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[ "SAGE-Hindawi", "Access", "to", "Research", "Veterinary", "Medicine", "International", "Volume", "2010,", "Article", "ID", "485060,", "5", "pages", "doi:10.4061/2010/485060", "Research", "Article", "The", "Immune", "Enhancement", "of", "Sodium", "Lauryl", "Sulfoacetate", "in", "Chickens", "DaRong", "Cheng,1", "ShanYuan", "Zhu,2", "and", "HuaiChang", "Sun1", "1", "College", "of", "Veterinary", "Medicine,", "Yangzhou", "University,", "Yangzhou", "225009,", "China", "2", "Department", "of", "Pharmacy,", "Jiangsu", "Animal", "Husbandry", "and", "Veterinary", "College,", "Taizhou", "225300,", "China", "Correspondence", "should", "be", "addressed", "to", "DaRong", "Cheng,", "jsyzcdr@yahoo.com.cn", "Received", "27", "August", "2009;", "Revised", "10", "January", "2010;", "Accepted", "2", "March", "2010", "Academic", "Editor:", "Maurice", "Pensaert", "Copyright", "©", "2010", "DaRong", "Cheng", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "The", "purpose", "of", "this", "study", "is", "to", "investigate", "feasibility", "of", "sodium", "lauryl", "sulfoacetate", "(SLS)", "as", "an", "immunoadjuvant", "in", "chickens.", "After", "treating", "with", "62.5,", "125,", "250,", "or", "500", "μg/mL", "SLS", "in", "vitro,", "lymphocyte", "proliferation", "assay", "of", "chicken", "peripheral", "blood", "mononuclear", "cells", "showed", "that", "the", "OD570", "values", "of", "all", "experimental", "groups,", "as", "well", "as", "Con", "A-stimulated", "group,", "were", "significantly", "higher", "than", "that", "of", "the", "untreated", "control", "group.", "After", "injection", "with", "1.0,", "2.0,", "or", "4.0", "mg/kg", "of", "SLS", "for", "3", "consecutive", "days,", "chickens", "were", "vaccinated", "with", "an", "attenuated", "vaccine", "against", "Newcastle", "disease", "virus", "(NDV),", "and", "the", "immunoadjuvant", "effects", "of", "SLS", "were", "evaluated", "on", "the", "basis", "of", "immune", "organ", "index,", "antibody", "response,", "and", "CD4+/CD8+", "T-cell", "ratio.", "The", "results", "confirmed", "that", "SLS", "could", "enhance", "NDV-", "specific", "antibody", "response", "and", "increase", "CD4+/CD8+", "T-cell", "ratio", "in", "vivo.", "Furthermore,", "SLS", "could", "improve", "NDV-specific", "antibody", "response", "in", "thiamphenicol-treated", "chickens.", "These", "data", "indicate", "that", "SLS", "not", "only", "can", "improve", "humoral", "immune", "response", "but", "also", "reverse", "the", "immunosuppressive", "effect", "of", "thiamphenicol", "in", "chickens.", "1.", "Introduction", "Houttuynia", "cordata", "thunb", "(Saururaceae,", "HC)", "is", "a", "therapeutic", "drug", "which", "has", "been", "used", "for", "the", "treatment", "of", "infections,", "allergy", "and", "cancers", "[1–9].", "The", "major", "active", "component", "of", "the", "herb", "is", "houttuynin,", "which", "is", "present", "in", "the", "fraction", "of", "volatile", "oil", "with", "antimicrobial,", "antioxidative,", "antimuta-", "genic,", "and", "immunoadjuvant", "effects", "[10–12].", "The", "modified", "form", "of", "houttuynin,", "called", "sodium", "houttuyfonate", "(SH,", "C12H23NaO5S,", "MW", "302.36),", "has", "potent", "immunoadjuvant", "effects", "including", "promotion", "of", "phagocytosis", "and", "secretion", "of", "lysozyme,", "acidic", "phosphatase", "and", "IL-1β", "by", "macrophages", "[13–16].", "To", "reduce", "the", "cytotoxicitic", "effect", "of", "SH,", "sodium", "lauryl", "sulfoacetate", "(SLS,", "brand", "name", "is", "sodium", "new", "houttuy-", "fonate,", "SNH,", "C14H27NaO5S,", "MW", "330.4,", "Figure", "1)", "has", "been", "generated", "by", "additive", "reaction", "with", "houttuynin", "and", "sodium", "bisulfite,", "which", "has", "also", "been", "widely", "used", "for", "the", "treat-", "ment", "of", "infections,", "inflammation,", "anaphylaxis,", "and", "cancers", "[17,", "18].", "To", "investigate", "the", "feasibility", "of", "SLS", "as", "an", "immunoad-", "juvant", "for", "chickens,", "in", "this", "study", "lymphocyte", "prolifera-", "tion", "assay", "was", "performed", "using", "chicken", "peripheral", "blood", "mononuclear", "cells", "(PBMCs)", "in", "the", "presence", "of", "different", "doses", "of", "SLS.", "Then,", "the", "in", "vivo", "immunoadjuvant", "effect", "was", "confirmed", "according", "to", "the", "immune", "organ", "index,", "antibody", "response,", "and", "CD4+/CD8+", "T-cell", "ratio", "of", "the", "chickens", "vaccinated", "with", "an", "attenuated", "vaccine", "against", "Newcastle", "disease", "virus", "(NDV)", "with", "SLS", "or", "SLS", "plus", "thiamphenicol", "treatment.", "2.", "Materials", "and", "Methods", "2.1.", "Materials", "and", "Animals.", "11-day-old", 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[ "Three", "Dimensional", "Assessment", "of", "the", "Pharyngeal", "Airway", "in", "Individuals", "with", "Non-Syndromic", "Cleft", "Lip", "and", "Palate", "Tracy", "Cheung1,", "Snehlata", "Oberoi2*", "1", "University", "of", "California", "Los", "Angeles,", "Los", "Angeles,", "California,", "United", "States", "of", "America,", "2", "Division", "of", "Orthodontics,", "Department", "of", "Orofacial", "Sciences,", "School", "of", "Dentistry,", "University", "of", "California", "San", "Francisco,", "San", "Francisco,", "California,", "United", "States", "of", "America", "Abstract", "Introduction:", "Children", "with", "cleft", "lip", "and", "palate", "(CLP)", "are", "known", "to", "have", "airway", "problems.", "Previous", "studies", "have", "shown", "that", "individuals", "with", "CLP", "have", "a", "30%", "reduction", "in", "nasal", "airway", "size", "compared", "to", "non-cleft", "controls.", "No", "reports", "have", "been", "found", "on", "cross-sectional", "area", "and", "volume", "of", "the", "pharyngeal", "airway", "in", "clefts.", "Introduction", "of", "Cone-Beam", "CT", "(CBCT)", "and", "imaging", "software", "has", "facilitated", "generation", "of", "3D", "images", "for", "assessment", "of", "the", "cross-sectional", "area", "and", "volume", "of", "the", "airway.", "Objective:", "To", "assess", "the", "pharyngeal", "airway", "in", "individuals", "with", "CLP", "using", "CBCT", "by", "measuring", "volume", "and", "smallest", "cross-", "sectional", "areas", "and", "compare", "with", "19", "age-", "and", "sex-matched", "non-cleft", "controls.", "Methods:", "Retrospective", "study", "of", "CBCT", "data", "of", "pre-adolescent", "individuals", "(N", "=", "19,", "Mean", "age", "=", "10.6,", "7", "females,", "12", "males,", "UCLP", "=", "6,", "BCLP", "=", "3)", "from", "the", "Center", "for", "Craniofacial", "Anomalies.", "Volumetric", "analysis", "was", "performed", "using", "image", "segmentation", "features", "in", "CB", "Works", "3.0.", "Volume", "and", "smallest", "cross-sectional", "were", "studied", "in", "both", "groups.", "Seven", "measurements", "were", "repeated", "to", "verify", "reliability", "using", "Pearson", "correlation", "coefficient.", "Volume", "and", "cross-sectional", "area", "differences", "were", "analyzed", "using", "paired", "t-tests.", "Results:", "The", "method", "was", "found", "to", "be", "reliable.", "Individuals", "with", "CLP", "did", "not", "exhibit", "smaller", "total", "airway", "volume", "and", "cross", "sectional", "area", "than", "non-CLP", "controls.", "Conclusion:", "3D", "imaging", "using", "CBCT", "and", "CB", "Works", "is", "reliable", "for", "assessing", "airway", "volume.", "Previous", "studies", "have", "shown", "that", "the", "nasal", "airway", "is", "restricted", "in", "individuals", "with", "CLP.", "In", "our", "study,", "we", "found", "that", "the", "pharyngeal", "airway", "is", "not", "compromised", "in", "these", "individuals.", "Citation:", "Cheung", "T,", "Oberoi", "S", "(2012)", "Three", "Dimensional", "Assessment", "of", "the", "Pharyngeal", "Airway", "in", "Individuals", "with", "Non-Syndromic", "Cleft", "Lip", "and", "Palate.", "PLoS", "ONE", "7(8):", "e43405.", "doi:10.1371/journal.pone.0043405", "Editor:", "Noam", "A.", "Cohen,", "Hospital", "of", "the", "University", "of", "Pennsylvania,", "United", "States", "of", "America", "Received", "March", "21,", "2012;", "Accepted", "July", "20,", "2012;", "Published", "August", "29,", "2012", "Copyright:", "2012", "Cheung,", "Oberoi.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "No", "current", "external", "funding", "sources", "for", "this", "study.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "sneha.oberoi@ucsf.edu", "Introduction", "Birth", "defects", "affect", "approximately", "3%", "of", "all", "births", "and", "contribute", "substantially", "to", "childhood", "morbidity", "in", "the", "United", "States", "[1].", "Orofacial", "defects", "like", "cleft", "lip", "and/or", "palate", "(CLP)", "occur", "in", "an", "estimated", "6,800", "children", "annually,", "making", "it", "the", "most", "common", "birth", "defect", "in", "the", "United", "States", "[2].", "Anatomical", "abnormalities", "associated", "with", "CLP", "increase", "the", "risk", "of", "airway", "complications", "[3].", "CLP", "are", "frequently", "associated", "with", "nasal", "abnormalities", "such", "as", "septal", "deviation,", "nostril", "atresia,", "turbinate", "hypertrophy,", "maxillary", "constriction,", "vomerine", "spurs,", "and", "alar", "constriction", "[4,5,6,7,8].", "These", "abnormalities", "are", "attributed", "in", "part", "to", "the", "congenital", "defect", "itself", "and", "partly", "to", "the", "surgeries", "done", "to", "repair", "the", "orofacial", "defect", "[9,10].", "Collectively,", "the", "nasal", "abnormalities", "tend", "to", "reduce", "the", "dimensions", "of", "the", "nasal", "cavity", "and", "lower", "airway", "function", "[6,11].", "Airway", "patency", "has", "been", "evaluated", "by", "two-dimensional", "(2D)", "radiographic", "imaging", "such", "as", "lateral", "and", "anterior-posterior", "cephalometric", "films", "and", "functional", "studies", "such", "as", "rhinomano-", "metry", "and", "plethysmography", "[12,13,14,15].", "A", "rhinomanometry", "study", "showed", "that", "individuals", "with", "bilateral", "CLP", "had", "a", "41%", "reduction", "in", "nasal", "airway", "compared", "to", "a", "19%", "reduction", "in", "individuals", "with", "unilateral", "CLP", "[15].", "Plethysmography", "showed", "that", "individuals", "with", "CLP", "had", "a", "30%", "reduction", "in", "the", "nasal", "airway", "compared", "to", "non-cleft", "controls", "[12].", "Lateral", "cephalometric", "films", "of", "children", "with", "CLP", "were", "compared", "with", "non-cleft", "controls", "and", "showed", "a", "reduction", "in", "the", "nasopharyngeal", "bony", "framework", "and", "pharyngeal", "airway", "[16].", "Furthermore,", "a", "reduction", "in", "the", "upper", "airway", "in", "juveniles", "with", "CLP", "was", "found", "when", "compared", "to", "gender", "and", "age", "matched", "non-cleft", "controls", "and", "were", "found", "to", "persist", "through", "adolescence", "when", "lateral", "cephalometric", "films", "were", "compared", "[13].", "Until", "recently,", "diagnostic", "imaging", "of", "the", "airway", "has", "been", "limited", "to", "2D", "studies.", "Two-dimensional", "imaging", "using", "lateral", "head", "films", "is", "useful", "for", "analyzing", "airway", "size", "in", "the", "sagittal", "plane,", "but", "does", "not", "depict", "the", "three-dimensional", "anatomy.", "The", "physiologi-", "cally", "most", "relevant", "information", "is", "obtained", "from", "axial", "images", "which", "are", "perpendicular", "to", "the", "direction", "of", "airflow,", "but", "the", "axial", "plane", "is", "not", "visualized", "on", "lateral", "cephalograms", "[17].", "In", "addition,", "lateral", "cephalometric", "films", "have", "many", "limitations,", "such", "as", "image", "enlargement", "and", "distortion,", "structure", "overlap,", "limited", "identifiable", "landmarks,", "and", "positioning", "problems", "that", "may", "adversely", "affect", "PLOS", "ONE", "|", "www.plosone.org", "1", "August", "2012", "|", "Volume", "7", "|", "Issue", "8", "|", "e43405" ]

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"Toronto,", "Canada", "B.", "L.", "Daniel", ".", "M.", "A.", "A.", "J.", "van", "den", "Bosch", "Department", "of", "Radiology,", "Stanford", "University,", "Stanford,", "CA,", "USA", "M.", "A.", "A.", "J.", "van", "den", "Bosch", "(*)", "Department", "of", "Radiology,", "Lucas", "MR", "Imaging", "Center,", "1201", "Welch", "Road,", "Stanford,", "CA,", "94305-5488,", "USA", "e-mail:", "mbosch@stanford.edu", "Tel.:", "+1-650-4987550", "Fax:", "+1-650-7367925", "Abstract", "Image-guided", "focussed", "ul-", "trasound", "(FUS)", "ablation", "is", "a", "non-", "invasive", "procedure", "that", "has", "been", "used", "for", "treatment", "of", "benign", "or", "malignant", "breast", "tumours.", "Image-guidance", "dur-", "ing", "ablation", "is", "achieved", "either", "by", "using", "real-time", "ultrasound", "(US)", "or", "magnetic", "resonance", "imaging", "(MRI).", "The", "past", "decade", "phase", "I", "studies", "have", "proven", "MRI-guided", "and", "US-guided", "FUS", "ablation", "of", "breast", "cancer", "to", "be", "technically", "feasible", "and", "safe.", "We", "provide", "an", "overview", "of", "studies", "asses-", "sing", "the", "efficacy", "of", "FUS", "for", "breast", "tumour", "ablation", "as", "measured", "by", "per-", "centages", "of", "complete", "tumour", "necrosis.", "Successful", "ablation", "ranged", "from", "20%", "to", "100%,", "depending", "on", "FUS", "system", "type,", "imaging", "technique,", "ablation", "protocol,", "and", "patient", "selection.", "Spe-", "cific", "issues", "related", "to", "FUS", "ablation", "of", "breast", "cancer,", "such", "as", "increased", "treat-", "ment", "time", "for", "larger", "tumours,", "size", "of", "ablation", "margins,", "methods", "used", "for", "margin", "assessment", "and", "residual", "tu-", "mour", "detection", "after", "FUS", "ablation,", "and", "impact", "of", "FUS", "ablation", "on", "senti-", "nel", "node", "procedure", "are", "presented.", "Finally,", "potential", "future", "applications", "of", "FUS", "for", "breast", "cancer", "treatment", "such", "as", "FUS-induced", "anti-tumour", "im-", "mune", "response,", "FUS-mediated", "gene", "transfer,", "and", "enhanced", "drug", "delivery", "are", "discussed.", "Currently,", "breast-", "conserving", "surgery", "remains", "the", "gold", "standard", "for", "breast", "cancer", "treatment.", "Keywords", "Image-guided", "therapy", ".", "Focussed", "ultrasound", ".", "Breast", "cancer", ".", "Tumour", "ablation", ".", "Magnetic", "resonance", "imaging", "Evolution", "of", "breast", "cancer", "treatment", "Breast", "cancer", "is", "the", "most", "frequently", "occurring", "malignant", "disease", "and", "leading", "cause", "of", "cancer-related", "death", "in", "women", "in", "the", "Western", "world.", "The", "number", "of", "new", "cases", "and", "deaths", "from", "breast", "cancer", "for", "women", "in", "the", "US", "in", "2007", "was", "estimated", "to", "be", "178,480", "and", "40,460,", "respectively", "[1].", "Radical", "mastectomy,", "i.e.,", "breast", "amputation", "with", "or", "without", "excision", "of", "the", "pectoral", "muscle,", "has", "long", "been", "accepted", "as", "an", "appropriate", "therapy", "for", "breast", "cancer.", "This", "treatment", "was", "based", "on", "the", "theory", "of", "Dr.", "William", "Halsted", "that", "aggressive", "local", "therapy", "for", "control", "of", "breast", "cancer,", "chest", "wall", "and", "regional", "lymph", "nodes", "would", "have", "a", "substantial", "benefit", "on", "survival", "[2].", "In", "the", "1970s,", "an", "increased", "understanding", "of", "the", "natural", "history", "of", "breast", "cancer", "resulted", "in", "the", "use", "of", "breast-conserving", "surgery,", "i.e.,", "local", "excision", "as", "proposed", "by", "Dr.", "Bernard", "Fisher,", "for", "treatment", "of", "breast", "cancer", "[3,", "4].", "After", "results", "of", "randomized", "studies", "demonstrated", "similar", "survival", "rates", "for", "both", "treatment", "groups,", "breast-conserving", "surgery", "combined", "with", "radiotherapy", "became", "standard", "treatment", "for", "patients", "with", "localized", "breast", "cancer", "[3].", "Parallel", "to", "this", "development,", "nationwide", "breast", "cancer", "screening", "programmes", "were", "implemented", "in", "many", "Western", "countries", "in", "the", "1990s,", "resulting", "in", "an", "increased", "proportion" ]

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[ "Original", "Article", "Clinics", "in", "Orthopedic", "Surgery", "2011;3:279-284", "http://dx.doi.org/10.4055/cios.2011.3.4.279", "Medial", "Unicompartmental", "Knee", "Arthroplasty", "in", "Patients", "with", "Spontaneous", "Osteonecrosis", "of", "the", "Knee", "Won-Sik", "Choy,", "MD,", "Kap", "Jung", "Kim,", "MD,", "Sang", "Ki", "Lee,", "MD,", "Dae", "Suk", "Yang,", "MD,", "Choon", "Myeon", "Kim,", "MD,", "Ju", "Sang", "Park,", "MD", "Department", "of", "Orthopaedic", "Surgery,", "Eulji", "University", "School", "of", "Medicine,", "Daejeon,", "Korea", "Background:", "We", "analyzed", "the", "clinical", "and", "radiologic", "results", "of", "patients", "with", "spontaneous", "osteonecrosis", "of", "the", "knee", "treated", "by", "minimally", "invasive", "medial", "unicompartmental", "arthroplasty", "using", "Oxford", "Uni.", "Methods:", "We", "reviewed", "22", "knees", "in", "21", "patients", "which", "were", "treated", "for", "spontaneous", "osteonecrosis", "between", "2002", "and", "2006.", "Pa-", "tients", "included", "one", "male", "and", "20", "females.", "The", "mean", "age", "was", "70.8", "years", "(range,", "53", "to", "82", "years).", "The", "mean", "follow-up", "period", "was", "70.3", "months", "(range,", "48", "to", "93", "months).", "The", "clinical", "results", "were", "evaluated", "using", "the", "Hospital", "for", "Special", "Surgery", "(HSS)", "knee", "score", "and", "the", "range", "of", "motion", "of", "the", "knee", "preoperatively", "and", "at", "the", "final", "follow-up.", "Preoperative", "plain", "radiographs", "and", "magnetic", "reso-", "nance", "images", "were", "analyzed", "to", "determine", "the", "size", "and", "stage", "of", "osteonecrotic", "lesions.", "Results:", "The", "mean", "HSS", "knee", "score", "was", "64.3", "(range,", "54", "to", "75)", "preoperatively", "and", "92.0", "(range,", "71", "to", "100)", "at", "the", "final", "follow-up.", "The", "mean", "preoperative", "flexion", "contracture", "was", "8.9o", "(range,", "0", "to", "15o)", "and", "0.2o", "(range,", "0", "to", "5o)", "at", "the", "final", "follow-up.", "The", "mean", "fur-", "ther", "flexion", "increased", "from", "138.6o", "(range,", "100", "to", "145o)", "preoperatively", "to", "145.6o", "(range,", "140", "to", "150o)", "at", "the", "final", "follow-up.", "Active", "full", "flexion", "was", "possible", "within", "2", "months", "of", "the", "operation.", "The", "squatting", "position", "was", "possible", "in", "16", "patients", "(84.2%)", "out", "of", "19,", "except", "one", "case", "of", "bronchiectasis", "and", "one", "case", "of", "spine", "fracture.", "The", "cross-leg", "posture", "was", "possible", "in", "19", "patients", "(90.5%)", "out", "of", "21.", "The", "mean", "tibiofemoral", "angle", "was", "improved", "from", "varus", "0.98o", "to", "valgus", "3.22o.", "Meniscal", "bearing", "dislocation", "occurred", "in", "2", "cases", "and", "femoral", "component", "loosening", "occurred", "in", "1", "case.", "Conclusions:", "Unicompartmental", "knee", "arthroplasty", "using", "Oxford", "Uni", "could", "be", "an", "alternative", "treatment", "option", "in", "spontaneous", "os-", "teonecrosis", "of", "the", "knee.", "Keywords:", "Knee,", "Spontaneous", "osteonecrosis,", "Unicompartmental", "knee", "arthroplasty", "Spontaneous", "osteonecrosis", "of", "the", "knee", "(SPONK)", "was", "first", "reported", "by", "Ahlback", "et", "al.1)", "in", "1968.", "Since", "then,", "the", "terms", "SPONK", "and", "Ahlback’s", "disease", "have", "been", "used", "synony-", "mously.1)", "The", "typical", "SPONK", "patient", "is", "fifty-five", "years", "of", "age", "or", "older,", "has", "no", "risk", "factors,", "has", "unilateral", "monoar-", "ticular", "pain,", "has", "limited", "involvement", "of", "the", "periarticular", "Received", "April", "13,", "2011;", "Accepted", "August", "24,", "2011", "Correspondence", "to:", "Kap", "Jung", "Kim,", "MD", "Department", "of", "Orthopaedic", "Surgery,", "Eulji", "University", "School", "of", "Medicine,", "1306", "Dunsan-dong,", "Seo-gu,", "Daejeon", "322-799,", "Korea", "Tel:", "+82-42-611-3278,", "Fax:", "+82-42-259-1289", "E-mail:", "oskkj@eulji.ac.kr", "bone,", "and", "is", "involved", "mainly", "in", "medial", "femoral", "condyle.2)", "The", "clinical", "presentation", "of", "SPONK", "commonly", "includes", "sudden", "onset", "of", "acute", "pain", "which", "is", "frequently", "worse", "at", "night.2)", "The", "sudden", "acute", "onset", "of", "pain", "correlates", "with", "reports", "in", "the", "literature", "stating", "that", "insufficiency", "fractures", "with", "natural", "and", "expected", "surrounding", "necrosis", "of", "bone", "may", "be", "the", "underlying", "clinical", "pathology", "of", "this", "disorder.", "However,", "the", "exact", "pathogenesis", "is", "still", "unknown.", "The", "treatment", "options", "of", "SPONK", "are", "microfracture", "technique,", "high", "tibial", "osteotomy,", "unicompartmental", "knee", "arthroplas-", "ty,", "or", "total", "knee", "arthroplasty", "depending", "on", "the", "location,", "size,", "and", "progression", "of", "lesion,", "and", "on", "the", "patient's", "age", "and", "activity.", "In", "stages", "described", "as", "advanced", "by", "Mont", "clas-", "Copyright", "©", "2011", "by", "The", "Korean", "Orthopaedic", "Association", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Clinics", "in", "Orthopedic", "Surgery", "pISSN", "2005-291X", "eISSN", "2005-4408" ]

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[ "Critical", "Care", "June", "2004", "Vol", "8", "Suppl", "2", "Corwin", "Review", "Anemia", "and", "blood", "transfusion", "in", "the", "critically", "ill", "patient:", "role", "of", "erythropoietin", "Howard", "L", "Corwin", "Professor", "of", "Medicine", "and", "Anesthesiology,", "Dartmouth", "Medical", "School;", "Section", "Chief,", "Critical", "Care", "Medicine;", "Medical", "Director,", "Intensive", "Care", "Unit,", "Dartmouth-Hitchcock", "Medical", "Center,", "Lebanon,", "New", "Hampshire,", "USA", "Correspondence:", "Howard", "L", "Corwin,", "Howard.L.Corwin@Hitchcock.org", "Published", "online:", "14", "June", "2004", "This", "article", "is", "online", "at", "http://ccforum.com/content/8/S2/S42", "©", "2004", "BioMed", "Central", "Ltd", "Critical", "Care", "2004,", "8(Suppl", "2):S42-S44", "(DOI", "10.1186/cc2411)", "Abstract", "Critically", "ill", "patients", "receive", "an", "extraordinarily", "large", "number", "of", "blood", "transfusions.", "Between", "40%", "and", "50%", "of", "all", "patients", "admitted", "to", "intensive", "care", "units", "receive", "at", "least", "1", "red", "blood", "cell", "(RBC)", "unit", "during", "their", "stay,", "and", "the", "average", "is", "close", "to", "5", "RBC", "units.", "RBC", "transfusion", "is", "not", "risk", "free.", "There", "is", "little", "evidence", "that", "‘routine’", "transfusion", "of", "stored", "allogeneic", "RBCs", "is", "beneficial", "to", "critically", "ill", "patients.", "The", "efficacy", "of", "perioperative", "recombinant", "human", "erythropoietin", "(rHuEPO)", "has", "been", "demonstrated", "in", "a", "variety", "of", "elective", "surgical", "settings.", "Similarly,", "in", "critically", "ill", "patients", "with", "multiple", "organ", "failure,", "rHuEPO", "therapy", "will", "also", "stimulate", "erythropoiesis.", "In", "a", "randomized,", "placebo-controlled", "trial,", "therapy", "with", "rHuEPO", "resulted", "in", "a", "significant", "reduction", "in", "RBC", "transfusions.", "Despite", "receiving", "fewer", "RBC", "transfusions,", "patients", "in", "the", "rHuEPO", "group", "had", "a", "significantly", "greater", "increase", "in", "hematocrit.", "Strategies", "to", "increase", "the", "production", "of", "RBCs", "are", "complementary", "to", "other", "approaches", "to", "reduce", "blood", "loss", "in", "the", "intensive", "care", "unit,", "and", "they", "decrease", "the", "transfusion", "threshold", "in", "the", "management", "of", "all", "critically", "ill", "patients.", "Keywords", "anemia,", "blood", "transfusion,", "critical", "illness,", "erythropoietin", "Anemia", "is", "common", "in", "critically", "ill", "patients", "and", "appears", "early", "during", "their", "intensive", "care", "unit", "(ICU)", "course.", "By", "day", "3", "after", "ICU", "admission,", "almost", "95%", "of", "patients", "are", "anemic", "[1–3].", "The", "anemia", "in", "these", "critically", "ill", "patients", "persists", "throughout", "their", "ICU", "and", "hospital", "stay,", "with", "or", "without", "red", "blood", "cell", "(RBC)", "transfusion", "[3].", "Historically,", "the", "anemia", "observed", "in", "the", "critically", "ill", "resulted", "in", "a", "high", "number", "of", "RBC", "transfusions.", "Studies", "conducted", "a", "decade", "ago", "[4]", "revealed", "that", "50%", "of", "all", "patients", "admitted", "to", "the", "ICU", "are", "transfused", "during", "their", "stay.", "In", "addition,", "85%", "of", "patients", "with", "a", "prolonged", "ICU", "stay", "(>", "1", "week)", "received", "trans-", "fusions", "[5].", "On", "average,", "these", "latter", "patients", "were", "transfused", "9.5", "RBC", "units", "during", "their", "ICU", "stay.", "These", "transfusions", "are", "not", "restricted", "to", "the", "early", "ICU", "course;", "rather,", "patients", "are", "transfused", "at", "a", "rate", "of", "2–3", "units", "per", "week.", "An", "observational", "study", "of", "4892", "patients", "admitted", "to", "ICUs", "in", "the", "USA", "throughout", "2000", "and", "2001", "[3]", "found", "that", "almost", "50%", "of", "patients", "are", "still", "transfused.", "The", "results", "also", "showed", "that", "initial", "RBC", "transfusion", "tends", "to", "occur", "early", "in", "the", "ICU", "stay,", "with", "ongoing", "RBC", "transfusions", "throughout", "the", "ICU", "stay.", "The", "mean", "pretransfusion", "hemoglobin", "observed", "(i.e.", "the", "‘transfusion", "trigger’)", "was", "8.6", "±", "1.7", "g/dl", "–", "a", "value", "that", "is", "com-", "parable", "to", "that", "described", "in", "earlier", "reports", "[4,5].", "Interestingly,", "RBC", "transfusions", "were", "not", "restricted", "to", "the", "ICU;", "13%", "of", "patients", "received", "on", "average", "almost", "3", "units", "after", "ICU", "dis-", "charge.", "A", "similar", "observational", "study", "of", "transfusion", "practice", "in", "ICUs", "was", "performed", "across", "Western", "Europe", "[6].", "Data", "were", "col-", "lected", "for", "a", "maximum", "of", "28", "days", "on", "3534", "patients", "admitted", "to", "the", "ICU", "during", "a", "2-week", "period", "in", "late", "1999.", "Of", "these", "patients", "37%", "received", "a", "mean", "of", "4.8", "RBC", "units", "while", "in", "the", "ICU", "and", "12.7%", "of", "patients", "were", "transfused", "during", "the", "post-", "ICU", "period,", "for", "an", "overall", "transfusion", "rate", "of", "42%", "during", "the", "28-day", "study", "period.", "The", "mean", "pretransfusion", "hemoglobin", "level", "was", "8.4", "g/dl.", "S42", "EPO", "=", "erythropoietin;", "ICU", "=", "intensive", "care", "unit;", "RBC", "=", "red", "blood", "cell;", "rHuEPO", "=", "recombinant", "human", "erythropoietin." ]

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[ "Kruse", "et", "al.", "Head", "&", "Neck", "Oncology", "2010,", "2:24", "http://www.headandneckoncology.org/content/2/1/24", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Oral", "squamous", "cell", "carcinoma", "in", "non-smoking", "and", "non-drinking", "patients", "Astrid", "L", "Kruse*,", "Marius", "Bredell,", "Klaus", "W", "Grätz", "Abstract", "Introduction:", "Of", "the", "many", "different", "factors", "associated", "with", "an", "increased", "risk", "for", "oral", "squamous", "cell", "carcinoma", "(SCC),", "tobacco", "and", "alcohol", "seem", "to", "be", "the", "most", "studied.", "The", "aim", "of", "the", "current", "study", "was", "to", "evaluate", "the", "clinicopathologic", "characteristics", "of", "patients", "without", "the", "mentioned", "risk", "factors.", "Patients", "and", "Methods:", "Out", "of", "278", "patients", "(159", "male", "and", "119", "female", "patients)", "with", "oral", "SCC,", "67", "patients", "had", "no", "history", "of", "tobacco", "or", "alcohol", "use.", "The", "minimum", "follow-up", "time", "was", "12", "months.", "Results:", "Of", "the", "67", "patients,", "45", "(67.2%)", "were", "women,", "and", "the", "mean", "age", "was", "70", "years.", "The", "most", "common", "tumor", "sites", "were", "mandibular", "alveolar", "ridge", "(22)", "and", "maxilla", "(18).", "Fifteen", "patients", "experienced", "a", "recurrence,", "and", "10", "developed", "lymph", "node", "metastases", "during", "the", "follow-up", "period.", "Conclusion:", "The", "group", "of", "patients", "with", "no", "tobacco", "and", "alcohol", "use", "tends", "toward", "a", "higher", "proportion", "of", "females,", "a", "higher", "proportion", "of", "patients", "over", "70", "years,", "and", "a", "higher", "number", "of", "oral", "maxillary", "SCC.", "Introduction", "Of", "the", "many", "different", "factors", "associated", "with", "an", "increased", "risk", "for", "oral", "squamous", "cell", "carcinoma", "(SCC),", "tobacco", "and", "alcohol", "seem", "to", "be", "the", "most", "studied.", "Indi-", "viduals", "who", "smoke", "more", "than", "20", "cigarettes", "a", "day", "and", "consume", "more", "than", "100", "g", "of", "alcohol", "a", "day", "are", "at", "increased", "risk", "for", "oral", "epithelial", "dysplasia,", "but", "ex-smo-", "kers", "of", "10", "or", "more", "years", "seem", "to", "have", "no", "greater", "risk", "than", "non-smokers", "[1].", "In", "addition,", "alcohol", "has", "been", "found", "to", "be", "an", "independent", "risk", "factor", "for", "oral", "SCC", "among", "non-smokers", "[2]", "and", "tobacco", "smoke", "in", "non-", "drinkers", "[3,4].", "The", "combination", "of", "both", "factors", "seems", "to", "enhance", "the", "carcinogenic", "effect", "[5,6].", "Blot", "et", "al.", "(1988)", "[6]", "stated", "that", "tobacco", "smoking", "and", "alcohol", "drinking", "combine", "to", "account", "for", "approximately", "three-fourths", "of", "all", "oral", "and", "pharyngeal", "cancers", "in", "the", "United", "States.", "However,", "the", "other", "fourth", "of", "patients", "are", "then", "of", "special", "interest,", "because", "this", "group", "has", "rarely", "been", "studied.", "Regarding", "lung", "cancer", "in", "patients", "without", "tobacco", "use,", "some", "authors", "have", "stated", "that", "these", "cancers", "are", "their", "own", "entity", "due", "to", "their", "special", "characteristics.", "Therefore,", "the", "aim", "of", "the", "current", "study", "was", "to", "evalu-", "ate", "the", "clinicopathologic", "characteristics", "of", "the", "patient", "*", "Correspondence:", "astridkruse@gmx.ch", "University", "Hospital", "Zurich,", "Department", "of", "Craniomaxillofacial", "and", "Oral", "Surgery,", "Zurich/Switzerland", "group", "without", "the", "tobacco", "and", "alcohol", "risk", "factors,", "in", "particular", "concerning", "gender,", "location,", "TN", "status,", "and", "rates", "of", "metastases", "or", "recurrence.", "Patients", "and", "Methods", "The", "files", "of", "278", "patients", "(159", "male", "and", "119", "female", "patients)", "with", "newly", "diagnosed,", "previously", "untreated", "oral", "SCC", "and", "who", "were", "treated", "between", "1999", "and", "2008,", "with", "a", "minimum", "follow-up", "time", "of", "12", "months,", "were", "searched", "for", "patients", "without", "the", "risk", "factors", "of", "tobacco", "or", "alcohol", "use.", "Out", "of", "these", "67", "patients,", "tumor", "data–", "including", "site,", "grade,", "TN", "status,", "recurrence,", "and", "metas-", "tases–were", "obtained", "from", "a", "review", "of", "the", "medical", "records.", "Results", "In", "sum,", "22", "male", "and", "45", "female", "patients", "were", "without", "the", "tobacco", "or", "alcohol", "risk", "factors.", "Of", "these", "67", "patients,", "43", "(64.2%)", "patients", "were", "over", "70", "years", "and", "only", "3", "(6%)", "below", "the", "age", "of", "40.", "The", "mean", "age", "was", "70", "years", "(Fig.", "1).", "The", "most", "common", "tumor", "sites", "were", "the", "mandibular", "alveolar", "ridge", "(22", "patients)", "and", "the", "maxilla", "(18", "patients).", "The", "most", "frequent", "sites", "in", "female", "patients", "were", "oral", "maxillary", "SCC", "(15/67),", "followed", "by", "the", "mandibular", "alveolar", "ridge", "(16/67)", "(Fig.", "2).", "©", "2010", "Kruse", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Neurology", "Research", "article", "Prediction", "of", "the", "survival", "and", "functional", "ability", "of", "severe", "stroke", "patients", "after", "ICU", "therapeutic", "intervention", "Moussa", "Riachy*1,", "Frida", "Sfeir1,", "Ghassan", "Sleilaty2,", "Samer", "Hage-Chahine†3,", "Georges", "Dabar1,", "Taha", "Bazerbachi1,", "Zeina", "Aoun-Bacha1,", "Georges", "Khayat1", "and", "Salam", "Koussa†3", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Hotel", "Dieu", "de", "France,", "Beirut,", "Lebanon,", "2Department", "of", "Cardiothoracic", "Surgery,", "Hotel", "Dieu", "de", "France,", "Beirut,", "Lebanon", "and", "3Department", "of", "Neurology,", "Hotel", "Dieu", "de", "France,", "Beirut,", "Lebanon", "Email:", "Moussa", "Riachy*", "-", "riachy@dm.net.lb;", "Frida", "Sfeir", "-", "fridasfeir@hotmail.com;", "Ghassan", "Sleilaty", "-", "sanasl@inco.com.lb;", "Samer", "Hage-", "Chahine", "-", "samerhagechahine@hotmail.com;", "Georges", "Dabar", "-", "gdabar@cyberia.net.lb;", "Taha", "Bazerbachi", "-", "tbazarbachi@hotmail.com;", "Zeina", "Aoun-Bacha", "-", "zeinaabacha@yahoo.com;", "Georges", "Khayat", "-", "gck@data2.dm.net.lb;", "Salam", "Koussa", "-", "koussalam@hotmail.com", "*", "Corresponding", "author", "†Equal", "contributors", "Published:", "26", "June", "2008", "BMC", "Neurology", "2008,", "8:24", "doi:10.1186/1471-2377-8-24", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2377/8/24", "Received:", "16", "December", "2007", "Accepted:", "26", "June", "2008", "©", "2008", "Riachy", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "This", "study", "evaluated", "the", "benefits", "and", "impact", "of", "ICU", "therapeutic", "interventions", "on", "the", "survival", "and", "functional", "ability", "of", "severe", "cerebrovascular", "accident", "(CVA)", "patients.", "Methods:", "Sixty-two", "ICU", "patients", "suffering", "from", "severe", "ischemic/haemorrhagic", "stroke", "were", "evaluated", "for", "CVA", "severity", "using", "APACHE", "II", "and", "the", "Glasgow", "coma", "scale", "(GCS).", "Survival", "was", "determined", "using", "Kaplan-Meier", "survival", "tables", "and", "survival", "prediction", "factors", "were", "determined", "by", "Cox", "multivariate", "analysis.", "Functional", "ability", "was", "assessed", "using", "the", "stroke", "impact", "scale", "(SIS-16)", "and", "Karnofsky", "score.", "Risk", "factors,", "life", "support", "techniques", "and", "neurosurgical", "interventions", "were", "recorded.", "One", "year", "post-CVA", "dependency", "was", "investigated", "using", "multivariate", "analysis", "based", "on", "linear", "regression.", "Results:", "The", "study", "cohort", "constituted", "6%", "of", "all", "CVA", "(37.8%", "haemorrhagic/62.2%", "ischemic)", "admissions.", "Patient", "mean(SD)", "age", "was", "65.8(12.3)", "years", "with", "a", "1:1", "male:", "female", "ratio.", "During", "the", "study", "period", "16", "patients", "had", "died", "within", "the", "ICU", "and", "seven", "in", "the", "year", "following", "hospital", "release.", "The", "mean(SD)", "APACHE", "II", "score", "at", "hospital", "admission", "was", "14.9(6.0)", "and", "ICU", "mean", "duration", "of", "stay", "was", "11.2(15.4)", "days.", "Mechanical", "ventilation", "was", "required", "in", "37.1%", "of", "cases.", "Risk", "ratios", "were;", "GCS", "at", "admission", "0.8(0.14),", "(p", "=", "0.024),", "APACHE", "II", "1.11(0.11),", "(p", "=", "0.05)", "and", "duration", "of", "mechanical", "ventilation", "1.07(0.07),", "(p", "=", "0.046).", "Linear", "coefficients", "were:", "type", "of", "CVA", "–", "haemorrhagic", "versus", "ischemic:", "-18.95(4.58)", "(p", "=", "0.007),", "GCS", "at", "hospital", "admission:", "-6.83(1.08),", "(p", "=", "0.001),", "and", "duration", "of", "hospital", "stay", "-0.38(0.14),", "(p", "=", "0.40).", "Conclusion:", "To", "ensure", "a", "better", "prognosis", "CVA", "patients", "require", "ICU", "therapeutic", "interventions.", "However,", "as", "we", "have", "shown,", "where", "tests", "can", "determine", "the", "worst", "affected", "patients", "with", "a", "poor", "vital", "and", "functional", "outcome", "should", "treatment", "be", "withheld?", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Effect", "of", "C-factor", "and", "LED", "Curing", "Mode", "on", "Microleakage", "of", "Class", "V", "Resin", "Composite", "Restorations", "Qasem", "Diefallah", "Alomaria", "Kefah", "Barrieshi-Nusairb", "Mohammad", "Alic", "AbstrAct", "Objectives:", "To", "investigate", "the", "effects", "of", "cavity", "C-factor", "and", "LED", "curing", "mode", "on", "microleakage", "of", "class", "V", "resin", "composite", "restorations.", "Methods:", "Eighty", "extracted", "human", "maxillary", "premolars", "were", "divided", "into", "four", "groups.", "In", "groups", "I", "and", "II,", "V-shaped", "class", "V", "cavities", "(C-factor", "≈", "1.5)", "were", "prepared", "while", "box-shaped", "class", "V", "cavities", "(high", "C-factor", "≈", "4)", "were", "prepared", "in", "groups", "III", "and", "IV.", "All", "the", "cavities", "were", "prepared", "on", "the", "vestibular", "surfaces", "of", "the", "teeth.", "All", "the", "cavities", "were", "prepared", "by", "one", "operator", "with", "specific", "dimensions.", "The", "same", "adhesive", "system", "(Excite)", "and", "the", "same", "restorative", "composite", "(Tetric", "Ceram)", "were", "used", "in", "all", "the", "groups.", "The", "restorations", "in", "groups", "I", "and", "III", "were", "cured", "with", "the", "fast", "curing", "mode", "of", "LED", "curing", "light,", "while", "the", "restorations", "in", "groups", "II", "and", "IV", "were", "cured", "with", "the", "soft-start", "mode", "of", "the", "same", "cur-", "ing", "light.", "The", "samples", "were", "thermocycled,", "immersed", "in", "a", "0.5%", "basic", "fuchsin", "solution", "for", "24", "hours,", "and", "sectioned.", "The", "degree", "of", "dye", "penetration", "was", "measured", "quantitatively", "and", "then", "qualitatively", "at", "both", "enamel", "and", "dentin/cementum", "margins.", "Results:", "Quantitatively,", "there", "was", "no", "statistical", "difference", "in", "the", "degree", "of", "microleakage", "between", "the", "groups", "at", "the", "enamel", "margin", "(P>.05).", "At", "the", "dentin/cementum", "margin,", "group", "III", "showed", "signifi-", "cantly", "more", "dye", "penetration", "than", "the", "other", "groups", "(P<.001).", "Similarly,", "qualitative", "measurements", "of", "dye", "penetration", "showed", "that", "group", "III", "had", "higher", "microleakage", "at", "dentin/cementum", "margin", "than", "the", "remaining", "groups", "(I", "and", "III", "P<.001;", "II", "and", "III", "P<.01;", "III", "and", "IV", "P<.01).", "Paired", "sample", "statistics", "showed", "that", "microleakage", "at", "the", "dentin/cementum", "margin", "was", "not", "statistically", "different", "from", "enamel", "mi-", "croleakage", "(P>.05),", "except", "for", "group", "III", "(P<.000).", "Conclusions:", "Fast", "curing", "mode", "of", "LED", "curing", "light", "resulted", "in", "more", "microleakage", "at", "the", "gingi-", "val", "floor", "of", "class", "V", "cavities", "with", "high", "C-factor.", "There", "was", "no", "difference", "in", "dye", "penetration", "between", "enamel", "and", "dentin", "margins", "of", "the", "cavities", "except", "when", "the", "fast", "curing", "mode", "was", "used", "with", "high", "C-factor", "cavities.", "Both", "quantitative", "and", "qualitative", "measurements", "of", "microleakage", "gave", "the", "same", "results", "at", "both", "enamel", "and", "dentin", "margins.", "(Eur", "J", "Dent", "2011;5:400-408)", "Key", "words:", "Resin", "composite;", "Microleakage;", "C-factor;", "LED", "curing", "units;", "Curing", "modes.", "a", "Department", "of", "Restorative", "Sciences,", "Faculty", "of", "Dentistry,", "Kuwait", "University,", "Kuwait.", "b", "Deceased.", "c", "Department", "of", "Diagnostic", "Sciences,", "Faculty", "of", "Dentistry,", "Kuwait", "University,", "Kuwait.", "Corresponding", "author:", "Qasem", "Diefallah", "Alomari", "Department", "of", "Restorative", "Sciences,", "Faculty", "of", "Dentistry,", "Kuwait", "University,", "P.", "O.", "Box", "24923,", "Alsafat", "13110,", "Kuwait.", "E-mail:", "qalomari@hsc.edu.kw", "qasemalomari70@yahoo.com", "400", "European", "Journal", "of", "Dentistry" ]

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[ "Restless", "leg", "syndrome:", "is", "it", "a", "real", "problem?", "Paul", "E", "Cotter", "Shaun", "T", "O’Keeffe", "Department", "of", "Geriatric", "Medicine,", "Galway", "University", "Hospitals,", "Galway,", "Ireland", "Correspondence:", "S", "O’Keeffe", "Unit", "4,", "Merlin", "Park", "Regional", "Hospital,", "Galway,", "Ireland", "Tel", "+", "353", "91", "775", "561", "Fax", "+", "353", "91", "770", "515", "Email", "s.okeeffe@mailn.hse.ie", "R", "E", "V", "I", "E", "W", "Abstract:", "Restless", "legs", "syndrome", "(RLS)", "is", "a", "common", "condition", "that", "is", "frequently", "unrecognized,", "misdiagnosed", "and", "poorly", "managed.", "It", "is", "characterized", "by", "uncomfortable", "sensations", "deep", "in", "the", "legs", "developing", "at", "rest", "that", "compel", "the", "person", "to", "move;", "symptoms", "are", "worst", "at", "night", "and", "sleep", "disturbance", "is", "common.", "RLS", "occurs", "in", "7%–11%", "of", "the", "population", "in", "Western", "countries,", "and", "many", "such", "people", "experience", "troublesome", "symptoms.", "Primary", "RLS", "is", "familial", "in", "up", "to", "two", "thirds", "of", "patients.", "RLS", "may", "also", "be", "secondary", "to", "a", "number", "of", "conditions", "including", "iron", "deficiency,", "pregnancy", "and", "end-stage", "renal", "failure", "and,", "perhaps,", "neuropathy.", "Secondary", "RLS", "is", "most", "common", "in", "those", "presenting", "for", "the", "first", "time", "in", "later", "life.", "The", "pathogenesis", "of", "RLS", "probably", "involves", "the", "interplay", "of", "systemic", "or", "brain", "iron", "deficiency", "and", "impaired", "dopaminergic", "neurotransmission", "in", "the", "subcortex", "of", "the", "brain.", "RLS", "is", "very", "responsive", "to", "dopaminergic", "therapies.", "Rebound", "of", "RLS", "symptoms", "during", "the", "early", "morning", "and", "development", "of", "severe", "symptoms", "earlier", "in", "the", "day", "(augmentation)", "are", "problematic", "in", "those", "treated", "for", "a", "prolonged", "period", "with", "levodopa.", "Consequently,", "dopamine", "agonists", "have", "become", "first", "line", "treatment.", "Anti-convulsant", "medications", "and", "opioids", "are", "helpful", "in", "some", "patients.", "Correction", "of", "underlying", "problem", "wherever", "possible", "is", "important", "in", "the", "management", "of", "secondary", "RLS.", "Keywords:", "Restless", "legs", "syndrome;", "sleep;", "iron", "deficiency;", "neuropathy", "Introduction", "Restless", "Legs", "Syndrome", "(RLS)", "was", "first", "described", "in", "the", "medical", "literature", "by", "the", "anatomist", "and", "physician", "Thomas", "Willis", "in", "1685", "and", "has", "been", "recognized", "as", "a", "well-", "defined,", "common", "and", "frequently", "distressing", "entity", "since", "Ekbom’s", "classic", "description", "in", "1945.", "Nevertheless,", "RLS", "has", "attracted", "little", "attention", "in", "medical", "textbooks", "until", "recently,", "and,", "even", "now,", "it", "is", "often", "unrecognized,", "misdiagnosed", "and", "poorly", "managed.", "In", "this", "paper,", "we", "explore", "the", "reasons", "for", "the", "relative", "neglect", "of", "RLS,", "explain", "current", "thinking", "regarding", "the", "pathogenesis", "and", "management", "of", "the", "condition", "and", "show", "why", "patients", "with", "RLS", "will", "benefit", "from", "careful", "investigation", "and", "treatment.", "What", "is", "RLS?", "RLS", "is", "both", "a", "sensorimotor", "and", "a", "sleep", "disorder.", "It", "is", "characterized", "by", "unusual,", "uncomfortable", "sensations", "deep", "in", "the", "legs", "(and", "sometimes", "arms)", "that", "compel", "the", "person", "to", "move", "to", "relieve", "the", "sensation", "and", "that", "are", "brought", "on", "and", "exacerbated", "by", "rest;", "symptoms", "are", "particularly", "troublesome", "in", "the", "evening", "and", "at", "night,", "and", "sleep", "disturbance", "is", "common.", "The", "original", "report", "by", "Willis", "(1685)", "described", "the", "motor", "features", "and", "the", "sleep", "disruption", "but", "did", "not", "mention", "the", "sensory", "features", "that", "are", "often", "the", "main", "complaint", "of", "patients.", "In", "contrast,", "Karl-Axel", "Ekbom", "(1945)", "emphasized", "the", "importance", "of", "the", "sensory", "component", "of", "the", "condition.", "The", "current", "diagnostic", "criteria", "were", "developed", "at", "an", "National", "Institutes", "of", "Health", "(NIH)-supported", "workgroup", "on", "RLS", "and", "represent", "a", "slight", "modification", "of", "the", "original", "diagnostic", "criteria", "published", "by", "the", "International", "RLS", "Study", "Group", "in", "1995", "(Walters", "1995;", "Allen", "et", "al", "2003).", "There", "are", "four", "essential", "criteria", "and", "three", "supportive", "clinical", "features", "(Table", "1).", "Therapeutics", "and", "Clinical", "Risk", "Management", "2006:2(4)", "465–475", "©", "2006", "Dove", "Medical", "Press", "Limited.", "All", "rights", "reserved", "465" ]

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[ "Qian", "et", "al.", "Journal", "of", "Experimental", "&", "Clinical", "Cancer", "Research", "2010,", "29:111", "http://www.jeccr.com/content/29/1/111", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "GTPase", "regulator", "associated", "with", "the", "focal", "adhesion", "kinase", "(GRAF)", "transcript", "was", "down-", "regulated", "in", "patients", "with", "myeloid", "malignancies", "Zhen", "Qian1,", "Jun", "Qian1*,", "Jiang", "Lin1,", "Dong-ming", "Yao1,", "Qin", "Chen1,", "Run-bi", "Ji1,", "Yun", "Li1,", "Gao-fei", "Xiao1,", "Jian-yong", "Li2", "Abstract", "Background:", "GTPase", "regulator", "associated", "with", "the", "focal", "adhesion", "kinase", "(GRAF),", "a", "putative", "tumor", "suppressor", "gene,", "is", "found", "inactivated", "in", "hematopoietic", "malignancies", "by", "either", "genetic", "or", "epigenetic", "abnormalities.", "However,", "the", "expression", "level", "of", "GRAF", "gene", "has", "not", "yet", "been", "studied", "in", "leukemia.", "The", "aim", "of", "this", "study", "was", "to", "investigate", "the", "expression", "level", "of", "GRAF", "gene", "in", "those", "patients", "with", "myeloid", "malignancies", "including", "acute", "myeloid", "leukemia", "(AML),", "myelodysplastic", "syndrome", "(MDS)", "and", "chronic", "myeloid", "leukemia", "(CML).", "Methods:", "The", "expression", "levels", "of", "GRAF", "transcript", "were", "determined", "in", "94", "patients", "using", "real-time", "quantitative", "PCR", "(RQ-PCR).", "Clinical", "and", "laboratory", "data", "of", "these", "patients", "were", "collected", "and", "analyzed.", "Results:", "The", "significantly", "decreased", "level", "of", "GRAF", "transcript", "was", "observed", "in", "three", "myeloid", "malignancies", "compared", "to", "controls.", "Within", "AML,", "there", "was", "no", "difference", "in", "the", "level", "of", "GRAF", "transcript", "among", "different", "FAB", "subtypes", "(P", ">", "0.05).", "Difference", "was", "not", "observed", "in", "the", "amount", "of", "GRAF", "mRNA", "between", "CML", "at", "chronic", "phase", "and", "controls.", "As", "CML", "progressed,", "GRAF", "transcript", "significantly", "decreased.", "In", "MDS,", "three", "cases", "with", "5q", "deletion", "had", "lower", "GRAF", "transcript", "than", "four", "without", "5q", "deletion", "(median", "0.76", "vs", "2.99)", "(P", ">", "0.05).", "Conclusion:", "our", "results", "demonstrate", "that", "the", "GRAF", "transcript", "is", "decreased", "in", "myeloid", "malignancies.", "Background", "Focal", "adhesion", "kinase", "(FAK),", "a", "non-receptor", "tyrosine", "kinase", "that", "resides", "at", "the", "sites", "of", "integrin", "clustering", "[1],", "plays", "an", "important", "role", "in", "the", "modulation", "of", "cell", "growth,", "proliferation,", "survival", "and", "migration", "[2].", "Recently,", "FAK", "has", "been", "found", "to", "be", "overexpressed", "and/", "or", "constitutively", "activated", "and", "correlated", "with", "increased", "motility,", "invasiveness,", "and", "proliferation", "of", "neoplastic", "cells", "of", "various", "tissue", "types", "[2].", "Two", "published", "articles", "revealed", "that", "aberrant", "expression", "of", "FAK", "was", "observed", "in", "CD34+", "leukemic", "cells", "and", "associated", "with", "enhanced", "blast", "migration,", "increased", "cellularity", "and", "poor", "prognosis", "[3,4].", "Le", "et", "al", "showed", "that", "FAK", "silencing", "inhibited", "leu-", "kemogenesis", "in", "BCR/ABL-transformed", "hematopoietic", "cells", "[5].", "Tyner", "et", "al", "also", "identified", "FAK", "as", "one", "of", "thera-", "peutic", "molecular", "targets", "in", "acute", "myeloid", "leukemia", "(AML)", "[6].", "*", "Correspondence:", "qianjun0007@hotmail.com", "1Department", "of", "Hematology,", "Affiliated", "People’s", "Hospital", "of", "Jiangsu", "University,", "Zhenjiang,", "Jiangsu", "212002,", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "FAK", "protein", "is", "composed", "of", "an", "N-terminal", "FERM", "domain,", "a", "central", "kinase", "domain,", "and", "a", "C-terminal", "domain", "that", "includes", "the", "focal", "adhesion", "targeting", "(FAT)", "sequence", "responsible", "for", "FAK’s", "localization", "to", "focal", "adhesions.", "Both", "the", "N-terminal", "and", "C-terminal", "domains", "have", "been", "shown", "to", "mediate", "FAK", "interaction", "with", "a", "variety", "of", "other", "proteins", "critical", "for", "activation", "of", "FAK", "by", "integrins", "or", "other", "cell", "surface", "receptors", "as", "well", "as", "FAK", "regulation", "of", "different", "cellular", "functions", "[2].", "GTPase", "regulator", "associated", "with", "focal", "adhesion", "kinase", "(GRAF)", "is", "a", "newly", "identified", "protein", "specifically", "binding", "to", "the", "proline-rich", "region", "in", "the", "COOH", "termi-", "nus", "of", "FAK", "and", "negatively", "regulates", "the", "small", "GTP-", "binding", "protein", "RhoA,", "which", "is", "well", "known", "for", "its", "growth-promoting", "effect", "in", "RAS-mediated", "malignant", "transformation", "[7,8].", "GRAF", "gene", "is", "located", "at", "chromo-", "some", "5q31", "and", "its", "protein", "is", "ubiquitously", "expressed", "in", "various", "tissues", "[9].", "Mutations", "and", "deletions", "of", "GRAF", "gene", "were", "found", "in", "some", "cases", "with", "AML", "or", "myelodys-", "plastic", "syndrome", "(MDS)", "with", "a", "deletion", "5q", "[9].", "Further-", "more,", "Bojesen", "et", "al", "[10]", "found", "that", "GRAF", "gene", "©", "2010", "Qian", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "CELLULAR", "NEUROSCIENCE", "How", "do", "soluble", "oligomers", "of", "amyloid", "β-protein", "impair", "hippocampal", "synaptic", "plasticity?", "Shaomin", "Li,", "Ganesh", "M.", "Shankar", "and", "Dennis", "J.", "Selkoe*", "Center", "for", "Neurologic", "Diseases,", "Brigham", "and", "Women’s", "Hospital,", "Harvard", "Medical", "School,", "Boston,", "MA,", "USA", "*Correspondence:", "dselkoe@rics.bwh.harvard.edu", "GENERAL", "COMMENTARY", "published:", "19", "March", "2010", "doi:", "10.3389/fncel.2010.00005", "A", "commentary", "on", "Soluble", "oligomers", "of", "amyloid", "β-protein", "facilitate", "hippocampal", "long-term", "depres-", "sion", "by", "disrupting", "neuronal", "glutamate", "uptake", "by", "Li,", "S.,", "Hong,", "S.,", "Shepardson,", "N.E.,", "Walsh,", "D.M.,", "Shankar,", "G.M.,", "Selkoe,", "D.", "Neuron", "2009;", "62,", "788–801.", "Alzheimer’s", "disease", "(AD),", "the", "most", "common", "neurodegenerative", "disorder,", "is", "character-", "ized", "by", "progressive", "memory", "and", "cognitive", "impairment", "and", "the", "cerebral", "accumula-", "tion", "of", "extracellular", "amyloid", "plaques", "and", "intraneuronal", "neurofibrillary", "tangles.", "A", "principal", "neuropathological", "finding", "in", "AD", "subjects", "is", "cortical", "atrophy", "associated", "with", "degeneration", "of", "neurites,", "decreased", "den-", "dritic", "spine", "density", "and", "frank", "neuronal", "loss", "(Terry", "et", "al.,", "1991;", "Knobloch", "and", "Mansuy,", "2008).", "Although", "the", "specific", "molecular", "initi-", "ators", "of", "the", "AD", "process", "remain", "unknown", "in", "most", "patients,", "biochemical", "studies", "indicate", "that", "the", "severity", "of", "cognitive", "impairment", "in", "AD", "correlates", "more", "strongly", "with", "the", "corti-", "cal", "levels", "of", "soluble", "amyloid", "β-protein", "(Aβ", "assemblies", "than", "with", "the", "burden", "of", "insoluble", "amyloid", "plaques", "(Lue", "et", "al.,", "1999;", "McLean", "et", "al.,", "1999;", "Shankar", "et", "al.,", "2008).", "Extensive", "experimental", "work", "on", "hippocampal", "plastic-", "ity", "has", "indicated", "that", "the", "induction", "of", "long-", "term", "synaptic", "depression", "(LTD)", "results", "in", "decreased", "dendritic", "spine", "volume", "or", "out-", "right", "elimination", "of", "spines", "(Matsuzaki", "et", "al.,", "2004;", "Nägerl", "et", "al.,", "2004;", "Zhou", "et", "al.,", "2004),", "changes", "which", "may", "parallel", "molecular", "and", "structural", "aspects", "of", "synaptic", "failure", "in", "AD.", "Therefore,", "understanding", "how", "Aβ", "impairs", "hippocampal", "synaptic", "function", "at", "the", "molecular", "level", "could", "enable", "the", "develop-", "ment", "of", "specific", "neuroprotective", "therapies", "for", "AD.", "Studies", "from", "numerous", "laboratories", "have", "now", "established", "that", "soluble", "Aβ", "oligomers", "can", "inhibit", "long-term", "potentiation", "(LTP),", "or", "the", "strengthening", "of", "synapses,", "in", "the", "hippocampus.", "But", "heretofore,", "only", "a", "few", "studies", "have", "examined", "the", "effects", "of", "Aβ", "on", "the", "induction", "of", "LTD,", "and", "those", "few", "have", "yielded", "inconsistent", "results.", "For", "example,", "synthetic", "Aβ", "peptides", "were", "reported", "to", "potently", "enable", "the", "induction", "of", "LTD", "in", "CA1", "in", "an", "NMDAR-", "dependent", "manner", "in", "vivo", "(Kim", "et", "al.,", "2001;", "Cheng", "et", "al.,", "2009),", "whereas", "other", "studies", "found", "no", "effect", "on", "LTD", "in", "slices", "(Wang", "et", "al.,", "2002,", "2004;", "Raymond", "et", "al.,", "2003).", "To", "address", "this", "problem,", "we", "recently", "extracted", "buffer-", "soluble", "Aβ", "oligomers", "directly", "from", "the", "brains", "of", "typical", "AD", "patients", "and", "demonstrated", "that", "these", "species", "can", "facilitate", "LTD", "induc-", "tion", "in", "hippocampal", "slices", "of", "wild-type", "mice", "(Shankar", "et", "al.,", "2008).", "While", "the", "induction", "of", "both", "LTP", "and", "LTD", "requires", "glutamatergic", "transmission,", "the", "direction", "in", "which", "synaptic", "strength", "is", "modulated", "by", "the", "specific", "class", "of", "glutamate", "receptor", "that", "is", "activated,", "the", "kinetics", "of", "cytosolic", "calcium", "concentration,", "and", "the", "initiation", "of", "intracellular", "signaling", "cascades.", "Specifically,", "we", "found", "that", "LTD", "induction", "was", "facilitated", "by", "pathophysiologi-", "cally", "relevant", "low", "concentrations", "of", "soluble", "Aβ", "oligomers", "through", "activation", "of", "either", "NMDA", "receptors", "or", "metabotropic", "glutamate", "receptors", "(mGluRs),", "depending", "on", "the", "elec-", "trical", "stimulation", "protocol", "used", "to", "induce", "the", "LTD", "(Li", "et", "al.,", "2009).", "Given", "that", "several", "prior", "studies,", "including", "our", "own,", "have", "already", "shown", "that", "Aβ", "has", "little", "or", "no", "effect", "on", "pre-", "synaptic", "neurotransmitter", "release", "probability", "(e.g.,", "Townsend", "et", "al.,", "2006;", "Shankar", "et", "al.,", "2008;", "Cheng", "et", "al.,", "2009),", "we", "hypothesized", "that", "the", "Aβ", "oligomers", "alter", "synaptic", "gluta-", "mate", "concentration", "by", "disrupting", "glutamate", "transport", "mechanisms.", "In", "the", "current", "study,", "we", "report", "that", "pharmacologically", "blocking", "glutamate", "uptake", "closely", "recapitulates", "the", "effects", "of", "Aβ", "on", "LTD", "induction,", "suggest-", "ing", "that", "Aβ", "oligomers", "bias", "towards", "synapse", "weakening", "in", "part", "through", "such", "a", "mecha-", "nism", "(Li", "et", "al.,", "2009).", "A", "growing", "number", "of", "reports", "indicate", "that", "glutamate", "transporters", "are", "disturbed", "in", "AD", "(Masliah", "et", "al.,", "1996).", "The", "levels", "of", "transporters", "such", "as", "GLAST/EAAT1", "and", "GLT-1/EAAT2", "are", "reduced", "in", "postmor-", "tem", "AD", "brain", "tissue", "and", "in", "APP", "transgenic", "mice", "(Maragakis", "et", "al.,", "2004;", "Jacob", "et", "al.,", "2007).", "Synthetic", "Aβ", "(at", "supraphysiological", "concentrations)", "has", "been", "shown", "to", "inhibit", "glutamate", "uptake", "in", "cultured", "neurons", "and", "astrocytes", "(Harris", "et", "al.,", "1996;", "Harkany", "et", "al.,", "2000;", "Fernández-Tomé", "et", "al.,", "2004)", "and", "in", "oocytes", "(Gu", "et", "al.,", "2004).", "Although", "most", "glutamate", "transporters", "are", "located", "on", "astrocytes,", "reduced", "neuronal", "expression", "of", "EAAT1", "was", "also", "suggested", "to", "be", "an", "early", "marker", "of", "neuronal", "dysfunction", "in", "AD,", "pre-", "ceding", "or", "occurring", "on", "a", "similar", "timeline", "to", "the", "expression", "of", "hyper-phosphorylated", "tau", "protein", "in", "the", "same", "neurons", "of", "AD", "brains", "(Scott", "et", "al.,", "2002).", "Interestingly,", "it", "was", "dem-", "onstrated", "recently", "that", "detergent", "insoluble", "EAAC1/EAAT3", "transporters", "accumulate", "aberrantly", "in", "hippocampus", "in", "AD", "subjects", "(Duerson", "et", "al.,", "2009).", "Taken", "together,", "these", "various", "reports", "suggest", "that", "neuronal", "and/or", "glial", "glutamate", "uptake", "may", "be", "interrupted", "in", "AD.", "Glutamate", "transporters", "play", "the", "impor-", "tant", "role", "of", "regulating", "concentrations", "of", "glutamate", "in", "the", "extracellular", "space,", "keep-", "ing", "it", "at", "low", "levels.", "Without", "normal", "activ-", "ity", "of", "glutamate", "transporters,", "glutamate", "would", "accumulate", "to", "cytotoxic", "levels", "and", "could", "contribute", "to", "progressive", "neuronal", "loss", "in", "AD", "(Pomara", "et", "al.,", "1992;", "Harkany", "et", "al.,", "2000).", "Early", "AD", "studies", "focused", "on", "frank", "Aβ-enhanced", "excitotoxicity", "medi-", "ated", "through", "glutamate", "receptors,", "espe-", "cially", "NMDA", "receptors", "(Greenamyre", "and", "Young,", "1989;", "Mattson", "et", "al.,", "1992;", "Hynd", "et", "al.,", "2004).", "However,", "the", "perturbations", "in", "extracellular", "glutamate", "levels", "result-", "ing", "from", "altered", "transport", "kinetics", "could", "even", "be", "responsible", "for", "the", "more", "subtle", "ultrastructural", "alterations", "noted", "in", "AD,", "such", "as", "dendritic", "spine", "loss.", "In", "vivo", "microdialysis", "recently", "revealed", "that", "soluble", "Aβ", "oligom-", "ers", "secreted", "by", "APP-transfected", "cells,", "when", "microinjected", "into", "wild-type", "rat", "brain,", "can", "Frontiers", "in", "Cellular", "Neuroscience", "www.frontiersin.org", "March", "2010", "|", "Volume", "4", "|", "Article", "5", "|", "1" ]

