded warblers [Geothlypis formosaandSetophaga citrina], respectively). Furthermore, the number of small trees likely drove the positive relationship between density of wood thrush (Hylocichla mustelina), a subcanopy nester. After accounting for temporal variability in daily nest survival rates, the odds of nest survival for all species increased 10.5% for every 1% increase in canopy openness and decreased 1.4% for each 5% increase in understory vegetation density. Habitat–nest survival relationships were not apparent at the level of the individual species. Our results suggest that structural attributes produced by increasing habitat heterogeneity may be necessary for conservation of forest bird communities. © 2012 The Wildlife Society.
Tunable photonic delay lines in optical fibers
Authors: Chin S. , Thévenaz L. 
Published: February 2012

AbstractA comprehensive overview is presented about optical fiber‐based tunable photonic delay lines, which have been steadily developed over the last decade for the realization of all‐optically controlled timing functions. The most widely used techniques, such as those based on slow & fast light and wavelength conversion associated to dispersion, are described and their physical limitations are discussed in terms of the maximal achievable delay, the associated signal distortion and signal bandwidth. Besides, an entirely different approach for all‐optical signal delaying is introduced. This technique is based on movable grating reflectors dynamically generated in highly birefringent optical fibers. This type of delay line has experimentally demonstrated large tunable delaying with a moderate signal distortion for high capacity optical data streams and even for wideband analog signals.
Two‐Component In situ Forming Supramolecular Hydrogels as Advanced Biomaterials in Vitreous Body Surgery
Authors: Böhm Indra , Strotmann Falko , Koopmans Carsten , Wolf Isabel , Galla Hans‐Joachim , Ritter Helmut 
Published: February 2012

AbstractPolymeric β‐CD and poly{(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid sodium salt)‐co‐[6‐(acrylamido)‐N‐adamantylhexaneamide]} are synthesized to build in situ forming hydrogels based on host/guest interactions, so called physical hydrogels. The use of these hydrogels as a potential vitreous body substitute is discussed and recommended. Potential changes in cell morphology and cell vitality of the retinal ganglion cell line RGC‐5 are determined. DSC experiments with artificial membrane structures are performed. The analyses show that β‐CD overrides the harmful effects of the highly toxic adamantyl‐modified polymer. Although the final hydrogel is considered to be biocompatible, the application as a biomaterial has to be reconsidered.magnified image
Schur–Weyl Theory for C*‐algebras
Authors: Beltiţă Daniel , Neeb Karl‐Hermann 
Published: February 2012

AbstractTo each irreducible infinite dimensional representation of a C*‐algebra , we associate a collection of irreducible norm‐continuous unitary representations of its unitary group , whose equivalence classes are parameterized by highest weights in the same way as the irreducible bounded unitary representations of the group are. These are precisely the representations arising in the decomposition of the tensor products under . We show that these representations can be realized by sections of holomorphic line bundles over homogeneous Kähler manifolds on which acts transitively and that the corresponding norm‐closed momentum sets distinguish inequivalent representations of this type.