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[ "Nucleic", "Acids", "Research,", "2006,", "Vol.", "34,", "Web", "Server", "issue", "W729–W732", "doi:10.1093/nar/gkl320", "Taverna:", "a", "tool", "for", "building", "and", "running", "workflows", "of", "services", "1", "Duncan", "Hull*,", "Katy", "Wolstencroft,", "Robert", "Stevens,", "Carole", "Goble,", "Mathew", "R.", "Pocock", ",", "Peter", "Li2", "and", "Tom", "Oinn3", "School", "of", "Computer", "Science,", "University", "of", "Manchester,", "M13", "9PL,", "UK,", "1School", "of", "Computing", "Science,", "University", "of", "Newcastle,", "NE1", "7RU,", "UK,", "2School", "of", "Chemistry,", "University", "of", "Manchester,", "M60", "1QD,", "UK", "and", "3EMBL", "European", "Bioinformatics", "Institute,", "Hinxton,", "Cambridge,", "CB10", "1SD,", "UK", "Received", "February", "14,", "2006;", "Revised", "March", "1,", "2006;", "Accepted", "April", "13,", "2006", "ABSTRACT", "Taverna", "is", "an", "application", "that", "eases", "the", "use", "and", "inte-", "gration", "of", "the", "growing", "number", "of", "molecular", "biology", "tools", "and", "databases", "available", "on", "the", "web,", "especially", "web", "services.", "It", "allows", "bioinformaticians", "to", "construct", "workflows", "or", "pipelines", "of", "services", "to", "perform", "a", "range", "of", "different", "analyses,", "such", "as", "sequence", "analysis", "and", "genome", "annotation.", "These", "high-level", "workflows", "can", "integrate", "many", "different", "resources", "into", "a", "single", "analysis.", "Taverna", "is", "available", "freely", "under", "the", "terms", "of", "the", "GNU", "Lesser", "General", "Public", "License", "(LGPL)", "from", "http://taverna.sourceforge.net/.", "INTRODUCTION", "The", "number", "of", "applications", "and", "databases", "providing", "tools", "to", "perform", "computations", "on", "DNA,", "RNA", "and", "proteins", "are", "rapidly", "growing.", "However,", "the", "lack", "of", "communication", "between", "such", "tools", "in", "molecular", "biology", "is", "commonly", "a", "barrier", "to", "extracting", "new", "knowledge", "using", "these", "resources.", "Many", "tools", "and", "databases", "already", "communicate", "using", "the", "web,", "as", "shown", "by", "the", "ever-growing", "list", "of", "servers", "in", "this", "issue", "of", "Nucleic", "Acids", "Research.", "Currently,", "integrating", "tools", "and", "databases", "available", "on", "the", "web", "frequently", "involves", "either", "‘screen-scraping’", "web", "pages", "using", "scripting", "languages", "like", "PERL", "or", "manual", "cut-and-", "paste", "of", "data", "between", "applications.", "Each", "of", "these", "methods", "has", "its", "problems.", "Screen-scraping", "is", "notoriously", "fragile,", "because", "the", "integrating", "script", "is", "prone", "to", "break", "when", "the", "web", "page", "or", "form", "changes,", "and", "for", "this", "reason", "has", "been", "likened", "to", "‘medieval", "torture’", "(1).", "Cutting", "and", "pasting", "data", "between", "applications", "is", "another", "common", "way", "to", "quickly", "achieve", "interoperation.", "However,", "cut-and-paste", "procedures", "are", "laborious", "to", "repeat", "and", "verify.", "Web", "services", "technology", "provides", "some", "solutions", "for", "improving", "this", "situation.", "In", "addition", "to", "providing", "form-", "based", "interfaces,", "tool", "and", "database", "providers", "can", "describe", "their", "application", "or", "database", "using", "the", "standard", "Web", "Services", "Description", "Language", "(WSDL).", "These", "WSDL", "descriptions", "can", "then", "be", "indexed", "to", "build", "a", "searchable", "and", "browsable", "registry", "of", "operations", "for", "end-users.", "Applications", "can", "then", "exchange", "data,", "typically", "using", "SOAP,", "a", "protocol", "for", "exchang-", "ing", "XML-based", "messages", "over", "a", "network,", "normally", "using", "HTTP.", "For", "a", "full", "description", "of", "web", "service", "technology,", "lan-", "guages", "and", "protocols", "see", "(2).", "Using", "web", "services", "has", "several", "advantages:", "Tools", "and", "databases", "do", "not", "need", "to", "be", "installed", "locally", "on", "the", "users", "machine", "or", "laboratory", "server,", "as", "they", "are", "program-", "matically", "accessible", "over", "the", "web.", "Tools", "created", "using", "different", "programming", "languages", "(e.g.", "Python,", "PERL,", "Java,", "etc.)", "and", "platforms", "(e.g.", "Unix,", "Windows,", "etc.)", "can", "be", "accessed", "through", "the", "same", "web", "service", "interface.", "This", "removes", "the", "need", "for", "the", "user", "to", "know", "about", "all", "the", "different", "platforms", "and", "programming", "languages", "underneath.", "The", "need", "for", "fragile", "screen-scraping", "integration", "scripts", "is", "reduced.", "It", "provides", "an", "alternative", "to", "time-consuming", "and", "laborious", "‘cut-and-paste’", "integration", "between", "web", "applications.", "Workflows,", "or", "pipelines,", "of", "web", "services", "can", "be", "built", "to", "provide", "high-level", "descriptions", "of", "analyses.", "These", "can", "be", "created", "and", "tested", "relatively", "quickly", "to", "integrate", "many", "dif-", "ferent", "tools", "and", "applications", "in", "a", "single", "analysis", "However,", "there", "are", "also", "several", "limitations", "of", "using", "web", "services:", "Since", "services", "are", "provided", "by", "autonomous", "third-parties", "around", "the", "world,", "they", "frequently", "have", "insufficient", "or", "non-existent", "metadata.", "Where", "metadata", "exists", "it", "often", "pro-", "vides", "little", "indication", "of", "the", "purpose", "of", "a", "service.", "So", "for", "example,", "inputs", "can", "have", "cryptic", "names", "like", "‘in1’", "with", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+44", "0", "161", "275", "0677;", "Fax:", "+44", "0", "161", "275", "6204;", "Email:", "duncan.hull@cs.man.ac.uk", "The", "Author", "2006.", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oxfordjournals.org" ]

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[ "O", "R", "I", "G", "I", "N", "A", "L", "R", "E", "S", "E", "A", "R", "C", "H", "Pain", "and", "efficacy", "of", "local", "anesthetics", "for", "central", "venous", "access", "William", "C", "Culp", "Jr1", "Mohammed", "Yousaf2", "Benjamin", "Lowr", "y1", "Timothy", "C", "McCowan3", "William", "C", "Culp2", "1Division", "of", "Cardiothoracic", "Anesthesiology,", "Scott", "and", "White", "Hospital,", "The", "Texas", "A&M", "University", "College", "of", "Medicine,", "Temple,", "TX,", "USA;", "2Division", "of", "Interventional", "Radiology,", "University", "of", "Arkansas", "for", "Medical", "Sciences,", "Little", "Rock,", "AR,", "USA;", "3Department", "of", "Radiology,", "University", "of", "Mississippi", "Medical", "Center,", "Jackson,", "MS,", "USA", "Correspondence:William", "C", "Culp", "Division", "of", "Interventional", "Radiology,", "4301", "West", "Markham", "Street,", "#556,", "Little", "Rock,AR", "72205-7199,", "USA", "Tel", "+1", "501", "686", "6910", "Fax", "+1", "501", "686", "6900", "Email", "culpwilliamc@uams.edu", "Purpose:", "To", "compare", "pain", "during", "injection", "and", "efficacy", "of", "analgesia", "of", "local", "anesthetics", "during", "central", "venous", "line", "placement.", "Methods:", "Sixty-two", "patients", "were", "studied", "in", "a", "randomized,", "double-blinded", "prospective", "fashion.", "Patients", "received", "1%", "lidocaine", "(L),", "buffered", "1%", "lidocaine", "(LB),", "or", "2%", "chloroprocaine", "(CP)", "injected", "around", "the", "internal", "jugular", "vein", "for", "procedural", "analgesia", "for", "central", "venous", "access.", "Patients", "reported", "pain", "via", "a", "standard", "linear", "visual", "analog", "scale,", "with", "0", "representing", "no", "pain", "and", "10", "being", "the", "worst", "pain", "imaginable.", "Results:", "Overall", "patient", "perception", "of", "pain", "was", "better", "with", "CP", "and", "L", "than", "LB", "with", "mean", "scores", "of", "CP", "2.4,", "L", "2.6,", "LB", "4.2.", "Pain", "with", "injection", "mean", "scores", "were", "CP", "2.1,", "L", "2.5,", "LB", "3.2.", "Pain", "with", "catheter", "placement", "scores", "were", "CP", "2.5,", "L", "1.7,", "LB", "3.4.", "Operator", "assessment", "of", "overall", "pain", "values", "were", "CP", "1.9,", "L", "2.2,", "LB", "3.4.", "LB", "consistently", "scored", "the", "worst,", "though", "compared", "with", "CP,", "this", "only", "reached", "statistical", "significance", "in", "overall", "patient", "pain", "and", "pain", "at", "catheter", "insertion", "compared", "with", "L.", "Conclusion:", "Though", "chloroprocaine", "scored", "better", "than", "lidocaine", "in", "3", "of", "4", "parameters,", "this", "trend", "did", "not", "achieve", "statistical", "significance.", "Adding", "sodium", "bicarbonate", "to", "lidocaine", "isn’t", "justified", "in", "routine", "practice,", "nor", "is", "routine", "replacement", "of", "lidocaine", "with", "chloroprocaine.", "Keywords:", "local", "anesthesia,", "analgesia,", "central", "venous", "access,", "lidocaine,", "chloroprocaine", "Introduction", "Central", "venous", "catheter", "placement", "as", "well", "as", "many", "other", "surgical", "procedures", "can", "be", "painful,", "and", "this", "pain", "is", "often", "reduced", "with", "the", "use", "of", "local", "anesthetics.", "The", "local", "anes-", "thetic", "used", "to", "reduce", "pain,", "however,", "often", "causes", "pain", "itself.", "The", "best", "local", "anesthetic", "compound", "to", "utilize", "in", "order", "to", "minimize", "this", "pain", "upon", "injection", "while", "still", "providing", "adequate", "and", "effective", "anesthesia", "for", "various", "procedures", "has", "long", "been", "the", "center", "of", "controversy.", "Several", "studies", "have", "suggested", "that", "a", "buffered", "lidocaine", "(LB)", "solution", "causes", "less", "pain", "during", "intra-", "and", "subdermal", "injection", "in", "comparison", "with", "the", "most", "commonly", "used", "local", "anesthetic,", "lidocaine", "(L)", "(Nuttal", "et", "al", "1993;", "Prien", "1994;", "Xia", "et", "al", "2002;", "Davies", "2003).", "Alternatively,", "other", "data", "suggest", "that", "chloroprocaine", "(CP)", "is", "associated", "with", "the", "least", "amount", "of", "pain", "on", "injection", "and/or", "that", "buffering", "L", "does", "not", "decrease", "pain", "on", "injection", "(Marica", "et", "al", "2002;", "Burns", "et", "al", "2006).", "This", "study", "attempts", "to", "assess", "the", "analgesic", "efficacy", "and", "associated", "pain", "on", "injection", "of", "three", "local", "anesthetic", "solutions", "used", "for", "procedural", "analgesia", "for", "central", "venous", "access.", "Methods", "After", "approval", "of", "the", "local", "Institutional", "Review", "Board,", "62", "consecutive", "patients", "requir-", "ing", "central", "venous", "access", "with", "planned", "placement", "in", "the", "internal", "jugular", "vein", "were", "consented", "and", 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[ "MEDITERRANEAN", "JOURNAL", "OF", "HEMATOLOGY", "AND", "INFECTIOUS", "DISEASES", "www.mjhid.org", "ISSN", "2035-3006", "Case", "Reports", "Takayasu", "Arteritis", "Initially", "Mimicking", "Infective", "Endocarditis", "Aytekin", "Alcelik,", "Sevim", "Karacay,", "Ismail", "Necati", "Hakyemez,", "Busra", "Akin,", "Serkan", "Ozturk", "and", "Haluk", "Savli", "Deparment", "of", "Internal", "Medicine,", "Abant", "Izzet", "Baysal", "University,", "Bolu,", "Turkey", "Correspondance:", "Dr.", "Aytekin", "Alcelik.", "E-mail:", "aytekinalcelik@yahoo.com", "Competing", "interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "Published:", "September", "8,", "2011", "Received:", "June", "8,", "2011", "Accepted:", "August", "3,", "2011", "Mediterr", "J", "Hematol", "Infect", "Dis", "2011,", "3:", "e2011040,", "DOI", "10.4084/MJHID.2011.040", "This", "article", "is", "available", "from:", "http://www.mjhid.org/article/view/8801", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Takayasu’s", "arteritis", "(TA)", "is", "a", "chronic", "inflammatory", "disease", "that", "affects", "large", "vessels,", "predominantly", "the", "aorta", "and", "its", "main", "branches,", "leading", "to", "vessel", "wall", "thickening,", "fibrosis", "and", "stenosis.", "Cardiac", "and", "vascular", "symptoms", "are", "also", "commonly", "present", "at", "disease", "onset.", "In", "TA", "with", "thoracic", "or", "abdominal", "involvement,", "although", "murmur", "can", "be", "present", "at", "physical", "examination,", "the", "pulse", "difference", "may", "be", "absent.", "Here,", "we", "report", "a", "case", "of", "TA", "who", "initially", "resembled", "infective", "endocarditis", "and", "had", "widespread", "thoracic", "murmur.", "Introduction:", "Takayasu’s", "arteritis", "(TA)", "is", "a", "chronic", "inflammatory", "disease", "that", "affects", "large", "vessels,", "predominantly", "the", "aorta", "and", "its", "main", "branches,", "leading", "to", "vessel", "wall", "thickening,", "fibrosis", "and", "stenosis.", "The", "etiology", "and", "predisposing", "factors", "of", "TA", "are", "so", "far", "unknown.", "The", "main", "clinical", "symptoms", "and", "signs", "are", "weakness,", "fever,", "arthralgia,", "hypertension,", "intermittent", "claudication", "of", "the", "upper", "or", "lower", "limbs,", "cardiac", "diseases", "(cardiac", "failure,", "valvular", "or", "ischemic", "heart", "disease)", "and", "impaired", "renal", "function.", "Laboratory", "findings", "are", "non-specific.", "Treatment", "of", "the", "active", "disease", "is", "primarily", "based", "on", "corticosteroids.1-2", "Cardiac", "and", "vascular", "symptoms", "are", "also", "commonly", "present", "at", "disease", "onset.", "In", "TA", "with", "thoracic", "or", "abdominal", "involvement,", "although", "murmur", "can", "be", "present", "at", "physical", "examination,", "the", "pulse", "difference", "may", "be", "absent.3-4", "Therefore,", "TA", "can", "be", "misdiagnosed", "as", "infective", "endocarditis", "because", "of", "murmur", "and", "fever", "associated", "with", "the", "active", "phase", "of", "the", "disease.", "Here,", "we", "report", "a", "case", "of", "TA", "who", "initially", "resembled", "infective", "endocarditis", "and", "had", "widespread", "Mediterr", "J", "Hematol", "Infect", "Dis", "2011;", "3;", "Open", "Journal", "System", "thoracic", "murmur.", "Case:", "A", "30-year-old", "woman", "was", "admitted", "with", "the", "complaint", "of", "sore", "throat", "and", "polyarthralgia", "for", "five", "days.", "The", "patient", "also", "reported", "headache,", "dizziness", "and", "fever.", "At", "presentation,", "her", "body", "temperature", "was", "37.5°C", "and", "blood", "pressure", "in", "right", "arm", "was", "180/90", "mmHg", "and", "in", "left", "arm", "was", "170/80", "mmHg.", "Physical", "examination", "showed", "widespread", "thoracic", "murmur", "and", "weak", "pulses", "in", "both", "arms.", "Ophthalmoscopic", "examination", "was", "normal.", "Laboratory", "findings", "were", "as", "follows:", "hemoglobin", "was", "12.2", "g/dL,", "hematocrit", "was", "36%,", "white", "blood", "cell", "count", "was", "12,500/mm3,", "platelet", "count", "was", "296,000/mm3", "and", "mean", "corpuscular", "volume", "was", "80", "femtoliter.", "Fasting", "glucose", "level,", "calcium,", "albumin,", "urea", "and", "creatinine", "levels", "were", "within", "the", "normal", "range.", "Sedimentation", "rate", "was", "31", "mm,", "C", "reactive", "protein", "(CRP)", "was", "52", "mg/dL", "(range", "from", "0-", "3.19", "mg/dL).", "Urine", "examination", "was", "normal.", "Throat", "culture", "did", "not", "yield", "beta", "hemolytic", "Streptococci.", "Telecardiography", "(Figure1)", "and", "electrocardiogram" ]

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[ "Liu", "et", "al.", "Molecular", "Neurodegeneration", "2011,", "6:21", "http://www.molecularneurodegeneration.com/content/6/1/21", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Transcriptional", "Regulation", "of", "TMP21", "by", "NFAT", "Shengchun", "Liu1,2*†,", "Si", "Zhang2†,", "Kelley", "Bromley-Brits2,", "Fang", "Cai2,", "Weihui", "Zhou2,", "Kun", "Xia3,", "Jill", "Mittelholtz2,", "Weihong", "Song2*", "Abstract", "Background:", "TMP21", "is", "a", "member", "of", "the", "p24", "cargo", "protein", "family,", "which", "is", "involved", "in", "protein", "transport", "between", "the", "Golgi", "apparatus", "and", "ER.", "Alzheimer’s", "Disease", "(AD)", "is", "the", "most", "common", "neurodegenerative", "disorder", "leading", "to", "dementia", "and", "deposition", "of", "amyloid", "b", "protein", "(Ab)", "is", "the", "pathological", "feature", "of", "AD", "pathogenesis.", "Knockdown", "of", "TMP21", "expression", "by", "siRNA", "causes", "a", "sharp", "increase", "in", "Ab", "production;", "however", "the", "underlying", "mechanism", "by", "which", "TMP21", "regulates", "Ab", "generation", "is", "unknown,", "and", "human", "TMP21", "gene", "expression", "regulation", "has", "not", "yet", "been", "studied.", "Results:", "In", "this", "report", "we", "have", "cloned", "a", "3.3-kb", "fragment", "upstream", "of", "the", "human", "TMP21", "gene.", "The", "transcription", "start", "site", "(TSS)", "of", "the", "human", "TMP21", "gene", "was", "identified.", "A", "series", "of", "nested", "deletions", "of", "the", "5’", "flanking", "region", "of", "the", "human", "TMP21", "gene", "were", "subcloned", "into", "the", "pGL3-basic", "luciferase", "reporter", "plasmid.", "We", "identified", "the", "-120", "to", "+2", "region", "as", "containing", "the", "minimal", "sequence", "necessary", "for", "TMP21", "gene", "promoter", "activity.", "Gel", "shift", "assays", "revealed", "that", "the", "human", "TMP21", "gene", "promoter", "contains", "NFAT", "response", "elements.", "Expression", "of", "NFAT", "increased", "TMP21", "gene", "expression", "and", "inhibition", "of", "NFAT", "by", "siRNA", "reduced", "TMP21", "gene", "expression.", "Conclusion:", "NFAT", "plays", "a", "very", "important", "role", "in", "the", "regulation", "of", "human", "TMP21", "gene", "expression.", "This", "study", "demonstrates", "that", "the", "human", "TMP21", "gene", "expression", "is", "transcriptionally", "regulated", "by", "NFAT", "signaling.", "Background", "Alzheimer’s", "disease", "is", "the", "most", "common", "neurodegen-", "erative", "disorder", "leading", "to", "dementia.", "Deposition", "of", "amy-", "loid", "b", "protein", "(Ab)", "in", "the", "brain", "is", "one", "of", "the", "hallmarks", "of", "AD", "pathogenesis.", "Ab", "is", "generated", "from", "a", "larger", "b-", "amyloid", "precursor", "protein", "(APP)", "by", "sequential", "cleavages", "of", "b-secretase", "and", "g-secretase", "[1-4].", "Beta-site", "APP", "cleav-", "ing", "enzyme", "1", "(BACE1)", "is", "the", "b-secretase", "in", "vivo", "[5,6],", "and", "g-secretase", "activity", "is", "catalyzed", "by", "a", "presenilin", "(PS)-", "containing", "macromolecular", "complex", "[7].", "This", "high", "molecular", "weight", "complex", "also", "requires", "nicastrin", "(Nct)", "[8],", "anterior", "pharynx-defective", "1", "(Aph-1)", "[9-11],", "and", "presenilin", "enhancer", "2", "(Pen-2)", "[9,10]", "for", "its", "enzymatic", "activity", "[7,11-13].", "CD147", "was", "also", "found", "to", "closely", "associate", "with", "the", "g-secretase", "complex", "[14].", "Despite", "robust", "expression", "of", "the", "APP", "gene", "resulting", "in", "a", "high", "*", "Correspondence:", "liushengchun1968@163.com;", "weihong@exchange.ubc.ca", "†", "Contributed", "equally", "1Department", "of", "Surgery,", "The", "First", "Affiliated", "Hospital,", "Chongqing", "University", "of", "Medical", "Sciences,", "Chongqing", "410006,", "China", "2Townsend", "Family", "Laboratories,", "Department", "of", "Psychiatry,", "Brain", "Research", "Center,", "Graduate", "Program", "in", "Neuroscience,", "The", "University", "of", "British", "Columbia,", "2255", "Wesbrook", "Mall,", "Vancouver,", "BC", "V6T", "1Z3,", "Canada", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "level", "of", "APP", "protein", "in", "vivo,", "Ab", "production", "through", "the", "amyloidogenic", "pathway", "of", "APP", "processing", "is", "a", "rare", "occurrence", "under", "normal", "conditions", "[15,16].", "Missense", "mutations", "in", "PS1", "and", "PS2", "are", "a", "major", "cause", "of", "early-onset", "familial", "AD", "(FAD).", "PS", "mutant", "forms", "have", "been", "shown", "to", "increase", "g-secretase", "activity,", "resulting", "in", "elevated", "Ab42", "production", "[17-19].", "In", "addition", "to", "its", "pathogenic", "g-secretase", "activity,", "the", "PS", "complex", "can", "cleave", "Notch", "[20,21]", "at", "a", "separate", "ε-cleavage", "site", "which", "may", "be", "involved", "in", "learning", "and", "memory.", "Intramembra-", "nous", "cleavage", "of", "Notch", "to", "release", "the", "Notch", "intracellu-", "lar", "domain", "(NICD)", "is", "inhibited", "in", "PS1-deficient", "cells", "[8,20,22-24].", "In", "addition", "to", "APP", "and", "Notch,", "the", "sub-", "strates", "for", "g-secretase", "include", "Jagged,", "Delta,", "E-cadherin,", "ErbB-4,", "Nectin-1a,", "CD44", "and", "LRP.", "The", "ε-", "and", "g-secre-", "tase", "activities", "of", "the", "presenilin", "complex", "seem", "to", "be", "inde-", "pendently", "regulated,", "as", "certain", "g-secretase", "inhibitors", "can", "affect", "APP", "cleavage", "without", "affecting", "Notch", "cleavage,", "and", "presenilin", "mutations", "can", "increase", "Ab-42", "production", "while", "decreasing", "Notch", "cleavage", "[25,26].", "Human", "TMP21,", "a", "member", "of", "the", "p24", "protein", "family,", "is", "a", "type", "I", "transmembrane", "protein", "with", "a", "large", "luminal", "domain", "[27].", "It", "is", "ubiquitously", "transcribed", "with", "higher", "©", "2011", "Liu", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "International", "Journal", "for", "Equity", "in", "Health", "Research", "Area", "deprivation", "and", "its", "association", "with", "health", "in", "a", "cross-sectional", "study:", "are", "the", "results", "biased", "by", "recent", "migration?", "Fredrik", "Niclas", "Piro*,", "Øyvind", "Næss", "and", "Bjørgulf", "Claussen", "BioMed", "Central", "Open", "Access", "Address:", "Institute", "of", "General", "Practice", "and", "Community", "Medicine,", "University", "of", "Oslo,", "Norway", "Email:", "Fredrik", "Niclas", "Piro*", "-", "fnp@econ.no;", "Øyvind", "Næss", "-", "oyvind.nass@medisin.uio.no;", "Bjørgulf", "Claussen", "-", "bjorgulf.claussen@medisin.uio.no", "*", "Corresponding", "author", "Published:", "20", "September", "2007", "International", "Journal", "for", "Equity", "in", "Health", "2007,", "6:10", "doi:10.1186/1475-9276-6-10", "This", "article", "is", "available", "from:", "http://www.equityhealthj.com/content/6/1/10", "Received:", "12", "October", "2006", "Accepted:", "20", "September", "2007", "©", "2007", "Piro", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "association", "between", "area", "deprivation", "and", "health", "has", "mostly", "been", "examined", "in", "cross-sectional", "studies", "or", "prospective", "studies", "with", "short", "follow-up.", "These", "studies", "have", "rarely", "taken", "migration", "into", "account.", "This", "is", "a", "possible", "source", "of", "misclassification", "of", "exposure,", "i.e.", "an", "unknown", "number", "of", "study", "participants", "are", "attributed", "an", "exposure", "of", "area", "deprivation", "that", "they", "may", "have", "experienced", "too", "short", "for", "it", "to", "have", "any", "influence.", "The", "aim", "of", "this", "article", "was", "to", "examine", "to", "what", "extent", "associations", "between", "area", "deprivation", "and", "health", "outcomes", "were", "biased", "by", "recent", "migration.", "Methods:", "Based", "on", "data", "from", "the", "Oslo", "Health", "Study,", "a", "cross-sectional", "study", "conducted", "in", "2000", "in", "Oslo,", "Norway,", "we", "used", "six", "health", "outcomes", "(self", "rated", "health,", "mental", "health,", "coronary", "heart", "disease,", "chronic", "obstructive", "pulmonary", "disease,", "smoking", "and", "exercise)", "and", "considered", "migration", "nine", "years", "prior", "to", "the", "study", "conduct.", "Migration", "into", "Oslo,", "between", "the", "areas", "of", "Oslo,", "and", "the", "changes", "in", "area", "deprivation", "during", "the", "period", "were", "taken", "into", "account.", "Associations", "were", "investigated", "by", "multilevel", "logistic", "regression", "analyses.", "Results:", "After", "adjustment", "for", "individual", "socio-demographic", "variables", "we", "found", "significant", "associations", "between", "area", "deprivation", "and", "all", "health", "outcomes.", "Accounting", "for", "migration", "into", "Oslo", "and", "between", "areas", "of", "Oslo", "did", "not", "change", "these", "associations", "much.", "However,", "the", "people", "who", "migrated", "into", "Oslo", "were", "younger", "and", "had", "lower", "prevalences", "of", "unfavourable", "health", "outcomes", "than", "those", "who", "were", "already", "living", "in", "Oslo.", "But", "since", "they", "were", "evenly", "distributed", "across", "the", "area", "deprivation", "quintiles,", "they", "had", "little", "influence", "on", "the", "associations", "between", "area", "deprivation", "and", "health.", "Evidence", "of", "selective", "migration", "within", "Oslo", "was", "weak,", "as", "both", "moving", "up", "and", "down", "in", "the", "deprivation", "hierarchy", "was", "associated", "with", "significantly", "worse", "health", "than", "not", "moving.", "Conclusion:", "We", "have", "documented", "significant", "associations", "between", "area", "deprivation", "and", "health", "outcomes", "in", "Oslo", "after", "adjustment", "for", "socio-demographic", "variables", "in", "a", "cross-sectional", "study.", "These", "associations", "were", "weakly", "biased", "by", "recent", "migration.", "From", "our", "results", "it", "still", "appears", "that", "migration", "prior", "to", "study", "conduct", "may", "be", "relevant", "to", "investigate", "even", "within", "a", "relatively", "short", "period", "of", "time,", "whereas", "changes", "in", "area", "deprivation", "during", "such", "a", "period", "is", "of", "limited", "interest.", "Page", "1", "of", "15", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "The", "Scientific", "World", "Journal", "Volume", "2012,", "Article", "ID", "615057,", "6", "pages", "doi:10.1100/2012/615057", "Clinical", "Study", "The", "cientificWorldJOURNAL", "Ultrasonographic", "Prevalence", "and", "Factors", "Predicting", "Left", "Ventricular", "Diastolic", "Dysfunction", "in", "Patients", "with", "Liver", "Cirrhosis:", "Is", "There", "a", "Correlation", "between", "the", "Grade", "of", "Diastolic", "Dysfunction", "and", "the", "Grade", "of", "Liver", "Disease?", "Vasilios", "Papastergiou,1", "Lamprini", "Skorda,2", "Phillipos", "Lisgos,1", "Nikolaos", "Papakonstantinou,3", "Tsampikos", "Giakoumakis,3", "Konstantinos", "Ntousikos,3", "and", "Stylianos", "Karatapanis1", "1", "Liver", "Clinic,", "First", "Department", "of", "Internal", "Medicine,", "General", "Hospital", "of", "Rhodes,", "85100", "Rhodes,", "Greece", "2", "Department", "of", "Internal", "Medicine,", "“Konstantopoulio”", "General", "Hospital,", "14233", "Athens,", "Greece", "3", "Cardiology", "Department,", "General", "Hospital", "of", "Rhodes,", "85100", "Rhodes,", "Greece", "Correspondence", "should", "be", "addressed", "to", "Stylianos", "Karatapanis,", "stylkar@otenet.gr", "Received", "12", "October", "2011;", "Accepted", "20", "November", "2011", "Academic", "Editors:", "R.", "Moreno", "Gomez", "and", "P.", "Muiesan", "Copyright", "©", "2012", "Vasilios", "Papastergiou", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Presence", "of", "cardiac", "dysfunction", "has", "been", "associated", "with", "an", "unfavorable", "prognosis", "in", "patients", "with", "liver", "cirrhosis.", "In", "the", "present", "study,", "92", "consecutive,", "newly-diagnosed", "patients", "with", "liver", "cirrhosis", "were", "prospectively", "evaluated.", "Liver", "disease", "was", "graded", "according", "to", "the", "modified", "Child-Turcotte-Pugh", "(CTP)", "score", "whereas", "left", "ventricular", "diastolic", "function", "was", "assessed", "by", "Doppler-", "echocardiography", "and", "graded", "(Stage", "0", "to", "4)", "according", "to", "current", "guidelines.", "Overall,", "DD", "was", "diagnosed", "in", "55/92", "(59.8%)", "patients", "[DD-stage-1:", "36/92", "(39.1%),", "DD-stage-2:", "19/92", "(20.6%)].", "Prevalence", "of", "DD-stage-1", "among", "the", "different", "stages", "of", "liver", "cirrhosis", "was:", "CTP-class", "A:", "11/29", "(37.9%),", "B:", "15/39", "(38.5%),", "C:", "10/24", "(41.6%),", "(P", ">", "0.05", "in", "all", "comparisons),", "whereas", "for", "DD-stage-2", "the", "corresponding", "proportions", "were", "CTP-class", "A:", "3/29", "(10.3%),", "B:", "5/39", "(12.8%),", "C:", "11/24", "(45.8%),", "(P", "=", "0.0009", "between", "CTP-class", "C", "versus", "A", "and", "B).", "Age", ">", "53", "years", "(Odd’s", "Ratio", "[OR]:", "4.2;", "95%", "confidence", "interval", "[CI]:", "1.5–12.1)", "and", "CTP-class", "C", "(OR:", "4.6;", "95%", "CI:", "1.1–20)", "could", "independently", "predict", "DD.", "No", "relation", "between", "presence", "of", "DD", "and", "the", "etiology", "of", "the", "liver", "disease", "was", "found.", "We", "conclude", "that", "DD", "is", "a", "common", "feature", "in", "liver", "cirrhosis.", "DD-stage-1", "is", "fairly", "prevalent", "among", "all", "CTP-classes", "whereas", "DD-stage-2", "seems", "to", "be", "characteristic", "of", "the", "advanced", "liver", "disease", "(CTP-class", "C).", "A", "high", "level", "of", "awareness", "for", "the", "presence", "of", "the", "syndrome", "is", "required,", "especially", "if", "cirrhotic", "patients", "are", "CTP-class", "C", "and/or", "of", "older", "age.", "1.", "Introduction", "Hemodynamic", "alterations", "characterized", "by", "increased", "cardiac", "output", "and", "decreased", "systemic", "vascular", "resistances", "are", "well", "known", "to", "be", "extremely", "common", "among", "patients", "with", "liver", "cirrhosis", "[1,", "2].", "During", "the", "past", "2", "decades,", "various", "obser-", "vations", "have", "indicated", "the", "presence", "of", "a", "latent", "cardiac", "dys-", "function", "which", "includes", "a", "combination", "of", "blunted", "myocar-", "dial", "contractility,", "altered", "diastolic", "relaxation,", "and", "electro-", "physiological", "abnormalities,", "all", "occurring", "in", "the", "absence", "of", "a", "concomitant", "heart", "disease", "[3–5].", "This", "clinical", "entity,", "called", "“cirrhotic", "cardiomyopathy,”", "has", "been", "repeatedly", "shown", "to", "have", "a", "negative", "prognostic", "impact,", "especially", "on", "the", "outcome", "of", "invasive", "procedures", "such", "as", "surgery,", "transjugular", "intrahe-", "patic", "portosystemic", "shunt", "insertion", "(TIPS),", "and", "liver", "trans-", "plantation", "[6–9].", "Diastolic", "dysfunction", "(DD),", "caused", "by", "de-", "creased", "left", "ventricular", "compliance", "and", "relaxation,", "is", "believed", "by", "some", "authors", "to", "be", "present", "virtually", "in", "every", "patient", "with", "cirrhotic", "cardiomyopathy", "[10–13].", "Doppler", "echocardiogra-", "phy", "directed", "to", "detect", "simple", "echocardiographic", "indices,", "such", "as", "a", "reduced", "early/late", "filling", "velocity", "ratio", "(E/A", "ratio", "≤1),", "has", "been", "proposed", "as", "an", "available", "screening", "test", "for", "the", "diagnosis", "of", "the", "syndrome.", "However,", "according", "to", "current", "recommen-", "dations,", "DD", "can", "be", "echocardiographically", "graded", "in", "four", "stages", "[14],", "and", "to", "date", "the", "prevalence", "of", "the", "different", "stages", "of", "DD", "among", "patients", "with", "cirrhosis", "remains", "unknown." ]

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[ "Salsolinol", "Facilitates", "Glutamatergic", "Transmission", "to", "Dopamine", "Neurons", "in", "the", "Posterior", "Ventral", "Tegmental", "Area", "of", "Rats", "Guiqin", "Xie,", "Jiang-Hong", "Ye*", "Department", "of", "Anesthesiology,", "Pharmacology", "and", "Physiology,", "University", "of", "Medicine", "and", "Dentistry", "of", "New", "Jersey,", "New", "Jersey", "Medical", "School,", "Newark,", "New", "Jersey,", "United", "States", "of", "America", "Abstract", "Although", "in", "vivo", "evidence", "indicates", "that", "salsolinol,", "the", "condensation", "product", "of", "acetaldehyde", "and", "dopamine,", "has", "properties", "that", "may", "contribute", "to", "alcohol", "abuse,", "the", "underlying", "mechanisms", "have", "not", "been", "fully", "elucidated.", "We", "have", "reported", "previously", "that", "salsolinol", "stimulates", "dopamine", "neurons", "in", "the", "posterior", "ventral", "tegmental", "area", "(p-VTA)", "partly", "by", "reducing", "inhibitory", "GABAergic", "transmission,", "and", "that", "ethanol", "increases", "glutamatergic", "transmission", "to", "VTA-dopamine", "neurons", "via", "the", "activation", "of", "dopamine", "D1", "receptors", "(D1Rs).", "In", "this", "study,", "we", "tested", "the", "hypothesis", "that", "salsolinol", "stimulates", "dopamine", "neurons", "involving", "activation", "of", "D1Rs.", "By", "using", "whole-cell", "recordings", "on", "p-VTA-dopamine", "neurons", "in", "acute", "brain", "slices", "of", "rats,", "we", "found", "that", "salsolinol-induced", "increase", "in", "spike", "frequency", "of", "dopamine", "neurons", "was", "substantially", "attenuated", "by", "DL-2-amino-5-", "phosphono-valeric", "acid", "and", "6,", "7-dinitroquinoxaline-2,", "3-dione,", "the", "antagonists", "of", "glutamatergic", "N-Methyl-D-aspartic", "acid", "and", "a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic", "acid", "receptors.", "Moreover,", "salsolinol", "increased", "the", "amplitude", "of", "evoked", "excitatory", "postsynaptic", "currents", "(EPSCs)", "and", "the", "frequency", "but", "not", "the", "amplitude", "of", "spontaneous", "EPSCs.", "Additionally,", "SKF83566,", "a", "D1R", "antagonist", "attenuated", "the", "salsolinol-induced", "facilitation", "of", "EPSCs", "and", "of", "spontaneous", "firing", "of", "dopamine", "neurons.", "Our", "data", "reveal", "that", "salsolinol", "enhances", "glutamatergic", "transmission", "onto", "dopamine", "neurons", "via", "activation", "of", "D1Rs", "at", "the", "glutamatergic", "afferents", "in", "dopamine", "neurons,", "which", "contributes", "to", "salsolinol’s", "stimulating", "effect", "on", "p-VTA", "dopamine", "neurons.", "This", "appears", "to", "be", "a", "novel", "mechanism", "which", "contributes", "toward", "rewarding", "properties", "of", "salsolinol.", "Citation:", "Xie", "G,", "Ye", "J-H", "(2012)", "Salsolinol", "Facilitates", "Glutamatergic", "Transmission", "to", "Dopamine", "Neurons", "in", "the", "Posterior", "Ventral", "Tegmental", "Area", "of", "Rats.", "PLoS", "ONE", "7(5):", "e36716.", "doi:10.1371/journal.pone.0036716", "Editor:", "Kuei-Sen", "Hsu,", "National", "Cheng", "Kung", "University,", "Taiwan", "Received", "February", "8,", "2012;", "Accepted", "April", "12,", "2012;", "Published", "May", "10,", "2012", "Copyright:", "2012", "Xie,", "Ye.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "is", "made", "possible", "by", "the", "support", "from", "National", "Institutes", "of", "Health", "–", "National", "Institute", "on", "Alcohol", "Abuse", "and", "Alcoholism", "[grants", "AA016964", "and", "AA016618]", "to", "JHY.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "ye@umdnj.edu", "Introduction", "The", "racemic", "mixture", "of", "salsolinol", "((R)", "+", "(s)-salsolinol)", "is", "formed", "by", "nonenzymatic", "Pictet-Spengler", "condensation", "of", "dopamine", "with", "acetaldehyde,", "the", "major", "metabolite", "of", "ethanol", "in", "the", "brains", "of", "mammals", "[1,2].", "Salsolinol", "has", "been", "proposed", "to", "play", "a", "role", "in", "the", "etiology", "of", "alcoholism", "[3],", "and", "to", "the", "rewarding", "properties", "of", "ethanol", "[4].", "Early", "animal", "studies", "revealed", "that", "salsolinol", "promotes", "alcohol", "drinking", "[5,6].", "More", "recent", "studies", "showed", "that", "rats", "self-administer", "salsolinol", "into", "posterior", "VTA", "(p-VTA),", "a", "key", "region", "in", "the", "brain", "reward", "system", "[7,8],", "and", "that", "microinjection", "of", "salsolinol", "into", "the", "p-VTA", "of", "rats", "induces", "conditioned", "place", "preference", "[9].", "Furthermore,", "such", "behaviors", "seem", "to", "depend", "on", "activation", "of", "dopaminergic", "(DA)", "neurons", "[8]", "and", "associated", "with", "enhanced", "dopamine", "levels", "in", "the", "ipsilateral", "nucleus", "accumbens", "shell", "[9].", "With", "patch", "clamp", "techniques,", "we", "recently", "showed", "that", "salsolinol", "(0.01–1", "mM)", "dose-dependently", "stimulates", "DA", "neurons", "in", "the", "p-VTA", "in", "acute", "midbrain", "slices", "of", "rats.", "Salsolinol", "decreased", "GABAergic", "synaptic", "transmission", "onto", "p-VTA", "DA", "neurons,", "and", "gabazine,", "an", "antagonist", "of", "GABAA", "receptors", "substantially", "attenuated", "salsolinol-induced", "increase", "in", "firing", "rate", "of", "DA", "neurons.", "This", "phenomenon", "suggests", "that", "salsolinol", "stimulates", "DA", "neurons", "through", "a", "mechanism", "of", "disinhibition", "[10].", "Interestingly,", "gabazine", "(10", "mM)", "failed", "to", "completely", "abolish", "salsolinol-induced", "increase", "in", "DA", "neuron", "firing,", "indicating", "that", "other", "mechanisms", "may", "also", "be", "involved.", "In", "addition", "to", "potent", "inhibitory", "GABAergic", "afferents", "[11],", "VTA", "DA", "neurons", "receive", "glutamatergic", "(Gluergic)", "inputs", "from", "diverse", "brain", "nuclei", "[12,13]", "and", "from", "the", "Gluergic", "neurons", "in", "the", "VTA", "[14].", "These", "diverse", "sources", "of", "Gluergic", "afferents", "may", "enable", "DA", "neurons", "to", "respond", "to", "a", "wide", "range", "of", "environmental", "stimuli.", "Such", "excitatory", "Gluergic", "synaptic", "input", "is", "a", "key", "component", "in", "the", "regulation", "of", "DA", "cell", "excitability", "[15,16]", "and", "is", "known", "to", "play", "an", "important", "role", "in", "the", "actions", "of", "many", "drugs", "of", "abuse", "[17,18]", "including", "ethanol", "[19].", "Previous", "in", "vivo", "evidence", "indicates", "that", "activation", "of", "dopamine", "D1", "receptors", "(D1Rs)", "can", "increase", "the", "release", "of", "glutamate", "in", "the", "VTA", "[20].", "In", "recent", "in", "vitro", "studies,", "we", "have", "demonstrated", "that", "acute", "ethanol", "facilitates", "Gluergic", "transmission", "to", "VTA", "DA", "neurons", "via", "the", "activation", "of", "D1Rs", "at", "Gluergic", "afferents", "[21,22].", "This", "study", "was", "set", "to", "test", "the", "hypothesis", "that", "salsolinol", "stimulates", "DA", "neurons", "involving", "activation", "of", "D1Rs", "at", "Gluergic", "afferents.", "Methods", "Experimental", "procedures", "All", "experiments", "were", "performed", "in", "accordance", "with", "the", "guidelines", "of", "the", "National", "Institutes", "of", "Health", "Guide", "for", "the", "Care", "PLoS", "ONE", "|", "www.plosone.org", "1", "May", "2012", "|", "Volume", "7", "|", "Issue", "5", "|", "e36716" ]

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[ "CLINICS", "2010;65(10):971-974", "CLINICAL", "SCIENCE", "DOI:10.1590/S1807-59322010001000008", "Markers", "of", "autoimmune", "liver", "diseases", "in", "postmenopausal", "women", "with", "osteoporosis", "Umit", "Secil", "Demirdal,I", "Ihsan", "Hakkı", "Ciftci,II", "Vural", "KavuncuI", "I", "Department", "of", "Physical", "Medicine", "and", "Rehabilitation,", "School", "of", "Medicine,", "Afyon", "Kocatepe", "University,", "Afyonkarahisar,", "Turkey.", "II", "Department", "of", "Microbiology,", "School", "of", "Medicine,", "Afyon", "Kocatepe", "University,", "Afyonkarahisar,", "Turkey.", "INTRODUCTION:", "Osteoporosis", "is", "a", "common", "complication", "of", "chronic", "liver", "diseases.", "However,", "there", "is", "limited", "information", "about", "autoimmune", "liver", "diseases", "as", "a", "factor", "of", "secondary", "osteoporosis.", "Therefore,", "we", "aimed", "to", "investigate", "the", "autoantibodies", "of", "autoimmune", "liver", "diseases", "in", "patients", "with", "osteoporosis.", "METHODS:", "One", "hundred", "fifty", "female", "patients", "with", "postmenopausal", "osteoporosis", "were", "included.", "Bone", "mineral", "density", "was", "measured", "by", "dual", "energy", "X-ray", "absorptiometry.", "We", "analysized", "autoantibodies", "including", "antinuclear", "antibodies,", "liver", "membrane", "antibodies,", "anti-liver/kidney", "microsomal", "autoantibodies1,", "liver-specific", "protein,", "anti-", "smooth", "muscle", "antibodies,", "and", "anti-mitochondrial", "antibodies", "by", "indirect", "immunofluorescence.", "Serum", "was", "assayed", "for", "the", "levels", "of", "aminotransferases.", "RESULTS:", "The", "mean", "age", "of", "the", "patients", "was", "63,13¡8,6", "years.", "The", "mean", "values", "of", "L1-L4", "T-scores", "and", "femur", "total", "T-scores", "were", "-3,08¡0,58", "and", "-1,53¡0,81,", "respectively.", "Among", "the", "150", "patients", "with", "osteoporosis,", "14", "(9.3%)", "were", "antinuclear", "antibodies,", "four", "(2.7%)", "were", "liver", "membrane", "antibodies,", "three", "(2.0%)", "were", "anti-liver/kidney", "microsomal", "autoantibodies1,", "and", "two", "(1.3%)", "were", "liver-specific", "protein", "positive.", "None", "of", "the", "patients", "had", "anti-mitochondrial", "antibodies", "or", "smooth", "muscle", "antibodies", "positivity.", "The", "mean", "values", "of", "levels", "of", "aminotransferases", "were", "within", "normal", "range.", "CONCLUSIONS:", "The", "presence", "of", "liver", "membrane", "antibodies,", "liver-specific", "protein,", "and", "anti-liver/kidney", "microsomal", "autoantibodies1", "has", "permitted", "us", "to", "see", "that", "there", "may", "be", "some", "suspicious", "clues", "of", "autoimmune", "liver", "diseases", "in", "patients", "with", "osteoporosis", "as", "a", "secondary", "risk", "factor.", "On", "the", "other", "hand,", "there", "is", "a", "need", "for", "comprehensive", "studies", "with", "a", "larger", "sample", "size", "and", "studies", "designed", "to", "compare", "the", "results", "with", "a", "normal", "population", "to", "understand", "the", "clinical", "importance", "of", "our", "findings.", "KEYWORDS:", "Osteoporosis;", "Autoimmune;", "Liver", "disease;", "liver", "autoantibodies;", "Aminotransferases.", "Demirdal", "US,", "Ciftci", "IH,", "Kavuncu", "V.", "Markers", "of", "autoimmune", "liver", "diseases", "in", "postmenopausal", "women", "with", "osteoporosis.", "Clinics.", "2010;65(10):971-974.", "Received", "for", "publication", "on", "May", "2,", "2010;", "First", "review", "completed", "on", "May", "25,", "2010;", "Accepted", "for", "publication", "on", "July", "13,", "2010", "E-mail:", "secilbabaoglu@yahoo.com", "Tel.:", "+90", "272", "246", "33", "33-3012", "INTRODUCTION", "Osteoporosis", "(OP)", "is", "usually", "defined", "as", "a", "skeletal", "disease", "characterized", "by", "low", "bone", "mass", "and", "microarchitectural", "deterioration", "of", "bone", "tissue,", "leading", "to", "enhanced", "bone", "fragility", "and", "increase", "in", "fracture", "risk.1", "It", "affects", "up", "to", "one", "in", "two", "women", "and", "one", "in", "five", "men", "over", "the", "age", "of", "50.2", "It", "is", "a", "worldwide", "disease", "seen", "in", "all", "racial", "groups", "and", "in", "both", "males", "and", "females.3", "In", "addition", "to", "being", "a", "common", "disease,", "OP", "becomes", "a", "serious", "health", "issue", "due", "to", "the", "increase", "in", "morbidity,", "mortality,", "and", "financial", "burden", "related", "with", "osteoporotic", "fractures.4-6", "Osteoporosis", "can", "be", "classified", "as", "primary", "and", "secondary", "OP", "according", "to", "the", "underlying", "causes.", "Secondary", "OP", "may", "be", "described", "as", "the", "low", "mineral", "density", "in", "which", "an", "Copyright", "2010", "CLINICS", "–", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "underlying", "cause", "or", "factor", "can", "be", "defined", "other", "than", "those", "attributable", "to", "the", "postmenopausal", "state", "or", "aging.7", "Primary", "OP", "refers", "to", "OP", "when", "a", "secondary", "cause", "cannot", "be", "found.8", "There", "are", "a", "number", "of", "secondary", "causes", "of", "osteoporosis", "such", "as", "hypogonadism", "or", "hyperparathyroidism,", "which", "are", "treatable,", "and", "renal", "failure,", "which", "should", "be", "considered", "more", "seriously.", "Chronic", "liver", "diseases", "also", "play", "an", "important", "role", "among", "secondary", "factors", "of", "OP.9,10", "Bone", "disease", "is", "a", "major", "complication", "of", "chronic", "liver", "disease.", "OP", "is", "more", "commonly", "seen", "in", "patients", "with", "liver", "diseases", "as", "compared", "to", "the", "normal", "population,", "showing", "variable", "prevalence", "according", "to", "the", "patient", "selection", "and", "diagnostic", "criteria.11,12", "OP", "is", "a", "common", "complication", "of", "chronic", "liver", "diseases", "such", "as", "cholestatic", "disorders,", "alcoholic", "liver", "diseases,", "posthepatitic", "cirrhosis,", "and", "autoimmune", "liver", "diseases", "(ALD).13", "Types", "of", "ALD", "are", "autoimmune", "hepatitis", "(AH),", "primary", "biliary", "cirrhosis", "(PBC),", "and", "sclerosing", "cholangitis.", "ALD", "affects", "women", "at", "any", "age", "with", "a", "wide", "range", "of", "clinical", "presentations.", "In", "some", "cases,", "the", "disease", "is", "incidentally", "diagnosed", "during", "routine", "laboratory", "tests,", "while", "it", "shows", "a", "fulminate", "course", "in", "some", "others.14", "971" ]

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[ "Morrissey", "et", "al.", "BMC", "Developmental", "Biology", "2011,", "11:3", "http://www.biomedcentral.com/1471-213X/11/3", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "PRE-1,", "a", "cis", "element", "sufficient", "to", "enhance", "cone-", "and", "rod-", "specific", "expression", "in", "differentiating", "zebrafish", "photoreceptors", "Maria", "E", "Morrissey1,", "Sara", "Shelton2,", "Susan", "E", "Brockerhoff2,", "James", "B", "Hurley2,", "Breandán", "N", "Kennedy1*", "Abstract", "Background:", "Appropriate", "transcriptional", "regulation", "is", "required", "for", "cone", "photoreceptor", "development", "and", "integrity.", "To", "date,", "only", "a", "few", "cis-regulatory", "elements", "that", "control", "cone", "photoreceptor-specific", "expression", "have", "been", "characterised.", "The", "alpha-subunit", "of", "cone", "transducin", "(TaC)", "is", "specifically", "expressed", "in", "cone", "photoreceptors", "and", "is", "required", "for", "colour", "vision.", "In", "order", "to", "better", "understand", "the", "molecular", "genetics", "controlling", "the", "initiation", "of", "cone", "photoreceptor-specific", "expression", "in", "vivo,", "we", "have", "utilised", "zebrafish", "to", "identify", "cis-regulatory", "elements", "in", "the", "upstream", "promoter", "region", "of", "the", "TaC", "gene.", "Results:", "A", "0.5", "kb", "TaC", "promoter", "fragment", "is", "sufficient", "to", "direct", "cone-specific", "expression", "in", "transgenic", "larvae.", "Within", "this", "minimal", "promoter,", "we", "identify", "photoreceptor", "regulatory", "element-1", "(PRE-1),", "a", "unique", "41", "bp", "sequence.", "PRE-1", "specifically", "binds", "nuclear", "factors", "expressed", "in", "ocular", "tissue.", "PRE-1", "is", "not", "required", "for", "cone-specific", "expression", "directed", "from", "a", "2.5", "kb", "TaC", "promoter.", "However,", "PRE-1-like", "sequences,", "with", "potential", "functional", "redundancy,", "are", "located", "in", "this", "2.5", "kb", "promoter.", "PRE-1-rho", "which", "has", "the", "highest", "sequence", "and", "structural", "homology", "to", "PRE-1", "is", "located", "in", "the", "rhodopsin", "promoter.", "Surprisingly,", "PRE-1", "and", "PRE-1-rho", "are", "functionally", "distinct.", "We", "demonstrate", "that", "PRE-1,", "but", "not", "PRE-1-rho,", "is", "sufficient", "to", "enhance", "expression", "from", "a", "heterologous", "UV", "cone", "promoter.", "PRE-1", "is", "also", "sufficient", "to", "enhance", "expression", "from", "a", "heterologous", "rhodopsin", "promoter", "without", "altering", "its", "rod", "photoreceptor", "specificity.", "Finally,", "mutations", "in", "consensus", "E-box", "and", "Otx", "sites", "prevent", "PRE-1", "from", "forming", "complexes", "with", "eye", "nuclear", "protein", "and", "enhancing", "photoreceptor", "expression.", "Conclusions:", "PRE-1", "is", "a", "novel", "cis-regulatory", "module", "that", "is", "sufficient", "to", "enhance", "the", "initiation", "of", "photoreceptor-", "specific", "gene", "expression", "in", "differentiating", "rod", "and", "cone", "photoreceptors.", "Background", "Photoreceptors", "are", "specialised", "sensory", "neurons", "that", "enable", "images", "of", "the", "external", "environment", "to", "be", "cap-", "tured.", "Structurally,", "cone", "and", "rod", "photoreceptors", "appear", "grossly", "similar.", "Both", "have", "outer", "segments", "rich", "in", "photo-", "sensitive", "membranes,", "inner", "segments", "rich", "in", "transport", "and", "metabolic", "machinery,", "and", "synaptic", "termini", "that", "che-", "mically", "transmit", "light", "signals", "to", "downstream", "neurons", "[1].", "However,", "cone", "and", "rod", "photoreceptors", "function", "dis-", "tinctly.", "Rods", "are", "specialised", "to", "function", "in", "low-light,", "whereas", "cones", "enable", "colour", "vision", "and", "visual", "acuity", "[2].", "These", "functional", "differences", "are", "partly", "explained", "by", "the", "*", "Correspondence:", "brendan.kennedy@ucd.ie", "1UCD", "School", "of", "Biomolecular", "and", "Biomedical", "Sciences,", "UCD", "Conway", "Institute,", "University", "College", "Dublin,", "Dublin,", "Ireland", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "distinct", "morphological", "specialisations", "of", "outer", "segments", "and", "synaptic", "termini", "present", "in", "rods", "or", "cones", "[1].", "In", "addition,", "unique", "transcripts", "encode", "rod-", "or", "cone-specific", "components", "of", "the", "G-protein", "coupled", "receptor", "photo-", "transduction", "pathway.", "This", "includes", "the", "a-subunit", "of", "the", "heterotrimeric", "G-protein", "transducin", "(Ta)", "encoded", "by", "gnat1", "in", "rods", "and", "by", "gnat2", "in", "cones.", "Underlining", "these", "molecular", "differences,", "these", "photoreceptor-specific", "isoforms", "associate", "with", "distinct", "forms", "of", "blindness.", "Mutations", "in", "the", "gene", "encoding", "rod", "transducin", "alpha", "(TaR)", "cause", "inherited", "night", "blindness", "whereas", "muta-", "tions", "in", "the", "gene", "encoding", "cone", "transducin", "alpha", "(TaC)", "cause", "achromatopsia,", "or", "total", "colour", "blindness", "[3,4].", "During", "retinal", "neurogenesis,", "rod", "and", "cone", "photorecep-", "tors", "differentiate", "from", "a", "population", "of", "retinal", "progenitor", "cells", "[5].", "In", "2", "day", "post-fertilisation", "(dpf)", "zebrafish,", "©", "2011", "Morrissey", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Original", "article", "http://dx.doi.org/10.3345/kjp.2012.55.3.100", "Korean", "J", "Pediatr", "2012;55(3):100-106", "Outcome", "of", "allogeneic", "hematopoietic", "stem", "cell", "transplantation", "for", "childhood", "acute", "lymphoblastic", "leukemia", "in", "second", "complete", "remission:", "a", "single", "institution", "study", "Copyright", "©", "2012", "by", "The", "Korean", "Pediatric", "Society", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-", "nc/3.0/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Key", "words:", "Acute", "lymphoblastic", "leukemia,", "Child,", "Second", "complete", "remission,", "Transplantation", "Eun-Jung", "Lee,", "MD,", "Ji", "Yoon", "Han,", "MD,", "Jae", "Wook", "Lee,", "MD,", "Pil-Sang", "Jang,", "MD,", "PhD,", "Nack-Gyun", "Chung,", "MD,", "PhD,", "Dae-Chul", "Jeong,", "MD,", "PhD,", "Bin", "Cho,", "MD,", "PhD,", "Hack-Ki", "Kim,", "MD,", "PhD", "Department", "of", "Pediatrics,", "The", "Catholic", "University", "of", "Korea,", "School", "of", "Medicine,", "Seoul,", "Korea", "Received:", "15", "September", "2011,", "Revised:", "31", "October", "2011", "Accepted:", "14", "November", "2011", "Corresponding", "author:", "Bin", "Cho,", "MD,", "PhD", "Department", "of", "Pediatrics,", "Seoul", "St.", "Mary’s", "Hospital,", "The", "Catholic", "University", "of", "Korea", "School", "of", "Medicine,", "222", "Ban-", "po-daero,", "Seocho-gu,", "Seoul", "137-701,", "Korea", "Tel:", "+82-2-2258-6187,", "Fax:", "+82-2-588-3589", "E-mail:", "chobinkr@catholic.ac.kr", "Purpose:", "The", "survival", "rate", "for", "childhood", "acute", "lymphoblastic", "leukemia", "(ALL)", "has", "improved", "significantly.", "However,", "overall", "prognosis", "for", "the", "20", "to", "25%", "of", "patients", "who", "relapse", "is", "poor,", "and", "allogeneic", "hematopoietic", "stem", "cell", "transplantation", "(HSCT)", "offers", "the", "best", "chance", "for", "cure.", "In", "this", "study,", "we", "identified", "significant", "prognostic", "variables", "by", "analyzing", "the", "outcomes", "of", "allogeneic", "HSCT", "in", "ALL", "patients", "in", "second", "complete", "remission", "(CR).", "Methods:", "Fifty-three", "ALL", "patients", "(42", "men,", "79%)", "who", "received", "HSCT", "in", "second", "CR", "from", "August", "1991", "to", "February", "2009", "were", "included", "(26", "sibling", "donor", "HSCTs,", "49%;", "42", "bone", "marrow", "transplantations,", "79%).", "Study", "endpoints", "included", "cumulative", "incidence", "of", "acute", "and", "chronic", "graft-versus-host", "disease", "(GVHD),", "relapse,", "1-year", "transplant-related", "mortality", "(TRM),", "disease-free", "survival", "(DFS),", "and", "overall", "survival", "(OS).", "Results:", "Cumulative", "incidences", "of", "acute", "GVHD", "(grade", "2", "or", "above)", "and", "chronic", "GVHD", "were", "45.3%", "and", "28.5%,", "respectively.", "The", "estimated", "5-year", "DFS", "and", "OS", "for", "the", "cohort", "was", "45.2±6.8%", "and", "48.3±7%,", "respectively.", "Only", "donor", "type,", "i.e.,", "sibling", "versus", "unrelated,", "showed", "significant", "correlation", "with", "DFS", "in", "multivariate", "analysis", "(P", "=0.010).", "The", "rates", "of", "relapse", "and", "1", "year", "TRM", "were", "28.9±6.4%", "and", "26.4±6.1%,", "respectively,", "and", "unrelated", "donor", "HSCT", "(P", "=0.002)", "and", "HLA", "mismatch", "(P", "=0.022)", "were", "significantly", "correlated", "with", "increased", "TRM", "in", "univariate", "analysis.", "Conclusion:", "In", "this", "single", "institution", "study", "spanning", "more", "than", "17", "years,", "sibling", "donor", "HSCT", "was", "the", "only", "factor", "predicting", "a", "favorable", "result", "in", "multivariate", "analysis,", "possibly", "due", "to", "increased", "TRM", "resulting", "from", "unrelated", "donor", "HSCT.", "100" ]

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[ "Yonsei", "Med", "J", "49(6):1052", "-", "1054,", "2008", "DOI", "10.3349/ymj.2008.49.6.1052", "Gastric", "Schwannoma", "Ho", "Young", "Yoon,1", "Choong", "Bai", "Kim,1", "Yoon", "Hee", "Lee,2", "and", "Ho", "Guen", "Kim2", "Departments", "of", "1Surgery", "and", "2Pathology,", "Yonsei", "University", "College", "of", "Medicine,", "Seoul,", "Korea.", "Schwannomas,", "also", "known", "as", "neurinomas", "or", "neurilem-", "momas,", "are", "generally", "benign,", "slow-growing", "neoplasms", "origi-", "nating", "in", "any", "nerve", "that", "has", "a", "Schwann", "cell", "sheath.", "These", "neoplasms", "are", "rare", "among", "the", "spindle", "cell", "mesenchymal", "tumors", "of", "the", "gastrointestinal", "tract,", "but", "develop", "most", "commonly", "in", "the", "stomach", "representing", "0.2%", "of", "all", "gastric", "tumors.", "We", "present", "the", "case", "of", "a", "57-year-old", "female", "patient", "with", "a", "large", "schwannoma", "in", "the", "stomach", "that", "was", "palpable", "in", "the", "abdomen.", "She", "under-", "went", "subtotal", "gastrectomy", "under", "suspicion", "of", "gastrointestinal", "stromal", "tumor", "(GIST),", "but", "post-operative", "histopathological", "and", "immunohistochemical", "findings", "showed", "a", "fascicular", "arrange-", "ment", "of", "spindle", "cell", "with", "pallisading", "nuclei,", "and", "positive", "for", "S-100", "protein", "with", "negative", "smooth", "muscle", "actin", "(SMA).", "These", "results", "confirmed", "schwannoma", "as", "the", "diagnosis.", "Key", "Words:", "Schwannoma,", "stomach,", "submucosal", "tumor,", "S-100", "protein", "INTRODUCTION", "Schwannomas", "also", "known", "as", "neurinomas", "or", "neurilemmomas,", "are", "tumors", "originating", "from", "any", "nerve", "that", "has", "a", "Schwann", "cell", "sheath.", "These", "rarely", "develop", "in", "the", "gastrointestinal", "tract,", "and", "the", "most", "common", "site", "along", "the", "GI", "tract", "is", "the", "stomach.", "Schwannomas", "make-up", "0.2%", "of", "all", "gastric", "neo-", "plasm.1", "The", "tumors", "are", "usually", "benign,", "slow-gro-", "wing,", "and", "asymptomatic,", "but", "in", "some", "cases,", "bleeding", "or", "a", "palpable", "mass", "is", "present.", "Gastroin-", "testinal", "endoscopy", "is", "the", "principal", "diagnostic", "tool.", "However,", "when", "the", "tumor", "has", "the", "characteristics", "of", "an", "exophytic", "mass", "from", "the", "gastric", "wall", "to", "the", "abdominal", "cavity,", "the", "differentiation", "of", "a", "schwan-", "noma", "from", "other", "submucosal", "tumors", "is", "very", "dif-", "Received", "June", "12,", "2007", "Accepted", "July", "4,", "2007", "Reprint", "address:", "requests", "to", "Dr.", "Choong", "Bai", "Kim,", "Department", "of", "surgery,", "Yonsei", "University", "College", "of", "Medicine,", "250", "Seongsanno,", "Seodaemun-gu,", "Seoul", "120-752,", "Korea.", "Tel:", "82-2-2228-2113,", "Fax:", "82-2-313-8289,", "E-mail:", "cbkimmd@yuhs.ac", "Yonsei", "Med", "J", "Vol.", "49,", "No.", "6,", "2008", "ficult", "on", "pre-operative", "examination.", "The", "diagno-", "stic", "determination", "of", "schwannomas", "requires", "his-", "tological", "testing", "to", "be", "positive", "for", "the", "S-100", "pro-", "tein", "and", "vimentin", "but", "negative", "for", "both", "smooth", "muscle", "actin", "and", "c-KIT.", "Because", "most", "schwan-", "nomas", "have", "an", "excellent", "prognosis,", "surgical", "removal", "is", "sufficient", "for", "treatment.", "Here", "we", "present", "a", "57-year-old", "woman", "with", "a", "gastric", "schwannoma", "manifesting", "as", "a", "palpable", "mass", "in", "the", "abdomen,", "which", "was", "confirmed", "pathologi-", "cally", "after", "surgery.", "CASE", "REPORT", "A", "57-year-old", "woman", "with", "diabetic", "nephropathy,", "hypertension,", "and", "angina", "was", "referred", "to", "our", "institution", "for", "an", "incidentally-detected", "abdominal", "mass", "detected", "by", "sonography.", "She", "did", "not", "have", "any", "other", "clinical", "complaints.", "Physical", "examination", "revealed", "a", "palpated", "golf", "ball-sized", "mass", "in", "the", "epigastric", "area", "without", "tenderness", "or", "rebound", "tenderness.", "Gastrointestinal", "endoscopy", "was", "not", "performed", "due", "to", "her", "medical", "history", "of", "angina.", "Instead,", "an", "upper", "gastrointestinal", "barium", "study", "showed", "a", "large", "submucosal", "mass", "in", "the", "gastric", "angle", "(Fig.", "1).", "Computed", "tomography", "of", "the", "abdomen", "revealed", "an", "ovoid", "and", "homogenous", "7", "×", "5", "×", "4", "cm", "soft", "tissue", "mass", "at", "the", "lesser", "curvature", "in", "the", "lower", "body", "of", "the", "stomach", "(Fig.", "2).", "Aside", "from", "splenomegaly,", "there", "was", "no", "evidence", "of", "metastasis.", "To", "facilitate", "visualization", "of", "the", "mass,", "we", "performed", "a", "sono-", "graphy,", "which", "depicted", "an", "ill-defined", "round", "mass", "neighboring", "the", "antrum.", "The", "mass", "was", "approxi-", "mately", "6", "×", "5", "×", "4", "cm", "in", "diameter", "and", "had", "a", "homo-", "genous", "internal", "echo", "(Fig.", "3)." ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Ross", "M.", "Kedl:", "ross.kedl@uchsc.edu", "OR", "Stephen", "C.", "Jameson:", "james024@umn.edu", "Abbreviations", "used:", "BFA,", "brefeldin", "A;", "gB,", "glycoprotein", "B;", "GF,", "germ", "free;", "HP,", "homeostatic", "proliferation;", "SPF,", "specific", "pathogen", "free;", "VM,", "virtual", "memory.", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "206", "No.", "2", "435-448", "www.jem.org/cgi/doi/10.1084/jem.20081829", "A", "RT", "I", "C", "L", "E", "The", "antigen-specific", "CD8+", "T", "cell", "repertoire", "in", "unimmunized", "mice", "includes", "memory", "phenotype", "cells", "bear", "ing", "markers", "of", "homeostatic", "expansion", "Catherine", "Haluszczak,1", "Adovi", "D.", "Akue,2", "Sara", "E.", "Hamilton,2", "Lisa", "D.S.", "Johnson,2", "Lindsey", "Pujanauski,1", "Lenka", "Teodorovic,1", "Stephen", "C.", "Jameson,2", "and", "Ross", "M.", "Kedl1", "1Integrated", "Department", "of", "Immunology,", "University", "of", "Colorado", "Health", "Science", "Center,", "Denver,", "CO", "80045", "2Laboratory", "Medicine", "and", "Pathology,", "Center", "for", "Immunology,", "University", "of", "Minnesota,", "Minneapolis,", "MN", "55455", "Memory", "T", "cells", "exhibit", "superior", "responses", "to", "pathogens", "and", "tumors", "compared", "with", "their", "naive", "counterparts.", "Memory", "is", "typically", "generated", "via", "an", "immune", "response", "to", "a", "foreign", "antigen,", "but", "functional", "memory", "T", "cells", "can", "also", "be", "produced", "from", "naive", "cells", "by", "homeo-", "static", "mechanisms.", "Using", "a", "recently", "developed", "method,", "we", "studied", "CD8", "T", "cells,", "which", "are", "specific", "for", "model", "(ovalbumin)", "and", "viral", "(HSV,", "vaccinia)", "antigens,", "in", "unimmunized", "mice", "and", "found", "a", "subpopulation", "bearing", "markers", "of", "memory", "cells.", "Based", "on", "their", "phenotypic", "markers", "and", "by", "their", "presence", "in", "germ-free", "mice,", "these", "preexisting", "memory-like", "CD44hi", "CD8", "T", "cells", "are", "likely", "to", "arise", "via", "physiological", "homeostatic", "proliferation", "rather", "than", "a", "response", "to", "environmental", "microbes.", "These", "antigen-inexperienced", "memory", "phenotype", "CD8", "T", "cells", "display", "several", "functions", "that", "distinguish", "them", "from", "their", "CD44lo", "counterparts,", "including", "a", "rapid", "initiation", "of", "proliferation", "after", "T", "cell", "stimulation", "and", "rapid", "IFN-", "production", "after", "exposure", "to", "proinflammatory", "cytokines.", "Collectively,", "these", "data", "indicate", "that", "the", "unprimed", "antigen-specific", "CD8", "T", "cell", "repertoire", "contains", "antigen-inexperienced", "cells", "that", "display", "phenotypic", "and", "functional", "traits", "of", "memory", "cells.", "During", "normal", "primary", "T", "cell", "responses,", "naive", "T", "cells", "are", "induced", "to", "proliferate", "and", "differentiate,", "giving", "rise", "first", "to", "an", "effector", "pool", "and", "then", "to", "a", "long-lived", "memory", "population", "(1,", "2).", "The", "size", "of", "the", "antigen-specific", "memory", "T", "cell", "pool", "is", "typi-", "cally", "larger", "than", "the", "naive", "population", "from", "which", "they", "are", "derived,", "but", "in", "addition", "to", "their", "elevated", "frequency,", "memory", "T", "cells", "exhibit", "multiple", "qua-", "litative", "advantages", "over", "their", "naive", "counterparts", "with", "respect", "to", "their", "functional", "versatility,", "speed", "of", "response,", "and", "capacity", "to", "migrate", "to", "multiple", "sites", "besides", "lymphoid", "tissues", "(1,", "2).", "Aside", "from", "this", "standard", "pathway,", "however,", "there", "is", "accumulating", "data", "that", "memory", "pheno-", "type", "T", "cells", "can", "arise", "from", "naive", "T", "cells", "via", "ho-", "meostatic", "mechanisms", "without", "activation", "of", "the", "T", "cell", "by", "foreign", "antigen.", "This", "has", "been", "well", "studied", "in", "situations", "of", "extreme", "lymphopenia,", "as", "induced", "by", "irradiation", "or", "genetic", "T", "cell", "defi-", "C.", "Haluszczak,", "A.D.", "Akue,", "and", "S.E.", "Hamilton", "contributed", "equally", "to", "this", "paper.", "ciency,", "which", "induces", "homeostatic", "proliferation", "(HP)", "of", "naive", "T", "cells", "(3–5).", "In", "addition,", "there", "is", "also", "evidence", "that", "HP", "can", "occur", "within", "unprimed", "neonatal", "mice", "(3–9).", "T", "cell", "HP", "in", "the", "lympho-", "penic", "environment", "is", "thought", "to", "be", "driven", "by", "reduced", "competition", "for", "limiting", "resources,", "in-", "cluding", "IL-7", "and", "low-affinity", "TCR", "ligands", "(3–5,", "10,", "11),", "and", "can", "be", "further", "influenced", "by", "other", "cytokines", "(12–15).", "HP", "memory", "cells", "resemble", "conventional", "memory", "cells", "in", "many", "of", "their", "phenotypic", "and", "functional", "traits.", "After", "HP,", "T", "cells", "display", "nu-", "merous", "phenotypic", "markers", "that", "are", "similar", "to", "those", "of", "true", "antigen-driven", "memory", "cells,", "such", "as", "increased", "CD44,", "LFA1,", "Ly6C,", "and", "CD122", "expression", "(3–5,", "16,", "17).", "Antigen-driven", "mem-", "ory", "cells", "display", "increased", "sensitivity", "to", "antigen", "©", "2009", "Haluszczak", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribu-", "tion–Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", 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[ "Prolonged", "Antigen", "Presentation", "Is", "Required", "for", "Optimal", "CD8+", "T", "Cell", "Responses", "against", "Malaria", "Liver", "Stage", "Parasites", "Ian", "A.", "Cockburn1,", "Yun-Chi", "Chen1,", "Michael", "G.", "Overstreet1¤,", "Jason", "R.", "Lees2,", "Nico", "van", "Rooijen3,", "Donna", "L.", "Farber2,", "Fidel", "Zavala1*", "1", "Johns", "Hopkins", "Malaria", "Research", "Institute", "and", "Department", "of", "Molecular", "Microbiology", "and", "Immunology,", "Bloomberg", "School", "of", "Public", "Health,", "Baltimore,", "Maryland,", "United", "States", "of", "America,", "2", "Department", "of", "Surgery,", "University", "of", "Maryland", "at", "Baltimore,", "Baltimore,", "Maryland,", "United", "States", "of", "America,", "3", "Vrije", "Universiteit,", "VUMC,", "Department", "of", "Molecular", "Cell", "Biology,", "Faculty", "of", "Medicine,", "Amsterdam,", "The", "Netherlands", "Abstract", "Immunization", "with", "irradiated", "sporozoites", "is", "currently", "the", "most", "effective", "vaccination", "strategy", "against", "liver", "stages", "of", "malaria", "parasites,", "yet", "the", "mechanisms", "underpinning", "the", "success", "of", "this", "approach", "are", "unknown.", "Here", "we", "show", "that", "the", "complete", "development", "of", "protective", "CD8+", "T", "cell", "responses", "requires", "prolonged", "antigen", "presentation.", "Using", "TCR", "transgenic", "cells", "specific", "for", "the", "malaria", "circumsporozoite", "protein,", "a", "leading", "vaccine", "candidate,", "we", "found", "that", "sporozoite", "antigen", "persists", "for", "over", "8", "weeks", "after", "immunization—a", "remarkable", "finding", "since", "irradiated", "sporozoites", "are", "incapable", "of", "replication", "and", "do", "not", "differentiate", "beyond", "early", "liver", "stages.", "Persisting", "antigen", "was", "detected", "in", "lymphoid", "organs", "and", "depends", "on", "the", "presence", "of", "CD11c+", "cells.", "Prolonged", "antigen", "presentation", "enhanced", "the", "magnitude", "of", "the", "CD8+", "T", "cell", "response", "in", "a", "number", "of", "ways.", "Firstly,", "reducing", "the", "time", "primed", "CD8+", "T", "cells", "were", "exposed", "to", "antigen", "in", "vivo", "severely", "reduced", "the", "final", "size", "of", "the", "developing", "memory", "population.", "Secondly,", "fully", "developed", "memory", "cells", "expanded", "in", "previously", "immunized", "mice", "but", "not", "when", "transferred", "to", "na¨ıve", "animals.", "Finally,", "persisting", "antigen", "was", "able", "to", "prime", "na¨ıve", "cells,", "including", "recent", "thymic", "emigrants,", "to", "become", "functional", "effector", "cells", "capable", "of", "eliminating", "parasites", "in", "the", "liver.", "Together", "these", "data", "show", "that", "the", "optimal", "development", "of", "protective", "CD8+", "T", "cell", "immunity", "against", "malaria", "liver", "stages", "is", "dependent", "upon", "the", "prolonged", "presentation", "of", "sporozoite-derived", "antigen.", "Citation:", "Cockburn", "IA,", "Chen", "Y-C,", "Overstreet", "MG,", "Lees", "JR,", "van", "Rooijen", "N,", "et", "al.", "(2010)", "Prolonged", "Antigen", "Presentation", "Is", "Required", "for", "Optimal", "CD8+", "T", "Cell", "Responses", "against", "Malaria", "Liver", "Stage", "Parasites.", "PLoS", "Pathog", "6(5):", "e1000877.", "doi:10.1371/journal.ppat.1000877", "Editor:", "James", "W.", "Kazura,", "Case", "Western", "Reserve", "University,", "United", "States", "of", "America", "Received", "January", "14,", "2010;", "Accepted", "March", "25,", "2010;", "Published", "May", "6,", "2010", "Copyright:", "2010", "Cockburn", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "FZ", "is", "supported", "by", "NIH", "grant", "number", "AI44375", "(http://www.nih.gov/);", "IAC", "is", "supported", "by", "a", "post-doctoral", "fellowship", "from", "the", "Johns", "Hopkins", "Malaria", "Research", "Institute", "(http://malaria.jhsph.edu/).", "The", "authors", "are", "grateful", "for", "the", "support", "of", "the", "Bloomberg", "Family", "Foundation.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "fzavala@jhsph.edu", "¤", "Current", "address:", "David", "H.", "Smith", "Center", "for", "Vaccine", "Biology", "and", "Immunology,", "University", "of", "Rochester", "Medical", "Center,", "Rochester,", "New", "York,", "United", "States", "of", "America", "Introduction", "Immunization", "with", "irradiated", "malaria", "sporozoites", "can", "induce", "sterile", "protection", "against", "subsequent", "challenge", "with", "live", "parasites", "in", "both", "mice", "and", "men", "[1,2].", "In", "murine", "models", "protection", "is", "mediated", "at", "least", "in", "part", "by", "CD8+", "T", "cells", "[3,4].", "Understanding", "the", "mechanistic", "underpinnings", "of", "this", "protective", "response", "is", "consid-", "ered", "essential", "if", "we", "are", "to", "emulate", "it", "with", "a", "practical", "and", "effective", "vaccine.", "It", "has", "been", "proposed", "previously,", "based", "on", "the", "detection", "of", "parasite", "remnants", "in", "the", "livers", "of", "immunized", "mice,", "that", "antigen", "persists", "after", "sporozoite", "immunization", "and", "that", "this", "may", "help", "generate", "protective", "immune", "responses", "[5];", "however,", "there", "is", "no", "evidence", "that", "this", "material,", "assumed", "to", "be", "of", "parasite", "origin,", "is", "immunogenic", "or", "that", "it", "is", "presented", "to", "effector", "cells", "of", "the", "immune", "system.", "The", "requirement", "for", "antigen", "in", "the", "full", "development", "of", "effector", "and", "memory", "responses", "in", "different", "microbial", "systems", "is", "an", "area", "of", "controversy.", "Studies,", "that", "are", "now", "considered", "seminal,", "have", "proposed", "that", "only", "a", "short", "(,24", "hour)", "exposure", "to", "antigen", "is", "required", "to", "trigger", "the", "complete", "developmental", "program", "of", "CD8+", "T", "cells", "[6,7,8].", "Following", "initial", "antigen", "exposure", "CD8+", "T", "cells", "expand", "into", "effector", "cells", "before", "forming", "a", "numerically", "stable", "memory", "population,", "a", "process", "that", "has", "been", "characterized", "as", "T", "cells", "on", "‘‘autopilot’’", "[9].", "In", "the", "longer", "term,", "persisting", "antigen", "during", "chronic", "viral", "infection", "is", "often", "considered", "detrimental", "to", "T", "cell", "immunity", "as", "over-stimulated", "T", "cells", "may", "become", "exhausted", "and", "lose", "effector", "function", "[10,11].", "However,", "not", "all", "data", "suggests", "short", "exposures", "to", "antigen", "are", "optimal", "for", "T", "cell", "responses.", "The", "largest", "antigen", "specific", "CD8+", "T", "cell", "responses", "observed", "in", "humans", "are", "seen", "during", "chronic", "infection", "with", "various", "Herpesviruses", "[12,13].", "For", "Herpesviruses", "and", "other", "chronic", "infections", "it", "maybe", "that", "continued", "recruitment", "of", "thymic", "emigrants", "by", "the", "continued", "presence", "of", "foreign", "antigen", "can", "maximize", "and", "maintain", "the", "immune", "response", "[14,15].", "Recently", "a", "number", "of", "authors", "have", "reported", "antigen", "persistence", "after", "acute", "viral", "infections", "[16,17,18].", "Although", "the", "significance", "of", "this", "prolonged", "antigen", "presentation", "is", "not", "fully", "understood,", "some", "authors", "have", "suggested", "that", "it", "may", "have", "an", "important", "role", "in", "maintaining", "protective", "CD8+", "T", "cell", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1", "May", "2010", "|", "Volume", "6", "|", "Issue", "5", "|", "e1000877" ]

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[ "Retèl", "et", "al.", "BMC", "Research", "Notes", "2012,", "5:442", "http://www.biomedcentral.com/1756-0500/5/442", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Scenario", "drafting", "to", "anticipate", "future", "developments", "in", "technology", "assessment", "Valesca", "P", "Retèl1,", "Manuela", "A", "Joore2,3,", "Sabine", "C", "Linn4,", "Emiel", "JT", "Rutgers5", "and", "Wim", "H", "van", "Harten1,6*", "Abstract", "Background:", "Health", "Technology", "Assessment", "(HTA)", "information,", "and", "in", "particular", "cost-effectiveness", "data", "is", "needed", "to", "guide", "decisions,", "preferably", "already", "in", "early", "stages", "of", "technological", "development.", "However,", "at", "that", "moment", "there", "is", "usually", "a", "high", "degree", "of", "uncertainty,", "because", "evidence", "is", "limited", "and", "different", "development", "paths", "are", "still", "possible.", "We", "developed", "a", "multi-parameter", "framework", "to", "assess", "dynamic", "aspects", "of", "a", "technology", "-still", "in", "development-,", "by", "means", "of", "scenario", "drafting", "to", "determine", "the", "effects,", "costs", "and", "cost-effectiveness", "of", "possible", "future", "diffusion", "patterns.", "Secondly,", "we", "explored", "the", "value", "of", "this", "method", "on", "the", "case", "of", "the", "clinical", "implementation", "of", "the", "70-gene", "signature", "for", "breast", "cancer,", "a", "gene", "expression", "profile", "for", "selecting", "patients", "who", "will", "benefit", "most", "from", "chemotherapy.", "Methods:", "To", "incorporate", "process-uncertainty,", "ten", "possible", "scenarios", "regarding", "the", "introduction", "of", "the", "70-gene", "signature", "were", "drafted", "with", "European", "experts.", "Out", "of", "5", "most", "likely", "scenarios,", "3", "drivers", "of", "diffusion", "(non-compliance,", "technical", "failure,", "and", "uptake)", "were", "quantitatively", "integrated", "in", "a", "decision-analytical", "model.", "For", "these", "scenarios,", "the", "cost-effectiveness", "of", "the", "70-gene", "signature", "expressed", "in", "Incremental", "Cost-Effectiveness", "Ratios", "(ICERs)", "was", "compared", "to", "clinical", "guidelines,", "calculated", "from", "the", "past", "(2005)", "until", "the", "future", "(2020).", "Results:", "In", "2005", "the", "ICER", "was", "€1,9", "million/quality-adjusted-life-year", "(QALY),", "meaning", "that", "the", "70-gene", "signature", "was", "not", "yet", "cost-effective", "compared", "to", "the", "current", "clinical", "guideline.", "The", "ICER", "for", "the", "70-gene", "signature", "improved", "over", "time", "with", "a", "range", "of", "€1,9", "million", "to", "€26,145", "in", "2010", "and", "€1,9", "million", "to", "€11,123/QALY", "in", "2020", "depending", "on", "the", "separate", "scenario", "used.", "From", "2010,", "the", "70-gene", "signature", "should", "be", "cost-effective,", "based", "on", "the", "combined", "scenario.", "The", "uptake-scenario", "had", "strongest", "influence", "on", "the", "cost-effectiveness.", "Conclusions:", "When", "optimal", "diffusion", "of", "a", "technology", "is", "sought,", "incorporating", "process-uncertainty", "by", "means", "of", "scenario", "drafting", "into", "a", "decision", "model", "may", "reveal", "unanticipated", "developments", "and", "can", "demonstrate", "a", "range", "of", "possible", "cost-effectiveness", "outcomes.", "The", "effect", "of", "scenarios", "give", "additional", "information", "on", "the", "speed", "with", "cost", "effectiveness", "might", "be", "reached", "and", "thus", "provide", "a", "more", "realistic", "picture", "for", "policy", "makers,", "opinion", "leaders", "and", "manufacturers.", "Keywords:", "Early", "technology", "assessment,", "Scenario", "drafting,", "Genomic", "profiling,", "70-gene", "signature,", "Breast", "cancer", "Open", "Access", "*", "Correspondence:", "w.h.vanharten@utwente.nl", "1Netherlands", "Cancer", "Institute-Antoni", "van", "Leeuwenhoek", "Hospital", "(NKI-AVL),", "Department", "of", "Psychosocial", "Research", "and", "Epidemiology,", "Plesmanlaan", "121,", "Amsterdam", "1066", "CX,", "The", "Netherlands", "6University", "of", "Twente,", "School", "of", "Governance", "and", "Management,", "MB-HTSR,", "PO", "Box", "217,", "Enschede", "7500", "AE,", "The", "Netherlands", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2012", "Retèl", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "A", "Natural", "System", "of", "Chromosome", "Transfer", "in", "Yersinia", "pseudotuberculosis", "Biliana", "Lesic1,", "Mohamed", "Zouine2,", "Magaly", "Ducos-Galand", "2", ",", "Christe`", "le", "Huon", "1", ",", "Marie-Laure", "Rosso1,", "Marie-", "Christine", "Pre´", "vost3,", "Didier", "Mazel2*,", "Elisabeth", "Carniel1*", "1", "Yersinia", "Research", "Unit,", "Institut", "Pasteur,", "Paris,", "France,", "2", "Unite´", "Plasticite´", "du", "Ge´nome", "Bacte´rien,", "Institut", "Pasteur,", "CNRS", "UMR", "3525,", "Paris,", "France,", "3", "Plateforme", "de", "Microscopie", "Ultrastructurale,", "Institut", "Pasteur,", "Paris,", "France", "Abstract", "The", "High", "Pathogenicity", "Island", "of", "Yersinia", "pseudotuberculosis", "IP32637", "was", "previously", "shown", "to", "be", "horizontally", "transferable", "as", "part", "of", "a", "large", "chromosomal", "segment.", "We", "demonstrate", "here", "that", "at", "low", "temperature", "other", "chromosomal", "loci,", "as", "well", "as", "a", "non-mobilizable", "plasmid", "(pUC4K),", "are", "also", "transferable.", "This", "transfer,", "designated", "GDT4", "(Generalized", "DNA", "Transfer", "at", "4uC),", "required", "the", "presence", "of", "an", "IP32637", "endogenous", "plasmid", "(pGDT4)", "that", "carries", "several", "mobile", "genetic", "elements", "and", "a", "conjugation", "machinery.", "We", "established", "that", "cure", "of", "this", "plasmid", "or", "inactivation", "of", "its", "sex", "pilus", "fully", "abrogates", "this", "process.", "Analysis", "of", "the", "mobilized", "pUC4K", "recovered", "from", "transconjugants", "revealed", "the", "insertion", "of", "one", "of", "the", "pGDT4–borne", "ISs,", "designated", "ISYps1,", "at", "different", "sites", "on", "the", "transferred", "plasmid", "molecules.", "This", "IS", "belongs", "to", "the", "IS6", "family,", "which", "moves", "by", "replicative", "transposition,", "and", "thus", "could", "drive", "the", "formation", "of", "cointegrates", "between", "pGDT4", "and", "the", "host", "chromosome", "and", "could", "mediate", "the", "transfer", "of", "chromosomal", "regions", "in", "an", "Hfr-like", "manner.", "In", "support", "of", "this", "model,", "we", "show", "that", "a", "suicide", "plasmid", "carrying", "ISYps1", "is", "able", "to", "integrate", "itself,", "flanked", "by", "ISYps1", "copies,", "at", "multiple", "locations", "into", "the", "Escherichia", "coli", "chromosome.", "Furthermore,", "we", "demonstrate", "the", "formation", "of", "RecA-independent", "cointegrates", "between", "the", "ISYps1-", "harboring", "plasmid", "and", "an", "ISYps1-free", "replicon,", "leading", "to", "the", "passive", "transfer", "of", "the", "non-conjugative", "plasmid.", "We", "thus", "demonstrate", "here", "a", "natural", "mechanism", "of", "horizontal", "gene", "exchange,", "which", "is", "less", "constrained", "and", "more", "powerful", "than", "the", "classical", "Hfr", "mechanism,", "as", "it", "only", "requires", "the", "presence", "of", "an", "IS6-type", "element", "on", "a", "conjugative", "replicon", "to", "drive", "the", "horizontal", "transfer", "of", "any", "large", "block", "of", "plasmid", "or", "chromosomal", "DNA.", "This", "natural", "mechanism", "of", "chromosome", "transfer,", "which", "occurs", "under", "conditions", "mimicking", "those", "found", "in", "the", "environment,", "may", "thus", "play", "a", "significant", "role", "in", "bacterial", "evolution,", "pathogenesis,", "and", "adaptation", "to", "new", "ecological", "niches.", "Citation:", "Lesic", "B,", "Zouine", "M,", "Ducos-Galand", "M,", "Huon", "C,", "Rosso", "M-L,", "et", "al.", "(2012)", "A", "Natural", "System", "of", "Chromosome", "Transfer", "in", "Yersinia", "pseudotuberculosis.", "PLoS", "Genet", "8(3):", "e1002529.", "doi:10.1371/journal.pgen.1002529", "Editor:", "Josep", "Casadesu´", "s,", "Universidad", "de", "Sevilla,", "Spain", "Received", "September", "15,", "2011;", "Accepted", "December", "23,", "2011;", "Published", "March", "8,", "2012", "Copyright:", "2012", "Lesic", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "funded", "by", "a", "grant", "from", "the", "French", "‘‘Ministe`re", "de", "la", "Recherche", "et", "de", "la", "Technologie’’", "to", "BL", "and", "by", "the", "Centre", "National", "de", "la", "Recherche", "Scientifique", "(CNRS-URA", "2171),", "the", "Fondation", "pour", "la", "Recherche", "Me´dicale,", "and", "the", "EU", "(STREP", "CRAB,", "LSHM-CT-2005-019023,", "and", "NoE", "EuroPathoGenomics,", "LSHB-", "CT-2005-512061)", "to", "DM.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "didier.mazel@pasteur.fr", "(DM);", "elisabeth.carniel@pasteur.fr", "(EC)", "Introduction", "Horizontal", "gene", "transfer", "(HGT)", "is", "a", "driving", "force", "for", "bacterial", "evolution,", "as", "it", "allows", "the", "dispersion", "of", "adaptive", "loci", "between", "closely", "related", "and", "also", "phylogenetically", "distant", "bacterial", "species.", "Well-characterized", "mobile", "genetic", "elements", "such", "as", "conjugative", "plasmids,", "transposons,", "Integrative", "conjugative", "elements", "(ICE),", "pathogenicity", "islands", "(PAI),", "or", "phages", "are", "associated", "with", "HGT", "of", "specific", "adaptive", "functions", "(antibiotic", "resistance,", "virulence,", "meta-", "bolic", "pathways)", "and", "participate", "to", "genome", "plasticity.", "However,", "exchanges", "of", "chromosomal", "regions", "that", "form", "the", "core", "genome", "and", "are", "not", "part", "of", "the", "mobile", "genetic", "pool", "are", "also", "observed.", "While", "their", "importance", "in", "bacterial", "evolution", "and", "speciation", "is", "now", "well", "established,", "the", "underlying", "mechanisms", "are", "often", "loosely", "described", "and", "remain", "hypothetical", "in", "many", "cases.", "The", "Gram-negative", "enteropathogen", "Yersinia", "pseudotuberculosis", "carries", "a", "PAI", "termed", "High", "Pathogenicity", "Island", "(HPI)", "[1],", "which", "encodes", "the", "siderophore", "yersiniabactin", "[2].", "The", "fact", "that", "this", "island", "is", "mobile", "within", "the", "genome", "of", "its", "host", "strain", "[3],", "and", "is", "present", "and", "often", "conserved", "both", "in", "terms", "of", "genetic", "organization", "and", "nucleotide", "sequence", "in", "various", "bacterial", "genera", "such", "as", "Escherichia", "coli", "(various", "pathotypes),", "Klebsiella", "or", "Citrobacter", "[4],", "suggested", "that", "it", "may", "have", "retained", "its", "ability", "to", "be", "horizontally", "transmitted", "to", "new", "bacterial", "hosts.", "Indeed,", "we", "evidenced", "the", "transfer", "of", "the", "HPI", "between", "natural", "Y.", "pseudotuberculosis", "isolates", "[3].", "This", "phenomenon", "was", "observed", "only", "when", "the", "bacteria", "were", "incubated", "at", "low", "temperature", "(optimal", "at", "4uC)", "and", "in", "broth,", "and", "was", "more", "efficient", "in", "an", "iron-poor", "medium", "[5].", "However,", "this", "transfer", "did", "not", "require", "the", "integration/excision", "machinery", "encoded", "by", "the", "HPI,", "was", "RecA-dependent", "in", "the", "recipient", "strain,", "and", "involved", "not", "only", "the", "HPI", "but", "also", "adjacent", "sequences", "encompassing", "at", "least", "46", "kb", "of", "chromosomal", "DNA", "[3].", "Similar", "results", "were", "recently", "obtained", "for", "the", "HPI", "of", "natural", "Escherichia", "coli", "isolates,", "using", "a", "multi", "locus", "sequence", "typing", "approach.", "The", "E.", "coli", "HPI", "was", "found", "to", "have", "been", "acquired", "simultaneously", "with", "the", "chromosomal", "flanking", "regions", "of", "the", "donor", "strains", "[6],", "indicating", "again", "that", "the", "island", "was", "transmitted", "as", "part", "of", "a", "larger", "chromosomal", "region.", "This", "phenomenon", "is", "not", "restricted", "to", "the", "HPI", "and", "to", "enterobacteria", "since", "it", "has", "been", "recently", "reported", "that", "movement", "of", "the", "Enterococcus", "faecalis", "PAI", "was", "invariably", "accompanied", "by", "transfer", "of", "flanking", "donor", "chromosome", "sequences", "[7].", "PLoS", "Genetics", "|", "www.plosgenetics.org", "1", "March", "2012", "|", "Volume", "8", "|", "Issue", "3", "|", "e1002529" ]

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[ "Nucleic", "Acids", "Research,", "2005,", "Vol.", "33,", "No.", "22", "e189", "doi:10.1093/nar/gni192", "Iterative", "in", "vivo", "assembly", "of", "large", "and", "complex", "transgenes", "by", "combining", "the", "activities", "of", "fC31", "integrase", "and", "Cre", "recombinase", "Felix", "Dafhnis-Calas,", "Zhengyao", "Xu,", "Steve", "Haines,", "Sunir", "K.", "Malla,", "Margaret", "C.", "M.", "Smith", "and", "William", "R.", "A.", "Brown*", "Institute", "of", "Genetics,", "Queen’s", "Medical", "Centre,", "University", "of", "Nottingham,", "Nottingham", "NG7", "2UH,", "UK", "Received", "September", "21,", "2005;", "Revised", "October", "17,", "2005;", "Accepted", "November", "25,", "2005", "ABSTRACT", "We", "have", "used", "the", "fC31", "integrase", "to", "introduce", "large", "DNA", "sequences", "into", "a", "vertebrate", "genome", "and", "meas-", "ure", "the", "efficiency", "of", "integration", "of", "intact", "DNA", "as", "a", "function", "of", "insert", "size.", "Inserts", "of", "110", "kb", "and", "140", "kb", "in", "length", "may", "be", "integrated", "with", "about", "25%", "and", "10%", "efficiency", "respectively.", "In", "order", "to", "overcome", "the", "prob-", "lems", "of", "constructing", "transgenes", "longer", "than", "150", "kb", "we", "have", "established", "a", "method", "that", "we", "call;", "‘Iterative", "Site", "Specific", "Integration’", "(ISSI).", "ISSI", "combines", "the", "activities", "of", "fC31", "integrase", "and", "Cre", "recombinase", "to", "enable", "the", "iterative", "and", "serial", "integration", "of", "trans-", "genic", "DNA", "sequences.", "In", "principle", "the", "procedure", "may", "be", "repeated", "an", "arbitrary", "number", "of", "times", "and", "thereby", "allow", "the", "integration", "of", "tracts", "of", "DNA", "many", "hundreds", "of", "kilobase", "pairs", "long.", "In", "practice", "it", "may", "be", "limited", "by", "the", "time", "needed", "to", "check", "the", "accuracy", "of", "integration", "at", "each", "step", "of", "the", "procedure.", "We", "describe", "two", "ISSI", "experiments,", "in", "one", "of", "which", "we", "have", "constructed", "a", "complex", "array", "of", "vertebrate", "centromeric", "sequences", "of", "150", "kb", "in", "size.", "The", "principle", "that", "underlies", "ISSI", "is", "applicable", "to", "transgenesis", "in", "all", "organisms.", "ISSI", "may", "thus", "facilitate", "the", "reconstitution", "of", "biosynthetic", "pathways", "encoded", "by", "many", "different", "genes", "in", "trans-", "genic", "plants,", "the", "assembly", "of", "large", "vertebrate", "loci", "as", "transgenes", "and", "the", "synthesis", "of", "complete", "genomes", "in", "bacteria.", "INTRODUCTION", "Site-specific", "recombinases", "are", "used", "to", "manipulate", "chromo-", "somal", "DNA", "sequence", "organization", "in", "vivo,", "in", "vitro", "(1)", "and", "in", "a", "range", "of", "different", "experimental", "systems.", "The", "enzymes", "Cre", "and", "Flp", "(2)", "are", "the", "most", "widely", "employed,", "both", "are", "members", "of", "the", "tyrosine", "recombinase", "family", "and", "catalyse", "reversible", "reactions", "between", "identical", "sites", "of", "35", "bp", "in", "the", "absence", "of", "any", "accessory", "proteins.", "The", "reversibility", "of", "the", "reactions", "catalysed", "by", "these", "enzymes", "has", "limited", "their", "applicability.", "They", "are", "generally", "used", "to", "promote", "deletion", "reactions", "since", "integration", "reactions", "are", "kinetically", "unfavourable.", "However", "Cre", "and", "Flp", "have", "also", "been", "used", "to", "engineer", "integrations", "and", "translocations", "in", "cells", "in", "culture", "where", "it", "has", "been", "possible", "to", "provide", "the", "enzyme", "transiently", "and", "trap", "the", "potentially", "unstable", "product,", "often", "but", "not", "always,", "by", "selection", "(3,4).", "A", "technology", "that", "would", "allow", "the", "construction", "of", "large", "segments", "of", "transgenic", "DNA", "would", "be", "of", "widespread", "utility.", "Thus", "it", "would", "be", "valuable", "to", "be", "able", "to", "assemble", "large", "tracts", "of", "transgenic", "DNA", "at", "defined", "chromosomal", "loci", "in", "order", "to", "con-", "struct", "animal", "models", "of", "human", "genetic", "disease", "and", "to", "study", "the", "factors", "controlling", "expression", "of", "large", "genes.", "This", "goal", "has", "become", "more", "attractive", "with", "the", "ability", "to", "precisely", "and", "effi-", "ciently", "manipulate", "DNA", "cloned", "in", "Escherichia", "coli", "by", "homo-", "logous", "recombination", "(5,6)", "and", "with", "the", "availability", "of", "a", "complete", "genome", "sequence", "and", "well-characterized", "libraries", "of", "bacterial", "artificial", "chromosome", "(BAC)", "clones.", "Similarly", "it", "would", "be", "useful", "to", "be", "able", "to", "build", "plants", "with", "multiple", "transgenes", "at", "a", "single", "locus.", "Finally", "it", "would", "be", "interesting", "to", "be", "able", "to", "construct", "synthetic", "bacterial", "genomes", "in", "order", "to", "identify", "the", "minimal", "set", "of", "genes", "consistent", "with", "independent", "life", "(7).", "Strategies", "describing", "how", "Cre", "or", "Flp", "might", "be", "used", "to", "promote", "irreversible", "integrations", "have", "been", "presented", "(8–10)", "However", "all", "of", "these", "approaches", "suffer", "from", "the", "limitation", "that", "they", "only", "allow", "one", "cycle", "of", "site-specific", "recombination", "and", "thus", "cannot", "be", "used", "iteratively.", "It", "is", "difficult", "therefore", "to", "see", "how", "they", "could", "be", "used", "to", "construct", "large", "tracts", "of", "trans-", "genic", "DNA.", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+44", "115", "849", "3244;", "Fax:", "+44", "115", "970", "9906;", "Email:", "William.brown@nottingham.ac.uk", "Present", "address:", "Margaret", "C.", "M.", "Smith,", "Institute", "of", "Medical", "Sciences,", "University", "of", "Aberdeen,", "Aberdeen", "AB25", "2ZD,", "UK", "The", "Author", "2005.", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oxfordjournals.org" ]

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[ "Research", "Farmworkers", "Pneumoconiosis", "from", "Agricultural", "Dust", "Exposure", "among", "Young", "California", "Marc", "B.", "Schenker,1", "Kent", "E.", "Pinkerton,2", "Diane", "Mitchell,1", "Val", "Vallyathan,3", "Brenda", "Elvine-Kreis,1", "and", "Francis", "H.Y.", "Green", "4", "1Department", "of", "Public", "Health", "Sciences,", "and", "2Center", "for", "Health", "and", "the", "Environment", "University", "of", "California", "at", "Davis,", "Davis,", "California,", "USA;", "3Pathology", "and", "Physiology", "Research", "Branch,", "National", "Institute", "for", "Occupational", "Safety", "and", "Health,", "Morgantown,", "West", "Virginia,", "USA;", "4Department", "of", "Pathology", "and", "Laboratory", "Medicine,", "University", "of", "Calgary,", "Calgary,", "Alberta,", "Canada", "Background", "inorganic", "(mineral)", "dusts.", ":", "Agricultural", "workers", "are", "exposed", "to", "airborne", "pollutants,", "including", "organic", "and", "o", "Bjectivs", ":", "Lung", "autopsy", "specimens", "from", "consecutive", "coroner’s", "cases", "of", "Hispanic", "males", "in", "Fresno", "County,", "California,", "(n", "=", "112)", "were", "obtained", "to", "determine", "whether", "mineral", "dust", "exposure", "in", "agricul-", "tural", "work", "leads", "to", "pneumoconiosis.", "Methods", ":", "The", "left", "lung", "was", "fixed", "by", "inflation.", "We", "evaluated", "airway", "and", "parenchymal", "pathology", "using", "standardized", "diagnostic", "criteria", "and", "semiquantitative", "grading", "schemata,", "including", "the", "grading", "of", "small", "airways", "for", "fibrosis", "and", "birefringent", "mineral", "dust", "particles.", "We", "analyzed", "lung", "dust", "burden", "on", "a", "subset", "of", "37", "lungs", "following", "bleach", "digestion,", "using", "scanning", "electron", "microscopy", "(SEM),", "X-ray", "spectrometry", "(XRS)", "and", "image", "analysis,", "and", "by", "X-ray", "diffraction", "for", "crystalline", "silica", "(CSi).", "Farmworkers", "comprised", "51.5%", "and", "nonfarmworkers", "48.5%", "of", "the", "samples.", "words", "r", "esult", ":", "Proximal", "airways", "demonstrated", "little", "mineral", "dust", "accumulation,", "but", "membranous", "and", "respiratory", "bronchioles", "had", "wall", "thickening,", "remodeling,", "and", "inflammation", "associated", "with", "carbo-", "naceous", "and", "mineral", "dust", "deposition.", "These", "changes", "were", "independently", "associated", "with", "agricultural", "work,", "cigarette", "smoking,", "and", "increased", "age.", "Mineral", "dust", "small", "airways", "disease,", "pneumoconiosis", "(macules", "and", "nodules),", "and", "pathologic", "changes", "consistent", "with", "chronic", "bronchitis,", "emphysema,", "and", "interstitial", "fibrosis", "predominated", "in", "farmworkers", "compared", "with", "nonfarmworkers.", "CSi,", "determined", "gravimetrically,", "and", "aluminum", "silicate", "particles,", "determined", "by", "SEM/XRS,", "were", "increased", "in", "the", "lungs", "of", "farmworkers", "compared", "with", "nonfarmworkers", "and", "were", "significantly", "(p", "<", "0.05)", "associated", "with", "small", "airway", "disease", "and", "pneumoconiosis.", "c", "onclusi", ":", "Mineral", "dust", "exposure", "is", "associated", "with", "increased", "small", "airway", "disease", "and", "pneu-", "moconiosis", "among", "California", "farmworkers;", "however,", "the", "clinical", "significance", "and", "natural", "history", "of", "these", "changes", "remains", "to", "be", "determined.", "k", "ey", ":", "agriculture,", "dust,", "farmworker,", "interstitial", "fibrosis,", "pneumoconiosis,", "respiratory,", "small", "airways", "disease.", "Environ", "Health", "Perspect", "117:988–994", "(2009).", "doi:10.1289/ehp.0800144", "available", "via", "http://dx.doi.org/", "[Online", "25", "February", "2009]", "Approximately", "5", "million", "workers", "in", "the", "United", "States", "work", "in", "the", "agricultural", "industry", "with", "potential", "exposure", "to", "a", "wide", "variety", "of", "respiratory", "toxicants.", "Among", "the", "various", "respiratory", "hazards", "not", "well", "studied", "is", "obstructive", "and", "restrictive", "lung", "disease", "caused", "by", "inorganic", "minerals", "(American", "Thoracic", "Society", "1998).", "California", "agricultural", "work-", "ers", "have", "increased", "respiratory", "symptoms,", "decreased", "respiratory", "function,", "and", "increased", "mortality", "rates", "from", "chronic", "pulmonary", "disease", "compared", "with", "the", "general", "popula-", "tion", "(Schenker", "et", "al.", "2005;", "Singleton", "and", "Beaumont", "1989;", "Stubbs", "et", "al.", "1984).", "The", "agricultural", "environment", "of", "the", "Central", "Valley", "of", "California", "places", "individuals", "at", "increased", "risk", "of", "exposure", "to", "inorganic", "par-", "ticles.", "This", "region", "encompasses", "a", "rich", "farming", "area", "as", "well", "as", "extensive", "urban", "development.", "The", "predominantly", "dry", "farming", "techniques", "of", "the", "Central", "Valley", "result", "in", "high", "levels", "of", "air-", "borne", "dust", "from", "operations", "such", "as", "field", "prep-", "aration", "and", "harvesting", "of", "row", "crops", "and", "tree", "fruits", "(Nieuwenhuijsen", "and", "Schenker", "1998;", "Nieuwenhuijsen", "et", "al.", "1998).", "Although", "soil", "consists", "of", "a", "mixture", "of", "organic", "and", "inorganic", "988", "materials,", "potential", "health", "effects", "from", "the", "ever-present", "mineral", "dusts", "have", "been", "largely", "overlooked.", "In", "theory,", "soil", "should", "contain", "representative", "portions", "of", "all", "major", "mineral", "classes", "in", "the", "earth’s", "crust;", "in", "reality,", "most", "agricultural", "soils", "are", "composed", "largely", "of", "sili-", "cate", "materials", "(e.g.,", "feldspars,", "mica,", "clay", "min-", "erals)", "and", "crystalline", "silica", "(CSi)", "(quartz)", "with", "varying", "amounts", "of", "other", "mineral", "classes,", "depending", "on", "the", "local", "geologic", "history.", "The", "evidence", "that", "mineral", "dust", "exposure", "poses", "a", "significant", "hazard", "to", "agricultural", "workers", "for", "interstitial", "lung", "disease", "is", "based", "on", "a", "handful", "of", "case", "reports,", "inferences", "from", "exposures", "to", "mineral", "dusts", "in", "other", "industries,", "studies", "of", "wild", "and", "farm", "animals", "exposed", "to", "environ-", "mental", "dusts,", "and", "toxicologic", "studies", "(Gylseth", "et", "al.", "1984;", "Schenker", "2000;", "Schoning", "1996;", "Vallyathan", "et", "al.", "2007).", "The", "deposition", "and", "clearance", "of", "particles", "within", "the", "respiratory", "system", "occurs", "in", "an", "inhomogeneous", "manner.", "The", "fate", "of", "parti-", "cles", "is", "not", "well", "established,", "and", "there", "is", "little", "information", "on", "the", "distribution", "and", "reten-", "tion", "of", "particles", "under", "conditions", "of", "ambi-", "ent", "exposure.", "One", "purpose", "of", "this", "study", "was", "to", "design", "and", "implement", "an", "approach", "that", "would", "allow", "the", "assessment", "of", "particle", "reten-", "tion", "as", "well", "as", "histologic", "analysis", "of", "response", "in", "different", "lung", "compartments.", "Our", "findings", "in", "this", "regard", "have", "been", "previously", "published", "and", "show", "that", "the", "deposition", "of", "particles", "is", "primarily", "in", "the", "centriacinar", "portion", "of", "the", "lung", "lobule", "(Pinkerton", "et", "al.", "2000).", "Unfortunately,", "no", "reported", "epidemiologic", "studies", "have", "directly", "assessed", "environmental", "exposure", "to", "mineral", "dusts", "and", "interstitial", "lung", "and", "airway", "disease", "in", "farmers", "or", "farmworkers,", "although", "respiratory", "symptoms", "have", "been", "associated", "with", "exposure", "to", "agricultural", "dusts", "with", "high", "mineral", "content", "(Schenker", "et", "al.", "2005).", "A", "few", "studies,", "however,", "have", "suggested", "that", "pneumoconiosis", "(Gylseth", "et", "al.", "1984;", "Sherwin", "et", "al.", "1979)", "and", "restrictive", "lung", "disease", "(Sasagawa", "et", "al.", "1989)", "are", "increased", "in", "some", "agricultural", "populations", "exposed", "to", "mineral", "dusts.", "A", "fundamental", "question", "remains", "whether", "occupational", "exposure", "to", "agricultural", "dusts", "can", "cause", "pulmonary", "fibro-", "sis,", "persistent", "inflammation,", "and", "cell/tissue", "remodeling", "in", "specific", "regions", "of", "the", "lungs", "where", "these", "mineral", "dusts", "are", "present.", "The", "objective", "of", "this", "study", "was", "to", "docu-", "ment", "and", "quantify", "pathologic", "lesions", "in", "lung", "tissues", "from", "consecutive", "Hispanic", "males", "autopsied", "by", "the", "coroner’s", "office", "in", "Fresno,", "California,", "and", "to", "determine", "their", "relation-", "ship", "to", "agricultural", "work", "and", "to", "mineral", "dust", "retained", "in", "the", "lungs.", "We", "focused", "on", "pneu-", "moconiosis", "and", "lesions", "of", "the", "small", "airways.", "The", "latter", "are", "the", "primary", "target", "of", "mineral", "dusts", "(Churg", "et", "al.", "1999;", "Craighead", "et", "al.", "1982)", "and", "are", "most", "likely", "to", "reflect", "early", "dis-", "ease", "in", "a", "young", "population", "(Pinkerton", "et", "al.", "Address", "correspondence", "to", "M.", "Schenker,", "Department", "of", "Public", "Health", "Sciences,", "University", "of", "California,", "One", "Shields", "Ave.,", "Davis,", "California", "95616", "USA.", "Telephone:", "(530)", "752-5676.", "Fax:", "(530)", "752-3239.", "E-mail:", "mbschenker@ucdavis.edu", "Supplemental", "Material", "is", "available", "online", "at", "http://", "www.ehponline.org/members/2009/0800144/suppl.pdf", "We", "thank", "S.", "Smiley-Jewell", "for", "assisting", "with", "manu-", "script", "preparation.", "This", "research", "has", "been", "funded", "in", "part", "by", "National", "Institute", "for", "Occupational", "Safety", "and", "Health", "U07/", "CCU906162,", "U.S.", "Environmental", "Protection", "Agency", "grants", "R826246", "and", "RD832414,", "and", "the", "Alberta", "Lung", "Association.", "The", "authors", "declare", "they", "have", "no", "competing", "Received", "2", "September", "2008;", "accepted", "25", "February", "financial", "interests.", "2009.", "ovlume", "117", "|", "number", "6", "|", "June", "2009", "•", "Environmental", "Health", "Perspectives" ]

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[ "96", "Acta", "Orthopaedica", "2011;", "82", "(1):", "96–101", "Surgery", "for", "skeletal", "metastases", "in", "lung", "cancer", "Complications", "and", "survival", "in", "98", "patients", "Rudiger", "J", "Weiss", "and", "Rikard", "Wedin", "Department", "of", "Molecular", "Medicine", "and", "Surgery,", "Section", "of", "Orthopaedics", "and", "Sports", "Medicine,", "Karolinska", "University", "Hospital,", "Karolinska", "Institutet,", "Stockholm,", "Sweden", "Correspondence:", "rudiger.weiss@karolinska.se", "Submitted", "10-04-30", "Accepted", "10-09-17", "Background", "and", "purpose", "Most", "lung", "cancer", "patients", "with", "skeletal", "metastases", "have", "a", "short", "survival", "and", "it", "is", "difficult", "to", "identify", "those", "patients", "who", "will", "benefit", "from", "palliative", "surgery.", "We", "report", "com-", "plication", "and", "survival", "rates", "in", "a", "consecutive", "series", "of", "lung", "cancer", "patients", "who", "were", "operated", "for", "symptomatic", "skeletal", "metastases.", "Methods", "This", "study", "was", "based", "on", "data", "recorded", "in", "the", "Karolinska", "Skeletal", "Metastasis", "Register.", "The", "study", "period", "was", "1987–2006.", "We", "identified", "98", "lung", "cancer", "patients", "(52", "females).", "The", "median", "age", "at", "surgery", "was", "62", "(34–88)", "years.", "78", "lesions", "were", "located", "in", "the", "femur", "or", "spine.", "Results", "The", "median", "survival", "time", "after", "surgery", "was", "3", "(0–127)", "months.", "The", "cumulative", "12-month", "survival", "after", "surgery", "was", "13%", "(95%", "CI:", "6–20).", "There", "was", "a", "difference", "between", "the", "survival", "after", "spinal", "surgery", "(2", "months)", "and", "after", "extremity", "surgery", "(4", "months)", "(p", "=", "0.03).", "Complete", "pathological", "fracture", "in", "non-spinal", "metastases", "(50", "patients)", "was", "an", "independent", "negative", "predictor", "of", "survival", "(hazard", "ratio", "(HR)", "=", "1.8,", "95%", "CI:", "1–3).", "16", "of", "31", "patients", "with", "spinal", "metastases", "experienced", "a", "considerable", "improvement", "in", "their", "neurological", "function", "after", "surgery.", "The", "overall", "complica-", "tion", "rate", "was", "20%,", "including", "a", "reoperation", "rate", "of", "15%.", "Interpretation", "Bone", "metastases", "and", "their", "subsequent", "surgical", "treatment", "in", "lung", "cancer", "patients", "are", "associated", "with", "high", "mor-", "bidity", "and", "mortality.", "Our", "findings", "will", "help", "to", "set", "appropriate", "expectations", "for", "these", "patients,", "their", "families,", "and", "surgeons.", "", "Lung", "cancer", "has", "become", "one", "of", "the", "most", "common", "cancers", "worldwide", "and", "is", "the", "predominant", "cause", "of", "death", "among", "cancer", "patients.", "The", "American", "Cancer", "Society", "estimated", "that", "almost", "160,000", "patients", "would", "die", "from", "lung", "and", "bronchus", "cancer", "in", "the", "USA", "in", "2009", "(Jemal", "et", "al.", "2009).", "Some", "authors", "have", "stated", "that", "lung", "cancer", "is", "one", "of", "the", "most", "important", "chal-", "lenges", "in", "oncology", "at", "the", "present", "time", "(Boyle", "and", "Dresler", "2005).", "Historically,", "about", "one", "third", "of", "all", "lung", "cancer", "patients", "are", "found", "to", "have", "bone", "metastases", "during", "the", "course", "of", "the", "dis-", "ease.", "Symptoms", "and", "events", "of", "skeletal", "origin", "such", "as", "pain,", "pathological", "fractures,", "spinal", "cord", "compression", "with", "para-", "paresis,", "and", "hypercalcemia", "are", "common", "complications.", "The", "decline", "in", "quality", "of", "life", "and", "eventual", "death", "of", "these", "patients", "can", "be", "explained", "to", "some", "extent", "by", "skeletal", "complications", "and", "their", "treatment", "(Coleman", "1997).", "Lung", "cancer", "patients", "with", "skeletal", "events", "have", "a", "short", "expected", "survival;", "however,", "some", "case", "reports", "have", "involved", "patients", "who", "survived", "several", "years", "after", "pathological", "frac-", "tures", "(Agarwala", "and", "Hanna", "2005,", "Hirano", "et", "al.", "2005).", "A", "major", "problem", "in", "selecting", "patients", "for", "surgery", "is", "to", "avoid", "operat-", "ing", "on", "those", "who", "are", "likely", "to", "die", "very", "soon", "after", "surgery.", "Although", "several", "features", "help", "to", "identify", "patients", "with", "long", "survival", "(Bauer", "and", "Wedin", "1995,", "Tomita", "et", "al.", "2001),", "it", "is", "still", "difficult", "to", "identify", "those", "who", "will", "die", "early.", "We", "analyzed", "a", "consecutive", "series", "of", "lung", "cancer", "patients", "who", "were", "operated", "on", "for", "skeletal", "metastases", "at", "our", "depart-", "ment,", "to", "determine", "the", "complications", "and", "reoperation", "rates", "after", "surgery", "and", "to", "identify", "risk", "factors", "for", "early", "death.", "Patients", "and", "methods", "This", "study", "was", "based", "on", "data", "recorded", "in", "the", "Karolinska", "Skel-", "etal", "Metastasis", "Register", "(Wedin", "and", "Bauer", "2005).", "The", "reg-", "ister", "is", "a", "quality-control", "database", "that", "prospectively", "collects", "individual-based", "information", "for", "cancer", "patients", "admitted", "to", "Karolinska", "University", "Hospital", "in", "Stockholm.", "All", "data", "are", "col-", "lected", "based", "on", "the", "national", "registration", "number", "(a", "10-digit", "number),", "which", "is", "unique", "for", "each", "Swedish", "resident.", "The", "cri-", "terion", "for", "inclusion", "in", "the", "database", "is", "surgical", "treatment", "for", "complete", "or", "impending", "fractures", "due", "to", "skeletal", "metastasis.", "The", "register", "gathers", "data", "on", "patient", "identity,", "age,", "sex,", "pri-", "mary", "tumor,", "location", "of", "metastases,", "type", "of", "pathological", "fracture,", "and", "surgical", "treatment", "such", "as", "method", "of", "fixation,", "type", "of", "implant,", "and", "postoperative", "complications.", "It", "includes", "staging", "information", "for", "patients", "diagnosed", "with", "lung", "cancer", "Open", "Access", "-", "This", "article", "is", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Noncommercial", "License", "which", "permits", "any", "noncommercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "source", "is", "credited.", "DOI", "10.3109/17453674.2011.552779" ]

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[ "Cheng", "et", "al.", "BMC", "Infectious", "Diseases", "2010,", "10:126", "http://www.biomedcentral.com/1471-2334/10/126", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "RResiesakrchoarfticple", "neumocystosis", "after", "early", "discontinuation", "of", "prophylaxis", "among", "HIV-infected", "patients", "receiving", "highly", "active", "antiretroviral", "therapy", "Chien-Yu", "Cheng†1,", "Mao-Yuan", "Chen1,", "Szu-Min", "Hsieh1,", "Wang-Huei", "Sheng1,", "Hsin-Yun", "Sun1,", "Yi-Chun", "Lo2,", "Wen-", "Chun", "Liu1", "and", "Chien-Ching", "Hung*1", "Abstract", "Background:", "Risk", "of", "pneumocystosis", "after", "discontinuation", "of", "primary", "or", "secondary", "prophylaxis", "among", "HIV-infected", "patients", "before", "CD4", "counts", "increase", "to", "^200", "cells/μL", "(early", "discontinuation)", "after", "receiving", "highly", "active", "antiretroviral", "therapy", "(HAART)", "is", "rarely", "investigated.", "Methods:", "Medical", "records", "of", "660", "HIV-infected", "patients", "with", "baseline", "CD4", "counts", "<200", "cells/μL", "who", "sought", "HIV", "care", "and", "received", "HAART", "at", "a", "university", "hospital", "in", "Taiwan", "between", "1", "April,", "1997", "and", "30", "September,", "2007", "were", "reviewed", "to", "assess", "the", "incidence", "rate", "of", "pneumocystosis", "after", "discontinuation", "of", "prophylaxis", "for", "pneumocystosis.", "Results:", "The", "incidence", "rate", "of", "pneumocystosis", "after", "HAART", "was", "2.81", "per", "100", "person-years", "among", "521", "patients", "who", "did", "not", "initiate", "prophylaxis", "or", "had", "early", "discontinuation", "of", "prophylaxis,", "which", "was", "significantly", "higher", "than", "the", "incidence", "rate", "of", "0.45", "per", "100", "person-years", "among", "139", "patients", "who", "continued", "prophylaxis", "until", "CD4", "counts", "increased", "to", "^200", "cells/μL", "(adjusted", "risk", "ratio,", "5.32;", "95%", "confidence", "interval,", "1.18,", "23.94).", "Among", "the", "215", "patients", "who", "had", "early", "discontinuation", "of", "prophylaxis", "after", "achievement", "of", "undetectable", "plasma", "HIV", "RNA", "load,", "the", "incidence", "rate", "of", "pneumocystosis", "was", "reduced", "to", "0.31", "per", "100", "person-years,", "which", "was", "similar", "to", "that", "of", "the", "patients", "who", "continued", "prophylaxis", "until", "CD4", "counts", "increased", "to", "^200", "cells/μL", "(adjusted", "risk", "ratio,", "0.63;", "95%", "confidence", "interval,", "0.03,", "14.89).", "Conclusions:", "Compared", "with", "the", "risk", "of", "pneumocystosis", "among", "patients", "who", "continued", "prophylaxis", "until", "CD4", "counts", "increased", "to", "^200", "cells/μL", "after", "HAART,", "the", "risk", "was", "significantly", "higher", "among", "patients", "who", "discontinued", "prophylaxis", "when", "CD4", "counts", "remained", "<200", "cells/μL,", "while", "the", "risk", "could", "be", "reduced", "among", "patients", "who", "achieved", "undetectable", "plasma", "HIV", "RNA", "load", "after", "HAART.", "Background", "With", "the", "widespread", "use", "of", "highly", "active", "antiretroviral", "therapy", "(HAART)", "after", "1996,", "HIV-related", "mortality", "and", "the", "risks", "of", "several", "major", "opportunistic", "infections,", "such", "as", "Pneumocystis", "jirovecii", "pneumonia", "(formerly", "P.", "carinii", "pneumonia),", "disseminated", "Mycobacterium", "avium", "com-", "plex", "infection,", "and", "cytomegalovirus", "diseases,", "have", "signif-", "icantly", "declined", "in", "patients", "receiving", "HAART", "[1-3].", "For", "example,", "an", "incidence", "rate", "of", "20", "cases", "of", "pneumocystosis", "per", "100", "person-months", "was", "reported", "in", "the", "pre-HAART", "*", "Correspondence:", "hcc0401@ntu.edu.tw", "1", "Department", "of", "Internal", "Medicine,", "National", "Taiwan", "University", "Hospital", "and", "National", "Taiwan", "University", "College", "of", "Medicine,", "7", "Chung-Shan", "South", "Road,", "Taipei,", "Taiwan", "100", "†", "Contributed", "equally", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "era", "[4],", "which", "decreased", "to", "1.2", "cases", "per", "100", "person-years", "(100", "PY)", "of", "follow-up", "in", "the", "era", "of", "antimicrobial", "prophy-", "laxis", "for", "pneumocystosis", "and", "HAART", "[5].", "In", "the", "HAART", "era,", "the", "majority", "of", "cases", "of", "pneumocystosis", "occur", "in", "patients", "who", "are", "unaware", "of", "their", "HIV", "infection", "or", "have", "delay", "in", "seeking", "HIV", "care,", "or", "in", "those", "with", "advanced", "immunosuppression", "(CD4+", "count", "<", "100", "cells/μL)", "who", "have", "limited", "access", "to", "HAART", "and", "related", "HIV", "care", "[6,7].", "In", "the", "guidelines", "recommended", "by", "the", "National", "Insti-", "tutes", "of", "Health,", "the", "Centers", "for", "Disease", "Control", "and", "Pre-", "vention,", "and", "the", "HIV", "Medicine", "Association", "of", "the", "Infectious", "Diseases", "Society", "of", "America", "[8],", "HIV-infected", "patients", "should", "receive", "trimethoprim-sulfamethoxazole", "(TMP-SMX)", "as", "primary", "prophylaxis", "for", "pneumocystosis", "if", "they", "have", "CD4", "counts", "of", "<200", "cells/μL.", "Primary", "pro-", "©", "2010", "Cheng", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "BioMed", "Central", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"ESC", "differentiation.", "Sets", "of", "genes", "are", "induced", "in", "primary", "ectodermal", "lineages", "and", "then", "in", "differentiated", "neurons,", "constituting", "consecutive", "waves", "of", "known", "and", "novel", "genes.", "Pathway", "analysis", "revealed", "dynamic", "expression", "patterns", "of", "members", "of", "several", "signaling", "pathways,", "including", "NOTCH,", "mTOR", "and", "Toll", "like", "receptors", "(TLR),", "during", "neural", "differentiation.", "An", "interaction", "network", "analysis", "revealed", "that", "the", "TGFb", "family", "of", "genes,", "including", "LEFTY1,", "ID1", "and", "ID2,", "are", "possible", "key", "players", "in", "the", "proliferation", "and", "maintenance", "of", "neural", "ectoderm.", "Collectively,", "these", "results", "enhance", "our", "understanding", "of", "the", "molecular", "dynamics", "underlying", "neural", "commitment", "and", "differentiation.", "Citation:", "Fathi", "A,", "Hatami", "M,", "Hajihosseini", "V,", "Fattahi", "F,", "Kiani", "S,", "et", "al.", "(2011)", "Comprehensive", "Gene", "Expression", "Analysis", "of", "Human", "Embryonic", "Stem", "Cells", "during", "Differentiation", "into", "Neural", "Cells.", "PLoS", "ONE", "6(7):", "e22856.", "doi:10.1371/journal.pone.0022856", "Editor:", "Joseph", "Charles", "Glorioso,", "University", "of", "Pittsburgh", "School", "of", "Medicine,", "United", "States", "of", "America", "Received", "April", "16,", "2011;", "Accepted", "June", "29,", "2011;", "Published", "July", "28,", "2011", "Copyright:", "2011", "Fathi", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "study", "was", "funded", "by", "a", "grant", "provided", "from", "the", "Royan", "Institute.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "Salekdeh@Royaninstitute.org", "(GHS);", "Baharvand@RoyanInstitute.org", "(HB)", "Introduction", "Embryonic", "stem", "cells", "(ESCs)", "are", "a", "promising", "tool", "for", "the", "study", "of", "neural", "development", "and", "cell", "lineage", "specification.", "The", "current", "lack", "of", "knowledge", "about", "cues", "for", "mammalian", "neuronal", "commit-", "ment", "and", "differentiation", "is", "at", "least", "partly", "due", "to", "a", "paucity", "of", "available", "model", "systems", "that", "permit", "direct", "observation", "of", "developmental", "processes.", "Studies", "of", "the", "molecular", "mechanisms", "underlying", "the", "neural", "differentiation", "of", "human", "ESCs", "(hESCs)", "can", "help", "to", "unravel", "the", "complex", "gene", "pathways", "that", "are", "involved", "in", "neural", "cell", "commitment", "and", "differentiation", "processes.", "High", "throughput", "studies", "of", "gene", "expression", "have", "been", "applied", "to", "neural", "stem", "cells", "(NSCs)", "derived", "from", "the", "subventricular", "zone", "(SVZ)", "[1],", "NSCs", "derived", "from", "mouse", "ESCs", "and", "the", "fetal", "brain", "[2],", "dopaminergic", "neurons", "from", "mouse", "ESCs", "[3],", "heterogeneous", "neural", "cells", "from", "mouse", "ESCs", "[4]", "and", "neural", "progenitors", "(NPs)", "differentiated", "from", "mouse", "ESCs", "[5]", "and", "forebrain", "periventricular", "zone", "NPs", "compared", "to", "neuroectoderm", "from", "mESCs", "[6].", "Cytoskeletal", "genes,", "cell", "membrane", "receptor", "genes,", "and", "transcrip-", "tion", "factor", "genes", "are", "differentially", "expressed", "in", "most", "cell", "types.", "Recently,", "Wu", "et", "al.", "(2010)", "analyzed", "the", "transcriptome", "of", "hESCs", "during", "differentiation", "into", "the", "neural", "lineage", "at", "the", "early", "initiation,", "neural", "progenitor,", "and", "early", "glial-like", "stages", "[7]", "and", "found", "an", "extraordinary", "degree", "of", "stage-specific", "transcription", "and", "splicing.", "The", "diversity", "was", "highest", "in", "undifferentiated", "hESCs", "and", "decreased", "upon", "differentiation", "[7].", "Previously,", "we", "described", "the", "differentiation", "of", "hESCs", "into", "NPs", "and", "neural", "cells", "with", "typical", "cellular,", "molecular", "and", "ultrastructural", "markers", "using", "a", "defined", "adherent", "culture", "protocol", "[8,9].", "Here", "we", "analyzed", "the", "transcriptome", "of", "hESCs", "during", "differentiation", "into", "neural", "cells", "[8]", "using", "a", "whole", "genome", "microarray", "chip.", "We", "identified", "differentially", "expressed", "genes", "that", "may", "be", "linked", "to", "neural", "fate", "specification,", "proliferation,", "and", "differentiation.", "Our", "data", "extend", "the", "gene", "expression", "network", "for", "neural", "differentiation", "and", "reveal", "novel", "aspects", "of", "transcriptional", "control", "pathways", "underlying", "the", "multistep", "process", "of", "commitment", "and", "differentia-", "tion", "of", "hESCs", "into", "neural", "cells.", "Materials", "and", "Methods", "Human", "ESC", "culture", "and", "sample", "preparation", "The", "hESC", "line", "Royan", "H6", "[10]", "was", "passaged", "and", "cultured", "under", "feeder-free", "culture", "conditions", "on", "Matrigel", "in", "hESC", "medium", "containing", "DMEM/F12", "medium", "supplemented", "with", "20%", "knock-", "out", "serum", "replacement,", "2", "mM", "L-glutamine,", "1%", "nonessential", "amino", "acids,", "100", "units/ml", "penicillin", "and", "100", "mg/ml", "streptomycin,", "insulin-transferrin-selenite,", "(All", "from", "Invitrogen),", "0.1", "mM", "b-", "mercaptoethanol", "and", "100", "ng/ml", "basic-fibroblast", "growth", "factor", "PLoS", "ONE", "|", "www.plosone.org", "1", "July", "2011", "|", "Volume", "6", "|", "Issue", "7", "|", "e22856" ]

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[ "Ramsay", "et", "al.", "Implementation", "Science", "2010,", "5:71", "http://www.implementationscience.com/content/5/1/71", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Implementation", "Science", "Open", "Access", "Using", "the", "theory", "of", "planned", "behaviour", "as", "a", "process", "evaluation", "tool", "in", "randomised", "trials", "of", "knowledge", "translation", "strategies:", "A", "case", "study", "from", "UK", "primary", "care", "Craig", "R", "Ramsay1*,", "Ruth", "E", "Thomas1,", "Bernard", "L", "Croal2,", "Jeremy", "M", "Grimshaw3,", "Martin", "P", "Eccles4", "Abstract", "Background:", "Randomised", "trials", "of", "knowledge", "translation", "strategies", "for", "professional", "behaviour", "change", "can", "provide", "robust", "estimates", "of", "effectiveness,", "but", "offer", "little", "insight", "into", "the", "causal", "mechanisms", "by", "which", "any", "change", "is", "produced.", "To", "illustrate", "the", "applicability", "of", "causal", "methods", "within", "randomised", "trials,", "we", "undertook", "a", "theory-based", "process", "evaluation", "study", "within", "an", "implementation", "trial", "to", "explore", "whether", "the", "cognitions", "of", "primary", "care", "doctors’", "predicted", "their", "test", "requesting", "behaviours", "and,", "secondly,", "whether", "the", "trial", "results", "were", "mediated", "by", "the", "theoretical", "constructs.", "Methods:", "The", "process", "evaluation", "comprised", "a", "cross-sectional", "questionnaire", "survey", "of", "a", "random", "50%", "sample", "of", "the", "randomised", "groups", "of", "primary", "care", "practices", "in", "Grampian", "(NHS", "Grampian),", "UK,", "who", "took", "part", "in", "a", "trial", "of", "the", "effect", "of", "enhanced", "feedback", "and", "brief", "educational", "reminders", "on", "test", "requesting", "behaviour.", "The", "process", "evaluation", "was", "based", "upon", "the", "Theory", "of", "Planned", "Behaviour", "and", "focussed", "on", "three", "of", "the", "test", "requesting", "behaviours", "that", "were", "targeted", "in", "the", "trial", "–", "ferritin,", "follicle", "stimulating", "hormone", "(FSH),", "and", "Helicobacter", "Pylori", "serology", "(HPS).", "Results:", "The", "questionnaire", "was", "completed", "by", "131", "primary", "care", "doctors", "(56%)", "from", "42", "(98%)", "of", "the", "sampled", "practices.", "Behavioural", "intention,", "attitude,", "and", "subjective", "norm", "were", "highly", "correlated", "for", "all", "the", "tests.", "There", "was", "no", "evidence", "that", "perceived", "behavioural", "control", "was", "correlated", "with", "any", "of", "the", "other", "measures.", "Simple", "linear", "regression", "analysis", "of", "the", "rate", "of", "test", "requests", "on", "minimum", "behavioural", "intentions", "had", "R2", "of", "11.1%,", "12.5%,", "and", "0.1%", "for", "ferritin,", "FSH,", "and", "HPS", "requesting,", "respectively.", "Mediational", "analysis", "showed", "that", "the", "trial", "results", "for", "ferritin", "and", "FSH", "were", "partially", "mediated", "(between", "23%", "and", "78%", "mediation)", "through", "intentions.", "The", "HPS", "trial", "result", "was", "not", "mediated", "through", "intention.", "Conclusions:", "This", "study", "demonstrated", "that", "a", "theory-based", "process", "evaluation", "can", "provide", "useful", "information", "on", "causal", "mechanisms", "that", "aid", "not", "only", "interpretation", "of", "the", "trial", "but", "also", "inform", "future", "evaluations", "and", "intervention", "development.", "Introduction", "Randomised", "trials", "of", "knowledge", "translation", "(KT)", "strate-", "gies", "for", "professional", "behaviour", "change", "can", "provide", "robust", "estimates", "of", "effectiveness,", "but", "offer", "little", "insight", "into", "the", "causal", "mechanisms", "by", "which", "any", "change", "is", "pro-", "duced.", "This", "would", "not", "be", "an", "issue", "if", "interventions", "had", "a", "*", "Correspondence:", "c.r.ramsay@abdn.ac.uk", "1Health", "Services", "Research", "Unit,", "University", "of", "Aberdeen,", "Foresterhill,", "Aberdeen,", "AB25", "2ZD,", "UK", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "uniform", "effect", "across", "different", "conditions", "that", "could", "be", "generalised", "to", "all", "practitioners", "outside", "of", "the", "trials.", "However,", "the", "effects", "of", "interventions", "do", "appear", "to", "vary", "by", "condition,", "professional", "group,", "and", "context,", "presum-", "ably", "because", "the", "causal", "mechanisms", "of", "the", "interventions", "are", "modified", "in", "the", "presence", "of", "different", "barriers", "and", "enablers", "[1].", "Therefore", "the", "interpretation", "of", "a", "trial", "and", "assessment", "of", "its", "likely", "generalisability", "would", "be", "enhanced", "if", "additional", "information", "was", "obtained", "about", "the", "causal", "mechanisms", "through", "which", "the", "intervention", "©", "2010", "Ramsay", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Int.", "J.", "Environ.", "Res.", "Public", "Health", "2012,", "9,", "985-994;", "doi:10.3390/ijerph9030985", "OPEN", "ACCESS", "International", "Journal", "of", "Environmental", "Research", "and", "Public", "Health", "ISSN", "1660-4601", "www.mdpi.com/journal/ijerph", "Review", "Social", "Aspects", "of", "Suicidal", "Behavior", "and", "Prevention", "in", "Early", "Life:", "A", "Review", "Maya", "Amitai", "1,2", "and", "Alan", "Apter", "2,3,*", "1", "Child", "and", "Adolescent", "Division,", "Geha", "Mental", "Health", "Center,", "Petach", "Tikva,", "Israel;", "E-Mail:", "maya47@zahav.net.il", "2", "Sackler", "Faculty", "of", "Medicine,", "Tel", "Aviv", "University,", "Tel", "Aviv,", "Israel", "3", "Department", "of", "Psychiatry,", "The", "Feinberg", "Child", "Study", "Center,", "Schneider", "Children’s", "Medical", "Center", "of", "Israel,", "Petach", "Tikva,", "Israel", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "eapter@clalit.org.il;", "Tel.:", "+972-3-925-3617;", "Fax:", "+972-3-925-3864.", "Received:", "2", "February", "2012;", "in", "revised", "form:", "5", "March", "2012", "/", "Accepted:", "12", "March", "2012", "/", "Published:", "19", "March", "2012", "Abstract:", "Purpose:", "The", "present", "review", "summarizes", "the", "updated", "literature", "on", "the", "social", "aspects", "of", "suicidal", "behavior", "and", "prevention", "in", "adolescents.", "Recent", "findings:", "The", "predictive", "role", "of", "psychiatric", "disorders", "and", "past", "history", "are", "well", "recognized", "in", "adolescent", "suicide,", "but", "the", "role", "of", "social", "and", "cultural", "factors", "is", "less", "clear.", "Studies", "have", "focused", "on", "the", "importance", "of", "ethnicity,", "gender,", "family", "characteristics,", "and", "socioeconomic", "status.", "More", "recently,", "attention", "has", "been", "addressed", "to", "broader", "social", "risk", "factors,", "such", "as", "bullying", "in", "adolescents,", "suicide", "contagion,", "sexual", "orientation,", "and", "the", "popular", "media.", "Further", "empirical", "evidence", "is", "needed", "to", "advance", "our", "understanding", "of", "suicidal", "youth,", "develop", "better", "assessment", "tools,", "and", "formulate", "effective", "prevention", "and", "treatment", "programs.", "Summary:", "Suicidal", "behavior", "remains", "an", "important", "clinical", "problem", "and", "major", "cause", "of", "death", "in", "youth.", "Social", "factors", "may", "be", "at", "least", "as", "important", "as", "genetics.", "Advancing", "our", "understanding", "of", "underlying", "cultural", "and", "sociological", "issues", "in", "youth", "suicide", "will", "help", "clinicians", "achieve", "more", "efficient", "prediction,", "prevention", "and", "treatment.", "Keywords:", "adolescents;", "social;", "cultural;", "risk", "factors;", "suicide;", "bullying" ]

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[ "J", "Appl", "Genetics", "(2012)", "53:237–247", "DOI", "10.1007/s13353-012-0087-z", "MICROBIAL", "GENETICS", "·", "ORIGINAL", "PAPER", "Genetic", "variation", "of", "Fusarium", "oxysporum", "isolates", "forming", "fumonisin", "B1", "and", "moniliformin", "Lidia", "Irzykowska", "&", "Jan", "Bocianowski", "&", "Agnieszka", "Waśkiewicz", "&", "Zbigniew", "Weber", "&", "Zbigniew", "Karolewski", "&", "Piotr", "Goliński", "&", "Marian", "Kostecki", "&", "Witold", "Irzykowski", "Received:", "2", "December", "2011", "/", "Revised:", "21", "January", "2012", "/", "Accepted:", "27", "January", "2012", "/", "Published", "online:", "25", "February", "2012", "#", "The", "Author(s)", "2012.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Thirty", "single-spore", "isolates", "of", "a", "toxigenic", "fungus,", "Fusarium", "oxysporum,", "were", "isolated", "from", "asparagus", "spears", "and", "identified", "by", "species-specific", "polymerase", "chain", "reaction", "(PCR)", "and", "translation", "elongation", "factor", "1-α", "(TEF)", "sequence", "analysis.", "In", "the", "examined", "sets", "of", "F.", "oxysporum", "isolates,", "the", "DNA", "sequences", "of", "mating", "type", "genes", "(MAT)", "were", "identified.", "The", "distribution", "of", "MAT", "idiomorph", "may", "suggest", "that", "MAT1-2", "is", "a", "predominant", "mating", "type", "in", "the", "F.", "oxysporum", "population.", "F.", "oxysporum", "is", "mainly", "recognised", "as", "a", "producer", "of", "monili-", "formin—the", "highly", "toxic", "secondary", "metabolite.", "Moniliformin", "content", "was", "determined", "by", "high-performance", "liquid", "chroma-", "tography", "(HPLC)", "analysis", "in", "the", "range", "0.05–1,007.47", "μg", "g−1", "(mean", "115.93", "μg", "g−1)", "but,", "also,", "fumonisin", "B1", "was", "detected,", "in", "the", "concentration", "range", "0.01–0.91", "μg", "g−1", "(mean", "0.19", "μg", "g−1).", "L.", "Irzykowska", "(*)", ":", "Z.", "Weber", ":", "Z.", "Karolewski", "Department", "of", "Phytopathology,", "Poznan", "University", "of", "Life", "Sciences,", "Dąbrowskiego", "159,", "60-594", "Poznań,", "Poland", "e-mail:", "irzyk@up.poznan.pl", "J.", "Bocianowski", "Department", "of", "Mathematical", "and", "Statistical", "Methods,", "Poznan", "University", "of", "Life", "Sciences,", "Wojska", "Polskiego", "28,", "60-637", "Poznan,", "Poland", "A.", "Waśkiewicz", ":", "P.", "Goliński", ":", "M.", "Kostecki", "Department", "of", "Chemistry,", "Poznan", "University", "of", "Life", "Sciences,", "Wojska", "Polskiego", "75,", "60-625", "Poznań,", "Poland", "W.", "Irzykowski", "Institute", "of", "Plant", "Genetics", "Polish", "Academy", "of", "Science,", "Strzeszyńska", "34,", "60-479", "Poznań,", "Poland", "There", "was", "no", "association", "between", "mating", "types", "and", "the", "mycotoxins", "biosynthesis", "level.", "Additionally,", "a", "significant", "intra-species", "genetic", "diversity", "was", "revealed", "and", "molecular", "markers", "associated", "with", "toxins", "biosynthesis", "were", "identified.", "Keywords", "Fusarium", "oxysporum", ".", "Fumonisin", "B1", ".", "Moniliformin", ".", "Mating", "type", "idiomorphs", ".", "Genetic", "fingerprinting", ".", "HPLC", "analysis", "Introduction", "Asparagus", "(Asparagus", "officinalis", "L.)", "is", "a", "worldwide", "well-", "known", "vegetable", "not", "only", "due", "to", "its", "high", "nutritional", "value,", "but", "also", "because", "of", "the", "biologically", "active", "compounds", "present,", "including", "protodioscin", "and", "rutin,", "with", "a", "strong", "cytotoxic", "ac-", "tivity", "against", "many", "cancer", "cell", "lines", "(Kinghorn", "et", "al.", "2003;", "Chin", "and", "Garrison", "2008).", "However,", "the", "asparagus", "is", "often", "infected", "by", "fungi", "of", "the", "Fusarium", "genus,", "a", "causal", "agent", "of", "crown", "and", "root", "rot", "which", "decreases", "the", "quantity", "and", "quality", "of", "the", "yield.", "A", "visible", "chlorosis", "and", "wilting", "of", "the", "individual", "stalks,", "progressive", "discolouration", "of", "plants", "and", "destruction", "of", "roots", "and", "crown", "are", "the", "main", "symptoms", "of", "this", "serious", "disease", "(Logrieco", "et", "al.", "2003).", "F.", "oxysporum", "Schlechtend.", "emend.", "Snyder", "&", "Hansen", "and", "F.", "proliferatum", "(Matsus.)", "Nirenberg", "are", "the", "most", "severe", "asparagus", "pathogens", "(Blok", "and", "Bollen", "1995;", "von", "Bargen", "et", "al.", "2009).", "Both", "species", "are", "well-known", "mycotoxins", "producers,", "so", "their", "precise", "identification", "is", "of", "prime", "concern.", "New", "molecular", "methods", "have", "been", "applied", "to", "complement,", "support", "and", "confirm", "identification", "based", "on", "morphological", "characters", "(Geiser", "et", "al.", "2004).", "F.", "oxysporum", "is", "identified", "worldwide", "and", "is", "known", "to", "be", "phylogenetically", "diverse", "and", "recognised", "as", "a", "moniliformin" ]

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[ "Standards", "in", "Genomic", "Sciences", "(2011)", "5:211-223", "DOI:10.4056/sigs.2025347", "Minimal", "Information", "for", "Neural", "Electromagnetic", "Ontologies", "(MINEMO):", "A", "standards-compliant", "method", "for", "analysis", "and", "integration", "of", "event-related", "potentials", "(ERP)", "data", "Gwen", "Frishkoff1,", "2,", "3", "Jason", "Sydes4,", "Kurt", "Mueller4,", "Robert", "Frank2,", "Tim", "Curran3,5,", "John", "Connolly3,", "6,", "Kerry", "Kilborn3,7,", "Dennis", "Molfese3,8,", "Charles", "Perfetti3,9,", "&", "Allen", "Malony2,", "4", "1Department", "of", "Psychology", "&", "Neuroscience", "Institute,", "Georgia", "State", "University,", "Atlanta,", "GA", "2NeuroInformatics", "Center,", "University", "of", "Oregon,", "Eugene,", "OR", "3Neural", "ElectroMagnetic", "Ontologies", "(NEMO)", "ERP", "Consortium", "4Department", "of", "Computer", "&", "Information", "Science,", "University", "of", "Oregon,", "Eugene,", "OR", "5Department", "of", "Psychology", "&", "Neuroscience,", "University", "of", "Colorado,", "Boulder,", "CO", "6Department", "of", "Psychology", "and", "Linguistics,", "McMaster", "University,", "Ontario,", "CA", "7Department", "of", "Psychology,", "Glasgow", "University,", "Scotland,", "UK", "8Department", "of", "Psychology,", "University", "of", "Nebraska-Lincoln,", "Lincoln,", "NE", "9Department", "of", "Psychology", "and", "Linguistics,", "University", "of", "Pittsburgh,", "Pittsburgh,", "PA", "We", "present", "MINEMO", "(Minimal", "Information", "for", "Neural", "ElectroMagnetic", "Ontologies),", "a", "checklist", "for", "the", "description", "of", "event-related", "potentials", "(ERP)", "studies.", "MINEMO", "extends", "MINI", "(Minimal", "Information", "for", "Neuroscience", "Investigations)to", "the", "ERP", "domain.", "Checklist", "terms", "are", "explicated", "in", "NEMO,", "a", "formal", "ontology", "that", "is", "designed", "to", "support", "ERP", "data", "sharing", "and", "integration.", "MINEMO", "is", "also", "linked", "to", "an", "ERP", "database", "and", "web", "application", "(the", "NEMO", "portal).", "Users", "upload", "their", "data", "and", "enter", "MINEMO", "information", "through", "the", "portal.", "The", "database", "then", "stores", "these", "entries", "in", "RDF", "(Resource", "Description", "Framework),", "along", "with", "summary", "metrics,", "i.e.,", "spatial", "and", "temporal", "metadata.", "Together", "these", "spatial,", "temporal,", "and", "functional", "metadata", "provide", "a", "complete", "description", "of", "ERP", "data", "and", "the", "context", "in", "which", "these", "data", "were", "acquired.", "The", "RDF", "files", "then", "serve", "as", "inputs", "to", "ontology-based", "labeling", "and", "meta-analysis.", "Our", "ultimate", "goal", "is", "to", "represent", "ERPs", "using", "a", "rich", "semantic", "structure,", "so", "results", "can", "be", "queried", "at", "multiple", "levels,", "to", "stimulate", "novel", "hypotheses", "and", "to", "promote", "a", "high-level,", "integrative", "account", "of", "ERP", "results", "across", "diverse", "study", "methods", "and", "paradigms.", "Keywords:", "Ontology,", "database,", "data", "sharing,", "standardization,", "experiment", "metadata,", "neuroscience,", "electrophysiology,", "event-related", "potentials", "Introduction", "Over", "the", "last", "few", "decades,", "neuroscience", "has", "witnessed", "an", "explosion", "of", "methods", "for", "the", "measurement", "of", "human", "brain", "function,", "including", "high-density", "(multi-sensor)", "event-related", "potentials", "(ERPs).", "In", "comparison", "with", "other", "techniques,", "the", "ERP", "method", "has", "several", "advantages:", "it", "is", "completely", "safe", "and", "noninvasive,", "it", "is", "inexpensive", "and", "portable,", "and", "—", "unlike", "methods", "such", "as", "functional", "magnetic", "resonance", "imaging", "(fMRI)", "—", "it", "is", "a", "direct", "measure", "of", "neuronal", "activity.", "The", "ERP", "method", "also", "has", "excellent", "(millisecond)", "temporal", "resolution,", "which", "is", "critical", "for", "representation", "of", "neural", "dynamics.", "Remarkably,", "despite", "these", "many", "virtues,", "there", "are", "few", "quantitative", "comparisons", "(“meta-analyses”)", "of", "ERP", "results,", "reflecting", "the", "complexity", "of", "ERP", "data", "and", "the", "wide", "variety", "of", "methods", "that", "are", "used", "to", "extract", "and", "analyze", "ERP", "metadata", "[1-3].", "To", "address", "this", "gap,", "we", "have", "gathered", "an", "interdisciplinary", "team", "of", "researchers", "in", "informatics", "and", "human", "neuroscience", "to", "form", "project", "NEMO", "(Neural", "ElectroMagnetic", "Ontologies).", "Our", "neuroscience", "experts", "are", "internationally", "known", "for", "their", "ERP", "studies", "of", "language", "and", "cognition", "and", "have", "partnered", "to", "form", "a", "consortium.", "Consortium", "members", "provide", "ERP", "datasets", "and", "contribute", "to", "the", "design", "and", "testing", "of", "ERP", "ontologies", "and", "ontology-based", "methods", "for", "meta-analysis", "[3].", "The", "Genomic", "Standards", "Consortium" ]

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[ "Hindawi", "Publishing", "Corporation", "Infectious", "Diseases", "in", "Obstetrics", "and", "Gynecology", "Volume", "2006,", "Article", "ID", "79512,", "Pages", "1–5", "DOI", "10.1155/IDOG/2006/79512", "Clinical", "Study", "Postpartum", "Morbidity", "Associated", "With", "Advanced", "HIV", "Disease", "Judette", "Louis,1", "Mudathiru", "A.", "Buhari,2", "Dianne", "Allen,1", "Bernard", "Gonik,1", "and", "Theodore", "B.", "Jones1", "1", "Department", "of", "Obstetrics", "and", "Gynecology,", "Division", "of", "Maternal", "Fetal", "Medicine,", "Wayne", "State", "University,", "Detroit,", "MI", "48201,", "USA", "2", "Department", "of", "Internal", "Medicine,", "Division", "of", "Infectious", "Diseases,", "Wayne", "State", "University,", "Detroit,", "MI", "48201,", "USA", "Received", "28", "May", "2006;", "Revised", "25", "September", "2006;", "Accepted", "10", "October", "2006", "Objective.", "To", "investigate", "the", "postpartum", "morbidity", "and", "postpartum", "management", "of", "febrile", "morbidity", "associated", "with", "advanced", "HIV", "infection.", "Methods.", "A", "case", "control", "study", "of", "HIV", "infected", "women", "at", "a", "tertiary", "care", "center", "during", "January", "2000–June", "2005", "was", "performed.", "Postpartum", "morbidity", "was", "defined", "as", "endometritis,", "blood", "transfusion,", "wound", "complication,", "readmission,", "infectious", "morbidity,", "or", "unexpected", "surgery.", "Results.", "Women", "in", "Group", "1", "had", "AIDS", "(N", "=", "33),", "Group", "2", "were", "relatively", "immunocompetent", "HIV", "infected", "women", "(N", "=", "115),", "and", "Group", "3", "were", "uninfected", "women", "(N", "=", "152).", "Group", "1", "was", "more", "likely", "to", "have", "a", "postpartum", "morbidity", "(32.3", "versus", "19.3", "and", "13.2%,", "P", "=", ".03)", "and", "to", "have", "postpartum", "imaging", "18.8", "versus", "7.9", "and", "2.6%,", "P", "=", ".002.", "After", "controlling", "for", "potential", "confounders,", "cesarean", "delivery", "(OR", "6.2,", "95%", "CI", "2.1–505.5)", "but", "not", "advanced", "HIV", "disease", "was", "associated", "with", "an", "increased", "risk", "of", "postpartum", "morbidity.", "Conclusion.", "Cesarean", "delivery", "and", "not", "advanced", "HIV", "disease", "increases", "the", "risk", "of", "postpartum", "morbidity", "in", "women", "with", "AIDS.", "Copyright", "©", "2006", "Judette", "Louis", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "INTRODUCTION", "Women", "are", "making", "up", "an", "increasing", "part", "of", "the", "acquired", "im-", "mune", "deficiency", "syndrome", "(AIDS)", "epidemic", "in", "the", "United", "States", "[1].", "In", "2001", "HIV", "infection", "was", "the", "6th", "leading", "cause", "of", "death", "among", "all", "women", "aged", "25–34", "years", "and", "the", "4th", "lead-", "ing", "cause", "of", "death", "among", "all", "women", "aged", "35–44", "years.", "By", "the", "end", "of", "2003,", "women", "and", "adolescents", "represented", "22%", "of", "the", "people", "living", "with", "AIDS", "[1].", "With", "the", "considerable", "num-", "ber", "of", "women", "of", "childbearing", "age", "with", "AIDS,", "issues", "related", "to", "pregnancy", "remain", "a", "concern.", "Initial", "studies", "in", "the", "field", "of", "perinatal", "HIV", "focused", "on", "vertical", "transmission.", "As", "we", "have", "made", "great", "strides", "to", "reduce", "vertical", "transmission", "to", "less", "than", "2%", "in", "the", "US,", "there", "has", "been", "an", "increased", "focus", "on", "maternal", "health.", "While", "childbirth", "in", "developed", "countries", "is", "relatively", "safe,", "there", "exists", "a", "risk", "of", "morbidity.", "Of", "significance,", "cesarean", "sec-", "tion", "is", "associated", "with", "an", "increased", "risk", "and,", "in", "particu-", "lar,", "infectious", "morbidity", "[2].", "Risk", "factors", "for", "morbidity", "in-", "clude", "prolonged", "rupture", "of", "membranes,", "obesity,", "immune", "suppression,", "and", "type", "of", "anesthesia,", "nonelective", "cesarean", "de-", "livery,", "and", "a", "number", "of", "vaginal", "examinations", "among", "oth-", "ers", "[3].", "Women", "with", "AIDS", "are", "severely", "immunocompro-", "mised", "and", "may", "be", "at", "increased", "risk", "for", "postpartum", "morbid-", "ity.", "While", "studies", "have", "indicated", "that", "the", "risk", "may", "be", "greater", "for", "HIV-infected", "patients,", "few", "studies", "have", "estimated", "the", "risk", "among", "the", "most", "immunocompromised", "of", "these", "patients", "[4].", "Further", "more,", "no", "studies", "have", "examined", "the", "difference", 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[ "www.jkns.or.kr", "http://dx.doi.org/10.3340/jkns.2012.52.3.193", "J", "Korean", "Neurosurg", "Soc", "52", ":", "193-199,", "2012", "Print", "ISSN", "2005-3711", "On-line", "ISSN", "1598-7876", "Copyright", "©", "2012", "The", "Korean", "Neurosurgical", "Society", "Clinical", "Article", "Incidence", "and", "Risk", "Factors", "for", "Leptomeningeal", "Carcinomatosis", "in", "Breast", "Cancer", "Patients", "with", "Parenchymal", "Brain", "Metastases", "Jong-myung", "Jung,", "M.D.,1", "Sohee", "Kim,", "M.S.,2", "Jungnam", "Joo,", "Ph.D.,2", "Kyung", "Hwan", "Shin,", "M.D.,", "Ph.D.,3", "Ho-Shin", "Gwak,", "M.D.,", "Ph.D.,4", "Seung", "Hoon", "Lee,", "M.D.,", "Ph.D.4", "Department", "of", "Neurosurgery,1", "Seoul", "National", "University", "College", "of", "Medicine,", "Cancer", "Biostatistics", "Branch,2", "Seoul,", "Korea", "Department", "of", "Radiation", "Oncology,3", "Neuro-Oncology", "Clinic,4", "National", "Cancer", "Center,", "Goyang,", "Korea", "Objective", ":", "The", "objective", "of", "study", "is", "to", "evaluate", "the", "incidence", "of", "leptomeningeal", "carcinomatosis", "(LMC)", "in", "breast", "cancer", "patients", "with", "parenchymal", "brain", "metastases", "(PBM)", "and", "clinical", "risk", "factors", "for", "the", "development", "of", "LMC.", "Methods", ":", "We", "retrospectively", "analyzed", "27", "patients", "who", "had", "undergone", "surgical", "resection", "(SR)", "and", "156", "patients", "with", "whole", "brain", "radiation", "therapy", "(WBRT)", "as", "an", "initial", "treatment", "for", "their", "PBM", "from", "breast", "cancer", "in", "our", "institution", "and", "compared", "the", "difference", "of", "incidence", "of", "LMC", "according", "to", "clinical", "factors.", "The", "diagnosis", "of", "LMC", "was", "made", "by", "cerebrospinal", "fluid", "cytology", "and/or", "magnetic", "resonance", "imaging.", "Results", ":", "A", "total", "of", "27", "patients", "(14%)", "in", "the", "study", "population", "developed", "LMC", "at", "a", "median", "of", "6.0", "months", "(range,", "1.0-50).", "Ten", "of", "27", "patients", "(37%)", "developed", "LMC", "after", "SR,", "whereas", "17", "of", "156", "(11%)", "patients", "who", "received", "WBRT", "were", "diagnosed", "with", "LMC", "after", "the", "index", "procedure.", "The", "inci-", "dence", "of", "LMC", "was", "significantly", "higher", "in", "the", "SR", "group", "compared", "with", "the", "WBRT", "group", "and", "the", "hazard", "ratio", "was", "2.95", "(95%", "confidence", "interval;", "1.33-6.54,", "p<0.01).", "Three", "additional", "factors", "were", "identified", "in", "the", "multivariable", "analysis", ":", "the", "younger", "age", "group", "(<40", "years", "old),", "the", "progressing", "systemic", "disease", "showed", "significantly", "increased", "incidence", "of", "LMC,", "whereas", "the", "adjuvant", "chemotherapy", "reduce", "the", "incidence.", "Conclusion", ":", "There", "is", "an", "increased", "risk", "of", "LMC", "after", "SR", "for", "PBM", "from", "breast", "cancer", "compared", "with", "WBRT.", "The", "young", "age", "(<40)", "and", "systemic", "bur-", "den", "of", "cancer", "in", "terms", "of", "progressing", "systemic", "disease", "without", "adjuvant", "chemotherapy", "could", "be", "additional", "risk", "factors", "for", "the", "development", "of", "LMC.", "Key", "Words", ":", "Brain", "metastasis", "·", "Breast", "cancer", "·", "Leptomeningeal", "carcinomatosis", "·", "Surgery", "·", "Whole", "brain", "radiation", "therapy.", "INTRODUCTION", "The", "incidence", "of", "parenchymal", "brain", "metastasis", "(PBM)", "from", "primary", "systemic", "cancer", "has", "been", "increasing", "along", "with", "pro-", "longed", "survival", "of", "the", "patients", "with", "cancer.", "Recent", "report", "showed", "that", "up", "to", "30%", "of", "cancer", "patients", "can", "be", "expected", "to", "develop", "PBM", "according", "to", "the", "types", "of", "primary", "cancer6,12).", "A", "popula-", "tion-based", "estimate", "of", "the", "incidence", "proportion", "of", "PBM", "was", "highest", "for", "lung", "cancer", "followed", "by", "melanoma,", "renal-,", "and", "breast", "cancer3).", "However,", "leptomeningeal", "carcinomatosis", "(LMC),", "which", "is", "one", "of", "terminal", "manifestations", "of", "central", "nervous", "system", "(CNS)", "me-", "tastasis", "from", "systemic", "malignancy,", "remains", "incurable", "without", "a", "discernible", "advance", "in", "treatment", "over", "the", "past", "decades.", "LMC", "also", "has", "been", "diagnosed", "more", "frequently", "with", "the", "advancement", "of", "neuroimaging", "and", "prolonged", "survival", "of", "cancer", "patients8,13,29).", "Among", "the", "pathogenesis", "of", "LMC,", "spread", "of", "cancer", "cells", "fol-", "lowed", "by", "surgical", "resection", "(SR)", "has", "been", "suggested", "from", "sev-", "eral", "clinical", "observations", "of", "solid", "tumors", "including", "malignant", "brain", "tumors2,11,16,22,23,34).", "Although", "the", "overall", "incidence", "of", "LMC", "is", "difficult", "to", "estimate", "according", "to", "PBM", "status,", "it", "is", "apparent", "that", "the", "primary", "cancer", "showing", "a", "high", "incidence", "of", "PBM,", "such", "as", "lung", "cancer,", "breast", "cancer", "or", "melanoma,", "develops", "into", "a", "high", "proportion", "of", "LMC", "among", "those", "cancer", "patients5,35).", "Several", "reports", "suggested", "that", "the", "risk", "for", "development", "of", "LMC", "may", "increase", "in", "patients", "with", "PBM", "who", "underwent", "SR", "compared", "with", "non-surgical", "treatment,", "and", "at", "the", "same", "time,", "the", "risk", "may", "also", "be", "affected", "by", "factors", "such", "as", "location", "of", "the", "tu-", "•", "Received", ":", "January", "10,", "2012", "•", "Revised", ":", "June", "14,", "2012", "•", "Accepted", ":", "September", "17,", "2012", "•", "Address", "for", "reprints", ":", "Ho-Shin", "Gwak,", "M.D.,", "Ph.D.", "Neuro-Oncology", "Clinic,", "National", "Cancer", "Center,", "323", "Ilsan-ro,", "Ilsandong-gu,", "Goyang", "410-769,", "Korea", "Tel", ":", "+82-31-920-1666,", "Fax", ":", "+82-31-920-2798,", "E-mail", ":", "nsghs@ncc.re.kr", "•", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "193" ]

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[ "Pleiotrophin", "(PTN)", "Expression", "and", "Function", "and", "in", "the", "Mouse", "Mammary", "Gland", "and", "Mammary", "Epithelial", "Cells", "Sonia", "M.", "Rosenfield1,", "Emma", "T.", "Bowden2,", "Shani", "Cohen-Missner1,", "Krissa", "A.", "Gibby1,", "Virginie", "Ory1,", "Ralf", "T.", "Henke1,", "Anna", "T.", "Riegel1,", "Anton", "Wellstein1*", "1", "Lombardi", "Cancer", "Center,", "Georgetown", "University,", "Washington,", "District", "of", "Columbia,", "United", "States", "of", "America,", "2", "MedImmune,", "Gaithersburg,", "Maryland,", "United", "States", "of", "America", "Abstract", "Expression", "of", "the", "heparin-binding", "growth", "factor,", "pleiotrophin", "(PTN)", "in", "the", "mammary", "gland", "has", "been", "reported", "but", "its", "function", "during", "mammary", "gland", "development", "is", "not", "known.", "We", "examined", "the", "expression", "of", "PTN", "and", "its", "receptor", "ALK", "(Anaplastic", "Lymphoma", "Kinase)", "at", "various", "stages", "of", "mouse", "mammary", "gland", "development", "and", "found", "that", "their", "expression", "in", "epithelial", "cells", "is", "regulated", "in", "parallel", "during", "pregnancy.", "A", "30-fold", "downregulation", "of", "PTN", "mRNA", "expression", "was", "observed", "during", "mid-pregnancy", "when", "the", "mammary", "gland", "undergoes", "lobular-alveolar", "differentiation.", "After", "weaning", "of", "pups,", "PTN", "expression", "was", "restored", "although", "baseline", "expression", "of", "PTN", "was", "reduced", "significantly", "in", "mammary", "glands", "of", "mice", "that", "had", "undergone", "multiple", "pregnancies.", "We", "found", "PTN", "expressed", "in", "epithelial", "cells", "of", "the", "mammary", "gland", "and", "thus", "used", "a", "monoclonal", "anti-PTN", "blocking", "antibody", "to", "elucidate", "its", "function", "in", "cultured", "mammary", "epithelial", "cells", "(MECs)", "as", "well", "as", "during", "gland", "development.", "Real-time", "impedance", "monitoring", "of", "MECs", "growth,", "migration", "and", "invasion", "during", "anti-PTN", "blocking", "antibody", "treatment", "showed", "that", "MECs", "motility", "and", "invasion", "but", "not", "proliferation", "depend", "on", "the", "activity", "of", "endogenous", "PTN.", "Increased", "number", "of", "mammospheres", "with", "laminin", "deposition", "after", "anti-PTN", "blocking", "antibody", "treatment", "of", "MECs", "in", "3D", "culture", "and", "expression", "of", "progenitor", "markers", "suggest", "that", "the", "endogenously", "expressed", "PTN", "inhibits", "the", "expansion", "and", "differentiation", "of", "epithelial", "progenitor", "cells", "by", "disrupting", "cell-matrix", "adhesion.", "In", "vivo,", "PTN", "activity", "was", "found", "to", "inhibit", "ductal", "outgrowth", "and", "branching", "via", "the", "inhibition", "of", "phospho", "ERK1/2", "signaling", "in", "the", "mammary", "epithelial", "cells.", "We", "conclude", "that", "PTN", "delays", "the", "maturation", "of", "the", "mammary", "gland", "by", "maintaining", "mammary", "epithelial", "cells", "in", "a", "progenitor", "phenotype", "and", "by", "inhibiting", "their", "differentiation", "during", "mammary", "gland", "development.", "Citation:", "Rosenfield", "SM,", "Bowden", "ET,", "Cohen-Missner", "S,", "Gibby", "KA,", "Ory", "V,", "et", "al.", "(2012)", "Pleiotrophin", "(PTN)", "Expression", "and", "Function", "and", "in", "the", "Mouse", "Mammary", "Gland", "and", "Mammary", "Epithelial", "Cells.", "PLoS", "ONE", "7(10):", "e47876.", "doi:10.1371/journal.pone.0047876", "Editor:", "John", "P.", "Lydon,", "Baylor", "College", "of", "Medicine,", "United", "States", "of", "America", "Received", "February", "7,", "2012;", "Accepted", "September", "24,", "2012;", "Published", "October", "15,", "2012", "Copyright:", "2012", "Rosenfield", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "research", "was", "supported", "by", "grants", "awarded", "to", "AW", "from", "the", "NCI/NIH", "(RO1", "CA101811);", "to", "Shani", "Cohen-Missner", "from", "the", "Pharmaceutical", "Manufacturers", "Association", "(Fellowship);", "to", "Sonia", "M.", "Rosenfield", "from", "the", "Department", "of", "Defense", "Breast", "Cancer", "Research", "Program", "(Predoctoral", "Grant:", "BC083308).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "Dr.", "Wellstein", "is", "named", "as", "an", "inventor", "on", "Georgetown", "University", "owned", "patents", "related", "to", "pleiotrophin", "and", "ALK.", "Dr.", "Bowden", "is", "an", "employee", "at", "Medimmune", "Gaithersburg.", "This", "does", "not", "alter", "the", "authors9", "adherence", "to", "all", "the", "PLOS", "ONE", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "wellstea@georgetown.edu", "Introduction", "The", "heparin-binding", "growth", "factor", "pleiotrophin", "(PTN;", "also", "known", "as", "HB-GAM", "or", "HARP;", "reviewed", "in", "[1])", "is", "a", "15", "kDa", "secreted", "protein", "named", "for", "its", "pleiotrophic", "effects", "on", "different", "cell", "types.", "In", "mice,", "PTN", "and", "its", "tyrosine", "kinase", "receptor", "ALK", "are", "prominently", "expressed", "during", "embryonic", "and", "early", "postnatal", "development", "of", "the", "central", "and", "peripheral", "nervous", "system", "[2,3,4,5,6].", "In", "addition", "to", "neuronal", "functions,", "PTN", "contributes", "to", "the", "epithelial-mesenchymal", "interactions", "in", "organs", "undergoing", "branching", "morphogenesis", "and", "in", "bone", "formation", "[7,8,9,10,11,12].", "In", "the", "adult,", "PTN", "and", "ALK", "expressions", "are", "downregulated", "in", "most", "tissues,", "with", "residual", "expression", "in", "the", "nervous", "system", "[4,13].", "An", "increase", "in", "PTN", "expression", "has", "been", "observed", "in", "the", "uterus", "during", "gestation,", "in", "the", "human", "placenta", "and", "during", "bone", "repair,", "inflammatory", "diseases", "and", "in", "human", "cancers", "[2,13,14,15,16,17,18,19].", "The", "biological", "effects", "of", "PTN-mediated", "signaling", "include", "neurite", "outgrowth", "and", "repair,", "angiogenesis", "and", "mitogenesis", "of", "fibroblasts,", "endothelial", "and", "some", "tumor", "cell", "lines", "[19,20,21,22,23].", "PTN", "signaling", "can", "induce", "the", "activation", "of", "both", "the", "MAPK", "and", "PI3", "kinase", "pathways", "in", "epithelial", "cells", "[24]", "and", "a", "direct", "role", "for", "PTN", "in", "mitogenesis", "and", "anti-apoptotic", "signaling", "was", "previously", "reported", "[19,25,26,27,28].", "PTN", "activity", "has", "recently", "been", "shown", "to", "stimulate", "the", "differentiation", "and", "expansion", "of", "neuronal", "stem", "cells,", "osteoprogenitors", "and", "bone", "marrow", "stem", "cells", "[29,30,31].", "The", "PTN", "protein", "was", "first", "purified", "from", "the", "supernatants", "of", "human", "breast", "cancer", "cells", "[32].", "PTN", "mRNA", "expression", "has", "been", "shown", "in", "different", "estrogen", "receptor", "negative", "breast", "cancer", "cell", "lines", "and", "in", "primary", "breast", "cancers", "derived", "from", "different", "patients", "[19].", "In", "NIH3T3", "fibroblasts,", "PTN", "leads", "to", "transformation,", "whereas", "overexpression", "of", "a", "dominant", "negative,", "mutant", "PTN", "protein", "reverses", "the", "transformed", "phenotype", "of", "breast", "and", "other", "cancer", "cell", "lines", "[26,33].", "PTN", "has", "also", "been", "shown", "to", "be", "an", "angiogenic", "factor", "during", "tumor", "growth", "and", "a", "promoter", "of", "invasion", "and", "metastasis", "in", "different", "tumor", "types", "including", "breast", "cancers", "[19,22,34,35].", "A", "role", "for", "PTN-mediated", "signaling", "through", "the", "receptor", "tyrosine", "kinase", "ALK", "as", "well", "as", "the", "receptor", "phosphatase", "PTPRz", "has", "been", "suggested", "in", "breast", "cancers", "[36,37,38].", "In", "normal", "human", "breast", "tissues,", "PTN", "is", "expressed", "in", "the", "epithelial,", "myoepithelial", "and", "endothelial", "cells", "[39].", "In", "the", "mouse", "mammary", "gland,", "PTN", "expression", "has", "been", "described", "in", "both", "PLOS", "ONE", "|", "www.plosone.org", "1", "October", "2012", "|", "Volume", "7", "|", "Issue", "10", "|", "e47876" ]

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[ "Li", "et", "al.", "BMC", "Bioinformatics", "2010,", "11(Suppl", "2):S7", "http://www.biomedcentral.com/1471-2105/11/S2/S7", "P", "R", "O", "C", "E", "E", "D", "I", "N", "G", "S", "Open", "Access", "Learning", "an", "enriched", "representation", "from", "unlabeled", "data", "for", "protein-protein", "interaction", "extraction", "Yanpeng", "Li1,2*,", "Xiaohua", "Hu2,", "Hongfei", "Lin1,", "Zhihao", "Yang1", "From", "Third", "International", "Workshop", "on", "Data", "and", "Text", "Mining", "in", "Bioinformatics", "(DTMBio)", "2009", "Hong", "Kong.", "6", "November", "2009", "Abstract", "Background:", "Extracting", "protein-protein", "interactions", "from", "biomedical", "literature", "is", "an", "important", "task", "in", "biomedical", "text", "mining.", "Supervised", "machine", "learning", "methods", "have", "been", "used", "with", "great", "success", "in", "this", "task", "but", "they", "tend", "to", "suffer", "from", "data", "sparseness", "because", "of", "their", "restriction", "to", "obtain", "knowledge", "from", "limited", "amount", "of", "labelled", "data.", "In", "this", "work,", "we", "study", "the", "use", "of", "unlabeled", "biomedical", "texts", "to", "enhance", "the", "performance", "of", "supervised", "learning", "for", "this", "task.", "We", "use", "feature", "coupling", "generalization", "(FCG)", "–", "a", "recently", "proposed", "semi-supervised", "learning", "strategy", "–", "to", "learn", "an", "enriched", "representation", "of", "local", "contexts", "in", "sentences", "from", "47", "million", "unlabeled", "examples", "and", "investigate", "the", "performance", "of", "the", "new", "features", "on", "AIMED", "corpus.", "Results:", "The", "new", "features", "generated", "by", "FCG", "achieve", "a", "60.1", "F-score", "and", "produce", "significant", "improvement", "over", "supervised", "baselines.", "The", "experimental", "analysis", "shows", "that", "FCG", "can", "utilize", "well", "the", "sparse", "features", "which", "have", "little", "effect", "in", "supervised", "learning.", "The", "new", "features", "perform", "better", "in", "non-linear", "classifiers", "than", "linear", "ones.", "We", "combine", "the", "new", "features", "with", "local", "lexical", "features,", "obtaining", "an", "F-score", "of", "63.5", "on", "AIMED", "corpus,", "which", "is", "comparable", "with", "the", "current", "state-of-the-art", "results.", "We", "also", "find", "that", "simple", "Boolean", "lexical", "features", "derived", "only", "from", "local", "contexts", "are", "able", "to", "achieve", "competitive", "results", "against", "most", "syntactic", "feature/kernel", "based", "methods.", "Conclusions:", "FCG", "creates", "a", "lot", "of", "opportunities", "for", "designing", "new", "features,", "since", "a", "lot", "of", "sparse", "features", "ignored", "by", "supervised", "learning", "can", "be", "utilized", "well.", "Interestingly,", "our", "results", "also", "demonstrate", "that", "the", "state-of-the", "art", "performance", "can", "be", "achieved", "without", "using", "any", "syntactic", "information", "in", "this", "task.", "Background", "With", "the", "exponential", "explosion", "of", "biomedical", "literature", "such", "as", "MEDLINE,", "developing", "automatic", "information", "extraction", "(IE)", "tools", "is", "essential", "for", "people", "to", "seek", "information", "more", "accurately", "and", "efficiently", "[1].", "The", "task", "of", "protein-protein", "interaction", "extraction", "(PPIE)", "aims", "to", "extract", "interacting", "protein", "pairs", "from", "biomedi-", "cal", "literature,", "which", "contributes", "to", "PPI", "network", "analy-", "sis", "and", "discovery", "of", "new", "functions", "of", "proteins.", "In", "recent", "years,", "it", "has", "attracted", "a", "lot", "of", "research", "interests", "[2-16]", "from", "different", "domains", "such", "as", "bioinformatics,", "natural", "language", "processing", "(NLP),", "and", "machine", "*", "Correspondence:", "liyanpeng.lyp@gmail.com", "1Department", "of", "Computer", "Science", "and", "Engineering,", "Dalian", "University", "of", "Technology,", "Dalian,", "Liaoning,", "116024,", "China", "learning", "(ML).", "Bioinformatics", "researchers", "focus", "on", "constructing", "corpus", "[2,3],", "designing", "domain-specific", "rules", "for", "PPIE", "[4,5]", "and", "integrating", "the", "extraction", "results", "into", "PPI", "network", "analysis", "[6].", "In", "NLP", "commu-", "nity,", "a", "lot", "of", "works", "focus", "on", "how", "to", "apply", "linguistic", "parsing", "to", "enhance", "the", "extraction", "performance", "[7-12,15,16].", "People", "find", "that", "methods", "that", "incorporate", "syntactic", "parsing", "information", "can", "improve", "the", "extrac-", "tion", "performance", "significantly", "and", "outperform", "methods", "that", "use", "only", "lexical", "information.", "In", "addition,", "most", "of", "these", "methods", "are", "in", "the", "framework", "of", "machine", "learn-", "ing.", "Recent", "studies", "[10-12,16]", "show", "that", "integrating", "all", "the", "lexical", "and", "parsing", "features", "in", "a", "kernel-based", "supervised", "learning", "model", "achieves", "state-of-the-art", "performance", "on", "benchmark", "datasets.", "Since", "in", "©", "2010", "Li", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Phosphoinositide", "3-Kinase", "C2b", "Regulates", "RhoA", "and", "the", "Actin", "Cytoskeleton", "through", "an", "Interaction", "with", "Dbl", "Karolina", "Błajecka1.,", "Marin", "Marinov2.,", "Laura", "Leitner3,", "Kristin", "Uth1,", "Guido", "Posern3,", "Alexandre", "Arcaro1*", "1", "Department", "of", "Clinical", "Research,", "University", "of", "Bern,", "Bern,", "Switzerland,", "2", "Department", "of", "Oncology,", "University", "Children’s", "Hospital", "Zurich,", "Zurich,", "Switzerland,", "3", "Department", "of", "Molecular", "Biology,", "AG", "Regulation", "of", "Gene", "Expression,", "Max-Planck-Institute", "of", "Biochemistry,", "Martinsried,", "Germany", "Abstract", "The", "regulation", "of", "cell", "morphology", "is", "a", "dynamic", "process", "under", "the", "control", "of", "multiple", "protein", "complexes", "acting", "in", "a", "coordinated", "manner.", "Phosphoinositide", "3-kinases", "(PI3K)", "and", "their", "lipid", "products", "are", "widely", "involved", "in", "cytoskeletal", "regulation", "by", "interacting", "with", "proteins", "regulating", "RhoGTPases.", "Class", "II", "PI3K", "isoforms", "have", "been", "implicated", "in", "the", "regulation", "of", "the", "actin", "cytoskeleton,", "although", "their", "exact", "role", "and", "mechanism", "of", "action", "remain", "to", "be", "established.", "In", "this", "report,", "we", "have", "identified", "Dbl,", "a", "Rho", "family", "guanine", "nucleotide", "exchange", "factor", "(RhoGEF)", "as", "an", "interaction", "partner", "of", "PI3KC2b.", "Dbl", "was", "co-immunoprecipitated", "with", "PI3KC2b", "in", "NIH3T3", "cells", "and", "cancer", "cell", "lines.", "Over-expression", "of", "Class", "II", "phosphoinositide", "3-kinase", "PI3KC2b", "in", "NIH3T3", "fibroblasts", "led", "to", "increased", "stress", "fibres", "formation", "and", "cell", "spreading.", "Accordingly,", "we", "found", "high", "basal", "RhoA", "activity", "and", "increased", "serum", "response", "factor", "(SRF)", "activation", "downstream", "of", "RhoA", "upon", "serum", "stimulation.", "In", "contrast,", "the", "dominant-negative", "form", "of", "PI3KC2b", "strongly", "reduced", "cell", "spreading", "and", "stress", "fibres", "formation,", "as", "well", "as", "SRF", "response.", "Platelet-derived", "growth", "factor", "(PDGF)", "stimulation", "of", "wild-type", "PI3KC2b", "over-expressing", "NIH3T3", "cells", "strongly", "increased", "Rac", "and", "c-Jun", "N-terminal", "kinase", "(JNK)", "activation,", "but", "failed", "to", "show", "similar", "effect", "in", "the", "cells", "with", "the", "dominant-", "negative", "enzyme.", "Interestingly,", "epidermal", "growth", "factor", "(EGF)", "and", "PDGF", "stimulation", "led", "to", "increased", "extracellular", "signal-", "regulated", "kinase", "(Erk)", "and", "Akt", "pathway", "activation", "in", "cells", "with", "elevated", "wild-type", "PI3KC2b", "expression.", "Furthermore,", "increased", "expression", "of", "PI3KC2b", "protected", "NIH3T3", "from", "detachment-dependent", "death", "(anoikis)", "in", "a", "RhoA-dependent", "manner.", "Taken", "together,", "these", "findings", "suggest", "that", "PI3KC2b", "modulates", "the", "cell", "morphology", "and", "survival", "through", "a", "specific", "interaction", "with", "Dbl", "and", "the", "activation", "of", "RhoA.", "Citation:", "Błajecka", "K,", "Marinov", "M,", "Leitner", "L,", "Uth", "K,", "Posern", "G,", "et", "al.", "(2012)", "Phosphoinositide", "3-Kinase", "C2b", "Regulates", "RhoA", "and", "the", "Actin", "Cytoskeleton", "through", "an", "Interaction", "with", "Dbl.", "PLoS", "ONE", "7(9):", "e44945.", "doi:10.1371/journal.pone.0044945", "Editor:", "Pontus", "Aspenstrom,", "Karolinska", "Institutet,", "Sweden", "Received", "December", "20,", "2011;", "Accepted", "August", "14,", "2012;", "Published", "September", "12,", "2012", "Copyright:", "2012", "Błajecka", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "study", "was", "funded", "by", "the", "Swiss", "National", "Science", "Foundation", "(grants", "3100A0-105321", "and", "31003A-120294).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "alexandre.arcaro@dkf.unibe.ch", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "The", "phosphoinositide-3", "kinase", "(PI3K)", "family", "comprises", "evolu-", "tionary", "conserved", "lipid", "kinases", "characterised", "by", "their", "ability", "to", "phosphorylate", "phosphoinositides", "at", "the", "D-3", "position", "of", "the", "inositol", "ring.", "This", "reaction", "leads", "to", "the", "production", "of", "essential", "for", "the", "cell", "second", "messengers", "as", "PI(3)P,", "PI(3,4)P2", "and", "PI(3,4,5)P3", "[1].", "The", "subsequent", "membrane", "recruitment", "of", "enzymes", "recognizing", "and", "binding", "D-3", "phosphorylated", "phosphoinositides", "leads", "to", "their", "activation,", "which", "results", "in", "the", "initiation", "of", "multiple", "signalling", "cascades", "providing", "growth,", "survival", "and", "motility", "signals", "to", "the", "cell.", "The", "biological", "functions", "of", "PI3K", "have", "been", "widely", "investigated", "by", "the", "use", "of", "transgenic", "mouse", "models", "and", "in", "vitro", "cell", "systems.", "It", "became", "clear", "that", "PI3K", "are", "extremely", "important", "for", "cell", "proliferation,", "differentiation,", "chemotaxis", "and", "motility.", "Further-", "more,", "they", "are", "implicated", "in", "the", "embryonic", "development,", "immunity", "and", "the", "development", "of", "diseases", "such", "as", "cancer,", "inflammation", "and", "diabetes", "[1–3].", "The", "family", "of", "PI3K", "comprises", "three", "classes,", "based", "on", "structural", "similarity", "and", "in", "vitro", "substrate", "specificity.", "Class", "I", "PI3K", "is", "divided", "into", "Class", "IA,", "comprising", "three", "isoforms", "activated", "by", "growth", "factor", "receptor", "tyrosine", "kinases", "(RTKs)", "and", "Class", "IB", "with", "a", "single", "member", "activated", "by", "the", "Gbcsubunit", "downstream", "of", "activated", "G-protein", "coupled", "receptors", "(GPCR)", "[1].", "The", "main", "product", "of", "Class", "I", "PI3K", "activity,", "the", "lipid", "second", "messenger", "PI(3,4,5)P3,", "activates", "a", "plethora", "of", "downstream", "molecules", "by", "binding", "to", "their", "pleckstrin-homology", "(PH)", "domains", "[4].", "To", "one", "of", "the", "best", "studied", "effectors", "belong", "the", "serine/", "threonine", "kinase", "Akt", "[5]", "and", "RhoGEFs", "[6].", "Class", "II", "PI3K", "consists", "of", "three", "members", "termed", "PI3KC2a,", "PI3KC2b", "and", "PI3KC2c.", "In", "vitro,", "the", "main", "substrates", "of", "these", "enzymes", "are", "PI", "and", "PI(4)P", "[7,8].", "Class", "II", "PI3K", "are", "activated", "downstream", "of", "RTK", "(EGFR,", "PDGFR", "and", "Kit),", "cytokine", "receptors,", "insulin", "and", "integrins", "[9–13].", "Localisation", "of", "PI3KC2a", "in", "the", "trans-Golgi", "apparatus", "and", "in", "clathrin", "vesicles", "indicates", "function", "in", "clathrin", "assembly", "and", "clathrin", "mediated", "trafficking", "[14,15].", "Further", "studies", "have", "revealed", "that", "PI3KC2b", "is", "implicated", "in", "the", "cytoskeletal", "regulation", "and", "migration", "of", "cancer", "cells", "[16–", "18].", "However,", "the", "specific", "functions", "of", "Class", "II", "PI3K", "in", "response", "to", "their", "activators", "remain", "to", "be", "fully", "understood.", "The", "control", "of", "actin", "filaments", "dynamic", "is", "crucial", "for", "cell", "morphology,", "adhesion", "and", "movement", "[19].", "PI3Ks", "regulate", "cell", "polarity", "and", "motility", "by", "controlling", "multiple", "proteins", "and", "protein", "complexes", "implicated", "in", "cytoskeletal", "rearrangement", "and", "actin", "dynamics", "[20].", "It", "was", "recently", "demonstrated", "in", "Drosophila", "melanogaster", "hemocytes", "that", "Pi3K68D", "in", "collaboration", "with", "PLOS", "ONE", "|", "www.plosone.org", "1", "September", "2012", "|", "Volume", "7", "|", "Issue", "9", "|", "e44945" ]

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[ "Orthopedic", "Reviews", "2012;", "volume", "4:e11", "The", "correlation", "between", "the", "sagittal", "lumbopelvic", "alignments", "in", "standing", "position", "and", "the", "risk", "factors", "influencing", "low", "back", "pain", "Pongsthorn", "Chanplakorn,", "Paphon", "Sa-ngasoongsong,", "Siwadol", "Wongsak,", "Patarawan", "Woratanarat,", "Wiwat", "Wajanavisit,", "Wichien", "Laohacharoensombat", "Department", "of", "Orthopedics,", "Faculty", "of", "Medicine", "Ramathibodi", "Hospital,", "Mahidol", "University,", "Bangkok,", "Thailand", "Abstract", "Low", "back", "pain", "(LBP)", "is", "the", "most", "common", "health", "problem.", "Many", "factors", "have", "been", "demonstrated", "to", "be", "fundamental", "risk", "factors", "of", "LBP", "such", "as", "body", "mass", "index", "(BMI),", "age", "and", "sex.", "However,", "so", "far", "there", "have", "been", "few", "stud-", "ies", "demonstrating", "the", "association", "between", "lumbo-pelvic", "alignment", "(LPA)", "and", "these", "fac-", "tors.", "This", "present", "study", "was", "aimed", "to", "clarify", "the", "correlation", "between", "the", "LPA", "and", "the", "risk", "factors", "contributing", "to", "LBP.", "Standing", "lateral", "X-", "rays", "were", "taken", "from", "100", "healthy", "volunteers", "(70", "males", "and", "30", "females)", "with", "no", "history", "of", "low", "back", "pain", "before", "their", "participation.", "Average", "age", "of", "subjects", "was", "33.3±6.8", "years", "(rang", "21-50).", "Mean", "body", "weight", "was", "59.1±7.9kg", "(range", "40-82),", "mean", "body", "height", "was", "163.6±7.2", "cm", "(range", "145-178)", "and", "mean", "BMI", "was", "22.1±2.4", "kg/m2", "(range", "18.0-29.3).", "The", "LPA", "was", "classified", "into", "3", "types", "according", "to", "the", "recently", "proposed", "pelvic", "orientation", "guide-", "lines.", "No", "direct", "correlation", "was", "found", "between", "the", "pelvic", "orientation", "and", "age", "or", "BMI.", "Each", "LPA", "type", "was", "associated", "with", "sex", "but", "not", "BMI", "and", "age", "(P=0.00,", "0.71,", "and", "0.36,", "respectively).", "The", "results", "from", "this", "study", "demonstrated", "the", "differences", "in", "LPA", "between", "male", "and", "female,", "and", "also", "confirmed", "that", "the", "sagittal", "orienta-", "tion", "of", "the", "pelvis", "remained", "constant", "in", "adults.", "The", "high", "prevalence", "of", "LPA", "type", "1", "in", "males", "may", "reduce", "the", "occurrence", "of", "LBP", "in", "obese", "male", "individuals.", "Introduction", "Low", "back", "pain", "(LBP)", "is", "one", "of", "the", "most", "com-", "mon", "health", "problems", "and", "affects", "more", "than", "80%", "of", "people", "over", "their", "lifetime.1", "It", "is", "an", "enor-", "mous", "clinical", "and", "public", "health", "problem", "that", "is", "associated", "with", "high", "health", "care", "burden", "and", "[page", "50]", "social", "costs.1,2", "Moreover,", "despite", "its", "benign", "nature,", "in", "many", "countries,", "LBP", "is", "the", "leading", "activity-limiting", "complaint,", "cause", "of", "disability", "and", "sick", "leave,", "and", "with", "the", "highest", "cost", "of", "workers’", "compensation.1,3", "In", "addition,", "regard-", "ing", "therapeutic", "interventions,", "a", "large", "number", "of", "systematic", "reviews", "have", "been", "published", "concerning", "the", "effectiveness", "of", "a", "large", "variety", "of", "treatment", "available", "for", "the", "LBP;", "unfortu-", "nately", "the", "results", "have", "not", "been", "convincingly", "demonstrated.4", "Therefore,", "preventive", "strate-", "gies", "might", "be", "beneficial", "in", "the", "management", "of", "LBP,", "with", "regard", "to", "treatment", "costs,", "outcomes", "and", "disease", "burden.", "Given", "this,", "it", "is", "essential", "to", "know", "the", "potential", "risk", "factors.", "Numerous", "potential", "risk", "factors", "of", "the", "LBP", "have", "been", "suggested,", "such", "as", "age", "and", "gen-", "der,3,5", "body", "mass", "index", "(BMI),6,7", "or", "physical", "activity.5", "Unfortunately,", "despite", "many", "clinical", "studies,", "the", "associations", "between", "these", "fac-", "tors", "and", "LBP", "have", "remained", "inconclusive.", "The", "alteration", "in", "sagittal", "spinal", "alignment", "is", "thought", "to", "be", "one", "of", "the", "potential", "risk", "factor", "of", "LBP.8,9", "However,", "there", "is", "great", "variability", "in", "spinal", "alignment", "in", "the", "normal", "population", "and", "this", "makes", "it", "difficult", "to", "clarify", "whether", "the", "alteration", "in", "spinal", "posture", "has", "any", "influence", "and", "there", "is", "still", "some", "conflicting", "evidence", "linking", "different", "spinal", "postures", "to", "LBP", "in", "adults.10", "Recently,", "Pongsthorn", "et", "al.", "have", "suggested", "classifying", "lumbo-pelvic", "alignments", "(LPA)", "in", "the", "normal", "population.11", "In", "brief,", "LPA", "has", "been", "classified", "into", "3", "types", "according", "to", "the", "sagittal", "orientation", "of", "the", "pelvis:", "in", "type", "1,", "the", "sacro-", "pelvis", "is", "relatively", "horizontal", "with", "low", "lumbar", "lordosis,", "whereas", "in", "type", "3,", "the", "sacro-pelvis", "is", "more", "vertical", "with", "higher", "lumbar", "lordosis,", "and", "type", "2", "has", "the", "average", "sacro-pelvis", "and", "lumbar", "lordosis", "pattern.", "However,", "the", "association", "between", "the", "new", "LPA", "classification", "and", "the", "internal", "risk", "factors", "such", "as", "age,", "gender", "and", "BMI", "has", "not", "yet", "been", "studied.", "Therefore,", "the", "aim", "of", "this", "present", "study", "was", "to", "determine", "the", "correlation", "between", "LPA", "and", "the", "LPA", "classifi-", "cation", "and", "the", "contribution", "of", "internal", "risk", "fac-", "tors", "to", "low", "back", "pain.", "Materials", "and", "Methods", "Demographic", "data", "and", "X-ray", "parameters", "from", "100", "asymptomatic", "Thai", "volunteers", "who", "had", "previously", "participated", "in", "studies", "on", "lumbo-pelvic", "alignment", "analysis", "were", "used", "in", "this", "present", "study.", "Inclusion", "study", "criteria", "were:", "i)", "age", "20-60", "years;", "ii)", "no", "prior", "spine", "sur-", "gery;", "and", "iii)", "no", "history", "of", "low", "back", "pain,", "except", "for", "occasional", "episodes", "after", "work", "or", "exertion,", "for", "at", "least", "six", "months", "before", "their", "participation", "in", "the", "study.", "Exclusion", "criteria", "were:", "i)", "definite", "diagnosis", "of", "lumbar", "spinal", "pathology,", "such", "as", "spinal", "stenosis,", "spondylolis-", "[Orthopedic", "Reviews", "2012;", "4:e11]", "Correspondence:", "Pongsthorn", "Chanplakorn", "Department", "of", "Orthopedics,", "Faculty", "of", "Medicine", "Ramathibodi", "Hospital,", "Mahidol", "University,", "270", "Rama", "VI", "road,", "Payathai,", "Ratchathewi,", "Bangkok,", "10400,", "Thailand.", "Tel.", "+66.2.2011589", "-", "Fax:", "+66.2.2011599.", "E-mail:", "rapcl@mahidol.ac.th", "Key", "words:", "pelvic", "morphology,", "lumbar", "lordosis,", "sagittal", "spinal", "alignments,", "low", "back", "pain,", "risk", "factors.", "Received", "for", "publication:", "6", "December", "2011.", "Accepted", "for", "publication:", "28", "December", "2011.", "This", "work", "is", "licensed", "under", "a", "Creative", "Commons", "Attribution", "NonCommercial", "3.0", "License", "(CC", "BY-", "NC", "3.0).", "©Copyright", "P.", "Chanplakorn", "et", "al.,", "2012", "Licensee", "PAGEPress", "srl,", "Italy", "Orthopedic", "Reviews", "2012;", "4:e11", "doi:10.4081/or.2012.e11", "thesis,", "degenerative", "disc", "disease", "or", "inflamma-", "tory", "spinal", "diseases,", "or", "definite", "clinical", "spine", "deformities", "from", "physical", "examination", "or", "X-", "ray;", "ii)", "definite", "diagnosis", "of", "diabetic", "mellitus,", "hypertension,", "rickets,", "osteoporosis;", "iii)", "history", "of", "smoking;", "and", "iv)", "incomplete", "demographic", "data", "records.", "Age,", "gender,", "body", "weight", "and", "height", "were", "recorded", "and", "then", "the", "body", "mass", "index", "(BMI)", "for", "each", "subject", "was", "calculated.", "In", "order", "to", "better", "understand", "the", "correlation", "between", "the", "types", "of", "the", "lumbo-pelvic", "align-", "ment", "and", "the", "demographic", "parameters,", "we", "divided", "subjects", "into", "3", "subcategories", "according", "to", "age:", "group", "1,", "under", "30", "years", "of", "age", "(n=30);", "group", "2,", "aged", "between", "30", "and", "39", "years", "(n=46);", "and", "group", "3,", "over", "40", "years", "of", "age", "(n=20),", "according", "to", "the", "risk", "of", "low", "back", "pain", "in", "the", "Thai", "worker", "population.3", "The", "BMI", "was", "also", "sub-", "categorized", "into", "3", "groups:", "group", "1,", "BMI", "less", "than", "19", "kg/m2;", "group", "2,", "BMI", "between", "19", "and", "24.5", "kg/m2;", "and", "group", "3,", "BMI", "over", "24.5", "kg/m2", "according", "to", "the", "World", "Health", "Organization", "(WHO)", "criteria", "for", "the", "Asian", "population.12", "The", "previous", "standing", "lateral", "standing", "X-", "rays", "of", "the", "lumbar", "spine", "and", "pelvis", "in", "a", "stan-", "dardized", "position", "that", "were", "used", "in", "a", "previous", "study", "were", "reviewed", "by", "2", "of", "the", "authors", "(PC", "and", "SW)", "and", "then", "used", "for", "this", "correlation", "study.", "Details", "of", "the", "X-ray", "techniques", "were:", "i)", "all", "subjects", "had", "standing", "lateral", "X-ray", "of", "the", "spine", "and", "pelvis", "performed", "by", "the", "same", "radio-", "technologist", "using", "the", "same", "radiographic", "equipments;", "ii)", "X-ray", "cassettes", "were", "set", "into", "a", "standard", "upright", "cassette", "adjustment", "device", "then", "adjusted", "for", "a", "72-inch", "long", "focal", "film", "dis-", "tance", "from", "the", "radiation", "source;", "iii)", "the", "volun-", "teers", "were", "carefully", "positioned", "with", "their", "right", "side", "against", "the", "cassette.", "They", "were", "asked", "to", "stand", "up", "straight,", "but", "to", "remain", "in", "a", "relaxed", "position", "with", "the", "knees", "extended.", "The", "arms" ]

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[ "IEFS", "PROCEEDINGS", "A", "systematic", "approach", "to", "the", "failed", "plastic", "surgical", "reconstruction", "of", "the", "diabetic", "foot", "Ioannis", "I.", "Ignatiadis,", "MD,", "PhD1*,", "Vassiliki", "A.", "Tsiampa,", "MD2", "and", "Apostolos", "E.", "Papalois,", "PhD3", "1Hand", "Surgery", "and", "Microsurgery", "Department,", "KAT", "General", "Hospital,", "Athens,", "Greece;", "22nd", "Orthopaedic", "Department,", "University", "of", "Athens", "Medical", "School,", "Athens,", "Greece;", "3Head", "of", "Experimental-Research", "Center,", "ELPEN", "SA", "Pharma-Co,", "Pikermi-Attika,", "Greece", "Plastic", "reconstruction", "for", "diabetic", "foot", "wounds", "must", "be", "approached", "carefully", "and", "follow", "sound", "micro-surgical", "principles", "as", "it", "relates", "to", "the", "anatomy", "of", "the", "designated", "flap", "chosen", "for", "coverage.", "First,", "the", "surgeon", "always", "needs", "to", "evaluate", "the", "local", "and", "general", "conditions", "of", "the", "presenting", "pathology", "and", "patient,", "respectively", "when", "considering", "a", "flap", "for", "reconstruction.", "The", "flap", "that", "is", "chosen", "is", "based", "on", "the", "vascularity,", "location,", "and", "size", "of", "the", "defect.", "Salvage", "of", "the", "failed", "flap", "and", "revisional", "reconstructive", "procedures", "are", "very", "challenging.", "Often,", "adjunctive", "therapies", "such", "as", "hyperbaric", "oxygen,", "negative", "pressure", "wound", "therapy,", "vasodilators,", "and/or", "vascular", "surgery", "is", "required.", "In", "certain", "case", "scenarios,", "such", "as", "patients", "with", "poor", "general", "health", "and", "compromised", "local", "vascularity", "in", "which", "revisional", "flap", "coverage", "cannot", "be", "performed,", "the", "above", "mentioned", "adjunctive", "therapies", "could", "be", "used", "as", "a", "primary", "treatment", "to", "potentially", "salvage", "a", "failing", "flap.", "Keywords:", "pedicle", "flaps;", "muscle", "flaps;", "diabetic", "foot;", "osteomyelitis;", "plastic", "surgery", "Srepresents", "oft", "tissue", "coverage", "a", "challenge", "for", "most", "to", "the", "diabetic", "reconstructive", "foot", "wounds", "sur-", "geon.", "In", "our", "experience,", "patients", "suffering", "with", "diabetic", "foot", "and", "ankle", "soft", "tissue", "defects", "that", "require", "plastic", "reconstruction", "could", "be", "divided", "into", "two", "broad", "categories", "concerning", "their", "etiological", "mechanism:", "(1)", "traumatic", "wounds", "with", "a", "‘pathological", "evolution’", "such", "as", "degloving", "injuries,", "burns,", "and/or", "open", "fractures", "to", "diabetic", "patients", "and", "(2)", "chronic", "wounds", "that", "could", "be", "related", "to", "decubitus", "ulcerations", "in", "a", "diabetic", "background", "such", "as", "heel", "‘pressure’", "wounds,", "wounds", "associated", "with", "peripheral", "neuropathy", "including", "Charcot", "foot", "deformity", "or", "an", "osseous", "prominence", "with", "ulceration,", "with", "or", "without", "diabetic", "foot", "infections.", "Wounds", "could", "be", "associated", "with", "peripheral", "arterial", "disease", "or", "vascular", "insufficiency", "in", "diabetic", "patients.", "Concerning", "the", "nature", "and", "the", "morphological", "aspect", "of", "the", "wound", "we", "recom-", "mend", "the", "University", "of", "Texas", "Health", "Science", "Center", "San", "Antonio", "diabetic", "wound", "classification", "system", "(1)", "that", "presents", "the", "depth,", "quality,", "level", "of", "maturity", "and", "healing,", "This", "study", "was", "presented", "at", "the", "6th", "Annual", "International", "External", "Fixation", "Symposium", "(IEFS),", "December", "2010,", "San", "Antonio,", "Texas,", "USA.", "and", "the", "involvement", "or", "not", "of", "any", "local", "infectious", "factors", "(Table", "1).", "The", "most", "important", "initial", "step", "in", "treating", "soft", "tissue", "defects", "related", "to", "the", "diabetic", "foot", "is", "to", "perform", "a", "timely", "and", "complete", "surgical", "debridement.", "This", "entails", "the", "surgical", "excision", "of", "all", "non-viable", "and/or", "infected", "soft", "tissue", "and", "bone", "so", "that", "the", "wound", "margins", "and", "base", "of", "the", "soft", "tissue", "defect", "are", "healthy", "and", "viable.", "This", "does", "not", "imply", "that", "de´bridement", "should", "be", "limited", "because", "of", "the", "size", "or", "location", "of", "the", "index", "wound", "since", "proper", "soft", "tissue", "reconstruction", "can", "only", "be", "performed", "after", "suc-", "cessful", "de´bridement", "and", "wound", "preparation", "regardless", "of", "size,", "depth,", "or", "location.", "If", "there", "is", "exposed", "bone", "or", "suspicion", "for", "underlying", "osteomyelitis,", "then", "bone", "cultures", "and", "biopsies", "are", "obtained", "and", "empiric", "systemic", "antibiotic", "therapy", "is", "started", "and", "eventually", "tailored", "to", "the", "identified", "pathogen.", "It", "is", "common", "for", "a", "patient", "to", "be", "brought", "back", "to", "the", "operating", "room", "several", "times", "for", "de´bridement", "before", "the", "wound", "is", "optimized", "for", "flap", "coverage.", "Failure", "to", "have", "an", "adequately", "de´brided", "wound", "will", "most", "likely", "lead", "to", "failure", "of", "any", "attempt", "at", "flap", "coverage", "(2", "9).", "In", "addition", "to", "adequate", "soft", "tissue", "and", "bone", "debride-", "ment,", "the", "utilization", "of", "an", "external", "fixator", "is", "applied", "to", "stabilize", "significant", "osseous", "defects", "and/or", "unstable", "Diabetic", "Foot", "&", "Ankle", "2011.", "#", "2011", "Ioannis", "I.", "Ignatiadis", "et", "al.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "1", "Attribution-Noncommercial", "3.0", "Unported", "License", "(http://creativecommons.org/licenses/by-nc/3.0/),", "permitting", "all", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Citation:", "Diabetic", "Foot", "&", "Ankle", "2011,", "2:", "6435", "-", "DOI:", "10.3402/dfa.v2i0.6435", "(page", "number", "not", "for", "citation", "purpose)" ]

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[ "Sensors", "2010,", "10,", "5962-5974;", "doi:10.3390/s100605962", "OPEN", "ACCESS", "sensors", "ISSN", "1424-8220", "www.mdpi.com/journal/sensors", "Article", "Exploring", "Infrared", "Sensoring", "for", "Real", "Time", "Welding", "Defects", "Monitoring", "in", "GTAW", "Sadek", "C.", "A.", "Alfaro*", "and", "Fernand", "Díaz", "Franco", "Automation", "and", "Control", "Group,", "Departamento", "de", "Engenharia", "Mecânica/Mecatrônica,", "Faculdade", "de", "Tecnologia,", "The", "Brasilia", "University,", "Brasília–DF,", "CEP:", "70910-900,", "Brazil", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "sadek@unb.br;", "Tel.:", "+55-61-31075697;", "Fax:", "+55-61-31075707.", "Received:", "25", "April", "2010;", "in", "revised", "form:", "15", "May", "2010", "/", "Accepted:", "30", "May", "2010", "/", "Published:", "14", "June", "2010", "Abstract:", "This", "paper", "presents", "an", "evaluation", "of", "an", "infrared", "sensor", "for", "monitoring", "the", "welding", "pool", "temperature", "in", "a", "Gas", "Tungsten", "Arc", "Welding", "(GTAW)", "process.", "The", "purpose", "of", "the", "study", "is", "to", "develop", "a", "real", "time", "system", "control.", "It", "is", "known", "that", "the", "arc", "welding", "pool", "temperature", "is", "related", "to", "the", "weld", "penetration", "depth;", "therefore,", "by", "monitoring", "the", "temperature,", "the", "arc", "pool", "temperature", "and", "penetration", "depth", "are", "also", "monitored.", "Various", "experiments", "were", "performed;", "in", "some", "of", "them", "the", "current", "was", "varied", "and", "the", "temperature", "changes", "were", "registered,", "in", "others,", "defects", "were", "induced", "throughout", "the", "path", "of", "the", "weld", "bead", "for", "a", "fixed", "current.", "These", "simulated", "defects", "resulted", "in", "abrupt", "changes", "in", "the", "average", "temperature", "values,", "thus", "providing", "an", "indication", "of", "the", "presence", "of", "a", "defect.", "The", "data", "has", "been", "registered", "with", "an", "acquisition", "card.", "To", "identify", "defects", "in", "the", "samples", "under", "infrared", "emissions,", "the", "timing", "series", "were", "analyzed", "through", "graphics", "and", "statistic", "methods.", "The", "selection", "of", "this", "technique", "demonstrates", "the", "potential", "for", "infrared", "emission", "as", "a", "welding", "monitoring", "parameter", "sensor.", "Keywords:", "Gas", "Tungsten", "Arc", "Welding;", "welding", "monitoring;", "infrared;", "statistic", "methods", "1.", "Introduction", "Technology", "advancements", "seek", "to", "meet", "the", "demands", "for", "quality", "and", "performance", "through", "product", "improvements", "and", "cost", "reductions.", "An", "important", "area", "of", "research", "is", "the", "optimization", "of", "applications" ]

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[ "Avila", "et", "al.", "Parasites", "&", "Vectors", "2011,", "4:39", "http://www.parasitesandvectors.com/content/4/1/39", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Gene", "discovery", "in", "Triatoma", "infestans", "María", "L", "Avila1,", "Valeria", "Tekiel1,", "Georgina", "Moretti1,", "Soledad", "Nicosia1,", "Jacqueline", "Bua2,", "Estela", "M", "Lammel", "3", ",", "María", "M", "Stroppa4,", "Nelia", "M", "Gerez", "de", "Burgos4,", "Daniel", "O", "Sánchez1*", "Abstract", "Background:", "Triatoma", "infestans", "is", "the", "most", "relevant", "vector", "of", "Chagas", "disease", "in", "the", "southern", "cone", "of", "South", "America.", "Since", "its", "genome", "has", "not", "yet", "been", "studied,", "sequencing", "of", "Expressed", "Sequence", "Tags", "(ESTs)", "is", "one", "of", "the", "most", "powerful", "tools", "for", "efficiently", "identifying", "large", "numbers", "of", "expressed", "genes", "in", "this", "insect", "vector.", "Results:", "In", "this", "work,", "we", "generated", "826", "ESTs,", "resulting", "in", "an", "increase", "of", "47%", "in", "the", "number", "of", "ESTs", "available", "for", "T.", "infestans.", "These", "ESTs", "were", "assembled", "in", "471", "unique", "sequences,", "151", "of", "which", "represent", "136", "new", "genes", "for", "the", "Reduviidae", "family.", "Conclusions:", "Among", "the", "putative", "new", "genes", "for", "the", "Reduviidae", "family,", "we", "identified", "and", "described", "an", "interesting", "subset", "of", "genes", "involved", "in", "development", "and", "reproduction,", "which", "constitute", "potential", "targets", "for", "insecticide", "development.", "Background", "Chagas", "disease", "affects", "8", "million", "people,", "and", "~28", "million,", "in", "21", "endemic", "countries", "of", "Latin", "America,", "are", "at", "risk", "of", "infection", "[1].", "The", "etiologic", "agent", "of", "Chagas", "disease", "is", "the", "parasite", "Trypanosoma", "cruzi,", "which", "is", "mainly", "trans-", "mitted", "through", "blood-sucking", "insect", "vectors", "of", "the", "Tria-", "tominae", "subfamily,", "being", "Triatoma", "infestans,", "Rhodnius", "prolixus,", "and", "Triatoma", "dimidiata", "the", "most", "epidemiolo-", "gically", "important", "vectors.", "T.", "infestans", "is", "currently", "the", "main", "vector", "in", "the", "southern", "part", "of", "South", "America", "including", "regions", "of", "northern", "Argentina,", "Bolivia,", "Para-", "guay,", "and", "southern", "Peru.", "R.", "prolixus,", "on", "the", "other", "hand,", "is", "distributed", "in", "northern", "South", "America", "(mainly", "in", "Colombia", "and", "Venezuela)", "and", "has", "few", "foci", "in", "Central", "America.", "T.", "dimidiata,", "is", "present", "in", "Central", "America", "and", "Mexico,", "and", "also", "has", "limited", "foci", "in", "northern", "South", "America", "[2-4].", "Due", "to", "population", "migration", "from", "Latin", "America,", "Chagas", "disease", "is", "becoming", "an", "important", "health", "issue", "in", "North", "America,", "Europe", "and", "in", "the", "western", "Pacific", "region", "[5].", "Currently,", "there", "are", ">390,000", "individuals", "infected", "with", "T.", "cruzi", "in", "non-endemic", "regions", "and,", "accordingly,", "serological", "monitoring", "of", "blood", "banks", "and", "*", "Correspondence:", "dsanchez@unsam.edu.ar", "1Instituto", "de", "Investigaciones", "Biotecnológicas,", "Universidad", "Nacional", "de", "San", "Martín", "-", "CONICET.", "Av.", "Gral", "Paz", "5445,", "Edificio", "24,", "B1650KNA,", "San", "Martín,", "Provincia", "de", "Buenos", "Aires,", "Argentina", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "organ", "donors", "as", "well", "as", "additional", "controls", "to", "detect", "vertical", "transmission", "in", "newborns", "must", "be", "implemented", "to", "prevent", "the", "spread", "of", "the", "disease.", "As", "there", "are", "currently", "no", "vaccines", "available", "against", "T.", "cruzi", "and", "effective", "treatments", "are", "limited", "to", "che-", "motherapies", "that", "exhibit", "high", "toxicity,", "large", "efforts", "are", "being", "made", "to", "implement", "prevention", "strategies,", "such", "as", "domestic", "vector", "control", "and", "improvement", "of", "blood", "bank", "surveillance", "[6].", "Currently,", "the", "main", "method", "of", "vector", "control", "is", "spraying", "houses", "with", "residual", "insecti-", "cides.", "However,", "the", "occurrence", "of", "T.", "infestans", "popula-", "tions", "resistant", "to", "pyrethroid", "compounds", "in", "the", "north", "of", "Argentina", "and", "Bolivia", "[7,8]", "poses", "the", "alternative", "of", "orga-", "nophosphate", "insecticides.", "Unfortunately,", "these", "insecti-", "cides,", "although", "effective,", "are", "very", "toxic", "and", "less", "accepted", "by", "the", "community", "due", "to", "their", "unpleasant", "odor", "[9].", "Novel", "methods", "of", "control", "will", "undoubtedly", "require", "detailed", "understanding", "of", "the", "molecular", "biology", "of", "Chagas", "disease", "vectors.", "This", "will", "provide", "unique", "oppor-", "tunities", "to", "develop", "new", "vector", "control", "tools", "such", "as", "the", "use", "of", "transgenic", "vectors", "refractory", "to", "pathogens.", "The", "identification", "of", "trait", "genes", "linked", "to", "transposable", "ele-", "ments", "could", "drive", "those", "alleles", "into", "wild", "populations", "and", "interrupt", "disease", "transmission", "in", "the", "long-term", "[10,11].", "Although", "in", "the", "short", "run,", "this", "strategy", "is", "not", "feasible", "for", "Chagas", "disease", "control", "due", "to", "the", "need", "of", "an", "intense", "laboratory", "and", "field", "research,", "it", "is,", "nevertheless,", "an", "approach", "that", "deserves", "to", "be", "explored.", "©", "2011", "Avila", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Souza", "et", "al.", "BMC", "Infectious", "Diseases", "2010,", "10:209", "http://www.biomedcentral.com/1471-2334/10/209", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Resistance", "of", "Leishmania", "(Viannia)", "braziliensis", "to", "nitric", "oxide:", "correlation", "with", "antimony", "therapy", "and", "TNF-a", "production", "Anselmo", "S", "Souza1†,", "Angela", "Giudice1†,", "Júlia", "MB", "Pereira1,", "Luís", "H", "Guimarães1,", "Amelia", "R", "de", "Jesus2,", "Tatiana", "R", "de", "Moura2,", "Mary", "E", "Wilson3†,", "Edgar", "M", "Carvalho1,", "Roque", "P", "Almeida2*†", "Abstract", "Background:", "Nitric", "oxide", "(NO)", "produced", "in", "macrophages", "plays", "a", "pivotal", "role", "as", "a", "leishmanicidal", "agent.", "A", "previous", "study", "has", "demonstrated", "that", "20%", "of", "the", "L.", "(V.)", "braziliensis", "isolated", "from", "initial", "cutaneous", "lesions", "of", "patients", "from", "the", "endemic", "area", "of", "Corte", "de", "Pedra,", "Bahia,", "Brazil,", "were", "NO", "resistant.", "Additionally,", "5", "to", "11%", "of", "the", "patients", "did", "not", "respond", "to", "three", "or", "more", "antimony", "treatments”", "(refractory", "patients).", "The", "aim", "of", "this", "study", "is", "to", "investigate", "if", "there", "is", "an", "association", "between", "the", "resistance", "of", "L.", "(V.)", "braziliensis", "to", "NO", "and", "nonresponsiveness", "to", "antimony", "therapy", "and", "cytokine", "production.", "Methods:", "We", "evaluated", "the", "in", "vitro", "toxicity", "of", "NO", "against", "the", "promastigotes", "stages", "of", "L.", "(V.)", "braziliensis", "isolated", "from", "responsive", "and", "refractory", "patients,", "and", "the", "infectivity", "of", "the", "amastigote", "forms", "of", "these", "isolates", "against", "human", "macrophages.", "The", "supernatants", "from", "Leishmania", "infected", "macrophage", "were", "used", "to", "measure", "TNF-a", "and", "IL-10", "levels.", "Results:", "Using", "NaNO2", "(pH", "5.0)", "as", "the", "NO", "source,", "L.", "(V.)", "braziliensis", "isolated", "from", "refractory", "patients", "were", "more", "NO", "resistant", "(IC50", "=", "5.8", "±", "4.8)", "than", "L.", "(V.)", "braziliensis", "isolated", "from", "responsive", "patients", "(IC50", "=", "2.0", "±", "1.4).", "Four", "isolates", "were", "selected", "to", "infect", "human", "macrophages:", "NO-susceptible", "and", "NO-resistant", "L.", "(V.)", "braziliensis", "isolated", "from", "responsive", "and", "refractory", "patients.", "NO-resistant", "L.", "(V.)", "braziliensis", "isolated", "from", "refractory", "patients", "infected", "more", "macrophages", "stimulated", "with", "LPS", "and", "IFN-g", "at", "120", "hours", "than", "NO-susceptible", "L.", "(V.)", "braziliensis", "isolated", "from", "refractory", "patients.", "Also,", "lower", "levels", "of", "TNF-a", "were", "detected", "in", "supernatants", "of", "macrophages", "infected", "with", "NO-resistant", "L.", "(V.)", "braziliensis", "as", "compared", "to", "macrophages", "infected", "with", "NO-susceptible", "L.", "(V.)", "braziliensis", "(p", "<", "0.05", "at", "2,", "24", "and", "120", "hours),", "while", "no", "differences", "were", "detected", "in", "IL-10", "levels.", "Conclusion:", "These", "data", "suggest", "that", "NO", "resistance", "could", "be", "related", "to", "the", "nonresponsiveness", "to", "antimony", "therapy", "seen", "in", "American", "Tegumentary", "Leishmaniasis.", "Background", "Leishmaniasis", "is", "a", "parasitic", "disease", "considered", "a", "major", "public", "health", "problem", "affecting", "88", "countries", "throughout", "Europe,", "Asia,", "Africa", "and", "America,", "with", "an", "annual", "incidence", "of", "1", "to", "1.5", "million", "of", "cases,", "and", "350", "million", "exposures", "according", "to", "the", "World", "Health", "Organization.", "Specifically", "in", "Brazil,", "the", "Ministry", "of", "Health", "reports", "an", "annual", "incidence", "of", "around", "28.000", "cases.", "American", "Tegu-", "mentary", "Leishmaniasis", "(ATL)", "presents", "with", "a", "spectrum", "of", "*", "Correspondence:", "roquepacheco@uol.com.br", "†", "Contributed", "equally", "2Universidade", "Federal", "de", "Sergipe,", "Aracaju,", "Sergipe,", "Brazil", "clinical", "manifestations,", "including", "cutaneous", "(CL),", "mucosal", "(ML),", "disseminated", "(DL)", "and", "diffuse", "cutaneous", "leishmania-", "sis", "(DCL).", "The", "major", "species", "that", "cause", "ATL", "in", "the", "New", "World", "are", "L.", "(Viannia)", "braziliensis,", "L.", "(V.)", "guyanensis,", "L.", "(Leishmania)", "amazonensis", "and", "L.", "(L.)", "mexicana", "[1].", "In", "the", "Northeast", "region", "of", "Brazil,", "CL,", "ML", "and", "DL", "are", "caused", "most", "often", "by", "L.", "(V.)", "braziliensis;", "and", "DCL", "is", "most", "often", "caused", "by", "L.", "amazonensis", "in", "the", "New", "World", "[2].", "The", "typical", "clinical", "manifestation", "of", "cutaneous", "leishmaniasis", "(CL)", "is", "a", "single", "ulcerated", "lesion", "with", "elevated", "borders,", "frequently", "located", "on", "the", "inferior", "limbs", "[3].", "ML", "is", "a", "destructive", "disease", "that", "predominantly", "affects", "the", "©", "2010", "Souza", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "NAD(P)H:Quinone", "Oxidoreductase", "1", "(NQO1)", "Localizes", "to", "the", "Mitotic", "Spindle", "in", "Human", "Cells", "David", "Siegel*,", "Jadwiga", "K.", "Kepa,", "David", "Ross", "Department", "of", "Pharmaceutical", "Sciences,", "Skaggs", "School", "of", "Pharmacy", "and", "Pharmaceutical", "Sciences,", "University", "of", "Colorado", "Anschutz", "Medical", "Campus,", "Aurora,", "Colorado,", "United", "States", "of", "America", "Abstract", "NAD(P)H:quinone", "oxidoreductase", "1", "(NQO1)", "is", "an", "FAD", "containing", "quinone", "reductase", "that", "catalyzes", "the", "2-electron", "reduction", "of", "a", "broad", "range", "of", "quinones.", "The", "2-electron", "reduction", "of", "quinones", "to", "hydroquinones", "by", "NQO1", "is", "believed", "to", "be", "a", "detoxification", "process", "since", "this", "reaction", "bypasses", "the", "formation", "of", "the", "highly", "reactive", "semiquinone.", "NQO1", "is", "expressed", "at", "high", "levels", "in", "normal", "epithelium,", "endothelium", "and", "adipocytes", "as", "well", "as", "in", "many", "human", "solid", "tumors.", "In", "addition", "to", "its", "function", "as", "a", "quinone", "reductase", "NQO1", "has", "been", "shown", "to", "reduce", "superoxide", "and", "regulate", "the", "20", "S", "proteasomal", "degradation", "of", "proteins", "including", "p53.", "Biochemical", "studies", "have", "indicated", "that", "NQO1", "is", "primarily", "located", "in", "the", "cytosol,", "however,", "lower", "levels", "of", "NQO1", "have", "also", "been", "found", "in", "the", "nucleus.", "In", "these", "studies", "we", "demonstrate", "using", "immunocytochemistry", "and", "confocal", "imaging", "that", "NQO1", "was", "found", "associated", "with", "mitotic", "spindles", "in", "cells", "undergoing", "division.", "The", "association", "of", "NQO1", "with", "the", "mitotic", "spindles", "was", "observed", "in", "many", "different", "human", "cell", "lines", "including", "nontransformed", "cells", "(astrocytes,", "HUVEC)", "immortalized", "cell", "lines", "(HBMEC,", "16HBE)", "and", "cancer", "(pancreatic", "adenocarcinoma,", "BXPC3).", "Confocal", "analysis", "of", "double-labeling", "experiments", "demonstrated", "co-localization", "of", "NQO1with", "alpha-tubulin", "in", "mitotic", "spindles.", "In", "studies", "with", "BxPc-3", "human", "pancreatic", "cancer", "cells", "the", "association", "of", "NQO1", "with", "mitotic", "spindles", "appeared", "to", "be", "unchanged", "in", "the", "presence", "of", "NQO1", "inhibitors", "ES936", "or", "dicoumarol", "suggesting", "that", "NQO1", "can", "associate", "with", "the", "mitotic", "spindle", "and", "still", "retain", "catalytic", "activity.", "Analysis", "of", "archival", "human", "squamous", "lung", "carcinoma", "tissue", "immunostained", "for", "NQO1", "demonstrated", "positive", "staining", "for", "NQO1", "in", "the", "spindles", "of", "mitotic", "cells.", "The", "purpose", "of", "this", "study", "is", "to", "demonstrate", "for", "the", "first", "time", "the", "association", "of", "the", "quinone", "reductase", "NQO1", "with", "the", "mitotic", "spindle", "in", "human", "cells.", "Citation:", "Siegel", "D,", "Kepa", "JK,", "Ross", "D", "(2012)", "NAD(P)H:Quinone", "Oxidoreductase", "1", "(NQO1)", "Localizes", "to", "the", "Mitotic", "Spindle", "in", "Human", "Cells.", "PLoS", "ONE", "7(9):", "e44861.", "doi:10.1371/journal.pone.0044861", "Editor:", "Stefan", "Strack,", "University", "of", "Iowa,", "United", "States", "of", "America", "Received", "April", "12,", "2012;", "Accepted", "August", "8,", "2012;", "Published", "September", "11,", "2012", "Copyright:", "2012", "Siegel", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "National", "Institutes", "of", "Health", "grant", "R01ES108943.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "DS,", "DR", "and", "the", "University", "of", "Colorado", "are", "the", "licensor", "for", "the", "anti-NQO1", "monoclonal", "antibody", "(clone", "A180).", "This", "does", "not", "alter", "the", "authors’", "adherence", "to", "all", "the", "PLOS", "ONE", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "david.siegel@ucdenver.edu", "Introduction", "NAD(P)H:quinone", "oxidoreductase", "1", "(NQO1,", "DT-diaphorase,", "EC", "1.6.99.2)", "is", "a", "homodimeric", "flavoprotein", "that", "utilizes", "either", "NADH", "or", "NADPH", "and", "catalyzes", "the", "2-electron", "reduction", "of", "a", "broad", "range", "of", "substrates", "most", "notably", "quinones", "[1].", "The", "two-", "electron", "reduction", "of", "quinones", "to", "hydroquinones", "by", "NQO1", "is", "believed", "to", "be", "primarily", "a", "detoxification", "reaction", "since", "it", "bypasses", "the", "formation", "of", "the", "highly", "reactive", "semiquinone", "[1].", "In", "many", "cases,", "however,", "the", "reduction", "of", "quinones", "by", "NQO1", "results", "in", "the", "formation", "cytotoxic", "hydroquinones", "and", "the", "bioactivation", "of", "quinone", "prodrugs", "by", "NQO1", "has", "been", "utilized", "as", "a", "strategy", "to", "target", "NQO1-rich", "cancer", "cells", "[2].", "In", "normal", "tissues,", "NQO1", "is", "expressed", "at", "relatively", "high", "levels", "in", "epithelial", "tissues,", "vascular", "endothelium", "and", "adipocytes", "while", "in", "cancer,", "NQO1", "is", "expressed", "at", "high", "levels", "in", "many", "solid", "tumors", "including", "lung", "(NSCLC),", "breast", "and", "pancreatic", "[3,4].", "In", "humans,", "the", "NQO1*2", "polymorphism", "plays", "a", "major", "role", "in", "governing", "basal", "protein", "levels", "of", "NQO1", "[5].", "The", "NQO1*2", "polymorphism", "results", "in", "a", "proline", "to", "serine", "amino", "acid", "substitution", "at", "position", "187", "in", "NQO1", "and", "this", "mutant", "protein", "undergoes", "rapid", "polyubiquitina-", "tion", "by", "the", "E3", "ubiquitin", "ligase", "STUB1/CHIP", "with", "subsequent", "proteasomal", "degradation", "[6,7].", "Individuals", "homozygous", "for", "the", "NQO1*2", "polymorphism", "are", "NQO1", "null,", "while", "intermediate", "levels", "of", "NQO1", "protein", "are", "found", "in", "individuals", "with", "the", "heterozygous", "genotype", "[5].", "NQO1", "is", "under", "transcriptional", "regulation", "by", "the", "Keap1/NRF2", "pathway", "and", "upregulation", "of", "NQO1", "mRNA", "or", "protein", "has", "been", "used", "extensively", "as", "a", "biomarker", "for", "NRF2", "activation", "[8,9].", "Upregulation", "of", "NQO1", "may", "protect", "the", "cell", "from", "oxidative", "damage", "due", "to", "the", "ability", "of", "NQO1", "to", "reduce", "superoxide", "to", "hydrogen", "peroxide", "and", "generate", "antioxidant", "forms", "of", "vitamin", "E", "and", "co-enzyme", "Q", "[10,11,12].", "In", "addition", "to", "its", "role", "as", "an", "antioxidant", "enzyme,", "NQO1", "has", "been", "shown", "to", "protect", "a", "wide", "range", "of", "proteins", "including", "p53", "from", "ubiquitin-independent", "20", "S", "proteasomal", "degradation", "[13,14].", "The", "protection", "of", "target", "proteins", "by", "NQO1", "from", "20", "S", "proteasomal", "degradation", "is", "dependent", "upon", "the", "redox", "state", "of", "NQO1", "since", "treatment", "with", "the", "NQO1", "inhibitor", "dicoumarol", "has", "been", "shown", "to", "enhance", "the", "20", "S", "proteasomal", "degradation", "of", "several", "target", "proteins", "[13,14].", "NQO1", "is", "predominately", "located", "in", "the", "cytoplasm", "but", "low", "levels", "of", "NQO1", "have", "been", "found", "in", "the", "nucleus", "under", "normal", "conditions", "[15].", "Under", "conditions", "of", "stress", "NQO1", "has", "been", "shown", "to", "migrate", "to", "the", "nucleus", "where", "it", "is", "hypothesized", "that", "NQO1", "may", "protect", "PLOS", "ONE", "|", "www.plosone.org", "1", "September", "2012", "|", "Volume", "7", "|", "Issue", "9", "|", "e44861" ]

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[ "Irreversible", "EGFR", "Inhibitor", "EKB-569", "Targets", "Low-LET", "c-", "Radiation-Triggered", "Rel", "Orchestration", "and", "Potentiates", "Cell", "Death", "in", "Squamous", "Cell", "Carcinoma", "4", "1", "Natarajan", "Aravindan2,4,5,", "Charles", "R.", "Thomas", "Jr3.", ",", "Sheeja", "Aravindan", ",", "Aswathi", "S.", "Mohan", ",", "Jamunarani", "Veeraraghavan2,5,", "Mohan", "Natarajan", "1", "*", "1", "Department", "of", "Otolaryngology,", "Head", "and", "Neck", "Surgery,", "University", "of", "Texas", "Health", "Science", "Center", "at", "San", "Antonio,", "San", "Antonio,", "Texas,", "United", "States", "of", "America,", "2", "Department", "of", "Radiation", "Oncology,", "The", "University", "of", "Oklahoma", "Health", "Sciences", "Center,", "Oklahoma", "City,", "Oklahoma,", "United", "States", "of", "America,", "3", "Department", "of", "Radiation", "Medicine,", "Oregon", "Health", "and", "Science", "University", "Knight", "Cancer", "Institute,", "Portland,", "Oregon,", "United", "States", "of", "America,", "4", "Department", "of", "Pathology,", "The", "University", "of", "Oklahoma", "Health", "Sciences", "Center,", "Oklahoma", "City,", "Oklahoma,", "United", "States", "of", "America,", "5", "Department", "of", "Pediatrics,", "The", "University", "of", "Oklahoma", "Health", "Sciences", "Center,", "Oklahoma", "City,", "Oklahoma,", "United", "States", "of", "America", "Abstract", "EKB-569", "(Pelitinib),", "an", "irreversible", "EGFR", "tyrosine", "kinase", "inhibitor", "has", "shown", "potential", "therapeutic", "efficiency", "in", "solid", "tumors.", "However,", "cell-killing", "potential", "in", "combination", "with", "radiotherapy", "and", "its", "underlying", "molecular", "orchestration", "remain", "to", "be", "explored.", "The", "objective", "of", "this", "study", "was", "to", "determine", "the", "effect", "of", "EKB-569", "on", "ionizing", "radiation", "(IR)-", "associated", "NFkB-dependent", "cell", "death.", "SCC-4", "and", "SCC-9", "cells", "exposed", "to", "IR", "(2Gy)", "with", "and", "without", "EKB-569", "treatment", "were", "analyzed", "for", "transactivation", "of", "88", "NFkB", "pathway", "molecules,", "NFkB", "DNA-binding", "activity,", "translation", "of", "the", "NFkB", "downstream", "mediators,", "Birc1,", "2", "and", "5,", "cell", "viability,", "metabolic", "activity", "and", "apoptosis.", "Selective", "targeting", "of", "IR-induced", "NFkB", "by", "EKB-569", "and", "its", "influence", "on", "cell-fate", "were", "assessed", "by", "overexpressing", "(p50/p65)", "and", "silencing", "(DIkBa)", "NFkB.", "QPCR", "profiling", "after", "IR", "exposure", "revealed", "a", "significant", "induction", "of", "74", "NFkB", "signal", "transduction", "molecules.", "Of", "those,", "72", "were", "suppressed", "with", "EKB-569.", "EMSA", "revealed", "a", "dose", "dependent", "inhibition", "of", "NFkB", "by", "EKB-569.", "More", "importantly,", "EKB-", "569", "inhibited", "IR-induced", "NFkB", "in", "a", "dose-dependent", "manner,", "and", "this", "inhibition", "was", "sustained", "up", "to", "at", "least", "72", "h.", "Immunoblotting", "revealed", "a", "significant", "suppression", "of", "IR-induced", "Birc1,", "2", "and", "5", "by", "EKB-569.", "We", "observed", "a", "dose-", "dependent", "inhibition", "of", "cell", "viability,", "metabolic", "activity", "and", "apoptosis", "with", "EKB-569.", "EKB-569", "significantly", "enhanced", "IR-", "induced", "cell", "death", "and", "apoptosis.", "Blocking", "NFkB", "improved", "IR-induced", "cell", "death.", "Conversely,", "NFkB", "overexpression", "negates", "EKB-569", "-induced", "cell-killing.", "Together,", "these", "pre-clinical", "data", "suggest", "that", "EKB-569", "is", "a", "radiosensitizer", "of", "squamous", "cell", "carcinoma", "and", "may", "mechanistically", "involve", "selective", "targeting", "of", "IR-induced", "NFkB-dependent", "survival", "signaling.", "Further", "pre-clinical", "in-vivo", "studies", "are", "warranted.", "Citation:", "Aravindan", "N,", "Thomas", "CR", "Jr,", "Aravindan", "S,", "Mohan", "AS,", "Veeraraghavan", "J,", "et", "al.", "(2011)", "Irreversible", "EGFR", "Inhibitor", "EKB-569", "Targets", "Low-LET", "c-Radiation-", "Triggered", "Rel", "Orchestration", "and", "Potentiates", "Cell", "Death", "in", "Squamous", "Cell", "Carcinoma.", "PLoS", "ONE", "6(12):", "e29705.", "doi:10.1371/journal.pone.0029705", "Editor:", "Christina", "Lynn", "Addison,", "Ottawa", "Hospital", "Research", "Institute,", "Canada", "Received", "August", "8,", "2011;", "Accepted", "December", "1,", "2011;", "Published", "December", "29,", "2011", "Copyright:", "2011", "Aravindan", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported,", "in", "whole", "or", "in", "part,", "by", "National", "Institutes", "of", "Health", "Grant", "R01", "CA112175", "(to", "M.N.)", "and", "funds", "from", "the", "Office", "of", "Science", "(Biological", "and", "Environmental", "Research),", "United", "States", "Department", "of", "Energy", "Grant", "No.", "DE-FG03-02ER63449", "(to", "M.N.).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "natarajan@uthscsa.edu", "Introduction", "Head", "and", "neck", "squamous", "cell", "carcinoma", "(HNSCC)", "is", "the", "sixth", "most", "common", "cancer", "in", "the", "world", "and", "accounts", "for", "90%", "of", "malignant", "neoplasias", "of", "the", "upper", "respiratory", "system", "[1].", "Despite", "recent", "advances", "in", "the", "management", "of", "locally", "advanced", "HNSCC,", "the", "overall", "survival", "of", "patients", "has", "improved", "only", "marginally", "over", "the", "past", "three", "decades", "[2]", "mainly", "due", "to", "development", "of", "therapy-", "induced", "chemo", "and", "radioresistance.", "To", "that", "note,", "in", "recent", "years", "there", "has", "been", "substantial", "interest", "in", "developing", "novel", "therapeutic", "agents", "that", "specifically", "target", "growth", "factor", "pathways", "that,", "are", "dysregulated", "in", "tumor", "cells.", "Such", "targeted", "‘‘biological’’", "agents", "might", "offer", "alternative", "treatment", "options", "for", "patients", "refractive", "to", "chemoradiotherapy.", "Also,", "with", "unique", "mechanisms", "of", "action", "and", "toxic", "profiles", "that", "generally", "do", "not", "overlap,", "targeted", "agents", "and", "standard", "therapies", "can", "be", "used", "in", "combinations", "to", "enhance", "overall", "treatment", "efficacies", "and", "prevent", "dose", "reduction.", "Because", "many", "solid", "tumors,", "including", "HNSCC", "have", "hyper", "activated", "epidermal", "growth", "factor", "receptor", "(EGFR)", "[3,4],", "there", "has", "been", "great", "interest", "in", "the", "use", "of", "EGFR", "inhibitors", "to", "control", "cancer", "growth.", "EGFR", "is", "a", "170", "kDa", "glycoprotein", "containing", "an", "extracellular", "ligand", "binding", "domain,", "and", "an", "intracellular", "tyrosine", "kinase", "(TK)", "domain", "[5].", "Upon", "binding", "to", "ligands", "such", "as", "EGF", "or", "TGFa,", "EGFR", "dimerizes", "with", "itself", "(homodimers)", "or", "other", "members", "of", "the", "family", "such", "as", "c-ErbB-2", "(heterodimers).", "Upon", "dimerization,", "TK", "activation", "increases", "and", "receptor", "gets", "autopho-", "sphorylated", "at", "tyrosine", "residues.", "Phosphorylated", "EGFR", "(p-EGFR),", "like", "other", "activated", "receptor", "TKs,", "involved", "in", "phosphorylation", "and", "activation", "of", "several", "signal", "transduction", "pathways", "including", "phosphoinositide", "3-kinase-AKT,", "extra", "cellular", "signal-regulated", "kinase", "1and", "2", "(ERK1/2),", "and", "the", "signal", "transducer", "and", "activator", "of", "transcription", "3", "(STAT3).", "Activation", "of", "these", "signal", "transduction", "pathways", "subsequently", "activate", "key", "transcriptional", "machineries", "such", "as", "NFkB", "that", "promote", "tumor", "growth", "and", "progression", "by", "PLoS", "ONE", "|", "www.plosone.org", "1", "December", "2011", "|", "Volume", "6", "|", "Issue", "12", "|", "e29705" ]

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"Netherlands", "Received", "January", "28,", "2008;", "Revised", "April", "2,", "2008;", "Accepted", "April", "9,", "2008", "ABSTRACT", "The", "major", "public", "microarray", "repositories", "Gene", "Expression", "Omnibus", "and", "ArrayExpress", "are", "growing", "rapidly.", "This", "enables", "meta-analysis", "studies,", "in", "which", "expression", "data", "from", "multiple", "individual", "studies", "are", "combined.", "To", "facilitate", "these", "types", "of", "studies,", "we", "developed", "Microarray", "Retriever", "for", "searching", "and", "retrieval", "of", "data", "from", "GEO", "and", "ArrayExpress.", "The", "tool", "allows", "access", "to", "the", "two", "repositories", "simulta-", "neously,", "to", "search", "in", "the", "repositories", "using", "complex", "queries,", "to", "retrieve", "microarray", "data", "for", "published", "articles", "and", "to", "download", "data", "in", "one", "structured", "archive.", "The", "tool", "is", "available", "on", "the", "web", "at:", "http://", "www.lgtc.nl/MaRe/", "INTRODUCTION", "Microarray", "technology", "is", "now", "routinely", "used", "for", "genome-", "wide", "mRNA", "expression", "and", "epigenetic", "profiling.", "As", "a", "consequence,", "there", "is", "a", "quickly", "growing", "amount", "of", "microarray", "data", "made", "available", "in", "public", "databases.", "This", "may", "improve", "the", "interpretation", "of", "new", "experimental", "studies", "through", "comparison", "with", "data", "already", "publicly", "available,", "and", "allow", "for", "large-scale", "meta-analysis.", "Use", "of", "data", "in", "the", "repositories", "gives", "increased", "statistical", "power,", "and", "facilitates", "confirmation", "of", "hypotheses", "coming", "from", "one", "study", "with", "data", "from", "another", "study,", "identification", "of", "artifacts", "and", "separation", "of", "primary", "effects", "from", "secondary", "(1).", "For", "example,", "meta-analysis", "of", "microarray", "data", "was", "useful", "for", "identification", "of", "common", "transcriptional", "profiles", "of", "neoplastic", "transformation", "and", "progression", "(2),", "discovery", "of", "genes", "disproportionately", "overexpressed", "in", "specific", "cancer", "types", "(3),", "construction", "of", "robust", "high-", "resolution", "gene", "coexpression", "networks", "(4),", "and", "identifica-", "tion", "of", "rhythmically", "expressed", "genes", "in", "Drosophila", "(5).", "There", "are", "many", "hurdles", "to", "be", "taken", "when", "integrating", "data", "from", "different", "studies,", "such", "as", "the", "necessity", "to", "map", "the", "probes", "on", "different", "arrays", "to", "transcripts,", "the", "necessity", "to", "account", "for", "different", "experimental", "designs", "and", "analysis", "algorithms,", "and", "to", "retrieve", "the", "relevant", "datasets", "from", "microarray", "data", "repositories.", "The", "latter", "is", "addressed", "by", "MaRe,", "the", "tool", "that", "we", "developed.", "Currently,", "there", "are", "no", "public", "software", "tools,", "which", "provide", "combined", "and", "interactive", "access", "to", "the", "main", "microarray", "data", "repositories.", "Microarray", "Retriever", "(MaRe)", "facilitates", "meta-analysis", "by", "enabling", "searching", "and", "batch", "data", "retrieval", "from", "the", "two", "major", "public", "microarray", "repositories:", "Gene", "Expression", "Omnibus", "(GEO,", "National", "Center", "for", "Biotechnology", "Information;", "6,7)", "and", "ArrayExpress", "(AE,", "European", "Bioinformatics", "Institute;", "8,9).", "MaRe", "allows", "the", "user", "to", "search", "these", "repositories", "for", "experiments", "with", "accession", "numbers,", "authors,", "species,", "date", "of", "submission,", "array", "platform", "and", "keyword", "search", "terms.", "In", "addition,", "users", "can", "first", "search", "PubMed", "on", "authors", "and", "keywords", "for", "relevant", "literature", "and", "then", "search", "GEO", "and", "ArrayExpress", "for", "experimental", "data", "associated", "with", "this", "literature.", "Alternatively,", "a", "custom", "list", "of", "PubMed", "IDs", "can", "be", "uploaded", "to", "obtain", "data", "for", "specific", "articles", "known", "in", "advance.", "After", "the", "search", "is", "complete,", "MaRe", "enables", "downloading", "of", "selected", "results", "in", "one", "step.", "This", "avoids", "the", "time-consuming", "procedure", "of", "manual", "and", "sequential", "downloading", "from", "the", "web", "or", "ftp", "sites", "of", "the", "repositories.", "All", "retrieved", "results", "are", "stored", "using", "a", "clear", "directory", "structure.", "METHODS", "Implementation", "MaRe", "is", "written", "in", "Perl.", "Searches", "in", "GEO", "are", "performed", "remotely", "by", "sending", "queries", "to", "NCBI", "E-Utilities", "(10).", "A", "3-s", "delay", "between", "E-Utilities", "calls", "is", "implemented", "according", "to", "the", "NCBI", "guidelines.", "Search", "in", "ArrayExpress", "is", "done", "locally", "by", "parsing", "the", "ArrayExpress", "annotation", "XML", "file.", "The", "file", "is", "downloaded", "from", "the", "EBI", "during", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+31", "71", "5269421;", "Fax:", "+31", "71", "5268285;", "Email:", "p.a.c.hoen@lumc.nl", "2008", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Degradation", "of", "PsbO", "by", "the", "Deg", "Protease", "HhoA", "Is", "Thioredoxin", "Dependent", "Irma", "N.", "Roberts¤,", "Xuan", "Tam", "Lam,", "Helder", "Miranda,", "Thomas", "Kieselbach,", "Christiane", "Funk*", "Department", "of", "Chemistry", "and", "Umea˚", "Plant", "Science", "Centre,", "Umea˚", "University,", "Umea˚,", "Sweden", "Abstract", "The", "widely", "distributed", "members", "of", "the", "Deg/HtrA", "protease", "family", "play", "an", "important", "role", "in", "the", "proteolysis", "of", "misfolded", "and", "damaged", "proteins.", "Here", "we", "show", "that", "the", "Deg", "protease", "rHhoA", "is", "able", "to", "degrade", "PsbO,", "the", "extrinsic", "protein", "of", "the", "Photosystem", "II", "(PSII)", "oxygen-evolving", "complex", "in", "Synechocystis", "sp.", "PCC", "6803", "and", "in", "spinach.", "PsbO", "is", "known", "to", "be", "stable", "in", "its", "oxidized", "form,", "but", "after", "reduction", "by", "thioredoxin", "it", "became", "a", "substrate", "for", "recombinant", "HhoA", "(rHhoA).", "rHhoA", "cleaved", "reduced", "eukaryotic", "(specifically,", "spinach)", "PsbO", "at", "defined", "sites", "and", "created", "distinct", "PsbO", "fragments", "that", "were", "not", "further", "degraded.", "As", "for", "the", "corresponding", "prokaryotic", "substrate", "(reduced", "PsbO", "of", "Synechocystis", "sp.", "PCC", "6803),", "no", "PsbO", "fragments", "were", "observed.", "Assembly", "to", "PSII", "protected", "PsbO", "from", "degradation.", "For", "Synechocystis", "sp.", "PCC", "6803,", "our", "results", "show", "that", "HhoA,", "HhoB,", "and", "HtrA", "are", "localized", "in", "the", "periplasma", "and/or", "at", "the", "thylakoid", "membrane.", "In", "agreement", "with", "the", "idea", "that", "PsbO", "could", "be", "a", "physiological", "substrate", "for", "Deg", "proteases,", "part", "of", "the", "cellular", "fraction", "of", "the", "three", "Deg", "proteases", "of", "Synechocystis", "sp.", "PCC", "6803", "(HhoA,", "HhoB,", "and", "HtrA)", "was", "detected", "in", "the", "PSII-enriched", "membrane", "fraction.", "Citation:", "Roberts", "IN,", "Lam", "XT,", "Miranda", "H,", "Kieselbach", "T,", "Funk", "C", "(2012)", "Degradation", "of", "PsbO", "by", "the", "Deg", "Protease", "HhoA", "Is", "Thioredoxin", "Dependent.", "PLoS", "ONE", "7(9):", "e45713.", "doi:10.1371/journal.pone.0045713", "Editor:", "Frederik", "Bo¨", "rnke,", "Friedrich-Alexander-University", "Erlangen-Nurenberg,", "Germany", "Received", "May", "14,", "2012;", "Accepted", "August", "24,", "2012;", "Published", "September", "19,", "2012", "Copyright:", "2012", "Roberts", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "grants", "of", "the", "Swedish", "Energy", "Agency", "(2009-000928", "to", "CF),", "the", "Royal", "Swedish", "Academy", "of", "Sciences", "(312-3820-06", "to", "CF),", "the", "Lawsky", "Foundation", "(to", "XTL)", "and", "Umea˚", "University", "(to", "CF).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "Christiane.Funk@chem.umu.se", "€", "Current", "address:", "Instituto", "de", "Investigaciones", "en", "Biociencias", "Agr´ıcolas", "y", "Ambientales,", "Universidad", "de", "Buenos", "Aires,", "Buenos", "Aires,", "Argentina", "Introduction", "Cells", "have", "evolved", "an", "extensive", "system", "of", "molecular", "chaperones,", "folding", "catalysts,", "and", "proteases;", "that", "control", "protein", "quality", "and", "prevent", "protein", "damage.", "Biochemical", "and", "molecular", "biological", "studies", "have", "successfully", "identified", "many", "plastidic", "protease", "families,", "most", "of", "which", "are", "homologs", "of", "defined", "bacterial", "proteases.", "Deg/HtrA", "proteases", "were", "initially", "identified", "because", "of", "their", "essential", "role", "in", "the", "degradation", "of", "abnormal", "periplasmic", "proteins", "and", "because", "they", "are", "crucial", "for", "the", "survival", "of", "E.", "coli", "at", "high", "temperatures", "[1,2].", "They", "have", "since", "been", "found", "in", "nearly", "all", "organisms;", "including", "Archae,", "bacteria", "and", "eukaryotes.", "Deg", "proteases", "are", "ATP-independent", "serine", "endopeptidases,", "containing", "a", "trypsin/chymotrypsin-like", "protease", "domain,", "followed", "by", "zero", "to", "three", "PDZ", "or", "PDZ-like", "domains", "[3,4]–PDZ", "domains", "being", "those", "that", "mediate", "complex", "assembly,", "substrate", "binding,", "and/or", "regulation", "of", "proteolytic", "activity", "[5–7].", "In", "Arabidopsis", "thaliana,", "16", "genes", "coding", "for", "Deg-like", "proteases", "have", "been", "identified", "and", "at", "least", "seven", "gene", "products", "have", "been", "predicted", "to", "be", "located", "in", "chloroplasts", "[8–10].", "Based", "on", "biochemical", "data,", "five", "Deg", "proteases", "have", "been", "shown", "to", "be", "localized", "in", "the", "chloroplast:", "Deg1,", "Deg5,", "and", "Deg8", "are", "located", "in", "the", "thylakoid", "lumen", "[11,12],", "and", "Deg2", "[13]", "and", "Deg7", "[14]", "are", "peripherally", "associated", "with", "the", "stromal", "side", "of", "the", "thylakoid", "membrane.", "Degradation", "of", "the", "Photosystem", "II", "(PSII)", "reaction-center", "protein", "D1", "under", "photoinhibition", "has", "been", "linked", "to", "the", "lumen-located", "Deg1", "[15],", "and", "to", "Deg5", "and", "Deg8", "[16].", "Additionally,", "Deg1", "seems", "to", "assist", "the", "assembly", "of", "PSII", "via", "interaction", "with", "the", "PSII", "reaction-center", "D2", "protein", "[17].", "It", "has", "been", "shown", "in", "vitro", "that", "recombinant", "Deg1", "of", "Arabidopsis", "is", "able", "to", "degrade", "in", "vitro–translated", "plastocyanin", "and", "PsbO", "[18].", "So", "far,", "no", "details", "of", "the", "molecular", "mechanism", "of", "Deg", "function", "are", "known,", "but", "recently", "it", "has", "been", "suggested", "that", "some", "Deg", "proteases", "might", "be", "redox", "regulated.", "In", "one", "study", "it", "was", "found", "that", "the", "proteolysis", "of", "casein", "by", "recombinant", "Deg1", "and", "Deg2", "of", "Arabidopsis", "was", "dependent", "on", "the", "redox", "potential", "of", "the", "surrounding", "medium;", "and", "while", "the", "activity", "of", "Deg1", "was", "maximal", "under", "reducing", "conditions,", "the", "opposite", "was", "true", "for", "Deg2", "[19].", "Deg1", "and", "Deg5", "have", "been", "identified", "as", "potential", "thioredoxin", "targets", "from", "their", "ability", "to", "form", "mixed", "disulfides", "with", "Trx", "A", "(thioredoxin", "A)", "of", "the", "unicellular", "cyanobacterium", "Synechocystis", "sp.", "PCC", "6803", "(hereafter:", "Synechocystis", "6803)", "[20].", "In", "Synechocystis", "6803,", "three", "Deg/HtrA", "proteases", "have", "been", "identified.", "Owing", "to", "their", "relationship", "to", "E.", "coli", "they", "have", "been", "named", "DegP/HtrA", "(slr1204),", "DegQ/HhoA", "(sll1679),", "and", "DegS/", "HhoB", "(sll1427)", "[21].", "However,", "they", "are", "more", "closely", "related", "to", "each", "other", "than", "to", "the", "E.", "coli", "Deg", "proteases", "with", "the", "same", "name", "[8,9];", "so", "they", "are", "probably", "not", "orthologs", "of", "the", "E.", "coli", "Deg", "proteases.", "HhoA,", "HtrA,", "and", "HhoB", "have", "very", "high", "homology", "with", "the", "lumen-located", "plant", "Deg", "proteases", "Deg1,", "Deg5,", "and", "Deg8", "[8].", "Single-deletion", "mutants", "of", "HtrA", "[22]", "and", "HhoA", "[23]", "have", "been", "found", "to", "be", "more", "sensitive", "than", "wild", "type,", "towards", "light", "and", "heat", "stress,", "respectively.", "However,", "these", "results", "were", "controversial", "[24,25].", "While", "a", "triple", "Deg-deletion", "mutant", "displayed", "a", "significant", "phenotype", "towards", "light-", "and", "heat-stress", "and", "phototaxis,", "none", "of", "the", "double", "mutants", "did.", "Therefore", "it", "was", "concluded", "that", "the", "Deg", "PLOS", "ONE", "|", "www.plosone.org", "1", "September", "2012", "|", "Volume", "7", "|", "Issue", "9", "|", "e45713" ]

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"The", "histology", "of", "the", "gonads", "revealed", "a", "Leydig", "and", "Sertoli", "cell", "neoplasia.", "The", "contemporaneous", "presence", "of", "testicular", "tissue,", "vulva,", "male", "karyotype", "were", "compatible", "with", "a", "male", "pseudohermaphrodite", "(MPH)", "condition.", "Background", "Mammalian", "sexual", "development", "depends", "on", "the", "suc-", "cessful", "completion", "of", "a", "series", "of", "steps", "under", "genetic", "and", "hormonal", "control.", "This", "process", "requires", "the", "accomplish-", "ment", "of", "three", "steps:", "chromosomal", "sex,", "gonadal", "sex", "and", "phenotypic", "sex.", "At", "fertilization", "the", "chromosomal", "sex", "is", "determined", "and", "successively", "XY", "embryos", "will", "develop", "testes", "whereas", "XX", "ones", "will", "develop", "ovaries", "(gonadal", "sex).", "The", "process", "regulating", "gonadal", "development", "is", "under", "genetic", "control", "and", "is", "referred", "as", "sex", 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[ "Rotavirus", "NSP1", "Inhibits", "NFkB", "Activation", "by", "Inducing", "Proteasome-Dependent", "Degradation", "of", "b-TrCP:", "A", "Novel", "Mechanism", "of", "IFN", "Antagonism", "Joel", "W.", "Graff.,", "Khalil", "Ettayebi.,", "Michele", "E.", "Hardy*", "Veterinary", "Molecular", "Biology,", "Montana", "State", "University,", "Bozeman,", "Montana,", "United", "States", "of", "America", "Abstract", "Mechanisms", "by", "which", "viruses", "counter", "innate", "host", "defense", "responses", "generally", "involve", "inhibition", "of", "one", "or", "more", "components", "of", "the", "interferon", "(IFN)", "system.", "Multiple", "steps", "in", "the", "induction", "and", "amplification", "of", "IFN", "signaling", "are", "targeted", "for", "inhibition", "by", "viral", "proteins,", "and", "many", "of", "the", "IFN", "antagonists", "have", "direct", "or", "indirect", "effects", "on", "activation", "of", "latent", "cytoplasmic", "transcription", "factors.", "Rotavirus", "nonstructural", "protein", "NSP1", "blocks", "transcription", "of", "type", "I", "IFNa/b", "by", "inducing", "proteasome-dependent", "degradation", "of", "IFN-regulatory", "factors", "3", "(IRF3),", "IRF5,", "and", "IRF7.", "In", "this", "study,", "we", "show", "that", "rotavirus", "NSP1", "also", "inhibits", "activation", "of", "NFkB", "and", "does", "so", "by", "a", "novel", "mechanism.", "Proteasome-mediated", "degradation", "of", "inhibitor", "of", "kB", "(IkBa)", "is", "required", "for", "NFkB", "activation.", "Phosphorylated", "IkBa", "is", "a", "substrate", "for", "polyubiquitination", "by", "a", "multisubunit", "E3", "ubiquitin", "ligase", "complex,", "Skp1/Cul1/F-box,", "in", "which", "the", "F-box", "substrate", "recognition", "protein", "is", "b-transducin", "repeat", "containing", "protein", "(b-TrCP).", "The", "data", "presented", "show", "that", "phosphorylated", "IkBa", "is", "stable", "in", "rotavirus-infected", "cells", "because", "infection", "induces", "proteasome-dependent", "degradation", "of", "b-TrCP.", "NSP1", "expressed", "in", "isolation", "in", "transiently", "transfected", "cells", "is", "sufficient", "to", "induce", "this", "effect.", "Targeted", "degradation", "of", "an", "F-box", "protein", "of", "an", "E3", "ligase", "complex", "with", "a", "prominent", "role", "in", "modulation", "of", "innate", "immune", "signaling", "and", "cell", "proliferation", "pathways", "is", "a", "unique", "mechanism", "of", "IFN", "antagonism", "and", "defines", "a", "second", "strategy", "of", "immune", "evasion", "used", "by", "rotaviruses.", "Citation:", "Graff", "JW,", "Ettayebi", "K,", "Hardy", "ME", "(2009)", "Rotavirus", "NSP1", "Inhibits", "NFkB", "Activation", "by", "Inducing", "Proteasome-Dependent", "Degradation", "of", "b-TrCP:", "A", "Novel", "Mechanism", "of", "IFN", "Antagonism.", "PLoS", "Pathog", "5(1):", "e1000280.", "doi:10.1371/journal.ppat.1000280", "Editor:", "Barbara", "Sherry,", "North", "Carolina", "State", "University,", "United", "States", "of", "America", "Received", "July", "10,", "2008;", "Accepted", "December", "26,", "2008;", "Published", "January", "30,", "2009", "Copyright:", "2009", "Graff", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "study", "has", "been", "funded", "by", "USDA/NRICGP", "02657,", "DoD", "contract", "W9113M-04-1-0010,", "PHS", "grant", "P20", "RR020185,", "and", "the", "Montana", "Agriculture", "Experiment", "Station.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "mhardy@montana.edu", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "Research", "into", "mechanisms", "by", "which", "viruses", "evade", "host", "defense", "has", "received", "increased", "attention", "in", "the", "past", "several", "years", "because", "of", "the", "potential", "to", "develop", "attenuated", "vaccines", "based", "on", "viruses", "with", "weakened", "evasion", "strategies,", "or", "antiviral", "therapies", "that", "target", "specific", "immune", "system", "antagonists.", "Most,", "if", "not", "all,", "viruses", "encode", "proteins", "that", "interfere", "with", "signal", "transduction", "pathways", "involved", "in", "induction", "or", "amplification", "of", "the", "immune", "response,", "particularly", "the", "innate", "response", "driven", "by", "type", "I", "interferon", "(IFNa/b)", "[1].", "IFNa/b", "are", "cytokines", "that", "stimulate", "expression", "of", "genes", "that", "interfere", "directly", "with", "steps", "in", "the", "virus", "replication", "cycle,", "and", "genes", "whose", "protein", "products", "modulate", "and", "recruit", "the", "adaptive", "immune", "response.", "The", "antiviral", "state", "that", "is", "established", "by", "the", "IFN", "system", "serves", "to", "restrict", "virus", "replication", "and", "spread", "while", "effectors", "of", "the", "slower", "adaptive", "immune", "response", "are", "recruited", "to", "the", "site", "of", "infection.", "The", "mechanisms", "of", "IFNa/b", "induction", "are", "relatively", "well", "understood", "[2]", "although", "proteins", "involved", "in", "this", "pathway", "continue", "to", "be", "identified", "[3,4,5].", "Induction", "of", "IFNb", "transcription", "occurs", "through", "assembly", "of", "transcription", "factors", "interferon", "regulatory", "factor", "3", "(IRF3),", "NFkB,", "and", "ATF2/c-Jun", "on", "the", "positive", "regulatory", "domain", "enhancer", "element", "of", "the", "IFNb", "promoter,", "and", "the", "interferon", "stimulated", "response", "element", "(ISRE)", "in", "promoters", "of", "a", "subset", "IFN-stimulated", "genes", "(ISG)", "[6,7,8].", "Secreted", "IFNb", "binds", "to", "cell", "surface", "type", "I", "IFN", "receptors", "and", "activates", "the", "JAK/STAT", "pathway,", "resulting", "in", "formation", "of", "IFN-", "stimulated", "gene", "factor-3", "(ISGF3).", "ISGF3", "is", "a", "heterotrimeric", "complex", "consisting", "of", "STAT1,", "STAT2,", "and", "IRF9.", "ISGF3", "translocates", "to", "the", "nucleus", "and", "induces", "transcription", "of", "IFNa", "and", "numerous", "ISGs,", "thus", "amplifying", "the", "response", "through", "a", "positive", "feedback", "mechanism.", "Each", "of", "the", "steps", "in", "the", "IFN", "signaling", "pathway", "has", "been", "reported", "as", "targets", "for", "viral", "IFN", "antagonists.", "A", "recent", "summary", "of", "mechanisms", "viruses", "use", "to", "block", "the", "IFN", "response", "clearly", "illustrates", "that", "some", "viral", "proteins", "target", "more", "than", "one", "step", "in", "the", "pathway", "(e.g.", "influenza", "virus", "NS1)", "and", "some", "viruses", "encode", "more", "than", "one", "IFN", "antagonist", "(e.g.", "paramyxovirus", "V,", "C,", "and", "N", "proteins),", "exemplifying", "the", "impor-", "tance", "of", "IFN", "signaling", "to", "host", "defense", "[1,9].", "Signal", "transduction", "pathways", "that", "activate", "IRF3", "and", "NFkB", "have", "been", "well", "studied", "in", "the", "context", "of", "the", "virus-induced", "IFN", "response.", "Upon", "virus", "detection,", "IRF3", "is", "phosphorylated", "at", "its", "C", "terminus", "by", "kinases", "TBK1", "or", "IKKe", "[10],", "dimerizes", "and", "then", "translocates", "to", "the", "nucleus", "to", "assemble", "at", "the", "IFNb", "promoter", "and", "select", "ISRE-containing", "promoters", "in", "cooperation", "with", "transcrip-", "tion", "co-activators", "[8].", "IRF3", "activation", "is", "required", "for", "IFNb", "transcription,", "and", "the", "number", "of", "reports", "of", "viruses", "that", "interfere", "directly", "with", "the", "function", "of", "IRF3,", "or", "the", "steps", "preceding", "its", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1", "January", "2009", "|", "Volume", "5", "|", "Issue", "1", "|", "e1000280" ]

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"reduction", "in", "the", "probability", "of", "an", "event", "occurring.", "Copyright", "©", "2011", "John", "Wiley", "&", "Sons,", "Ltd.", "Keywords:", "propensity", "score;", "propensity-score", "matching;", "risk", "difference;", "absolute", "risk", "reduction;", "Monte", "Carlo", "simulations;", "statistical", "inference;", "hypothesis", "testing;", "type", "I", "error", "rate;", "categorical", "data", "analysis", "1.", "Introduction", "Propensity-score", "matching", "is", "increasingly", "being", "used", "to", "estimate", "the", "effects", "of", "treatments,", "exposures", "and", "interventions", "on", "outcomes", "in", "observational", "studies.", "The", "propensity", "score", "is", "the", "probability", "of", "treatment", "assignment", "conditional", "on", "the", "observed", "baseline", "covariates", "[1].", "If", "treatment", "assignment", "is", "strongly", "ignorable,", "then", "conditioning", "on", "the", "propensity", "score", "allows", "one", "to", "obtain", "an", 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"Toronto,", "Ont.,", "Canada", "M4N", "3M5.", "†E-mail:", "peter.austin@ices.on.ca", "Copyright", "©", "2011", "John", "Wiley", "&", "Sons,", "Ltd.", "Statist.", "Med.", "2011,", "30", "1292--1301" ]

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[ "Hindawi", "Publishing", "Corporation", "International", "Journal", "of", "Peptides", "Volume", "2011,", "Article", "ID", "708710,", "3", "pages", "doi:10.1155/2011/708710", "Research", "Article", "Activity", "of", "Cathelicidin", "Peptides", "against", "Simkania", "negevensis", "Manuela", "Donati,1", "Antonietta", "Di", "Francesco,2", "Maria", "Di", "Paolo,1", "Natascia", "Fiani,1", "Monica", "Benincasa,3", "Renato", "Gennaro,3", "Paola", "Nardini,1", "Claudio", "Foschi,1", "and", "Roberto", "Cevenini1", "1", "Section", "of", "Microbiology", "DESOS,", "Policlinico", "S.", "Orsola,", "University", "of", "Bologna,", "40138", "Bologna,", "Italy", "2", "Department", "of", "Veterinary", "Medical", "Sciences,", "University", "of", "Bologna,", "40064", "Ozzano", "dell’Emilia,", "Italy", "3", "Department", "of", "Life", "Sciences,", "University", "of", "Trieste,", "34127,", "Trieste,", "Italy", "Correspondence", "should", "be", "addressed", "to", "Antonietta", "Di", "Francesco,", "antoniet.difrancesco@unibo.it", "Received", "10", "December", "2010;", "Accepted", "30", "January", "2011", "Academic", "Editor:", "Peter", "Bergman", "Copyright", "©", "2011", "Manuela", "Donati", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "The", "in", "vitro", "activity", "of", "six", "cathelicidin", "peptides", "against", "the", "reference", "strain", "Z", "of", "Simkania", "negevensis", "was", "investigated.", "Five", "peptides—PG-1,", "Bac7,", "SMAP-29,", "BMAP-27,", "and", "BMAP-28—proved", "to", "be", "active", "at", "very", "low", "concentrations", "(1", "to", "0.1", "µg/mL),", "while", "LL-37", "cathelicidin", "was", "ineffective", "even", "at", "a", "concentration", "of", "100", "µg/mL.", "In", "comparison", "to", "chlamydiae,", "S.", "negevensis", "proved", "to", "be", "more", "susceptible", "to", "the", "antimicrobial", "peptides", "tested.", "1.", "Introduction", "Simkania", "negevensis", "is", "an", "obligate", "intracellular", "Gram-nega-", "tive", "bacterium", "belonging", "to", "the", "family", "of", "Simkaniaceae", "in", "the", "order", "Chlamydiales", "[1],", "discovered", "as", "a", "contaminant", "in", "a", "variety", "of", "cell", "cultures", "[2],", "and", "is", "able", "to", "grow", "also", "in", "various", "environmental", "free-living", "amoebae", "such", "as", "Acanthamoeba", "poliphaga", "[3].", "Epidemiologic", "studies", "have", "reported", "a", "human", "widesp-", "read", "exposure", "to", "this", "bacterium", "[4,", "5],", "both", "in", "healthy", "sub-", "jects", "and", "in", "association", "with", "respiratory", "diseases", "in", "infants", "and", "adults", "[6–10].", "Coinfections", "with", "other", "pathogens", "have", "been", "described,", "such", "as", "respiratory", "syncytial", "virus", "in", "children", "and", "influenza", "virus", "and", "other", "bacterial", "species", "in", "adults", "[7,", "8,", "11].", "A", "possible", "association", "between", "S.", "negevensis", "and", "acute", "rejection", "in", "lung", "transplant", "recipients", "has", "been", "suggested", "[12].", "S.", "negevensis", "DNA", "has", "also", "been", "amplified", "from", "an", "aortic", "aneurysm", "[13,", "14].", "Previous", "investigations", "reported", "S.", "negevensis", "in", "vitro", "sus-", "ceptibility", "to", "azithromycin,", "minocycline,", "erithromycin,", "dox-", "ycycline,", "and", "ofloxacin", "like", "chlamydiae", "[15]", "and", "the", "lack", "of", "susceptibility", "to", "ampicillin,", "penicillin", "G,", "bacitracin,", "cycl-", "osporine,", "and", "fluoroquinolones", "[2,", "15,", "16].", "Several", "studies", "[17–20]", "demonstrated", "the", "in", "vitro", "antich-", "lamydial", "activity", "of", "peptides,", "such", "as", "cathelicidins,", "stored", "by", "mammalian", "leucocytes", "and", "show", "an", "antimicrobial", "activity", "against", "bacteria,", "fungi,", "protozoa,", "and", "enveloped", "viruses.", "With", "regard", "to", "the", "mode", "of", "action", "of", "these", "peptides", "against", "chlamydiae,", "previous", "investigations", "on", "the", "activity", "of", "prote-", "grins", "[21]", "suggested", "an", "initial", "binding", "to", "lipopolysaccharide", "followed", "by", "insertion", "into", "the", "membrane", "that", "results", "in", "permeabilization.", "Yasin", "et", "al.", "[22]", "demonstrated", "that", "the", "antichlamydial", "activity", "of", "protegrins", "resided", "especially", "in", "residues", "5", "to", "15", "of", "native", "protegrin-1", "and", "required", "both", "intramolecular", "disulfide", "bonds.", "In", "the", "present", "study,", "we", "investigate", "the", "in", "vitro", "activity", "of", "six", "antimicrobial", "peptides", "against", "the", "reference", "strain", "Z", "of", "S.", "negevensis.", "2.", "Materials", "and", "Methods", "The", "cathelicidin", "peptides—PG-1", "from", "pig,", "Bac7", "(1–35)", "from", "cattle,", "SMAP-29", "from", "sheep,", "LL-37", "from", "human,", "BMAP-", "27,", "and", "BMAP-28", "from", "cattle—were", "chemically", "synthesized,", "purified,", "characterized,", "and", "provided", "as", "lyophilized", "peptide,", "as", "previously", "reported", "[19].", "The", "reference", "strain", "Z", "of", "S.", "negevensis", "(American", "Type", "Culture", "Collection", "VR-1471)", "was", "grown", "in", "LLC-MK2", "cells", "[23]", "in", "6-large", "well", "plates", "and", "elementary", "bodies", "(EBs)", "were", "purified", "by", "use", "of", "sucrose", "gradients", "[24],", "resuspended", "in", "sucrose-phosphate-glutamic" ]

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[ "Dubé", "et", "al.", "BMC", "Public", "Health", "2011,", "11:128", "http://www.biomedcentral.com/1471-2458/11/128", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "A(H1N1)", "pandemic", "influenza", "and", "its", "prevention", "by", "vaccination:", "Paediatricians’", "opinions", "before", "and", "after", "the", "beginning", "of", "the", "vaccination", "campaign", "Eve", "Dubé1,2*,", "Defay", "Fannie2,", "Gilca", "Vladimir1,2,", "Bettinger", "A", "Julie3,", "Sauvageau", "Chantal1,2,", "Lavoie", "France2,", "Boucher", "D", "François2,", "McNeil", "Shelly4,", "Gemmill", "Ian5,", "Boulianne", "Nicole1,2", "Abstract", "Background:", "In", "June", "2009,", "the", "World", "Health", "Organization", "declared", "an", "A(H1N1)", "influenza", "pandemic.", "In", "October", "2009,", "the", "largest", "vaccination", "campaign", "in", "Canadian", "history", "began.", "The", "aim", "of", "this", "study", "was", "to", "document", "paediatricians’", "knowledge,", "attitudes", "and", "practices", "(KAP)", "regarding", "A(H1N1)", "pandemic", "influenza", "and", "its", "prevention", "by", "vaccination", "just", "after", "the", "beginning", "of", "the", "A(H1N1)", "vaccination", "campaign", "and", "to", "compare", "the", "results", "with", "those", "obtained", "before", "campaign", "initiation.", "Methods:", "A", "self-administered", "mail-based", "questionnaire", "was", "sent", "to", "all", "Canadian", "paediatricians.", "Questionnaires", "were", "analyzed", "in", "two", "subsets:", "those", "received", "before", "and", "after", "the", "beginning", "of", "the", "vaccination", "campaign.", "Results:", "Overall", "the", "response", "rate", "was", "50%.", "Respondents’", "characteristics", "were", "comparable", "between", "the", "two", "subsets.", "Before", "the", "beginning", "of", "the", "campaign,", "63%", "of", "paediatricians", "perceived", "A(H1N1)", "pandemic", "infection", "as", "a", "serious", "disease,", "that", "would", "occur", "frequently", "without", "vaccination", "compared", "to", "more", "than", "75%", "after.", "Before", "the", "vaccination", "campaign,", "half", "of", "respondents", "or", "less", "thought", "that", "the", "A(H1N1)", "vaccine", "was", "safe", "(50%)", "and", "effective", "(35%)", "compared", "to", "77%", "and", "72%", "after.", "The", "proportion", "of", "paediatricians", "who", "reported", "they", "had", "received", "sufficient", "information", "on", "A", "(H1N1)", "vaccine", "increased", "from", "31%", "before", "to", "73%", "after", "the", "beginning", "of", "the", "vaccination", "campaign.", "The", "majority", "of", "respondents", "intended", "to", "get", "vaccinated", "against", "A(H1N1)", "influenza", "themselves", "(84%", "before", "and", "92%", "after).", "Respondents’", "intention", "to", "recommend", "the", "A(H1N1)", "vaccine", "to", "their", "patients", "increased", "from", "80%", "before", "the", "beginning", "of", "the", "campaign", "to", "92%", "after.", "In", "multivariate", "analysis,", "the", "main", "determinants", "of", "paediatricians’", "intention", "to", "recommend", "the", "A(H1N1)", "vaccine", "were", "their", "intention", "to", "get", "vaccinated", "against", "A(H1N1)", "influenza", "themselves", "and", "a", "belief", "that", "A", "(H1N1)", "vaccine", "would", "be", "well", "accepted", "by", "health", "professionals", "who", "administer", "vaccines", "to", "the", "public.", "Conclusion:", "Results", "of", "this", "study", "show", "important", "increases", "in", "physicians’", "level", "of", "confidence", "about", "A(H1N1)", "vaccine’s", "safety", "and", "immunogenicity", "and", "their", "willingness", "to", "recommend", "this", "vaccine", "to", "their", "patients.", "These", "changes", "could", "be", "explained,", "at", "least", "partially,", "by", "the", "important", "effort", "done", "by", "public", "health", "authorities", "to", "disseminate", "information", "regarding", "A(H1N1)", "vaccination.", "Background", "In", "June", "2009,", "the", "World", "Health", "Organization", "(WHO)", "declared", "an", "A(H1N1)", "influenza", "pandemic", "[1].", "In", "Octo-", "ber", "2009,", "the", "largest", "vaccination", "campaign", "in", "Canadian", "history", "began.", "Before", "the", "start", "of", "the", "A(H1N1)", "pan-", "demic", "influenza", "vaccination", "campaign,", "limited", "*", "Correspondence:", "eve.dube@ssss.gouv.qc.ca", "1Institut", "National", "de", "Santé", "publique", "du", "Québec,", "2400", "d’Estimauville,", "Québec,", "Canada", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "information", "on", "the", "safety", "and", "immunogenicity", "of", "A", "(H1N1)", "influenza", "vaccines", "was", "available.", "However,", "the", "spread", "of", "A(H1N1)", "influenza", "generated", "intense", "media", "interest", "in", "pandemic", "preparedness", "and", "contradictory", "information", "around", "the", "vaccine", "and", "the", "vaccination", "campaign", "was", "reported", "[2-6].", "During", "the", "first", "wave", "of", "A", "(H1N1)", "influenza", "in", "Canada,", "77", "deaths", "were", "reported,", "mostly", "in", "the", "provinces", "of", "Quebec", "and", "Ontario.", "During", "the", "second", "wave,", "in", "early", "fall", "2009,", "351", "deaths", "were", "reported", "across", "the", "country", "[7].", "In", "Canada,", "almost", "©", "2011", "Dubé", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Insights", "Imaging", "(2012)", "3:247–250", "DOI", "10.1007/s13244-012-0168-x", "PICTORIAL", "REVIEW", "Hypertrophic", "pyloric", "stenosis:", "tips", "and", "tricks", "for", "ultrasound", "diagnosis", "Sílvia", "Costa", "Dias", "&", "Sophie", "Swinson", "&", "Helena", "Torrão", "&", "Lígia", "Gonçalves", "&", "Svitlana", "Kurochka", "&", "Carlos", "Pina", "Vaz", "&", "Vasco", "Mendes", "Received:", "5", "October", "2011", "/", "Revised:", "11", "February", "2012", "/", "Accepted:", "19", "March", "2012", "/", "Published", "online:", "1", "May", "2012", "#", "European", "Society", "of", "Radiology", "2012", "Abstract", "We", "describe", "a", "systematic", "approach", "to", "the", "ultra-", "sound", "(US)", "examination", "of", "the", "antropyloric", "region", "in", "chil-", "dren.", "US", "is", "the", "modality", "of", "choice", "for", "the", "diagnosis", "of", "hypertrophic", "pyloric", "stenosis", "(HPS).", "The", "imaging", "features", "of", "the", "normal", "pylorus", "and", "the", "diagnostic", "findings", "in", "HPS", "are", "reviewed", "and", "illustrated", "in", "this", "pictorial", "essay.", "Common", "difficulties", "in", "performing", "the", "examination", "and", "tips", "to", "help", "overcome", "them", "will", "also", "be", "discussed.", "Main", "Messages", "Hypertrophic", "Pyloric", "Stenosis", "is", "defined", "by", "thickening", "of", "the", "muscular", "layer", "and", "failure", "in", "relaxation", "of", "the", "pyloric", "canal.", "The", "main", "diagnostic", "criterion", "is", "a", "measurement", "of", "more", "than", "3mm", "in", "thickness", "of", "the", "muscular", "layer.", "Abnormal", "elongation", "of", "the", "canal", "is", "characterised", "as", "greater", "than", "12", "mm", "in", "length.", "Keywords", "Hypertrophic", "pyloric", "stenosis", ".", "Ultrasound", "S.", "Costa", "Dias", ":", "H.", "Torrão", ":", "L.", "Gonçalves", ":", "S.", "Kurochka", ":", "C.", "P.", "Vaz", ":", "V.", "Mendes", "Radiology", "Department,", "Hospital", "de", "Braga,", "Braga,", "Portugal", "S.", "Costa", "Dias", "(*)", "Rua", "Pedro", "Hispano,", "n", "190,", "2", "Dto,", "4100-393", "Porto,", "Portugal", "e-mail:", "silviacostadias@hotmail.com", "S.", "Swinson", "Radiology", "Department,", "Great", "Ormond", "Street", "Hospital", "for", "Children", "NHS", "Trust,", "Great", "Ormond", "Street,", "London", "WC1N", "3JH,", "UK", "Introduction", "Hypertrophic", "pyloric", "stenosis", "(HPS)", "is", "the", "most", "frequent", "sur-", "gical", "condition", "in", "infants", "in", "the", "first", "few", "months", "of", "life", "[1].", "The", "condition", "is", "characterised", "by", "thickening", "of", "the", "muscular", "layer", "and", "failure", "of", "the", "pyloric", "canal", "to", "relax", "resulting", "in", "gastric", "outlet", "obstruction.", "Elongation", "of", "the", "canal", "and", "thickened", "mucosa", "are", "also", "seen.", "Ultrasound", "(US)", "is", "the", "preferred", "diagnostic", "modality", "[2]", "as", "it", "is", "a", "non-invasive", "technique,", "allowing", "direct", "observation", "of", "the", "pyloric", "canal", "morphology", "and", "behaviour.", "It", "is", "important", "to", "carry", "out", "a", "systematic", "and", "dynamic", "study", "and", "to", "be", "aware", "of", "the", "common", "technical", "difficulties", "and", "how", "to", "overcome", "them.", "Clinical", "features", "HPS", "is", "the", "most", "common", "surgical", "cause", "of", "vomiting", "in", "infants.", "It", "has", "an", "incidence", "of", "3", "per", "1,000", "live", "births", "per", "year,", "although", "wide", "variations", "have", "been", "documented", "with", "geographic", "location,", "season", "and", "ethnic", "origin", "[3].", "This", "dis-", "ease", "usually", "presents", "between", "the", "second", "and", "sixth", "weeks", "of", "life,", "more", "commonly", "in", "the", "white", "population,", "in", "males", "(male:female", "ratio", "4:1)", "and", "typically", "in", "first-born", "children", "[4].", "A", "history", "of", "an", "affected", "first-degree", "relative", "increases", "the", "risk", "more", "than", "five-fold", "[5].", "The", "US", "examination", "allows", "the", "radiologist", "to", "perform", "a", "brief", "clinical", "history,", "which", "can", "reveal", "essential", "clues", "to", "the", "diagnosis.", "A", "recent", "history", "of", "projectile", "and", "nonbilious", "vomiting,", "which", "may", "be", "intermittent", "or", "with", "every", "feeding", "is", "the", "classical", "com-", "plaint.", "Typically", "the", "infant", "has", "a", "voracious", "appetite.", "When", "the", "vomiting", "persists,", "other", "clinical", "and", "biochemical", "findings", "may", "occur", "such", "as", "dehydration,", "hypochloraemic" ]

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[ "J", "Neurodevelop", "Disord", "(2011)", "3:144–151", "DOI", "10.1007/s11689-011-9080-9", "Salivary", "biomarkers", "of", "HPA", "axis", "and", "autonomic", "activity", "in", "adults", "with", "intellectual", "disability", "with", "and", "without", "stereotyped", "and", "self-injurious", "behavior", "disorders", "Frank", "J.", "Symons", "&", "Jason", "J.", "Wolff", "&", "Laura", "S.", "Stone", "&", "Tony", "K.", "Y.", "Lim", "&", "James", "W.", "Bodfish", "Received:", "9", "September", "2010", "/", "Accepted:", "25", "March", "2011", "/", "Published", "online:", "12", "April", "2011", "#", "Springer", "Science+Business", "Media,", "LLC", "2011", "Abstract", "Salivary", "levels", "of", "biomarkers", "for", "the", "hypothalamic–", "pituitary–adrenal", "axis", "(HPA;", "cortisol)", "and", "sympatho-adreno-", "medullary", "system", "(SAM;", "α-amylase)", "were", "measured", "in", "51", "adults", "(57%", "male)", "with", "neurodevelopmental", "disorders", "associ-", "ated", "with", "intellectual", "disability", "(i.e.,", "mental", "retardation)", "and", "chronic", "self-injurious", "behavior", "(SIB)", "and", "compared", "with", "matched", "controls", "without", "SIB.", "Cortisol", "levels", "differed", "signif-", "icantly", "(p<0.01)", "between", "the", "SIB", "and", "control", "group", "(SIB>", "control).", "Within-group", "analyses", "showed", "significant", "differences", "(p<0.05)", "in", "levels", "of", "salivary", "α-amylase", "between", "individuals", "with", "SIB", "and", "those", "with", "SIB", "meeting", "criteria", "for", "stereotyped", "movement", "disorder", "(SMD;", "SIB+SMD>SIB).", "Salivary", "α-", "amylase", "was", "significantly", "correlated", "with", "frequency", "of", "stereotypy", "among", "the", "SIB", "group", "(r=0.36,", "p<0.05).", "These", "preliminary", "findings", "warrant", "further", "exploration", "into", "the", "role", "of", "the", "SAM", "system", "in", "the", "pathophysiology", "of", "SIB", "and", "related", "The", "preparation", "of", "this", "report", "was", "supported,", "in", "part,", "by", "NICHD", "Grant", "No.", "44763", "and", "47201", "to", "the", "University", "of", "Minnesota.", "We", "are", "grateful", "to", "Jamie", "Clary", "for", "assistance", "with", "saliva", "collection.", "Our", "sincere", "thanks", "go", "to", "a", "committed", "group", "of", "parents", "and", "staff", "for", "their", "support.", "F.", "J.", "Symons", "(*)", "Department", "of", "Educational", "Psychology,", "Center", "for", "Neurobehavioral", "Development,", "University", "of", "Minnesota,", "Education", "Science", "Building,", "56", "River", "Road,", "Minneapolis,", "MN", "55455,", "USA", "e-mail:", "symon007@umn.edu", "J.", "J.", "Wolff", ":", "J.", "W.", "Bodfish", "Carolina", "Institute", "for", "Developmental", "Disabilities,", "University", "of", "North", "Carolina", "at", "Chapel", "Hill,", "200", "East", "Cameron", "Avenue,", "Chapell", "Hill,", "NC,", "USA", "L.", "S.", "Stone", ":", "T.", "K.", "Y.", "Lim", "Alan", "Edwards", "Center", "for", "Research", "on", "Pain,", "McGill", "University,", "Montreal,", "QC,", "Canada", "repetitive", "behaviors", "among", "individuals", "with", "neurodevelop-", "mental", "disorders", "associated", "with", "intellectual", "disability.", "Keywords", "Salivary", ".", "Self-injury", ".", "Stereotypy", ".", "HPA", "axis", ".", "Hypothalamic–pituitary–adrenal", "axis", "(HPA)", ".", "Sympatho-", "adreno-medullary", "system", "(SAM)", "Self-injurious", "behavior", "(SIB)", "is", "a", "relatively", "prevalent", "behavior", "disorder", "among", "populations", "of", "people", "with", "neurodevelop-", "mental", "disorders", "associated", "with", "intellectual", "and", "develop-", "mental", "disabilities", "(IDD),", "with", "estimated", "prevalence", "rates", "between", "5–20%", "of", "persons", "with", "IDD", "engaging", "in", "SIB", "(Schroeder", "et", "al.", "2001).", "The", "presentation", "of", "SIB", "can", "be", "severe,", "characterized", "by", "non-accidental", "and", "self-inflicted", "head-banging,", "body-hitting,", "eye-gouging,", "self-biting,", "hair-", "pulling,", "and", "other", "activities", "causing", "injury.", "The", "pathophys-", "iology", "of", "SIB", "is", "poorly", "understood,", "and", "consequentially,", "the", "disorder", "can", "be", "difficult", "to", "treat", "effectively.", "There", "are", "no", "standard", "first", "choice", "pharmacological", "treatments", "for", "SIB,", "making", "the", "clinician’s", "judgement", "the", "primary", "determinant", "of", "treatment", "(Osman", "and", "Loschen", "1992).", "Limited", "research", "on", "biological", "mechanisms", "and", "their", "markers", "has", "impeded", "the", "identification", "of", "specific", "and", "effective", "forms", "of", "psychophar-", "macological", "treatment", "(but", "see", "Sandman", "et", "al.", "1999).", "The", "study", "of", "biological", "markers,", "therefore,", "may", "be", "especially", "useful", "in", "aiding", "diagnosis,", "treatment", "course", "decisions,", "and", "in", "gaining", "a", "greater", "understanding", "of", "SIB", "pathophysiology.", "Studies", "of", "biological", "markers", "among", "individuals", "with", "SIB", "and", "IDD", "have", "demonstrated", "a", "relationship", "between", "SIB", "and", "stress,", "which", "has", "mostly", "been", "focused", "around", "the", "hypothalamic–pituitary–adrenal", "(HPA)", "axis.", "After", "a", "SIB", "episode,", "plasma", "β-endorphin", "levels", "increase", "and", "uncouple", "from", "adrenocorticotropic", "hormone", "(ACTH;", "Sandman", "et", "al.", "1997;", "Sandman", "et", "al.", "2003).", "Under", "normal", "circumstances,", "ACTH", "and", "β-endorphin", "levels", "are", "highly", "correlated,", "as", "they" ]

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[ "Versican", "G3", "Domain", "Modulates", "Breast", "Cancer", "Cell", "Apoptosis:", "A", "Mechanism", "for", "Breast", "Cancer", "Cell", "Response", "to", "Chemotherapy", "and", "EGFR", "Therapy", "William", "Weidong", "Du1,2,", "Burton", "B.", "Yang2,3,", "Bing", "L.", "Yang1,2,", "Zhaoqun", "Deng2,3,", "Ling", "Fang2,3,", "Sze", "Wan", "Shan2,3,", "Zina", "Jeyapalan2,3,", "Yaou", "Zhang", "4", ",", "Arun", "Seth2,3,", "Albert", "J.", "Yee1*", "1", "Department", "of", "Surgery,", "Sunnybrook", "Health", "Sciences", "Centre", "and", "Centre", "for", "the", "Study", "of", "Bone", "Metastasis,", "Odette", "Cancer", "Centre,", "University", "of", "Toronto,", "Toronto,", "Canada,", "2", "Sunnybrook", "Research", "Institute,", "Toronto,", "Canada,", "3", "Department", "of", "Laboratory", "Medicine", "and", "Pathobiology,", "University", "of", "Toronto,", "Canada,", "4", "Division", "of", "Life", "Science,", "Graduate", "School", "at", "Shenzhen,", "Tsinghua", "University,", "Shenzhen,", "China", "Abstract", "Overexpression", "of", "EGFR", "and", "versican", "has", "been", "reported", "in", "association", "with", "breast", "cancers.", "Considered", "oncogenic,", "these", "molecules", "may", "be", "attractive", "therapeutic", "targets.", "Possessing", "anti-apoptotic", "and", "drug", "resistant", "properties,", "overexpression", "of", "these", "molecules", "is", "accompanied", "by", "selective", "sensitization", "to", "the", "process", "of", "apoptosis.", "In", "this", "study,", "we", "exogenously", "expressed", "a", "versican", "G3", "construct", "in", "breast", "cancer", "cell", "lines", "and", "analyzed", "the", "effects", "of", "G3", "on", "cell", "viability", "in", "fetal", "bovine", "serum", "free", "conditioned", "media", "and", "evaluated", "the", "effects", "of", "apoptotic", "agent", "C2-ceramide,", "and", "chemotherapeutic", "agents", "including", "Docetaxel,", "Doxorubicin,", "and", "Epirubicin.", "Versican", "G3", "domain", "enhanced", "tumor", "cell", "resistance", "to", "apoptosis", "when", "cultured", "in", "serum", "free", "medium,", "Doxorubicin,", "or", "Epirubicin", "by", "up-regulating", "pERK", "and", "GSK-3b", "(S9P).", "However,", "it", "could", "be", "prevented", "by", "selective", "EGFR", "inhibitor", "AG", "1478", "and", "selective", "MEK", "inhibitor", "PD", "98059.", "Both", "AG", "1478", "and", "PD", "98059", "enhanced", "expression", "of", "pSAPK/JNK,", "while", "selective", "JNK", "inhibitor", "SP", "600125", "enhanced", "expression", "of", "GSK-3b", "(S9P).", "Versican", "G3", "promoted", "cell", "apoptosis", "induced", "by", "C2-ceramide", "or", "Docetaxel", "by", "enhancing", "expression", "of", "pSAPK/JNK", "and", "decreasing", "expression", "of", "GSK-3b", "(S9P),", "an", "observation", "blocked", "by", "AG", "1478", "or", "SP", "6000125.", "Inhibition", "of", "endogenous", "versican", "expression", "by", "siRNA", "or", "reduction", "of", "versican", "G3’s", "expression", "by", "linking", "G3", "with", "39UTR", "prevented", "G3", "modulated", "cell", "apoptosis.", "The", "dual", "roles", "of", "G3", "in", "modulating", "breast", "cancer", "cell", "resistance", "to", "chemotherapeutic", "agents", "may", "in", "part", "explain", "a", "potential", "mechanism", "for", "breast", "cancer", "cell", "resistance", "to", "chemotherapy", "and", "EGFR", "therapy.", "The", "apoptotic", "effects", "of", "chemotherapeutics", "depend", "upon", "the", "activation", "and", "balance", "of", "down", "stream", "signals", "in", "the", "EGFR", "pathway.", "GSK-3b", "(S9P)", "appears", "to", "function", "as", "a", "key", "checkpoint", "in", "this", "balance", "of", "apoptosis", "and", "anti-apoptosis.", "Investigation", "and", "potential", "consideration", "of", "targeting", "GSK-3b", "(S9P)", "merits", "further", "study.", "Citation:", "Du", "WW,", "Yang", "BB,", "Yang", "BL,", "Deng", "Z,", "Fang", "L,", "et", "al.", "(2011)", "Versican", "G3", "Domain", "Modulates", "Breast", "Cancer", "Cell", "Apoptosis:", "A", "Mechanism", "for", "Breast", "Cancer", "Cell", "Response", "to", "Chemotherapy", "and", "EGFR", "Therapy.", "PLoS", "ONE", "6(11):", "e26396.", "doi:10.1371/journal.pone.0026396", "Editor:", "Ilya", "Ulasov,", "University", "of", "Chicago,", "United", "States", "of", "America", "Received", "March", "7,", "2011;", "Accepted", "September", "26,", "2011;", "Published", "November", "9,", "2011", "Copyright:", "2011", "Du", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "a", "grant", "from", "National", "Sciences", "and", "Engineering", "Research", "Council", "of", "Canada", "(227937-01)", "to", "Dr.", "Yang", "who", "is", "the", "recipient", "of", "a", "Career", "Investigator", "Award", "(CI5958)", "from", "the", "Heart", "and", "Stroke", "Foundation", "of", "Ontario.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "albert.yee@sunnybrook.ca", "Introduction", "Chemotherapeutic", "drugs", "exhibit", "varied", "selectivity", "for", "tumour", "cells", "dependent", "on", "cell", "origins", "and", "are", "capable", "of", "inducing", "tumour", "cell", "death", "[1,2].", "Additionally", "many", "of", "the", "commonly", "used", "chemotherapeutic", "drugs", "also", "appear", "to", "influence", "cellular", "signaling", "pathways", "that", "induce", "apoptosis", "in", "susceptible", "cancer", "cells", "[1,3].", "Apoptosis", "seems", "to", "be", "one", "of", "the", "major", "physiologic", "safeguards", "against", "uncontrolled", "proliferation", "[4].", "Growth", "and", "apoptosis", "are", "two", "diametrically", "opposed", "biological", "processes", "that", "ensure", "that", "multi-cellular", "organisms", "can", "cope", "with", "the", "normal", "physiologic", "yet", "mutagenic", "environment", "that", "generates", "millions", "of", "potential", "cancer", "cells", "every", "day", "[5].", "With", "its", "effects", "on", "tumor", "cell", "proliferation", "and", "migration,", "versican", "has", "been", "shown", "to", "increase", "the", "resistance", "of", "cancer", "cells", "to", "apoptosis", "[6].", "Our", "previous", "research", "demonstrated", "that", "versican", "appeared", "to", "confer", "cell", "resistance", "to", "apoptosis", "following", "treatment", "with", "low", "serum", "medium", "or", "hydrogen", "peroxide", "[7,8].", "The", "combination", "of", "selective", "apoptotic", "resistance", "and", "sensitivity", "has", "been", "reported", "in", "overexpression", "of", "the", "V1", "versican", "isoform", "[7];", "the", "intimate", "relationship", "between", "proliferation", "and", "apoptosis", "cannot", "be", "separated", "and", "cancer", "cells", "often", "express", "either", "hypersensitivity", "or", "resistance", "to", "apoptosis", "that", "is", "dependent", "upon", "tissue", "conditions.", "As", "a", "member", "of", "the", "large", "aggregating", "chondroitin", "sulfate", "proteoglycan", "family,", "versican", "is", "structurally", "composed", "of", "a", "N-", "terminal", "G1", "domain,", "a", "glycosaminoglycan", "(GAG)", "attachment", "region,", "and", "a", "C", "terminus", "(or", "G3)", "selectin-like", "domain", "[9,10].", "The", "G3", "domain", "interacts", "with", "different", "ECM", "proteins", "[11]", "and", "binds", "to", "certain", "cell", "surface", "proteins", "including", "epidermal", "growth", "factor", "receptor", "(EGFR)", "[12,13].", "Extracellular", "versican", "has", "been", "observed", "to", "be", "elevated", "in", "a", "variety", "of", "human", "tumors", "including", "breast", "carcinoma", "[14,15,16].", "High", "expression", "has", "been", "observed", "in", "the", "interstitial", "tissues", "at", "the", "invasive", "margins", "of", "breast", "carcinoma", "and", "appears", "prognositic", "being", "predictive", "of", "cancer", "relapse", "in", "patients", "PLoS", "ONE", "|", "www.plosone.org", "1", "November", "2011", "|", "Volume", "6", "|", "Issue", "11", "|", "e26396" ]

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[ "2596–2606", "Nucleic", "Acids", "Research,", "2009,", "Vol.", "37,", "No.", "8", "doi:10.1093/nar/gkp115", "Published", "online", "6", "March", "2009", "Plasmodium", "falciparum", "heterochromatin", "protein", "1", "binds", "to", "tri-methylated", "histone", "3", "lysine", "9", "and", "is", "linked", "to", "mutually", "exclusive", "expression", "of", "var", "genes", "Karla", "Pe´", "rez-Toledo", "1", ",", "Ana", "Paola", "Rojas-Meza1,2,", "Liliana", "Mancio-Silva2,", "Nora", "Adriana", "Herna´", "ndez-Cuevas1,", "Dulce", "Maria", "Delgadillo1,", "Miguel", "Vargas1,", "Santiago", "Martı´nez-Calvillo3,", "Artur", "Scherf2", "and", "Rosaura", "Hernandez-Rivas1,*", "1Departamento", "de", "Biomedicina", "Molecular,", "Centro", "de", "Investigacio´", "n", "y", "de", "Estudios", "Avanzados", "del", "Instituto", "Polite´", "cnico", "Nacional", "(IPN),", "Apartado", "Postal", "14-740,", "07360,", "Me´", "xico", "D.", "F.,", "Me´", "xico,", "2Institut", "Pasteur,", "Unite´", "de", "Biologie", "des", "Interactions", "H", "oˆte-Parasite", "–", "CNRS", "URA2581.", "25,", "Rue", "du", "Dr.", "Roux,", "75724", "Paris,", "France", "and", "3Unidad", "de", "Biomedicina,", "Facultad", "de", "Estudios", "Superiores", "Iztacala,", "Universidad", "Nacional", "Auto´", "noma", "de", "Me´", "xico.", "Av.", "de", "los", "Barrios", "1,", "Col.", "Los", "Reyes", "Iztacala,", "Tlalnepantla,", "Edo.", "de", "Me´", "xico,", "CP", "54090,", "Me´", "xico", "Received", "December", "1,", "2008;", "Revised", "February", "6,", "2009;", "Accepted", "February", "10,", "2009", "ABSTRACT", "Increasing", "experimental", "evidence", "shows", "a", "promi-", "nent", "role", "of", "histone", "modifications", "in", "the", "coordinated", "control", "of", "gene", "expression", "in", "the", "human", "malaria", "parasite", "Plasmodium", "falciparum.", "The", "search", "for", "the", "histone-mark-reading", "machinery", "that", "translates", "histone", "modifications", "into", "biological", "processes,", "such", "as", "formation", "of", "heterochromatin", "and", "antigenic", "variation", "is", "of", "foremost", "importance.", "In", "this", "work,", "we", "identified", "the", "first", "member", "of", "a", "histone", "modification", "specific", "recognition", "protein,", "an", "orthologue", "of", "heterochromatin", "protein", "1", "(PfHP1).", "Analysis", "of", "the", "PfHP1", "amino-acid", "sequence", "revealed", "the", "presence", "of", "the", "two", "characteristic", "HP1", "domains:", "a", "chromo-", "domain", "(CD)", "and", "a", "chromo", "shadow", "domain", "(CSD).", "Recombinant", "CD", "binds", "to", "di-", "and", "tri-methylated", "lysine", "9", "from", "histone", "H3,", "but", "not", "to", "unmodified", "or", "methylated", "histone", "H3", "in", "lysine", "4.", "PfHP1", "is", "able", "to", "interact", "with", "itself", "to", "form", "dimers,", "underlying", "its", "potential", "role", "in", "aggregating", "nucleosomes", "to", "form", "heterochromatin.", "Antibodies", "raised", "against", "PfHP1", "detect", "this", "molecule", "in", "foci", "at", "the", "perinuclear", "region.", "ChIP", "analysis", "using", "anti-PfHP1", "shows", "that", "this", "protein", "is", "linked", "to", "heterochromatin", "of", "subtelo-", "meric", "non-coding", "repeat", "regions", "and", "monoallelic", "expression", "of", "the", "major", "virulence", "var", "gene", "family.", "This", "is", "the", "first", "report", "implicating", "an", "HP1", "protein", "in", "the", "control", "of", "antigenic", "variation", "of", "a", "protozoan", "parasite.", "INTRODUCTION", "Plasmodium", "falciparum,", "the", "causal", "protozoan", "agent", "of", "the", "most", "severe", "form", "of", "human", "malaria,", "has", "a", "complex", "life", "cycle", "with", "two", "different", "hosts,", "the", "Anopheles", "mosquito", "and", "humans.", "In", "order", "to", "complete", "its", "life", "cycle,", "P.", "falciparum", "invades", "different", "types", "of", "cells", "and", "self-propagates", "in", "very", "distinct", "environments", "in", "the", "mosquito", "(gut,", "hemolymph", "and", "salivary", "glands)", "as", "well", "as", "in", "the", "human", "host", "(skin,", "liver", "and", "erythrocytes).", "Each", "of", "these", "distinct", "environ-", "ments", "exerts", "selective", "pressure", "related", "to", "morphological", "changes", "that", "force", "P.", "falciparum", "to", "exhibit", "differential", "gene", "expression", "during", "its", "life", "cycle", "(1,2).", "A", "surprising", "finding", "was", "the", "identification", "of", "a", "relatively", "low", "number", "of", "genes", "encoding", "transcription", "factors", "in", "the", "parasite,", "although", "the", "basal", "core", "transcriptional", "machinery", "and", "the", "protein-coding", "genes", "involved", "in", "nucleosome", "assembly", "and", "regulation", "of", "chromatin", "structure", "were", "found", "to", "be", "conserved", "(3–5).", "To", "date,", "no", "specific", "DNA-binding", "proteins", "have", "been", "identified", "other", "than", "PfMyb1", "(6)", "and", "the", "ApiAp2", "gene", "family", "(7).", "This", "suggested", "that", "epigenetic", "mechanisms", "play", "a", "significant", "role", "in", "controlling", "gene", "expression", "in", "Plasmodium", "(3,8–10).", "The", "importance", "of", "reversible", "chromatin", "modifications", "involving", "histone", "modifications", "and", "the", "chromatin-associated", "protein", "PfSir2", "was", "first", "demonstrated", "for", "a", "subtelomeric", "gene", "family", "(var", "gene", "family)", "involved", "in", "the", "control", "of", "anti-", "genic", "variation", "in", "P.", "falciparum", "(10).", "Knock", "out", "of", "PfSir2", "resulted", "in", "the", "de-repression", "of", "a", "fraction", "of", "the", "members", "of", "the", "var", "gene", "family", "(11).", "A", "screen", "for", "histone", "modifica-", "tions", "revealed", "that", "H3K9me3", "plays", "a", "particular", "role", "in", "var", "gene", "repression", "(12,13)", "and", "H3K4me2/3", "in", "transcriptional", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+(52)", "55", "5747", "3325;", "Fax:", "+(52)", "55", "5747", "3938;", "Email:", "rohernan@cinvestav.mx", "The", "authors", "wish", "it", "to", "be", "known", "that,", "in", "their", "opinion,", "the", "first", "two", "authors", "should", "be", "regarded", "as", "joint", "First", "Authors.", "2009", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Cellular", "Cytoskeleton", "Dynamics", "Modulates", "Non-Viral", "Gene", "Delivery", "through", "RhoGTPases", "Anandika", "Dhaliwal1,", "Maricela", "Maldonado", "2", ",", "Clayton", "Lin2,", "Tatiana", "Segura1,2*", "1", "Biomedical", "Engineering", "Interdepartmental", "Program,", "University", "of", "California", "Los", "Angeles,", "Los", "Angeles,", "California,", "United", "States", "of", "America,", "2", "Chemical", "and", "Biomolecular", "Engineering", "Department,", "University", "of", "California", "Los", "Angeles,", "Los", "Angeles,", "California,", "United", "States", "of", "America", "Abstract", "Although", "it", "is", "well", "accepted", "that", "the", "constituents", "of", "the", "cellular", "microenvironment", "modulate", "a", "myriad", "of", "cellular", "processes,", "including", "cell", "morphology,", "cytoskeletal", "dynamics", "and", "uptake", "pathways,", "the", "underlying", "mechanism", "of", "how", "these", "pathways", "influence", "non-viral", "gene", "transfer", "have", "not", "been", "studied.", "Transgene", "expression", "is", "increased", "on", "fibronectin", "(Fn)", "coated", "surfaces", "as", "a", "consequence", "of", "increased", "proliferation,", "cell", "spreading", "and", "active", "engagement", "of", "clathrin", "endocytosis", "pathway.", "RhoGTPases", "mediate", "the", "crosstalk", "between", "the", "cell", "and", "Fn,", "and", "regulate", "cellular", "processes", "involving", "filamentous", "actin,", "in-response", "to", "cellular", "interaction", "with", "Fn.", "Here", "the", "role", "of", "RhoGTPases", "specifically", "Rho,", "Rac", "and", "Cdc42", "in", "modulation", "of", "non-viral", "gene", "transfer", "in", "mouse", "mesenchymal", "stem", "(mMSCs)", "plated", "in", "a", "fibronectin", "microenvironment", "was", "studied.", "More", "than", "90%", "decrease", "in", "transgene", "expression", "was", "observed", "after", "inactivation", "of", "RhoGTPases", "using", "difficile", "toxin", "B", "(TcdB)", "and", "C3", "transferase.", "Expression", "of", "dominant", "negative", "RhoA", "(RhoAT19N),", "Rac1(Rac1T17N)", "and", "Cdc42", "(Cdc42T17N)", "also", "significantly", "reduced", "polyplex", "uptake", "and", "transgene", "expression.", "Interactions", "of", "cells", "with", "Fn", "lead", "to", "activation", "of", "RhoGTPases.", "However,", "further", "activation", "of", "RhoA,", "Rac1", "and", "Cdc42", "by", "expression", "of", "constitutively", "active", "genes", "(RhoAQ63L,", "Rac1Q61L", "and", "Cdc42Q61L)", "did", "not", "further", "enhance", "transgene", "expression", "in", "mMSCs,", "when", "plated", "on", "Fn.", "In", "contrast,", "activation", "of", "RhoA,", "Rac1", "and", "Cdc42", "by", "expression", "of", "constitutively", "active", "genes", "for", "cells", "plated", "on", "collagen", "I,", "which", "by", "itself", "did", "not", "increase", "RhoGTPase", "activation,", "resulted", "in", "enhanced", "transgene", "expression.", "Our", "study", "shows", "that", "RhoGTPases", "regulate", "internalization", "and", "effective", "intracellular", "processing", "of", "polyplexes", "that", "results", "in", "efficient", "gene", "transfer.", "Citation:", "Dhaliwal", "A,", "Maldonado", "M,", "Lin", "C,", "Segura", "T", "(2012)", "Cellular", "Cytoskeleton", "Dynamics", "Modulates", "Non-Viral", "Gene", "Delivery", "through", "RhoGTPases.", "PLoS", "ONE", "7(4):", "e35046.", "doi:10.1371/journal.pone.0035046", "Editor:", "Neil", "A.", "Hotchin,", "University", "of", "Birmingham,", "United", "Kingdom", "Received", "November", "30,", "2011;", "Accepted", "March", "12,", "2012;", "Published", "April", "11,", "2012", "Copyright:", "2012", "Dhaliwal", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Funding", "was", "provided", "by", "National", "Institutes", "of", "Health", "R21EB009516,", "Understanding", "the", "Role", "of", "the", "Extracellular", "Matrix", "on", "Non-Viral", "Gene", "Transfer", "(www.nih.gov).", "The", "funder", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "tsegura@ucla.edu", "Introduction", "Although", "gene", "delivery", "can", "be", "a", "robust", "approach", "to", "treat", "disease", "and", "augment", "tissue", "formation,", "limitations", "with", "effective", "and", "save", "delivery", "have", "limited", "its", "success", "as", "a", "therapy.", "Gene", "delivery", "to", "mammalian", "cells", "can", "be", "achieved", "using", "viral", "as", "well", "as", "non-viral", "delivery", "systems", "[1].", "Non-viral", "gene", "delivery", "systems", "have", "the", "advantage", "of", "being", "less", "immunogenic", "compared", "to", "viral", "gene", "delivery", "systems", "as", "well", "as", "allow", "for", "large-scale", "production", "and", "modularity.", "However,", "they", "are", "limited", "by", "their", "efficacy.", "Previous", "studies", "have", "focused", "on", "engineering", "more", "efficient", "delivery", "vehicles", "that", "can", "overcome", "one", "or", "more", "of", "the", "barriers", "to", "efficient", "gene", "transfer", "[2,3].", "Although", "less", "common,", "recent", "studies", "have", "looked", "at", "the", "cellular", "microenvironment", "and", "the", "cell", "itself", "to", "elucidate", "other", "approaches", "to", "enhance", "non-viral", "gene", "transfer", "[4–", "8].", "For", "example,", "the", "stiffness", "of", "the", "matrix", "where", "the", "cells", "are", "plated", "modulates", "non-viral", "gene", "delivery", "with", "cells", "plated", "on", "stiff", "surfaces", "(110", "KPa)", "resulting", "in", "enhanced", "gene", "transfer", "due", "to", "increased", "cell", "proliferation", "and", "survival", "[8].", "Collagen", "I", "and", "IV", "have", "been", "shown", "to", "enhance", "gene", "transfer", "in", "PC12", "cells,", "which", "was", "correlated", "with", "the", "relative", "projected", "nuclear", "area", "of", "the", "plated", "cells", "[9],", "while", "fibronectin", "and", "collagen", "I", "have", "been", "shown", "to", "enhance", "gene", "expression", "in", "NIH/3T3", "cells", "which", "has", "been", "correlated", "to", "the", "relative", "increased", "internalization", "on", "these", "surfaces", "and", "the", "pathway", "of", "internalization", "[11].", "Cationic", "lipid-", "mediated", "gene", "transfer", "to", "rat", "smooth", "muscle", "cells", "is", "enhanced", "when", "the", "cells", "are", "plated", "on", "surfaces", "that", "promote", "avß3", "binding,", "with", "antibodies", "against", "avß3", "and", "ß3", "decreasing", "the", "amount", "of", "gene", "transfer", "[9].", "Further,", "our", "laboratory", "has", "shown", "that", "cellular", "microenvironment", "modulates", "non-viral", "gene", "delivery", "to", "mouse", "mesenchymal", "stem", "cells", "(mMSCs),", "specifically", "we", "screened", "6", "different", "ECM", "proteins", "and", "their", "combinations", "for", "their", "ability", "to", "enhance", "gene", "transfer", "to", "mouse", "mesenchymal", "stem", "cells", "(mMSCs)", "using", "poly(ethylene", "imine)", "polyplexes.", "We", "found", "that", "proteins", "that", "promoted", "well", "spread", "cells", "(e.g.", "fibronectin", "and", "collagen", "IV)", "resulted", "in", "polyplexes", "being", "trafficked", "to", "the", "nucleus", "and", "enhanced", "gene", "transfer,", "while", "those", "that", "resulted", "in", "less", "spread", "cells", "(e.g.", "collagen", "I)", "resulted", "in", "polyplexes", "that", "did", "not", "colocalize", "with", "the", "nucleus", "and", "inhibited", "gene", "transfer", "[10].", "When", "comparing", "the", "internalization", "pathway", "of", "polyplexes", "for", "cells", "seeded", "on", "fibronectin", "or", "collagen", "I,", "we", "found", "that", "different", "endocytic", "pathways", "are", "used,", "with", "clathrin-mediated", "endocytosis", "being", "the", "primary", "pathway", "used", "for", "cells", "plated", "on", "fibronectin", "[6].", "Further,", "polymerized", "actin,", "actin-myosin", "interactions,", "and", "the", "microtubu-", "lar", "network", "were", "found", "to", "influence", "non-viral", "gene", "transfer", "to", "different", "extends", "for", "cells", "seeded", "on", "fibronectin", "versus", "collagen", "I", "[6].", "Structural", "components", "of", "the", "ECM", "such", "as", "Fn", "are", "able", "to", "actively", "mediate", "crosstalk", "between", "the", "ECM", "and", "RhoGTPases", "by", "associating", "with", "cell", "surface", "receptors,", "namely", "integrins", "[11]", "and", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2012", "|", "Volume", "7", "|", "Issue", "4", "|", "e35046" ]

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[ "Purinergic", "Signalling", "(2008)", "4:125–137", "DOI", "10.1007/s11302-007-9053-3", "ORIGINAL", "PAPER", "Endogenous", "ATP", "release", "inhibits", "electrogenic", "Na+", "absorption", "and", "stimulates", "Cl−", "secretion", "in", "MDCK", "cells", "Yi", "Xie", "&", "James", "A.", "Schafer", "Received:", "7", "December", "2006", "/", "Accepted:", "2", "February", "2007", "/", "Published", "online:", "8", "March", "2007", "#", "Springer", "Science", "+", "Business", "Media", "B.V.", "2007", "Abstract", "Our", "previous", "studies", "with", "a", "line", "of", "Madin-Darby", "canine", "kidney", "(MDCK)", "cells", "(FL-MDCK)", "transfected", "with", "FLAG-labeled", "a,", "b,", "and", "g", "subunits", "of", "epithelial", "Na+", "channel", "(ENaC)", "showed", "that,", "although", "most", "of", "the", "short-", "circuit", "current", "(Isc)", "was", "amiloride", "sensitive", "(AS-Isc),", "there", "was", "also", "an", "amiloride-insensitive", "component", "(NS-Isc)", "due", "to", "Cl−", "secretion", "(Morris", "and", "Schafer,", "J", "Gen", "Physiol", "120:71–", "85,", "2002).", "In", "the", "present", "studies,", "we", "observed", "a", "progressive", "increase", "in", "NS-Isc", "and", "a", "corresponding", "decrease", "in", "AS-Isc", "during", "experiments.", "There", "was", "a", "significant", "negative", "correlation", "between", "AS-Isc", "and", "NS-Isc", "both", "in", "the", "presence", "and", "absence", "of", "treatment", "with", "cyclic", "adenosine", "mono-", "phosphate", "(cAMP).", "NS-Isc", "could", "be", "attributed", "to", "both", "cystic", "fibrosis", "transmembrane", "conductance", "regulator", "(CFTR)", "and", "a", "4,", "4'-diisothiocyano-2,", "2'-disulfonic", "acid", "stilbene", "(DIDS)-", "sensitive", "Ca2+-activated", "Cl−", "channel", "(CaCC).", "Continuous", "perfusion", "of", "both", "sides", "of", "the", "Ussing", "chamber", "with", "fresh", "rather", "than", "recirculated", "bathing", "solutions,", "or", "addition", "of", "hexokinase", "(6", "U/ml),", "prevented", "the", "time-dependent", "changes", "and", "increased", "AS-Isc", "by", "40–60%,", "with", "a", "proportional", "decrease", "in", "NS-Isc.", "Addition", "of", "100", "μM", "adenosine", "Y.", "Xie", ":", "J.", "A.", "Schafer", "Department", "of", "Physiology", "and", "Biophysics,", "and", "Medicine,", "University", "of", "Alabama", "at", "Birmingham,", "Birmingham,", "AL", "35294,", "USA", "J.", "A.", "Schafer", "(*)", "Departments", "of", "Physiology", "and", "Biophysics,", "University", "of", "Alabama", "at", "Birmingham,", "1918", "University", "Blvd.,", "Rm.", "834", "MCLM,", "Birmingham,", "AL", "35294-0005,", "USA", "e-mail:", "jschafer@uab.edu", "Present", "address:", "Y.", "Xie", "Department", "of", "Physiology,", "UCLA", "School", "of", "Medicine,", "650", "Charles", "Young", "Dr.", "S.", "3-609", "MRL,", "Los", "Angeles,", "CA", "90095-1751,", "USA", "triphosphate", "(ATP)", "in", "the", "presence", "of", "luminal", "amiloride", "produced", "a", "transient", "four-fold", "increase", "in", "NS-Isc", "that", "was", "followed", "by", "a", "sustained", "increase", "of", "50–60%", "above", "the", "basal", "level.", "ATP", "release", "from", "the", "monolayers,", "measured", "by", "bioluminescence,", "was", "found", "to", "occur", "across", "the", "apical", "but", "not", "the", "basolateral", "membrane,", "and", "the", "apical", "release", "was", "tripled", "by", "cAMP", "treatment.", "These", "data", "show", "that", "constitu-", "tive", "apical", "ATP", "release,", "which", "occurs", "under", "both", "basal", "and", "cAMP-stimulated", "conditions,", "underlies", "the", "time-dependent", "rise", "in", "Cl−", "secretion", "and", "the", "proportional", "fall", "in", "ENaC-", "mediated", "Na+", "absorption", "in", "FL-MDCK", "cells.", "Thus,", "endog-", "enous", "ATP", "release", "can", "introduce", "a", "significant", "confounding", "variable", "in", "experiments", "with", "this", "and", "similar", "epithelial", "cells,", "and", "it", "may", "underlie", "at", "least", "some", "of", "the", "observed", "interaction", "between", "Cl−", "secretion", "and", "Na+", "absorption.", "Keywords", "ATP.", "CFTR", ".", "CLC", ".", "Calcium-activated", "Cl−", "channel", ".", "ENaC", ".", "Purinergic", "effects", "Introduction", "Madin-Darby", "canine", "kidney", "(MDCK,", "type", "I)", "cells", "grown", "as", "epithelial", "monolayers", "have", "been", "used", "extensively", "as", "a", "model", "of", "the", "mammalian", "collecting", "duct", "(CD).", "These", "monolayers", "exhibit", "many", "characteristics", "of", "the", "CD,", "including", "a", "high", "transepithelial", "resistance", "and", "amiloride-", "sensitive", "Na+", "reabsorption", "that", "is", "mediated", "by", "the", "epithelial", "Na+", "channel", "(ENaC)", "and", "stimulated", "by", "agonists", "that", "increase", "intracellular", "cyclic", "adenosine", "monophosphate", "(cAMP)", "[1,", "2].", "Similar", "cell", "lines", "that", "are", "derived", "from", "the", "CD,", "including", "mouse", "cortical", "CD", "(M-1)", "and", "inner", "medullary", "CD", "(mIMCD-K2)", "cells", "[3–5]", "and", "A6", "cells", "from", "the", "Xenopus", "distal", "nephron", "[6,", "7]", "share", "these", "character-", "istics.", "However,", "in", "contrast", "to", "the", "CD,", "all", "of", "these", "cell", "lines", "also", "have", "Cl−", "channels", "in", "their", "apical", "membranes,", "and," ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Journal", "of", "Osteoporosis", "Volume", "2011,", "Article", "ID", "924595,", "6", "pages", "doi:10.4061/2011/924595", "Clinical", "Study", "Predictors", "of", "Fracture", "Risk", "and", "Bone", "Mineral", "Density", "in", "Men", "with", "Prostate", "Cancer", "on", "Androgen", "Deprivation", "Therapy", "Katherine", "Neubecker,1", "Beverley", "Adams-Huet,2", "Irfan", "M.", "Farukhi,3", "Rosinda", "C.", "Delapena,3", "and", "Ugis", "Gruntmanis4", "1", "Department", "of", "Medicine,", "University", "of", "Texas,", "Southwestern", "Medical", "Center,", "Dallas,", "TX", "75390,", "USA", "2", "Departments", "of", "Clinical", "Sciences", "and", "Medicine,", "University", "of", "Texas,", "Southwestern", "Medical", "Center,", "Dallas,", "TX", "75390,", "USA", "3", "Department", "of", "Nuclear", "Medicine,", "Dallas", "Veterans", "Affairs", "Medical", "Center,", "Dallas,", "TX", "75216,", "USA", "4", "Department", "of", "Medicine,", "Dallas", "Veterans", "Affairs", "Medical", "Center", "and", "University", "of", "Texas,", "Southwestern", "Medical", "Center,", "Dallas,", "TX", "75216,", "USA", "Correspondence", "should", "be", "addressed", "to", "Ugis", "Gruntmanis,", "ugis.gruntmanis@utsouthwestern.edu", "Received", "8", "March", "2011;", "Revised", "26", "April", "2011;", "Accepted", "9", "May", "2011", "Academic", "Editor:", "Pawel", "Szulc", "Copyright", "©", "2011", "Katherine", "Neubecker", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Decrease", "of", "bone", "mineral", "density", "(BMD)", "and", "fracture", "risk", "is", "increased", "in", "men", "with", "prostate", "cancer", "receiving", "androgen", "deprivation", "therapy", "(ADT).", "We", "looked", "at", "possible", "predictors", "of", "decreased", "BMD", "and", "increased", "fracture", "risk", "in", "men", "with", "prostate", "cancer;", "most", "of", "whom", "were", "on", "ADT.", "In", "a", "retrospective", "study,", "we", "analyzed", "serum,", "BMD,", "and", "clinical", "risk", "factors", "used", "in", "the", "Fracture", "Risk", "Assessment", "(FRAX)", "tool", "and", "others", "in", "78", "men", "with", "prostate", "cancer", "with", "reported", "height", "loss.", "The", "subjects", "were", "divided", "in", "two", "groups:", "22", "men", "with", "and", "56", "without", "vertebral", "fractures.", "17", "of", "the", "22", "men", "with", "vertebral", "fractures", "on", "spine", "X-rays", "did", "not", "know", "they", "had", "a", "vertebral", "fracture.", "Of", "those", "17", "men,", "9", "had", "not", "previously", "qualified", "for", "treatment", "based", "on", "preradiograph", "FRAX", "score", "calculated", "with", "BMD,", "and", "6", "based", "on", "FRAX", "calculated", "without", "BMD.", "Performing", "spine", "films", "increased", "the", "predictive", "ability", "of", "FRAX", "for", "vertebral", "fracture.", "Vertebral", "fracture", "was", "better", "predicted", "by", "FRAX", "for", "other", "osteoporotic", "fractures", "than", "FRAX", "for", "hip", "fractures.", "The", "inclusion", "of", "BMD", "in", "FRAX", "calculations", "did", "not", "affect", "the", "predictive", "ability", "of", "FRAX.", "The", "PSA", "level", "showed", "a", "positive", "correlation", "with", "lumbar", "spine", "BMD", "and", "accounted", "for", "about", "9%", "of", "spine", "BMD.", "1.", "Introduction", "220,000", "men", "are", "diagnosed", "with", "prostate", "cancer", "each", "year,", "and", "more", "than", "40", "percent", "receive", "androgen", "deprivation", "therapy", "(ADT)", "as", "initial", "treatment", "[1,", "2].", "ADT", "has", "been", "shown", "to", "decrease", "bone", "mineral", "density", "(BMD)", "as", "measured", "by", "dual-energy", "X-ray", "absorptiometry", "(DXA)", "as", "well", "as", "increase", "risk", "of", "fracture.", "After", "initiating", "ADT,", "BMD", "decline", "starts", "shortly", "after", "[3,", "4].", "A", "meta-analysis", "of", "almost", "117,000", "men", "demonstrated", "that", "patients", "on", "ADT", "had", "lower", "total", "BMD,", "30%", "increased", "risk", "of", "osteoporosis,", "and", "70%", "increased", "risk", "of", "fractures", "[5].", "In", "a", "study", "of", "over", "47,000", "men", "with", "prostate", "cancer", "by", "the", "National", "Cancer", "Institute", "(NCI)", "and", "Medicare,", "those", "treated", "with", "ADT", "or", "bilateral", "orchiectomy", "within", "six", "months", "of", "diagnosis", "had", "a", "5-year", "fracture", "risk", "of", "19.4%", "versus", "12.6%", "in", "controls", "matched", "for", "patient", "and", "tumor", "characteristics", "[6].", "A", "systematic", "review", "of", "five", "studies", "on", "prostate", "cancer", "patients", "in", "the", "US", "and", "abroad,", "which", "included", "the", "NCI-Medicare", "study,", "found", "a", "23%", "increase", "in", "fracture", "risk", "for", "men", "treated", "with", "ADT", "[7].", "Fracture", "Risk", "Assessment", "(FRAX)", "is", "an", "algorithm", "devel-", "oped", "by", "the", "World", "Health", "Organization", "to", "determine", "fracture", "risk", "of", "men", "and", "women", "[8].", "The", "risk", "factors", "in", "the", "algorithm", "include", "age,", "current", "height,", "prior", "fracture,", "parental", "history", "of", "fracture,", "BMD", "of", "the", "femoral", "neck,", "and", "secondary", "osteoporosis", "risk", "factors", "such", "as", "hypogonadism.", "Yet,", "inclusion", "of", "secondary", "causes", "such", "as", "hypogonadism", "does", "not", "change", "FRAX-calculated", "risk", "of", "fracture", "when", "femoral", "neck", "BMD", "is", "included.", "The", "National", "Osteoporosis", "Foundation’s", "recommended", "treatment", "thresholds", "based", "on", "FRAX", "score", "are", "3%", "for", "hip", "(“Hip", "FRAX”)", "and", "20%", "for", "major", "osteoporotic", "fractures", "(“Osteoporotic", "FRAX”)", "[9]." ]

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[ "Journal", "of", "Experimental", "Botany,", "Vol.", "62,", "No.", "3,", "pp.", "1169–1177,", "2011", "doi:10.1093/jxb/erq347", "Advance", "Access", "publication", "1", "November,", "2010", "This", "paper", "is", "available", "online", "free", "of", "all", "access", "charges", "(see", "http://jxb.oxfordjournals.org/open_access.html", "for", "further", "details)", "RESEARCH", "PAPER", "Evidence", "for", "phenotypic", "plasticity", "in", "the", "Antarctic", "extremophile", "Chlamydomonas", "raudensis", "Ettl.", "UWO", "241", "Tessa", "Pocock*,", "Adrien", "Vetterli", "and", "Stefan", "Falk†", "Department", "of", "Natural", "Sciences,", "Engineering", "and", "Mathematics,", "Mid", "Sweden", "University,", "Sundsvall", "85170,", "Sweden", "*", "Present", "address:", "Department", "of", "Biological", "Research,", "Heliospectra", "AB,", "Bora˚", "s", "50630,", "Sweden.", "y", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "stefan.falk@miun.se", "Received", "20", "August", "2010;", "Revised", "11", "October", "2010;", "Accepted", "11", "October", "2010", "Abstract", "Life", "in", "extreme", "environments", "poses", "unique", "challenges", "to", "photosynthetic", "organisms.", "The", "ability", "for", "an", "extremophilic", "green", "alga", "and", "its", "genetic", "and", "mesophilic", "equivalent", "to", "acclimate", "to", "changes", "in", "their", "environment", "was", "examined", "to", "determine", "the", "extent", "of", "their", "phenotypic", "plasticities.", "The", "Antarctic", "extremophile", "Chlamydomonas", "raudensis", "Ettl.", "UWO", "241", "(UWO)", "was", "isolated", "from", "an", "ice-covered", "lake", "in", "Antarctica,", "whereas", "its", "mesophilic", "counterpart", "C.", "raudensis", "Ettl.", "SAG", "49.72", "(SAG)", "was", "isolated", "from", "a", "meadow", "pool", "in", "the", "Czech", "Republic.", "The", "effects", "of", "changes", "in", "temperature", "and", "salinity", "on", "growth,", "morphology,", "and", "photochemistry", "were", "examined", "in", "the", "two", "strains.", "Differential", "acclimative", "responses", "were", "observed", "in", "UWO", "which", "include", "a", "wider", "salinity", "range", "for", "growth,", "and", "broader", "temperature-", "and", "salt-induced", "fluctuations", "in", "Fv/Fm,", "relative", "to", "SAG.", "Furthermore,", "the", "redox", "state", "of", "the", "photosynthetic", "electron", "transport", "chain,", "measured", "as", "1–qP,", "was", "modulated", "in", "the", "extremophile", "whereas", "this", "was", "not", "observed", "in", "the", "mesophile.", "Interestingly,", "it", "is", "shown", "for", "the", "first", "time", "that", "SAG", "is", "similar", "to", "UWO", "in", "that", "it", "is", "unable", "to", "undergo", "state", "transitions.", "The", "different", "natural", "histories", "of", "these", "two", "strains", "exert", "different", "evolutionary", "pressures", "and,", "consequently,", "different", "abilities", "for", "acclimation,", "an", "important", "component", "of", "phenotypic", "plasticity.", "In", "contrast", "to", "SAG,", "UWO", "relied", "on", "a", "redox", "sensing", "and", "signalling", "system", "under", "the", "growth", "conditions", "used", "in", "this", "study.", "It", "is", "proposed", "that", "growth", "and", "adaptation", "of", "UWO", "under", "a", "stressful", "and", "extreme", "environment", "poises", "this", "extremophile", "for", "better", "success", "under", "changing", "environmental", "conditions.", "Key", "words:", "Acclimation,", "Antarctica,", "Chlamydomonas", "raudensis,", "climate", "change,", "phenotypic", "plasticity,", "photostasis,", "PSII", "excitation", "pressure.", "Introduction", "Over", "80%", "of", "the", "earth’s", "biosphere", "is", "permanently", "cold", "(Russel,", "1990),", "and", "many", "photoautotrophic", "organisms", "such", "as", "green", "algae", "are", "able", "to", "withstand,", "and", "even", "flourish", "under,", "conditions", "that", "are", "considered", "non-optimal", "for", "life.", "Algae", "living", "in", "the", "Arctic", "and", "Antarctic", "have", "been", "studied", "for", "the", "last", "170", "years,", "but", "it", "is", "only", "in", "the", "last", "20", "years", "that", "great", "effort", "and", "success", "has", "been", "achieved", "in", "isolating", "these", "unique", "organisms", "and", "cultivating", "them", "in", "the", "laboratory", "for", "physiological", "studies", "(reviewed", "in", "Mock", "and", "Thomas,", "2008).", "The", "extremophilic", "green", "alga,", "Chlamydomonas", "raudensis", "Ettl.", "UWO", "241", "(hereafter", "referred", "to", "as", "UWO),", "was", "isolated", "from", "the", "deepest", "photobiotic", "zone", "17", "m", "below", "the", "perma-", "nent", "ice", "cover", "of", "Lake", "Bonney,", "Antarctica", "(Lizotte", "and", "Priscu,", "1994).", "Photosynthetic", "organisms", "play", "a", "critical", "role", "in", "the", "permanently", "ice-covered", "lakes", "in", "West", "Antarctica", "as", "the", "primary", "productivity", "of", "the", "continent", "is", "largely", "provided", "by", "green", "algae", "and", "as", "algal", "symbionts", "with", "fungi.", "Temper-", "ature", "gradients", "are", "responsible", "for", "vertical", "stratification", "in", "aquatic", "systems;", "however,", "in", "Lake", "Bonney,", "stratification", "is", "Abbreviations:", "1–qP,", "PSII", "excitation", "pressure;", "Chl,", "chlorophyll;", "Fm,", "maximal", "fluorescence", "level", "in", "dark-adapted", "cultures;", "Fm’,", "maximal", "fluorescence", "level", "in", "light-", "adapted", "cultures;", "Fo,", "minimal", "fluorescence", "level", "in", "dark-adapted", "cultures;", "F", ",", "maximal", "variable", "fluorescence", "in", "dark-adapted", "cultures;", "Fv/Fm,", "maximum", "PSII", "v", "photochemical", "efficiciency;", "LHCII,", "light", "harvesting", "complexes", "associated", "with", "PSII;", "PSI,", "photosystem", "I;", "PSII,", "photosystem", "II;", "QA,", "first", "stable", "quinone", "electron", "acceptor", "in", "PSII;", "SAG,", "Chlamydomonas", "raudensis", "Ettl.", "49.72;", "UWO,", "Chlamydomonas", "raudensis", "Ettl.", "UWO", "241.", "ª", "2010", "The", "Author(s).", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-", "nc/2.5),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Huda", "et", "al.", "Mobile", "DNA", "2010,", "1:2", "http://www.mobilednajournal.com/content/1/1/2", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Epigenetic", "histone", "modifications", "of", "human", "transposable", "elements:", "genome", "defense", "versus", "exaptation", "Ahsan", "Huda1,", "Leonardo", "Mariño-Ramírez2,3,", "I", "King", "Jordan1*", "Abstract", "Background:", "Transposition", "is", "disruptive", "in", "nature", "and,", "thus,", "it", "is", "imperative", "for", "host", "genomes", "to", "evolve", "mechanisms", "that", "suppress", "the", "activity", "of", "transposable", "elements", "(TEs).", "At", "the", "same", "time,", "transposition", "also", "provides", "diverse", "sequences", "that", "can", "be", "exapted", "by", "host", "genomes", "as", "functional", "elements.", "These", "notions", "form", "the", "basis", "of", "two", "competing", "hypotheses", "pertaining", "to", "the", "role", "of", "epigenetic", "modifications", "of", "TEs", "in", "eukaryotic", "genomes:", "the", "genome", "defense", "hypothesis", "and", "the", "exaptation", "hypothesis.", "To", "date,", "all", "available", "evidence", "points", "to", "the", "genome", "defense", "hypothesis", "as", "the", "best", "explanation", "for", "the", "biological", "role", "of", "TE", "epigenetic", "modifications.", "Results:", "We", "evaluated", "several", "predictions", "generated", "by", "the", "genome", "defense", "hypothesis", "versus", "the", "exaptation", "hypothesis", "using", "recently", "characterized", "epigenetic", "histone", "modification", "data", "for", "the", "human", "genome.", "To", "this", "end,", "we", "mapped", "chromatin", "immunoprecipitation", "sequence", "tags", "from", "38", "histone", "modifications,", "characterized", "in", "CD4+", "T", "cells,", "to", "the", "human", "genome", "and", "calculated", "their", "enrichment", "and", "depletion", "in", "all", "families", "of", "human", "TEs.", "We", "found", "that", "several", "of", "these", "families", "are", "significantly", "enriched", "or", "depleted", "for", "various", "histone", "modifications,", "both", "active", "and", "repressive.", "The", "enrichment", "of", "human", "TE", "families", "with", "active", "histone", "modifications", "is", "consistent", "with", "the", "exaptation", "hypothesis", "and", "stands", "in", "contrast", "to", "previous", "analyses", "that", "have", "found", "mammalian", "TEs", "to", "be", "exclusively", "repressively", "modified.", "Comparisons", "between", "TE", "families", "revealed", "that", "older", "families", "carry", "more", "histone", "modifications", "than", "younger", "ones,", "another", "observation", "consistent", "with", "the", "exaptation", "hypothesis.", "However,", "data", "from", "within", "family", "analyses", "on", "the", "relative", "ages", "of", "epigenetically", "modified", "elements", "are", "consistent", "with", "both", "the", "genome", "defense", "and", "exaptation", "hypotheses.", "Finally,", "TEs", "located", "proximal", "to", "genes", "carry", "more", "histone", "modifications", "than", "the", "ones", "that", "are", "distal", "to", "genes,", "as", "may", "be", "expected", "if", "epigenetically", "modified", "TEs", "help", "to", "regulate", "the", "expression", "of", "nearby", "host", "genes.", "Conclusions:", "With", "a", "few", "exceptions,", "most", "of", "our", "findings", "support", "the", "exaptation", "hypothesis", "for", "the", "role", "of", "TE", "epigenetic", "modifications", "when", "vetted", "against", "the", "genome", "defense", "hypothesis.", "The", "recruitment", "of", "epigenetic", "modifications", "may", "represent", "an", "additional", "mechanism", "by", "which", "TEs", "can", "contribute", "to", "the", "regulatory", "functions", "of", "their", "host", "genomes.", "Background", "Transposable", "elements", "(TEs)", "are", "mobile", "DNA", "sequences", "that", "can", "replicate", "to", "extremely", "high", "genomic", "copy", "num-", "bers.", "TEs", "are", "also", "widely", "distributed;", "they", "have", "been", "found", "within", "genomes", "representing", "all", "major", "eukaryotic", "lineages.", "Accordingly,", "TEs", "have", "had", "a", "profound", "impact", "on", "the", "structure,", "function", "and", "evolution", "of", "their", "host", "genomes.", "In", "this", "study,", "we", "explore", "the", "relationship", "*", "Correspondence:", "king.jordan@biology.gatech.edu", "1School", "of", "Biology,", "Georgia", "Institute", "of", "Technology,", "310", "Ferst", "Drive,", "Atlanta,", "GA", "30332,", "USA", "between", "TEs", "and", "the", "epigenetic", "regulatory", "mechanisms", "that", "are", "thought", "to", "have", "evolved", "in", "response", "to", "their", "proliferation", "in", "eukaryotic", "genomes", "[1].", "Transposition", "is", "inherently", "disruptive", "in", "nature.", "Therefore,", "in", "order", "to", "ensure", "their", "own", "survival,", "host", "genomes", "must", "have", "evolved", "various", "repressive", "mechan-", "isms", "to", "guard", "against", "deleterious", "TE", "insertions.", "Epige-", "netic", "regulatory", "modifications", "represent", "a", "broad", "class", "of", "silencing", "mechanisms", "that", "may", "have", "come", "into", "exis-", "tence", "in", "response", "to", "the", "need", "to", "repress", "TEs", "[1-4].", "The", "notion", "that", "epigenetic", "regulatory", "systems", "evolved", "to", "©", "2010", "Huda", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Tan", "et", "al.", "BMC", "Pregnancy", "and", "Childbirth", "2010,", "10:3", "http://www.biomedcentral.com/1471-2393/10/3", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Cost-effectiveness", "of", "external", "cephalic", "version", "for", "term", "breech", "presentation", "Jonathan", "M", "Tan1*,", "Alex", "Macario2,3,", "Brendan", "Carvalho2,", "Maurice", "L", "Druzin4,", "Yasser", "Y", "El-Sayed4", "Abstract", "Background:", "External", "cephalic", "version", "(ECV)", "is", "recommended", "by", "the", "American", "College", "of", "Obstetricians", "and", "Gynecologists", "to", "convert", "a", "breech", "fetus", "to", "vertex", "position", "and", "reduce", "the", "need", "for", "cesarean", "delivery.", "The", "goal", "of", "this", "study", "was", "to", "determine", "the", "incremental", "cost-effectiveness", "ratio,", "from", "society’s", "perspective,", "of", "ECV", "compared", "to", "scheduled", "cesarean", "for", "term", "breech", "presentation.", "Methods:", "A", "computer-based", "decision", "model", "(TreeAge", "Pro", "2008,", "Tree", "Age", "Software,", "Inc.)", "was", "developed", "for", "a", "hypothetical", "base", "case", "parturient", "presenting", "with", "a", "term", "singleton", "breech", "fetus", "with", "no", "contraindications", "for", "vaginal", "delivery.", "The", "model", "incorporated", "actual", "hospital", "costs", "(e.g.,", "$8,023", "for", "cesarean", "and", "$5,581", "for", "vaginal", "delivery),", "utilities", "to", "quantify", "health-related", "quality", "of", "life,", "and", "probabilities", "based", "on", "analysis", "of", "published", "literature", "of", "successful", "ECV", "trial,", "spontaneous", "reversion,", "mode", "of", "delivery,", "and", "need", "for", "unanticipated", "emergency", "cesarean", "delivery.", "The", "primary", "endpoint", "was", "the", "incremental", "cost-effectiveness", "ratio", "in", "dollars", "per", "quality-adjusted", "year", "of", "life", "gained.", "A", "threshold", "of", "$50,000", "per", "quality-adjusted", "life-years", "(QALY)", "was", "used", "to", "determine", "cost-effectiveness.", "Results:", "The", "incremental", "cost-effectiveness", "of", "ECV,", "assuming", "a", "baseline", "58%", "success", "rate,", "equaled", "$7,900/QALY.", "If", "the", "estimated", "probability", "of", "successful", "ECV", "is", "less", "than", "32%,", "then", "ECV", "costs", "more", "to", "society", "and", "has", "poorer", "QALYs", "for", "the", "patient.", "However,", "as", "the", "probability", "of", "successful", "ECV", "was", "between", "32%", "and", "63%,", "ECV", "cost", "more", "than", "cesarean", "delivery", "but", "with", "greater", "associated", "QALY", "such", "that", "the", "cost-effectiveness", "ratio", "was", "less", "than", "$50,000/", "QALY.", "If", "the", "probability", "of", "successful", "ECV", "was", "greater", "than", "63%,", "the", "computer", "modeling", "indicated", "that", "a", "trial", "of", "ECV", "is", "less", "costly", "and", "with", "better", "QALYs", "than", "a", "scheduled", "cesarean.", "The", "cost-effectiveness", "of", "a", "trial", "of", "ECV", "is", "most", "sensitive", "to", "its", "probability", "of", "success,", "and", "not", "to", "the", "probabilities", "of", "a", "cesarean", "after", "ECV,", "spontaneous", "reversion", "to", "breech,", "successful", "second", "ECV", "trial,", "or", "adverse", "outcome", "from", "emergency", "cesarean.", "Conclusions:", "From", "society’s", "perspective,", "ECV", "trial", "is", "cost-effective", "when", "compared", "to", "a", "scheduled", "cesarean", "for", "breech", "presentation", "provided", "the", "probability", "of", "successful", "ECV", "is", ">", "32%.", "Improved", "algorithms", "are", "needed", "to", "more", "precisely", "estimate", "the", "likelihood", "that", "a", "patient", "will", "have", "a", "successful", "ECV.", "Background", "Breech", "presentation", "at", "term", "occurs", "in", "3-4%", "of", "pregnan-", "cies", "and", "is", "managed", "with", "elective", "cesarean,", "assisted", "vagi-", "nal", "delivery,", "or", "external", "cephalic", "version", "(ECV)", "[1,2].", "Approximately", "87%", "of", "breech", "presentations", "in", "the", "Uni-", "ted", "States", "resulted", "in", "cesarean", "delivery", "[3],", "a", "significant", "increase", "from", "previous", "years", "[4,5].", "Breech", "presentation", "is", "the", "third", "most", "common", "indication", "for", "cesarean", "and", "in", "some", "hospitals", "breech", "presentations", "are", "managed", "exclusively", "by", "cesarean", "delivery", "[6,7].", "This", "may", "in", "part", "be", "due", "to", "the", "Term", "Breech", "Trial", "in", "2000", "that", "confirmed", "*", "Correspondence:", "jonathan.tan@stonybrook.edu", "1Department", "of", "Anesthesiology,", "Stony", "Brook", "University", "Medical", "Center,", "Stony", "Brook,", "New", "York,", "11794-8480,", "USA", "that", "breech", "presentations", "delivered", "by", "cesareans", "resulted", "in", "less", "neonatal", "mortality", "and", "short-term", "morbidity", "compared", "to", "vaginal", "breech", "delivery", "[8].", "Maternal", "com-", "plications", "were", "also", "found", "to", "be", "similar", "for", "cesarean", "and", "vaginal", "delivery", "in", "the", "short", "[9]", "and", "long", "term", "[10,11].", "Practice", "guidelines", "from", "the", "American", "College", "of", "Obstetrics", "and", "Gynecologists", "(ACOG)", "in", "2006", "recom-", "mend", "that", "decisions", "regarding", "the", "mode", "of", "delivery", "for", "breech", "presentation", "are", "dependent", "on", "the", "health", "care", "provider’s", "experience.", "ACOG", "also", "suggests", "that", "cesarean", "deliveries", "are", "preferred", "over", "vaginal", "breech", "deliveries", "[12].", "The", "desire", "to", "decrease", "the", "number", "of", "cesareans", "has", "renewed", "interest", "in", "ECV", "[13,14].", "In", "fact,", "ACOG", "recommends", "ECV", "to", "lower", "the", "number", "of", "breech", "©", "2010", "Tan", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "CELLULAR", "NEUROSCIENCE", "At", "immature", "mossy", "fibers-CA3", "connections,", "activation", "of", "presynaptic", "GABA", "receptors", "by", "endogenously", "released", "B", "GABA", "contributes", "to", "synapses", "silencing", "Victoria", "F.", "Safiulina", "and", "Enrico", "Cherubini*", "Neuroscience", "Programme,", "International", "School", "for", "Advanced", "Studies,Trieste,", "Italy", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "26", "February", "2009", "doi:", "10.3389/neuro.03.001.2009", "Edited", "by:", "Daniel", "Johnston,", "University", "ofTexas,", "USA", "Reviewed", "by:", "Daniel", "Johnston,", "University", "ofTexas,", "USA", "German", "Barrionuevo,", "University", "of", "Pittsburgh,", "USA", "*Correspondence:", "Enrico", "Cherubini,", "International", "School", "of", "Advanced", "Studies", "(SISSA),", "Department", "of", "Neurobiology,", "Ed.", "Q1", "Area", "Science", "Park,", "S.S.14", "Km", "163.5,", "34012", "Basovizza,", "Trieste,", "Italy.", "e-mail:", "cher@sissa.it", "Early", "in", "postnatal", "life", "correlated", "GABAergic", "activity", "in", "the", "hippocampus", "is", "thought", "to", "play", "a", "crucial", "role", "in", "synaptogenesis", "and", "in", "the", "development", "of", "adult", "neuronal", "networks.", "Unlike", "adulthood,", "at", "this", "developmental", "stage,", "mossy", "fibers", "(MF)", "which", "are", "the", "axons", "of", "granule", "cells,", "release", "GABA", "into", "CA3", "principal", "cells", "and", "interneurons.", "Here,", "we", "tested", "the", "hypothesis", "that", "at", "MF-CA3", "connections,", "tonic", "activation", "of", "GABAB", "autoreceptors", "by", "GABA", "is", "responsible", "for", "the", "low", "probability", "of", "release", "and", "synapse", "silencing.", "Blocking", "GABAB", "receptors", "with", "CGP55845", "enhanced", "the", "probability", "of", "GABA", "release", "and", "switched", "on", "silent", "synapses", "while", "the", "opposite", "was", "observed", "with", "baclofen.", "Both", "these", "effects", "were", "presynaptic", "and", "were", "associated", "with", "changes", "in", "paired-pulse", "ratio", "and", "coefficient", "of", "variation.", "In", "addition,", "enhancing", "the", "extracellular", "GABA", "concentration", "by", "repetitive", "stimulation", "of", "MF", "or", "by", "blocking", "the", "GABA", "transporter", "GAT-1,", "switched", "off", "active", "synapses,", "an", "effect", "that", "was", "prevented", "by", "CGP55845.", "In", "the", "presence", "of", "CGP55845,", "stimulation", "of", "MF-induced", "synaptic", "potentiation.", "The", "shift", "of", "EGABA", "from", "the", "depolarizing", "to", "the", "hyperpolarizing", "direction", "with", "bumetanide,", "a", "blocker", "of", "the", "cation-chloride", "co-transporter", "NKCC1,", "prevented", "synaptic", "potentiation", "and", "caused", "synaptic", "depression,", "suggesting", "that", "the", "depolarizing", "action", "of", "GABA", "observed", "in", "the", "presence", "of", "CGP55845", "is", "responsible", "for", "the", "potentiating", "effect.", "It", "is", "proposed", "that,", "activation", "of", "GABAB", "receptors", "by", "spillover", "of", "GABA", "from", "MF", "terminals", "reduces", "the", "probability", "of", "release", "and", "contributes", "to", "synapses", "silencing.", "This", "would", "act", "as", "a", "filter", "to", "prevent", "excessive", "activation", "of", "the", "auto-associative", "CA3", "network", "and", "the", "emergence", "of", "seizures.", "Keywords:", "mossy", "fiber-CA3", "synapses,", "immature", "hippocampus,", "probability", "of", "GABA", "release,", "GABAA-mediated", "synaptic", "currents,", "GABAB", "autoreceptors,", "GABA", "transporters,", "frequency-dependent", "synaptic", "depression", "INTRODUCTION", "1998;", "Vogt", "and", "Nicoll,", "1999),", "adenosine", "receptors", "(Thompson", "In", "the", "developing", "hippocampus,", "GABAergic", "signaling", "plays", "a", "et", "al.,", "1992),", "kainate", "receptors", "(Castillo", "et", "al.,", "1997;", "Vignes", "and", "crucial", "role", "in", "generating", "primitive", "patterns", "of", "network", "activity", "Collingridge,", "1997)", "and", "peptides", "(Weisskopf", "et", "al.,", "1993).", "GABAB", "known", "as", "giant", "depolarizing", "potentials", "or", "GDPs", "(Ben-Ari", "et", "al.,", "receptors", "which", "are", "coupled", "to", "Gi", "and", "Go", "proteins", "are", "localized", "on", "2007).", "The", "higher", "intracellular", "chloride", "concentration", "present", "in", "both", "pre", "and", "postsynaptic", "membranes", "(Bettler", "et", "al.,", "2004;", "Misgeld", "immature", "neurons", "(Rivera", "et", "al.,", "1999)", "leads", "to", "an", "efflux", "of", "chlo-", "et", "al.,", "1995).", "Activation", "of", "postsynaptic", "GABAB", "receptors", "causes", "the", "ride", "and", "to", "a", "membrane", "depolarization", "which", "triggers", "sodium", "opening", "of", "inwardly", "rectifying", "potassium", "channels", "(Lüscher", "et", "al.,", "spikes", "and", "excites", "postsynaptic", "cells", "(Ben-Ari", "et", "al.,", "1989).", "1997)", "whereas", "activation", "of", "presynaptic", "GABAB", "receptors", "causes", "GABA-induced", "membrane", "depolarization", "activates", "N-methyl-", "a", "reduction", "in", "transmitter", "release", "mainly", "via", "inhibition", "of", "P/Q", "d-aspartate", "receptors", "and", "voltage-dependent", "calcium", "channels", "and", "N", "types", "of", "voltage-dependent", "calcium", "channels", "(Poncer", "et", "al.,", "with", "consequent", "calcium", "rise", "inside", "the", "cells", "and", "activation", "of", "1997).", "While", "postsynaptic", "GABAB", "receptors", "are", "developmentally", "intracellular", "signaling", "cascades.", "Such", "mechanisms", "are", "central", "to", "regulated", "(Cherubini", "et", "al.,", "1998;", "Gaiarsa", "et", "al.,", "1995),", "presynap-", "the", "well-known", "trophic", "action", "of", "GABA", "which", "regulates", "several", "tic", "GABAB", "receptors", "are", "present", "and", "functional", "already", "at", "birth.", "key", "developmental", "steps", "including", "DNA", "synthesis,", "cell", "migration,", "It", "has", "been", "shown", "that", "they", "control", "network", "activity", "(McLean", "cell", "growth", "and", "synapse", "formation", "(Owens", "and", "Kriegstein,", "2002).", "et", "al.,", "1996)", "and", "modulate", "the", "amplitude", "of", "glutamate-", "or", "GABA-", "In", "addition,", "evidence", "has", "been", "recently", "provided", "that", "the", "prin-", "mediated", "postsynaptic", "currents", "in", "CA3", "principal", "cells", "(Gaiarsa", "cipal", "neurotransmitter", "released", "from", "mossy", "fibers", "(MF)", "during", "et", "al.,", "1995).", "However,", "these", "studies", "failed", "in", "identifying", "where", "the", "first", "week", "of", "postnatal", "life", "is", "GABA", "(Safiulina", "et", "al.,", "2006).", "In", "GABAA-mediated", "synaptic", "currents", "originated", "from.", "adulthood,", "these", "fibers", "are", "glutamatergic", "and", "are", "endowed", "with", "a", "Here,", "we", "addressed", "whether,", "immediately", "after", "birth,", "number", "of", "receptor", "types", "which", "up", "or", "down-regulate", "the", "trans-", "MF-induced", "GABAergic", "responses", "in", "CA3", "principal", "cells", "could", "mitter", "release.", "These", "include", "metabotropic", "glutamate", "receptors", "be", "modulated", "by", "GABAB", "autoreceptors.", "We", "report", "that", "block-", "(Kamiya", "et", "al.,", "1996),", "GABAA", "and", "GABAB", "receptors", "(Min", "et", "al.,", "ing", "GABAB", "receptors", "with", "CGP55845", "enhanced", "synaptic", "efficacy", "Frontiers", "in", "Cellular", "Neuroscience", "www.frontiersin.org", "February", "2009", "|", "Volume", "3", "|", "Article", "1", "|", "1" ]

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[ "Tremblay", "et", "al.", "Diabetology", "&", "Metabolic", "Syndrome", "2012,", "4:4", "http://www.dmsjournal.com/content/4/1/4", "R", "E", "S", "E", "A", "R", "C", "H", "DIABETOLOGY", "&", "METABOLIC", "SYNDROME", "Open", "Access", "Salivary", "pH", "as", "a", "Marker", "of", "Plasma", "Adiponectin", "Concentrations", "in", "Women", "Monique", "Tremblay,", "Yacine", "Loucif,", "Julie", "Methot,", "Diane", "Brisson", "and", "Daniel", "Gaudet*", "Abstract", "Background:", "Plasma", "adiponectin", "is", "a", "significant", "correlate", "of", "the", "pro-inflammatory", "cardiometabolic", "risk", "profile", "associated", "with", "obesity", "and", "type", "2", "diabetes.", "Salivary", "pH", "is", "influenced", "by", "several", "cardiometabolic", "risk", "components", "such", "as", "inflammation,", "oxidation", "and", "numerous", "oral", "and", "systemic", "health", "modulators,", "including", "the", "menopausal", "status.", "This", "study", "aimed", "to", "assess", "the", "association", "between", "plasma", "adiponectin", "concentrations", "and", "salivary", "pH", "in", "women", "according", "to", "the", "menopausal", "status.", "Method:", "Unstimulated", "saliva", "collection", "was", "performed", "in", "151", "Caucasian", "women", "of", "French-Canadian", "origin", "(53", "premenopausal", "women", "(PMW)", "and", "98", "menopausal", "women", "(MW)).", "Student’s", "t", "test,", "ANOVA", "and", "linear", "regression", "models", "were", "used", "to", "assess", "the", "association", "between", "plasma", "adiponectin", "concentrations", "and", "salivary", "pH.", "Results:", "Plasma", "adiponectin", "levels", "increased", "as", "a", "function", "of", "salivary", "pH", "in", "the", "whole", "sample", "and", "among", "MW", "(r", "=", "0.29", "and", "r", "=", "0.36,", "p", "<", "0.001).", "The", "proportion", "of", "the", "variance", "of", "plasma", "adiponectin", "levels", "explained", "by", "the", "salivary", "pH", "(R2)", "was", "10.8%", "(p", "<", "0.001).", "Plasma", "adiponectin", "levels", "progressively", "increased", "across", "salivary", "pH", "quartiles", "(p", "=", "0.005).", "Conclusions:", "These", "results", "suggest", "that", "salivary", "pH", "is", "a", "significant", "correlate", "of", "plasma", "adiponectin", "levels", "in", "women.", "With", "the", "increasing", "prevalence", "of", "type", "2", "diabetes", "and", "obesity,", "new", "technologies", "should", "be", "developed", "to", "more", "easily", "monitor", "health", "status,", "disease", "onset", "and", "progression.", "Salivary", "pH,", "a", "simple,", "inexpensive", "and", "non-", "invasive", "measure,", "could", "be", "a", "very", "promising", "avenue.", "Keywords:", "Salivary", "pH,", "Adiponectin,", "Cardiometabolic", "risk,", "Diabetes", "Introduction", "According", "to", "the", "World", "Health", "Organization,", "by", "2015", "approximately", "2.3", "billion", "adults", "worldwide", "will", "be", "over-", "weight", "and", "more", "than", "700", "million", "obese", "[1].", "The", "bur-", "den", "of", "the", "associated", "cardiometabolic", "risk", "components,", "such", "as", "type", "2", "diabetes", "mellitus", "(T2DM),", "dyslipidemia", "and", "cardiovascular", "disease", "(CVD),", "is", "also", "set", "to", "grow", "rapidly.", "Not", "only", "is", "this", "epidemic", "progression", "observed", "in", "developed", "countries,", "but", "it", "increasingly", "affects", "devel-", "oping", "countries", "too.", "Moreover,", "it", "has", "been", "estimated", "that", "by", "2025,", "three", "out", "of", "four", "people", "with", "T2DM", "or", "other", "cardiometabolic", "risk", "components", "will", "be", "living", "in", "third", "world", "countries", "[2].", "It", "is", "therefore", "mandatory", "to", "develop", "improved", "and", "more", "accessible", "screening", "tools", "in", "order", "to", "devise", "finer", "preventive", "and", "therapeutic", "strategies.", "*", "Correspondence:", "daniel.gaudet@umontreal.ca", "Department", "of", "Medicine,", "Université", "de", "Montréal,", "ECOGENE-21", "and", "Lipid", "Clinic,", "Chicoutimi", "Hospital,", "Saguenay,", "QC,", "Canada", "Adiponectin", "has", "been", "identified", "as", "a", "new", "biochemical", "marker", "of", "visceral", "fat", "accumulation", "and", "could", "represent", "a", "critical", "link", "between", "obesity", "and", "the", "cardiometabolic", "risk", "profile", "[3].", "Adiponectin", "is", "an", "adipocyte-derived", "protein,", "highly", "abundant", "in", "plasma,", "with", "concentrations", "ranging", "from", "5", "to", "30", "μg/ml", "(0.01%", "of", "total", "plasma)", "[4].", "Its", "levels", "correlate", "with", "the", "development", "of", "T2DM", "[5,6],", "dyslipide-", "mia,", "hypertension", "[7]", "and", "CVD", "[8].", "Adiponectin", "may", "also", "have", "different", "immune", "functions", "in", "several", "biological", "systems.", "It", "exerts", "anti-inflammatory,", "insulin-sensitizing", "and", "anti-atherosclerotic", "effects", "when", "secreted", "into", "the", "circula-", "tion", "[9].", "Therefore,", "in", "the", "search", "for", "indexes", "of", "metabolic", "perturbations", "and", "proinflammatory", "status", "predisposing", "to", "a", "deteriorated", "cardiometabolic", "risk", "profile,", "the", "measure-", "ment", "of", "plasma", "adiponectin", "concentrations", "is", "increasingly", "studied.", "However,", "in", "the", "context", "of", "this", "epidemic", "progres-", "sion", "of", "T2DM", "and", "obesity", "and", "in", "order", "to", "develop", "accessi-", "ble", "tools", "without", "increasing", "the", "burden", "of", "healthcare", "costs,", "it", "is", "imperative", "to", "develop", "alternatives", "to", "the", "traditional", "©", "2012", "Tremblay", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "J", "Neurodevelop", "Disord", "(2011)", "3:257–269", "DOI", "10.1007/s11689-011-9087-2", "Regulation", "of", "molecular", "pathways", "in", "the", "Fragile", "X", "Syndrome:", "insights", "into", "Autism", "Spectrum", "Disorders", "Silvia", "De", "Rubeis", "&", "Claudia", "Bagni", "Received:", "20", "November", "2010", "/", "Accepted:", "7", "July", "2011", "/", "Published", "online:", "13", "August", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "The", "Fragile", "X", "syndrome", "(FXS)", "is", "a", "leading", "cause", "of", "intellectual", "disability", "(ID)", "and", "autism.", "The", "disease", "is", "caused", "by", "mutations", "or", "loss", "of", "the", "Fragile", "X", "Mental", "Retardation", "Protein", "(FMRP),", "an", "RNA-binding", "protein", "playing", "multiple", "functions", "in", "RNA", "metabolism.", "The", "expression", "of", "a", "large", "set", "of", "neuronal", "mRNAs", "is", "altered", "when", "FMRP", "is", "lost,", "thus", "causing", "defects", "in", "neuronal", "morphology", "and", "physiology.", "FMRP", "regulates", "mRNA", "stability,", "dendritic", "targeting,", "and", "protein", "synthesis.", "At", "synapses,", "FMRP", "represses", "protein", "synthesis", "by", "forming", "a", "complex", "with", "the", "Cytoplasmic", "FMRP", "Interacting", "Protein", "1", "(CYFIP1)", "and", "the", "cap-binding", "protein", "eIF4E.", "Here,", "we", "review", "the", "clinical,", "genetic,", "and", "molecular", "aspects", "of", "FXS", "with", "a", "special", "focus", "on", "the", "receptor", "signaling", "that", "regulates", "FMRP-dependent", "protein", "synthesis.", "We", "further", "discuss", "the", "FMRP–CYFIP1", "complex", "and", "its", "potential", "relevance", "for", "ID", "and", "autism.", "Keywords", "Fragile", "X", "syndrome", ".", "Autism", ".", "FMRP.", "Protein", "synthesis", ".", "mRNPs", ".", "mRNA", "metabolism", ".", "Synaptic", "plasticity", "S.", "De", "Rubeis", ":", "C.", "Bagni", "Center", "for", "Human", "Genetics,", "Katholieke", "Universiteit", "Leuven,", "3000", "Leuven,", "Belgium", "S.", "De", "Rubeis", ":", "C.", "Bagni", "Department", "of", "Molecular", "and", "Developmental", "Genetics,", "Flanders", "Institute", "for", "Biotechnology", "(VIB),", "3000", "Leuven,", "Belgium", "C.", "Bagni", "(*)", "Department", "of", "Experimental", "Medicine", "and", "Biochemical", "Sciences,", "University", "“Tor", "Vergata”,", "00133", "Rome,", "Italy", "e-mail:", "claudia.bagni@uniroma2.it", "e-mail:", "claudia.bagni@med.kuleuven.be", "Fragile", "X", "and", "fragile", "X", "tremor", "ataxia", "syndromes:", "clinical", "phenotypes", "The", "Fragile", "X", "syndrome", "(FXS)", "is", "the", "most", "frequent", "form", "of", "inherited", "intellectual", "disability", "(Jacquemont", "et", "al.", "2007).", "Patients", "with", "FXS", "have", "physical", "features,", "such", "as", "large", "ears,", "an", "elongated", "face,", "and", "a", "high", "arched", "palate,", "which", "have", "been", "reported", "in", "60%", "of", "prepubertal", "FXS", "boys.", "Other", "symptoms", "include", "connective", "tissue", "anomalies,", "which", "can", "lead", "to", "a", "prolapsed", "mitral", "valve,", "scoliosis,", "flat", "feet,", "and", "joint", "laxity", "and", "macro-orchidism", "in", "boys.", "Macro-orchidism", "affects", "about", "90%", "of", "boys", "with", "FXS", "(Jacquemont", "et", "al.", "2007)", "but", "the", "causes", "are", "still", "largely", "unknown.", "In", "addition,", "subtle", "dysfunctions", "of", "the", "hypothalamic-pituitary-thyroid", "axis", "have", "been", "reported", "in", "FXS", "patients", "(Bregman", "et", "al.", "1990).", "Studies", "performed", "in", "Fmr1", "KO", "animals", "did", "not", "reveal", "altered", "levels", "of", "the", "follicle-stimulating", "hormone,", "but", "an", "increase", "of", "Sertoli", "cell", "proliferation", "during", "testis", "development", "(Slegtenhorst-Eegdeman", "et", "al.", "1998).", "Patients", "display", "a", "broad", "spectrum", "of", "cognitive", "and", "behavioral", "deficits.", "The", "developmental", "delay", "is", "the", "most", "consistent", "feature,", "with", "a", "mean", "IQ", "of", "42", "in", "boys", "and", "severe", "mental", "retardation", "in", "about", "25%", "of", "cases.", "Since", "the", "disorder", "is", "X-linked", "and", "the", "penetrance", "is", "variable,", "females", "are", "usually", "in", "a", "low-normal", "range,", "with", "an", "IQ", "ranging", "from", "70", "to", "90", "(Jacquemont", "et", "al.", "2007).", "Moreover,", "epilepsy", "has", "been", "described", "in", "13–18%", "of", "boys", "and", "4%", "in", "girls,", "but", "the", "seizures", "tend", "to", "resolve", "during", "childhood", "(Berry-Kravis", "2002).", "Despite", "the", "severe", "neurobehavioral", "symptoms,", "the", "anatomical", "studies", "only", "revealed", "minor", "abnormalities", "in", "post", "mortem", "brains", "from", "FXS", "patients", "(Hallahan", "et", "al.", "2011;", "Reiss", "et", "al.", "1995).", "The", "most", "prominent", "neuroanatomical", "feature", "is", "the", "dysgenesis", "of", "dendritic", "spines", "that", "appear", "longer", "and", "thinner", "than", "normal,", "likely", "due", "to", "a", "developmen-", "tal", "delay", "in", "spine", "dynamics", "and", "in", "transition", "from", "immature" ]

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[ "Cherrier", "et", "al.", "BMC", "Cancer", "2010,", "10:1", "http://www.biomedcentral.com/1471-2407/10/1", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Changes", "in", "neuronal", "activation", "patterns", "in", "response", "to", "androgen", "deprivation", "therapy:", "a", "pilot", "study", "Monique", "M", "Cherrier1,3*,", "Paul", "R", "Borghesani1,", "Amy", "L", "Shelton4,", "Celestia", "S", "Higano2", "Abstract", "Background:", "A", "common", "treatment", "option", "for", "men", "with", "prostate", "cancer", "is", "androgen", "deprivation", "therapy", "(ADT).", "However,", "men", "undergoing", "ADT", "may", "experience", "physical", "side", "effects,", "changes", "in", "quality", "of", "life", "and", "sometimes", "psychiatric", "and", "cognitive", "side", "effects.", "Methods:", "In", "this", "study,", "hormone", "naïve", "patients", "without", "evidence", "of", "metastases", "with", "a", "rising", "PSA", "were", "treated", "with", "nine", "months", "of", "ADT.", "Functional", "magnetic", "resonance", "imaging", "(fMRI)", "of", "the", "brain", "during", "three", "visuospatial", "tasks", "was", "performed", "at", "baseline", "prior", "to", "treatment", "and", "after", "nine", "months", "of", "ADT", "in", "five", "subjects.", "Seven", "healthy", "control", "patients,", "underwent", "neuroimaging", "at", "the", "same", "time", "intervals.", "Results:", "ADT", "patients", "showed", "reduced,", "task-related", "BOLD-fMRI", "activation", "during", "treatment", "that", "was", "not", "observed", "in", "control", "subjects.", "Reduction", "in", "activation", "in", "right", "parietal-occipital", "regions", "from", "baseline", "was", "observed", "during", "recall", "of", "the", "spatial", "location", "of", "objects", "and", "mental", "rotation.", "Conclusions:", "Findings,", "while", "preliminary,", "suggest", "that", "ADT", "reduces", "task-related", "neural", "activation", "in", "brain", "regions", "that", "are", "involved", "in", "mental", "rotation", "and", "accurate", "recall", "of", "spatial", "information.", "Background", "Prostate", "cancer", "is", "the", "most", "common", "form", "of", "non-skin", "cancer", "diagnosed", "in", "U.S.", "men", "with", "over", "218,000", "newly", "diagnosed", "cases", "each", "year", "estimated", "per", "year", "[1].", "While", "androgen", "deprivation", "therapy", "(ADT)", "used", "to", "be", "reserved", "for", "those", "with", "metastatic", "disease", "and", "resulted", "in", "a", "med-", "ian", "survival", "of", "2-5", "years", "[2,3],", "ADT", "is", "now", "commonly", "prescribed", "in", "the", "setting", "of", "localized", "disease", "(e.g.", "in", "combination", "with", "radiation", "therapy)", "or", "for", "the", "22%", "of", "patients", "who", "fail", "primary", "therapy", "and", "have", "a", "rising", "PSA", "without", "evidence", "of", "metastases", "[4].", "In", "contrast", "to", "those", "with", "metastatic", "disease", "the", "latter", "patients", "often", "have", "no", "disease", "related", "symptoms", "and", "may", "live", "for", "many", "years.", "Physiological", "consequences", "of", "androgen", "deprivation", "include", "obesity,", "anemia,", "loss", "of", "bone", "mineral", "density,", "muscle", "atrophy,", "gynecomastia", "and", "mood", "changes", "[2,5,6].", "A", "recent", "population", "based", "study", "showed", "that", "ADT", "was", "associated", "with", "an", "increased", "risk", "of", "diabetes,", "*", "Correspondence:", "cherrier@u.washington.edu", "1Department", "of", "Psychiatry", "and", "Behavioral", "Sciences,", "University", "of", "Washington", "School", "of", "Medicine,", "Seattle,", "WA;", "98195;", "USA", "myocardial", "infarction,", "and", "hypertension", "[7].", "Psychiatric", "changes", "can", "include", "depression", "and", "anxiety", "[8]", "and", "cog-", "nitive", "problems", "can", "include", "impairments", "in", "verbal", "memory", "[9,10],", "spatial", "reasoning", "[11]", "and", "attention", "[12].", "Given", "these", "cognitive", "and", "medical", "side", "effects", "of", "ADT", "understanding", "the", "immediate", "and", "long-term", "conse-", "quence", "of", "treatment", "is", "essential.", "Based", "on", "findings", "from", "our", "previous", "study", "demon-", "strating", "a", "decline", "in", "spatial", "reasoning", "abilities", "in", "healthy", "men", "undergoing", "ADT", "[11],", "the", "aim", "of", "this", "study", "was", "to", "examine", "if", "neural", "activation", "changes", "were", "evident", "in", "response", "to", "androgen", "deprivation", "while", "performing", "spa-", "tial", "reasoning", "and", "spatial", "memory", "tasks", "using", "functional", "magnetic", "resonance", "imaging", "(fMRI).", "Spatial", "reasoning", "and", "spatial", "memory", "were", "specifically", "chosen", "to", "examine", "the", "effects", "of", "ADT", "on", "brain", "function", "because", "task-", "related", "brain", "activation", "has", "been", "clearly", "identified,", "parti-", "cularly", "in", "regions", "of", "the", "parietal", "cortex", "[13-16]", "along", "with", "evidence", "of", "hormone", "influences", "on", "these", "brain", "regions", "[17-19].", "The", "aim", "of", "the", "present", "study", "was", "to", "assess", "changes", "in", "neural", "activation", "in", "response", "to", "andro-", "gen", "deprivation", "using", "functional", "magnetic", "resonance", "©", "2010", "Cherrier", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Journal", "of", "Medical", "Case", "Reports", "Case", "report", "Combined", "adenocarcinoid", "and", "mucinous", "cystadenoma", "of", "the", "appendix:", "a", "case", "report", "A", "Velusamy*1,", "S", "Saw2,", "J", "Gossage1,", "STR", "Bailey1", "and", "J", "Schofield2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Surgery,", "Maidstone", "Hospital,", "Maidstone", "ME16", "9QQ,", "UK", "and", "2Department", "of", "Pathology,", "Preston", "Hall", "Hospital,", "Aylesford,", "Kent", "ME20", "7NJ,", "UK", "Email:", "A", "Velusamy*", "-", "avsamy@gmail.com;", "S", "Saw", "-", "soniasaw@nhs.net;", "J", "Gossage", "-", "jgossage@doctors.org.uk;", "STR", "Bailey", "-", "simonbailey@nhs.net;", "J", "Schofield", "-", "john.schofield@nhs.net", "*", "Corresponding", "author", "Published:", "26", "January", "2009", "Journal", "of", "Medical", "Case", "Reports", "2009,", "3:28", "doi:10.1186/1752-1947-3-28", "This", "article", "is", "available", "from:", "http://www.jmedicalcasereports.com/content/3/1/28", "Received:", "21", "February", "2008", "Accepted:", "26", "January", "2009", "©", "2009", "Velusamy", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Introduction:", "Adenocarcinoid", "of", "the", "appendix", "is", "a", "rare", "malignant", "tumour", "with", "features", "of", "both", "adenocarcinoma", "and", "carcinoid,", "showing", "both", "epithelial", "and", "endocrine", "differentiation.", "Mucinous", "cystadenoma", "is", "the", "commonest", "of", "the", "benign", "neoplasms", "of", "the", "appendix,", "with", "an", "incidence", "of", "0.6%", "in", "appendicectomy", "specimens.", "We", "report", "a", "rare", "combination", "of", "these", "tumours", "and", "discuss", "the", "latest", "treatment", "options.", "To", "the", "best", "of", "our", "knowledge,", "only", "six", "cases", "have", "been", "reported", "in", "the", "literature", "to", "date.", "Case", "presentation:", "A", "71-year-old", "Caucasian", "man", "presented", "to", "our", "department", "with", "a", "right", "iliac", "fossa", "mass", "associated", "with", "pain.", "Laparoscopy", "revealed", "an", "adenocarcinoid", "of", "the", "appendix", "in", "combination", "with", "mucinous", "cystadenoma.", "He", "underwent", "a", "radical", "right", "hemicolectomy", "with", "clear", "margins", "and", "lymph", "nodes.", "Conclusion:", "Adenocarcinoids", "account", "for", "2%", "of", "primary", "appendiceal", "malignancies.", "Most", "tumours", "are", "less", "than", "2", "cm", "in", "diameter", "and", "20%", "of", "them", "metastasize", "to", "the", "ovaries.", "The", "mean", "age", "for", "presentation", "is", "59", "years", "and", "the", "5-year", "survival", "rate", "ranges", "from", "60%", "to", "84%.", "Right", "hemicolectomy", "is", "generally", "advised", "if", "any", "of", "the", "following", "features", "are", "present:", "tumours", "greater", "than", "2", "cm,", "involvement", "of", "resection", "margins,", "greater", "than", "2", "mitoses/10", "high-power", "fields", "on", "histology,", "extension", "of", "tumour", "beyond", "serosa.", "Chemotherapy", "mostly", "with", "5-Fluorouracil", "and", "Leucovorin", "is", "advised", "for", "remnant", "disease", "after", "surgery.", "Cytoreductive", "surgery", "with", "intraperitoneal", "chemotherapy", "can", "offer", "improved", "survival", "for", "advanced", "peritoneal", "dissemination.", "Introduction", "Mucinous", "cystadenoma", "is", "the", "commonest", "of", "the", "benign", "neoplasms", "of", "the", "appendix,", "with", "an", "incidence", "of", "0.6%", "in", "appendicectomy", "specimens", "[1].", "Adenocarcinoid", "is", "a", "rare", "but", "well", "recognised", "tumour", "of", "the", "appendix", "which", "exhib-", "its", "features", "of", "both", "carcinoid", "and", "adenocarcinoma.", "We", "report", "a", "patient", "with", "combined", "adenocarcinoid", "and", "muci-", "nous", "cystadenoma", "of", "the", "appendix.", "To", "the", "best", "of", "our", "knowledge,", "only", "six", "cases", "have", "been", "reported", "in", "the", "liter-", "ature", "to", "date", "[2,3].", "Case", "presentation", "Case", "report", "A", "71-year-old", "man", "presented", "to", "the", "surgical", "department", "with", "a", "2-week", "history", "of", "colicky", "right", "iliac", "fossa", "pain", "and", "a", "1-week", "history", "of", "diarrhoea.", "He", "did", "not", "have", "rectal", "Page", "1", "of", "3", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Aging", "Cell", "(2008)", "7,", "pp451–458", "Doi:", "10.1111/j.1474-9726.2008.00397.x", "BLlackwel", "ePublishinguLtdkocyte", "telomeres", "are", "longer", "in", "African", "Americans", "than", "in", "whites:", "the", "National", "Heart,", "Lung,", "and", "Blood", "Institute", "Family", "Heart", "Study", "and", "the", "Bogalusa", "Heart", "Study", "Steven", "C.", "Hunt,1", "Wei", "Chen,2", "Jeffrey", "P.", "Gardner,3", "Masayuki", "Kimura,3", "Sathanur", "R.", "Srinivasan,2", "John", "H.", "Eckfeldt,4", "Gerald", "S.", "Berenson2", "and", "Abraham", "Aviv3", "1Cardiovascular", "Genetics", "Division,", "University", "of", "Utah", "School", "of", "Medicine,", "Salt", "Lake", "City,", "UT,", "USA", "(NHLBI", "Family", "Heart", "Study)", "2Tulane", "Center", "for", "Cardiovascular", "Health,", "Tulane", "University", "Health", "Sciences", "Center,", "New", "Orleans,", "LA,", "USA", "(The", "Bogalusa", "Heart", "Study)", "3Center", "of", "Human", "Development", "and", "Aging,", "University", "of", "Medicine", "and", "Dentistry", "of", "New", "Jersey,", "New", "Jersey", "Medical", "School,", "Newark,", "NJ,", "USA", "4Department", "of", "Laboratory", "Medicine", "and", "Pathology,", "University", "of", "Minnesota,", "Minneapolis,", "MN,", "USA", "(NHLBI", "Family", "Heart", "Study)", "Summary", "Leukocyte", "telomere", "length", "(LTL)", "is", "ostensibly", "a", "bio-", "indicator", "of", "human", "aging.", "Here", "we", "report", "that", "African", "Americans", "have", "longer", "LTL", "than", "whites.", "We", "studied", "cross-", "sectionally", "2453", "individuals", "from", "the", "National", "Heart,", "Lung,", "and", "Blood", "Institute", "(NHLBI)", "Family", "Heart", "Study", "(age", "=", "30–93", "years)", "and", "the", "Bogalusa", "Heart", "Study", "(age", "=", "19–37", "years),", "comprising", "1742", "whites", "and", "711", "Afri-", "can", "Americans.", "We", "measured", "LTL", "by", "Southern", "blots", "of", "the", "terminal", "restriction", "fragments", "length.", "In", "234", "participants,", "telomere", "repeats", "were", "also", "measured", "by", "quantitative", "polymerase", "chain", "reaction", "(qPCR).", "Adjusted", "for", "age", "and", "body", "mass", "index", "(BMI),", "the", "respective", "leukocyte", "telomere", "lengths", "(mean", "±", "SEM)", "were", "considerably", "longer", "in", "African", "Americans", "than", "in", "whites", "both", "in", "the", "Family", "Heart", "Study", "(7.004", "±", "0.033", "kb", "vs.", "6.735", "±", "0.024", "kb,", "p", "<", "0.0001)", "and", "the", "Bogalusa", "Heart", "Study", "(7.923", "±", "0.063", "kb", "vs.", "7.296", "±", "0.039", "kb,", "p", "<", "0.0001).", "We", "confirmed", "the", "racial", "effect", "on", "LTL", "by", "qPCR", "(3.038", "±", "0.565", "T/S", "units", "for", "African", "Americans", "vs.", "2.714", "±", "0.487", "T/S", "units", "for", "whites,", "p", "<", "0.001).", "Cross-sectionally,", "sex-", "and", "BMI-adjusted", "LTL", "became", "shorter", "with", "age", "(range", "Correspondence", "Abraham", "Aviv,", "Center", "of", "Human", "Development", "and", "Aging,", "Room", "F-464,", "University", "of", "Medicine", "and", "Dentistry", "of", "New", "Jersey,", "New", "Jersey", "Medical", "School,", "185", "South", "Orange", "Ave.,", "Newark,", "NJ", "07103,", "USA,", "Tel.:", "973", "972", "5280;", "fax:", "973", "972", "5576;", "e-mail:", "avivab@umdnj.edu", "Accepted", "for", "publication", "01", "March", "2008", "Re-use", "of", "this", "article", "is", "permitted", "in", "accordance", "with", "the", "Creative", "Commons", "Deed,", "Attribution", "2·5,", "which", "does", "not", "permit", "commercial", "exploitation.", "19–93", "years)", "at", "a", "steeper", "slope", "in", "African", "Americans", "than", "in", "whites", "(0.029", "kb", "year–1", "vs.", "0.020", "kb", "year–1,", "respectively,", "p", "=", "0.0001).", "We", "suggest", "that", "racial", "difference", "in", "LTL", "arises", "from", "a", "host", "of", "interacting", "biological", "factors,", "including", "replication", "rates", "of", "hematopoietic", "stem", "cells.", "Key", "words:", "age;", "demography;", "gender;", "leukocyte;", "race;", "telomere.", "Introduction", "Mounting", "evidence", "suggests", "that", "leukocyte", "telomere", "length", "(LTL)", "is", "a", "bio-indicator", "of", "human", "aging,", "cardiovascular", "aging", "in", "particular.", "LTL", "is", "heritable", "(Slagboom", "et", "al.,", "1994;", "Jeanclos", "et", "al.,", "2000;", "Vasa-Nicotera", "et", "al.,", "2005;", "Andrew", "et", "al.,", "2006),", "although", "it", "is", "unknown", "how", "much", "of", "this", "heritability", "relates", "to", "birth", "LTL", "and", "the", "rate", "of", "its", "shortening", "from", "birth", "onward.", "Age-dependent", "LTL", "shortening", "is", "due", "to", "successive", "divisions", "of", "hematopoietic", "stem", "cells", "(HSCs)", "and", "progenitor", "cells", "(PCs)", "that", "form", "peripheral", "leukocytes.", "Inflammation", "and", "oxidative", "stress", "–", "two", "central", "elements", "in", "the", "biology", "of", "aging", "and", "aging-related", "diseases", "(Finch", "&", "Crimmins,", "2004;", "Balaban", "et", "al.,", "2005)", "–", "were", "reported", "to", "be", "associated", "with", "LTL", "(Aviv", "et", "al.,", "2006a;", "Demissie", "et", "al.,", "2006;", "Bekaert", "et", "al.,", "2007;", "Fitzpatrick", "et", "al.,", "2007).", "Inflammation", "entails", "an", "increase", "in", "number", "and", "diminished", "biological", "life", "of", "leukocyte", "subsets", "in", "the", "circulation,", "which", "would", "heighten", "the", "demand", "on", "HSCs/PCs", "to", "replicate,", "a", "phenomenon", "expressed", "in", "an", "accelerated", "telomere", "attrition", "and", "ultimately", "shortened", "LTL.", "Oxidative", "stress", "heightens", "the", "loss", "of", "telomere", "repeats", "per", "cell", "division", "(Sitte", "et", "al.,", "1998;", "Saretzki", "et", "al.,", "1999;", "Tchirkov", "&", "Lansdorp,", "2003).", "The", "compounded", "effect", "of", "inflam-", "mation/oxidative", "stress", "on", "the", "paces", "of", "both", "aging", "and", "LTL", "attrition", "conceivably", "explains", "the", "shortened", "LTL", "observed", "in", "individuals", "with", "aging-related", "diseases,", "particularly", "atherosclerotic", "cardiovascular", "(CV)", "disease", "(Brouilette", "et", "al.,", "2003;", "Cawthon", "et", "al.,", "2003;", "Benetos", "et", "al.,", "2004;", "Martin-Ruiz", "et", "al.,", "2005;", "Matsubara", "et", "al.,", "2006;", "Brouilette", "et", "al.,", "2007;", "Fitzpatrick", "et", "al.,", "2007;", "van", "der", "Harst", "et", "al.,", "2007),", "which", "is", "strongly", "linked", "to", "inflammation", "(Hansson", "&", "Libby,", "2006).", "The", "paradigm", "that", "links", "LTL", "to", "CV", "disease", "draws", "on", "data", "derived", "mainly", "from", "non-African", "American", "populations.", "But", "the", "developmental", "pattern", "of", "CV", "disease", "differs", "between", "African", "Americans", "and", "whites.", "For", "instance,", "African", "Americans", "are", "more", "prone", "to", "heart", "failure", "due", "to", "hypertension", "(Yancy,", "2005;", "Whittle", "et", "al.,", "2006),", "but", "they", "have", "considerably", "less", "coronary", "©", "2008", "The", "Authors", "Journal", "compilation", "©", "Blackwell", "Publishing", "Ltd/Anatomical", "Society", "of", "Great", "Britain", "and", "Ireland", "2008", "451" ]

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[ "J", "Headache", "Pain", "(2008)", "9:29–32", "DOI", "10.1007/s10194-008-0004-3", "O", "R", "I", "G", "I", "N", "A", "L", "Performances", "in", "cerebellar", "and", "neuromuscular", "transmission", "tests", "are", "correlated", "in", "migraine", "with", "aura", "Anna", "Ambrosini", "Æ", "Peter", "S.", "Sa´", "ndor", "Æ", "Victor", "De", "Pasqua", "Æ", "Francesco", "Pierelli", "Æ", "Jean", "Schoenen", "Received:", "2", "October", "2007", "/", "Accepted:", "24", "November", "2007", "/", "Published", "online:", "5", "February", "2008", "Springer-Verlag", "2008", "Abstract", "In", "previous", "studies,", "we", "described", "subclinical", "abnormalities", "of", "neuromuscular", "transmission", "and", "cerebel-", "lar", "functions", "in", "migraineurs.", "The", "aim", "of", "this", "study", "was", "to", "search", "if", "these", "two", "functions", "are", "correlated", "in", "the", "same", "patient.", "Thirteen", "migraineurs", "[five", "without", "aura", "(MO)", "and", "eight", "with", "aura", "(MA)]", "underwent", "both", "stimulation-SFEMG", "and", "3D-movement", "analysis.", "Single", "fiber", "EMG", "(SFEMG)", "results", "were", "expressed", "as", "the", "‘‘mean", "value", "of", "consecutive", "differences’’", "(mean", "MCD).", "Precision", "of", "arm-reaching", "movements", "(measured", "with", "an", "infrared", "optoelectronic", "tracking", "system)", "was", "expressed", "as", "the", "average", "deviation", "in", "the", "horizontal", "plane.", "Median", "values", "of", "mean", "MCD", "and", "mean", "horizontal", "deviation", "were", "not", "different", "between", "MO", "and", "MA.", "However,", "in", "MA,", "but", "not", "in", "MO,", "both", "variables", "were", "positively", "correlated.", "Thus,", "we", "conclude", "that", "neuro-", "muscular", "transmission", "and", "cerebellar", "functions", "are", "correlated", "in", "the", "same", "patient", "when", "affected", "by", "migraine", "A.", "Ambrosini", "(&)", "Headache", "Clinic,", "IRCCS", "INM", "Neuromed,", "via", "Atinense", "18,", "86077", "Pozzilli,", "Isernia,", "Italy", "e-mail:", "anna.ambrosini@neuromed.it", "P.", "S.", "Sa´ndor", "Headache", "and", "Pain", "Unit,", "Department", "of", "Neurology,", "University", "of", "Zurich,", "Zurich,", "Switzerland", "V.", "De", "Pasqua", "Headache", "Research", "Unit,", "Department", "of", "Neurology,", "University", "of", "Lie`ge,", "Lie`ge,", "Belgium", "F.", "Pierelli", "Department", "of", "Neurorehabilitation,", "University", "‘‘La", "Sapienza’’", "of", "Rome,", "Polo", "Pontino,", "ICOT,", "Latina,", "Italy", "J.", "Schoenen", "Headache", "Research", "Unit,", "Departments", "of", "Neurology", "and", "Neuroanatomy,", "University", "of", "Lie`ge,", "Lie`ge,", "Belgium", "with", "aura.", "We", "suggest", "that", "this", "correlation", "might", "be", "due", "to", "a", "common", "molecular", "abnormality.", "Keywords", "junction", "Migraine", "Genetics", "Introduction", "Cerebellum", "Neuromuscular", "Migraine", "is", "a", "paroxysmal", "neurological", "disorder", "with", "a", "high", "prevalence", "in", "the", "general", "population.", "There", "is", "strong", "epi-", "demiological", "and", "genetic", "evidence", "that", "genetic", "factors", "play", "a", "major,", "though", "variable", "role,", "in", "its", "pathogenesis.", "Migraine", "patients", "are", "characterized", "between", "attacks", "on", "various", "CNS-", "evoked", "responses", "by", "a", "deficit", "of", "habituation", "[1,", "2],", "which", "may", "have", "a", "familial", "character", "[3–5].", "The", "lack", "of", "habitua-", "tion", "may", "play", "a", "role", "in", "migraine", "pathogenesis", "[6].", "By", "contrast,", "other", "mild", "abnormalities", "have", "been", "identified", "that", "are", "unlikely", "to", "play", "a", "pathogenic", "role:", "a", "decreased", "safety", "factor", "at", "the", "neuromuscular", "junction", "on", "single", "fiber", "EMG", "(SFEMG)", "[7–9]", "and", "subclinical", "cerebellar", "hypermetria", "in", "the", "horizontal", "plane", "on", "opto-electronic", "analysis", "of", "upper", "arm-reaching", "movements", "[10].", "It", "was", "suggested", "that", "these", "two", "abnormalities", "might", "reflect", "the", "same", "underlying", "genetic", "abnormality.", "If", "this", "is", "correct,", "one", "may", "expect", "that", "in", "the", "same", "individual", "they", "be", "of", "a", "similar", "degree.", "We", "have", "therefore", "compared", "in", "the", "same", "migraine", "patient", "the", "SFEMG", "and", "3D-movement", "analysis.", "Materials", "and", "methods", "Patients", "Thirteen", "migraine", "patients", "(ICHD-II)", "[11]", "were", "recruited", "from", "the", "Headache", "Clinic", "of", "the", "Headache", "Research", "Unit", "123" ]

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[ "organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "6-Allyl-8-methoxy-3-phenyl-3,4-dihydro-", "2H-benzo[e][1,3]oxazine", "Jing", "Zhu,*", "Zhi-Dong", "Ren,", "Yang", "Liu,", "Lei", "Zhao", "and", "Yong", "Wu", "School", "of", "Chemistry", "and", "Chemical", "Engineering,", "Henan", "University", "of", "Technology,", "Zhengzhou", "450001,", "People’s", "Republic", "of", "China", "Correspondence", "e-mail:", "jingzhuhaut@126.com", "Received", "27", "June", "2011;", "accepted", "8", "July", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "291", "K;", "mean", "(C–C)", "=", "0.003", "A˚;", "disorder", "in", "main", "residue;", "R", "factor", "=", "0.047;", "wR", "factor", "=", "0.137;", "data-to-parameter", "ratio", "=", "13.9.", "In", "the", "title", "compound,", "C18H19NO2,", "the", "allyl", "group", "is", "disordered", "over", "two", "sets", "of", "sites", "[occupancy", "ratio", "0.662", "(4):0.338", "(4)].", "The", "dihedral", "angle", "between", "the", "phenyl", "and", "benzene", "rings", "is", "87.44", "(10)", ".", "The", "oxazinane", "ring", "adopts", "a", "sofa", "conformation.", "Related", "literature", "For", "similar", "heterocyclic", "compounds,", "see:", "Chen", "et", "al.", "(2007);", "Kiskan", "et", "al.", "(2007);", "Liu", "et", "al.", "(2007);", "Ran", "&", "Gu", "(2011);", "Sawaryn", "et", "al.", "(2010);", "Su", "et", "al.", "(2005).", "For", "puckering", "para-", "meters,", "see:", "Cremer", "&", "Pople", "(1975).", "Experimental", "Crystal", "data", "C18H19NO2", "Mr", "=", "281.34", "Triclinic,", "P1", "a", "=", "8.4087", "(5)", "A˚", "b", "=", "9.4852", "(5)", "A˚", "c", "=", "10.7735", "(7)", "A˚", "=", "99.193", "(5)", "=", "98.900", "(5)", "=", "115.476", "(6)", "Data", "collection", "Oxford", "Diffraction", "Xcalibur,", "Eos,", "Gemini", "diffractometer", "Absorption", "correction:", "multi-scan", "(CrysAlis", "PRO;", "Oxford", "Diffraction,", "2010)", "Tmin", "=", "0.659,", "Tmax", "=", "1.000", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.047", "wR(F", "2)", "=", "0.137", "S", "=", "1.05", "2644", "reflections", "V", "=", "741.30", "(9)", "A˚", "3", "Z", "=", "2", "Cu", "K", "radiation", "=", "0.65", "mm", "1", "T", "=", "291", "K", "0.20", "0.18", "0.18", "mm", "5471", "measured", "reflections", "2644", "independent", "reflections", "2282", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.015", "190", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.48", "e", "A˚", "3", "min", "=", "0.50", "e", "A˚", "3", "Data", "collection:", "CrysAlis", "PRO", "(Oxford", "Diffraction,", "2010);", "cell", "refinement:", "CrysAlis", "PRO;", "data", "reduction:", "CrysAlis", "PRO;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "OLEX2", "(Dolomanov", "et", "al.,", "2009);", "software", "used", "to", "prepare", "material", "for", "publication:", "OLEX2.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "BX2360).", "References", "Chen,", "X.-L.,", "Diao,", "X.-J.", "&", "Wu,", "M.-H.", "(2007).", "Acta", "Cryst.", "E63,", "o3580.", "Cremer,", "D.", "&", "Pople,", "J.", "A.", "(1975).", "J.", "Am.", "Chem.", "Soc.", "97,", "1354–1358.", "Dolomanov,", "O.", "V.,", "Bourhis,", "L.", "J.,", "Gildea,", "R.", "J.,", "Howard,", "J.", "A.", "K.", "&", "Puschmann,", "H.", "(2009).", "J.", "Appl.", "Cryst.", "42,", "339–341.", "Kiskan,", "B.,", "Yagci,", "Y.,", "Sahmetlioglu,", "E.", "&", "Toppare,", "L.", "(2007).", "J.", "Polym.", "Sci.", "Part", "A", "Polym.", "Chem.", "45,", "999–1006.", "Liu,", "Y.-L.,", "Hsu,", "C.-W.", "&", "Chou,", "C.-I.", "(2007).", "J.", "Polym.", "Sci.", "Part", "A", "Polym.", "Chem.", "45,", "1007–1015.", "Oxford", "Diffraction", "(2010).", "CrysAlis", "PRO", ".", "Oxford", "Diffraction", "Ltd,", "Yarnton,", "England.", "Ran,", "Q.-C.", "&", "Gu,", "Y.", "(2011).", "J.", "Polym.", "Sci.", "Part", "A", "Polym.", "Chem.", "49,", "1671–1677.", "Sawaryn,", "C.,", "Landfester,", "K.", "&", "Taden,", "A.", "(2010).", "Macromolecules,", "43,", "8933–", "8941.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Su,", "Y.-C.,", "Yei,", "D.-R.", "&", "Chang,", "F.-C.", "(2005).", "J.", "Appl.", "Polym.", "Sci.", "95,", "730–737.", "o2056", "Zhu", "et", "al.", "doi:10.1107/S1600536811027474", "Acta", "Cryst.", "(2011).", "E67,", "o2056" ]

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[ "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "09", "April", "2012", "doi:", "10.3389/fonc.2012.00032", "Cytotoxic", "capacity", "of", "IL-15-stimulated", "cytokine-induced", "killer", "cells", "against", "human", "acute", "myeloid", "leukemia", "and", "rhabdomyosarcoma", "in", "humanized", "preclinical", "mouse", "models", "Eva", "Rettinger", "1*,", "Vida", "Meyer", "1,", "Hermann", "Kreyenberg", "1,", "Andreas", "Volk", "2,", "Selim", "Kuçi", "1,", "Andre", "Willasch1,", "Ewa", "Koscielniak", "3,", "Simone", "Fulda4,", "Winfried", "S.", "Wels", "2,", "Halvard", "Boenig", "5,", "Thomas", "Klingebiel", "1", "and", "Peter", "Bader", "1*", "1", "Department", "of", "Pediatric", "Hematology,", "Oncology", "and", "Hemostaseology,", "University", "Children’s", "Hospital", "of", "Frankfurt/Main,", "Goethe-University", "Frankfurt/Main,", "Frankfurt/Main,", "Germany", "2", "Chemotherapeutisches", "Forschungsinstitut,", "Georg-Speyer-Haus,", "Frankfurt/Main,", "Germany", "3", "Department", "of", "Pediatric", "Oncology", "and", "Hematology,", "Olgahospital", "Stuttgart,", "Stuttgart,", "Germany", "4", "Institute", "for", "Experimental", "Cancer", "Research", "in", "Pediatrics,", "Goethe-University", "Frankfurt/Main,", "Frankfurt/Main,", "Germany", "5", "Institute", "for", "Transfusion", "Medicine", "and", "Immunohematology,", "Goethe-University", "Frankfurt/Main,", "Division", "for", "Cell", "Processing,", "German", "Red", "Cross", "Blood", "Donor", "Service", "Baden-Württemberg-Hessen,", "Frankfurt/Main,", "Germany", "Edited", "by:", "Charles", "G.", "Mullighan,", "St.", "Jude", "Children’s", "Research", "Hospital,", "USA", "Reviewed", "by:", "David", "Shook,", "St.", "Jude", "Children’s", "Research", "Hospital,", "USA", "Michael", "R.", "Verneris,", "University", "of", "Minnesota,", "USA", "*Correspondence:", "Eva", "Rettinger", "and", "Peter", "Bader", ",", "Department", "of", "Pediatric", "Hematology,", "Oncology", "and", "Hemostaseology,", "University", "Children’s", "Hospital", "of", "Frankfurt/Main,", "Goethe-University", "Frankfurt/Main,", "Theodor-Stern-Kai", "7,", "60590", "Frankfurt/Main,", "Germany.", "e-mail:", "eva.rettinger@kgu.de;", "peter.bader@kgu.de", "Allogeneic", "stem", "cell", "transplantation", "(allo-SCT)", "has", "become", "an", "important", "treatment", "modal-", "ity", "for", "patients", "with", "high-risk", "acute", "myeloid", "leukemia", "(AML)", "and", "is", "also", "under", "investigation", "for", "soft", "tissue", "sarcomas.", "The", "therapeutic", "success", "is", "still", "limited", "by", "minimal", "residual", "disease", "(MRD)", "status", "ultimately", "leading", "to", "patients’", "relapse.", "Adoptive", "donor", "lymphocyte", "infusions", "based", "on", "MRD", "status", "using", "IL-15-expanded", "cytokine-induced", "killer", "(CIK)", "cells", "may", "pre-", "vent", "relapse", "without", "causing", "graft-versus-host-disease", "(GvHD).", "To", "generate", "preclinical", "data", "we", "developed", "mouse", "models", "to", "study", "anti-leukemic-", "and", "anti-tumor-potential", "of", "CIK", "cells", "in", "vivo.", "Immunodeficient", "mice", "(NOD/SCID/IL-2Rγc−,", "NSG)", "were", "injected", "intravenously", "with", "human", "leukemic", "cell", "linesTHP-1,", "SH-2", "and", "with", "human", "rhabdomyosarcoma", "(RMS)", "cell", "lines", "RH41", "and", "RH30", "at", "minimal", "doses", "required", "for", "leukemia", "or", "tumor", "engraftment.", "Mice", "trans-", "planted", "withTHP-1", "or", "RH41", "cells", "were", "randomly", "assigned", "for", "analysis", "of", "CIK", "cell", "treatment.", "Organs", "of", "mice", "were", "analyzed", "by", "flow", "cytometry", "as", "well", "as", "quantitative", "polymerase", "chain", "reaction", "for", "engraftment", "of", "malignant", "cells", "and", "CIK", "cells.", "Potential", "of", "CIK", "cells", "to", "induce", "GvHD", "was", "determined", "by", "histological", "analysis.", "Tissues", "of", "the", "highest", "degree", "of", "THP-1", "cell", "expansion", "included", "bone", "marrow", "followed", "by", "liver,", "lung,", "spleen,", "peripheral", "blood", "(PB),", "and", "brain.", "RH30", "and", "RH41", "engraftment", "mainly", "took", "place", "in", "liver", "and", "lung,", "but", "was", "also", "detectable", "in", "spleen", "and", "PB.", "In", "spite", "of", "delayed", "CIK", "cell", "expansion", "compared", "with", "malig-", "nant", "cells,", "CIK", "cells", "injected", "at", "equal", "amounts", "were", "sufficient", "for", "significant", "reduction", "of", "RH41", "cells,", "whereas", "against", "fast-expanding", "THP-1", "cells", "250", "times", "more", "CIK", "than", "THP-1", "cells", "were", "needed", "to", "achieve", "comparable", "results.", "Our", "preclinical", "in", "vivo", "mouse", "models", "showed", "a", "reliable", "100%", "engraftment", "of", "malignant", "cells", "which", "is", "essential", "for", "analysis", "of", "anti-cancer", "therapy.", "Furthermore", "our", "data", "demonstrated", "that", "IL-15-activated", "CIK", "cells", "have", "potent", "cytotoxic", "capacity", "against", "AML", "and", "RMS", "cells", "without", "causing", "GvHD.", "Keywords:", "preclinical,", "NSG", "mice,", "CIK", "cells,", "rhabdomyosarcoma,", "leukemia,", "immunotherapy", "INTRODUCTION", "Allogeneic", "stem", "cell", "transplantation", "(allo-SCT)", "is", "an", "established", "method", "in", "the", "treatment", "of", "high-risk", "acute", "leukemia", "in", "children", "(Bader", "et", "al.,", "2004;", "Rettinger", "et", "al.,", "2011),", "and", "may", "also", "play", "a", "role", "in", "the", "treatment", "of", "high-risk", "soft", "tissue", "sarcoma", "in", "children.", "Espe-", "cially", "patients", "with", "primary", "alveolar", "rhabdomyosarcoma", "(RMS)", "above", "the", "age", "of", "10", "years", "with", "bone", "or", "bone", "marrow", "(BM)", "metas-", "tases", "have", "no", "realistic", "chance", "to", "survive", "their", "disease", "with", "conven-", "tional", "treatment", "(Koscielniak", "et", "al.,", "1997;", "Klingebiel", "et", "al.,", "2008;", "Perez", "et", "al.,", "2011).", "By", "evaluating", "the", "impact", "of", "allo-SCT", "in", "both,", "leukemia", "and", "soft", "tissue", "sarcoma", "patients,", "minimal", "residual", "disease", "(MRD)", "after", "transplantation", "is", "the", "reason", "for", "disease", "recurrence,", "and", "therefore", "is", "the", "strongest", "negative", "effector", "of", "the", "therapeutic", "success", "of", "allo-SCT.", "Once", "a", "stem", "cell", "recipient", "relapses,", "further", "therapeutic", "options", "are", "limited.", "For", "instance,", "donor", "lymphocyte", "infusion", "(DLI)", "is", "only", "efficacious", "for", "a", "limited", "number", "of", "diseases,", "and", "the", "high", "T", "cell", "doses", "required", "for", "DLI", "raise", "the", "risk", "for", "severe", "graft-versus-host-disease", "(GvHD;", "Rettinger", "et", "al.,", "2011).", "Cytokine-induced", "killer", "(CIK)", "cells", "are", "known", "in", "principle", "to", "be", "capable", "of", "eradicating", "a", "variety", "of", "both", "hematological", "and", "solid", "malignancies", "in", "a", "non-MHC-restricted", "manner,", "without", "possess-", "ing", "significant", "alloreactive", "potential", "(Takayama", "et", "al.,", "2000;", "Baker", "www.frontiersin.org", "April", "2012", "|", "Volume", "2", "|", "Article", "32", "|", "1" ]

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[ "R", "E", "V", "I", "E", "W", "Role", "of", "5", "alpha-reductase", "inhibitors", "in", "the", "management", "of", "prostate", "cancer", "Steven", "J", "Hudak1", "Javier", "Hernandez1", "Ian", "M", "Thompson2", "1Urology", "Service,", "Department", "of", "Surgery,", "Brooke", "Army", "Medical", "Center,", "Fort", "Sam", "Houston,", "TX,", "USA;", "2Department", "of", "Urology,", "University", "of", "Texas", "Health", "Science", "Center", "at", "San", "Antonio,", "San", "Antonio,", "TX,", "USA", "Correspondence:", "Javier", "Hernandez", "Urology", "Service,", "Department", "of", "Surgery,", "Brooke", "Army", "Medical", "Center,", "3851", "Roger", "Brooke", "Drive,", "Fort", "Sam", "Houston,", "TX", "78234-6200,", "Tel", "+1", "210", "916", "1163", "Fax", "+1", "210", "916", "5076", "Email", "javier.hernandez@us.army.mil", "Note:", "The", "views", "expressed", "in", "this", "article", "are", "those", "of", "the", "authors", "and", "do", "not", "reflect", "the", "official", "policy", "of", "the", "Department", "of", "Defense", "or", "other", "Departments", "of", "the", "US", "Government.", "Abstract:", "Prostate", "cancer", "is", "one", "of", "the", "most", "complex", "and", "enigmatic", "oncologic", "problems", "in", "medicine.", "It", "is", "highly", "prevalent,", "particularly", "in", "elderly", "males.", "Unfortunately,", "its", "generally", "protracted", "and", "variable", "clinical", "course", "and", "high", "association", "with", "treatment-related", "morbidity", "raise", "serious", "questions", "about", "the", "ideal", "treatment", "strategy", "for", "the", "individual", "patient.", "5", "alpha-", "reductase", "(5AR)", "inhibitors", "have", "a", "dramatic", "effect", "on", "benign", "prostatic", "disease", "with", "low", "toxicity.", "Thus,", "there", "is", "much", "interest", "in", "the", "potential", "role", "of", "5AR", "inhibitors", "in", "the", "prevention", "and", "treatment", "of", "prostate", "cancer.", "Finasteride", "is", "the", "only", "agent", "that", "has", "been", "shown", "in", "a", "randomized", "clinical", "trial", "to", "decrease", "the", "risk", "of", "prostate", "cancer", "with", "a", "reduction", "of", "almost", "25%.", "Additionally,", "a", "recent", "analysis", "of", "the", "Prostate", "Cancer", "Prevention", "Trial", "(PCPT)", "has", "found", "that", "finasteride", "improves", "the", "performance", "characteristics", "of", "prostate-specific", "antigen", "(PSA)", "blood", "test", "as", "a", "screening", "tool", "for", "prostate", "cancer,", "for", "both", "cancer", "detection", "as", "well", "as", "for", "detection", "of", "high", "risk", "disease.", "Finally,", "5AR", "inhibitors", "have", "been", "studied", "as", "a", "component", "of", "multimodal", "therapy", "for", "all", "stages", "of", "prostate", "cancer,", "with", "the", "goal", "of", "improving", "oncologic", "outcomes", "while", "avoiding", "the", "toxicity", "of", "medical", "and", "surgical", "castration.", "Keywords:", "prostate", "cancer,", "5-α-reductase", "inhibitors,", "finasteride,", "dutasteride,", "chemoprevention", "Introduction", "Prostate", "cancer", "is", "the", "most", "common", "noncutaneous", "malignancy", "in", "males.", "The", "American", "Cancer", "Society", "estimates", "that", "in", "the", "year", "2006,", "a", "total", "of", "234", "460", "men", "will", "be", "diagnosed", "with", "prostate", "cancer", "and", "27", "350", "will", "die", "of", "this", "disease", "(Jemal", "et", "al", "2006).", "At", "the", "start", "of", "the", "year", "2003,", "nearly", "2", "million", "American", "men", "were", "living", "with", "prostate", "cancer.", "Most", "commonly", "a", "disease", "of", "elderly", "men,", "the", "average", "age", "at", "diagnosis", "is", "68", "and", "27.3%", "of", "all", "new", "diagnoses", "are", "in", "men", "75", "years", "of", "age", "or", "older", "(Ries", "et", "al", "2006).", "The", "characteristics", "of", "prostate", "cancer", "have", "changed", "dramatically", "since", "the", "introduction", "of", "prostate-specific", "antigen", "(PSA)-based", "screening", "in", "1986.", "PSA", "screening", "has", "led", "to", "a", "drastic", "increase", "in", "the", "detection", "rate", "of", "prostate", "cancer", "along", "with", "an", "associated", "downward", "stage", "migration.", "While", "there", "are", "no", "prospective,", "randomized", "studies", "that", "prove", "earlier", "detection", "of", "prostate", "cancer", "leads", "to", "decreased", "mortality,", "the", "reality", "is", "that", "widespread", "PSA-based", "screening", "for", "prostate", "cancer", "has", "continued.", "Taking", "into", "consideration", "that", "many", "tumors", "currently", "detected", "may", "be", "of", "an", "indolent", "nature,", "a", "current", "challenge", "is", "identifying", "the", "patient", "who", "may", "benefit", "from", "treatment", "for", "whom", "side", "effects", "of", "treatment", "may", "be", "acceptable.", "The", "high", "prevalence", "and", "considerably", "lower", "mortality", "of", "prostate", "cancer,", "coupled", "with", "the", "significant", "potential", "morbidity", "of", "therapy", "for", "prostate", "cancer,", "have", "sparked", "much", "interest", "in", "alternative", "approaches", "against", "prostate", "cancer", "such", "as", "prevention", "(Thompson", "et", "al", "2003),", "minimally", "invasive", "surgical", "therapies", "(Ahmed", "et", "al", "2005;", "Tooher", "et", "al", "2006)", "and", "active", "surveillance", "strategies", "(Carter", "et", "al", "2002).", "Well", "designed", "randomized", "clinical", "trials", "addressing", "questions", "in", "these", "areas", "will", "hopefully", "lead", "to", "more", "efficacious", "and", "appropriate", "treatment", "of", "prostate", "cancer", "with", "lower", "disease", "specific", "mortality,", "while", "minimizing", "treatment", "related", "morbidity.", "Medical", "therapy", "Clinical", "Interventions", "in", "Aging", "2006:1(4)", "425–431", "©", "2006", "Dove", "Medical", "Press", "Limited.", "All", "rights", "reserved", "425" ]

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[ "Rudwaleit", "et", "al.", "Arthritis", "Research", "&", "Therapy", "2010,", "12:R117", "http://arthritis-research.com/content/12/3/R117", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "REefsefaercch", "taritvicleeness", "and", "safety", "of", "adalimumab", "in", "patients", "with", "ankylosing", "spondylitis", "or", "psoriatic", "arthritis", "and", "history", "of", "anti-tumor", "necrosis", "factor", "therapy", "Martin", "Rudwaleit*1,", "Filip", "Van", "den", "Bosch2,", "Martina", "Kron3,", "Sonja", "Kary3", "and", "Hartmut", "Kupper3", "Abstract", "Introduction:", "Tumor", "necrosis", "factor", "(TNF)", "antagonists", "reduce", "the", "signs", "and", "symptoms", "of", "spondyloarthritides,", "including", "ankylosing", "spondylitis", "(AS)", "and", "psoriatic", "arthritis", "(PsA).", "Our", "objective", "was", "to", "evaluate", "the", "effectiveness", "and", "safety", "of", "adalimumab,", "40", "mg", "every", "other", "week,", "for", "patients", "with", "AS", "or", "PsA", "and", "prior", "treatment", "with", "infliximab", "(IFX)", "and/or", "etanercept", "(ETN).", "Methods:", "Both", "trials", "were", "12-week,", "open-label", "studies", "with", "an", "optional", "extension", "period", "up", "to", "week", "20.", "Patients", "were", "stratified", "by", "history", "of", "anti-TNF", "treatment,", "prior", "anti-TNF", "therapy", "received", "(IFX,", "ETN,", "or", "both),", "and", "reason", "for", "discontinuation", "of", "prior", "TNF", "antagonist.", "ETN", "was", "discontinued", "≥", "3", "weeks,", "and", "IFX", "was", "discontinued", "≥", "2", "months", "before", "the", "first", "adalimumab", "administration.", "Effectiveness", "at", "week", "12", "was", "evaluated", "by", "using", "observed", "standard-outcome", "measurements", "for", "AS", "and", "PsA.", "Results:", "At", "week", "12", "of", "adalimumab", "treatment,", "Bath", "Ankylosing", "Spondylitis", "Disease", "Activity", "Index", "50", "responses", "were", "achieved", "by", "40.8%", "of", "326", "patients", "with", "AS", "who", "had", "received", "prior", "anti-TNF", "therapy", "and", "by", "63.0%", "of", "924", "patients", "with", "AS", "who", "were", "naive", "to", "TNF", "antagonist.", "Observed", "response", "rates", "were", "generally", "greater", "for", "patients", "who", "discontinued", "the", "prior", "anti-TNF", "therapy", "because", "of", "loss", "of", "response", "or", "intolerance", "than", "for", "patients", "who", "discontinued", "because", "of", "lack", "of", "response.", "Median", "changes", "in", "swollen-joint", "count", "and", "in", "enthesitis", "score", "were", "similar", "in", "patients", "with", "and", "without", "prior", "TNF-antagonist", "treatment.", "Modified", "PsA", "response", "criteria", "were", "fulfilled", "by", "71.2%", "of", "66", "patients", "with", "PsA,", "with", "prior", "exposure", "to", "TNF", "antagonists,", "and", "by", "78.8%", "of", "376", "patients", "with", "no", "history", "of", "anti-TNF", "therapy.", "The", "percentages", "of", "patients", "with", "PsA", "attaining", "a", "Physician's", "Global", "Assessment", "of", "psoriasis", "of", "\"Clear/Almost", "clear\"", "increased", "from", "33.3%", "to", "61.0%", "for", "patients", "with", "prior", "IFX", "and/or", "ETN", "treatment", "and", "from", "34.6%", "to", "69.7%", "for", "patients", "without", "anti-TNF", "therapy.", "The", "median", "change", "in", "the", "Nail", "Psoriasis", "Severity", "Index", "was", "-6", "for", "both", "groups.", "In", "both", "studies,", "patterns", "of", "adverse", "events", "were", "similar", "for", "patients", "with", "and", "without", "prior", "anti-TNF", "therapy", "and", "were", "consistent", "with", "the", "known", "safety", "profile", "of", "adalimumab.", "Conclusions:", "Patients", "with", "AS", "or", "PsA", "previously", "treated", "with", "IFX", "and/or", "ETN", "experienced", "clinically", "relevant", "improvements", "of", "their", "diseases", "after", "12", "weeks", "of", "adalimumab.", "Trial", "registrations:", "ClinicalTrials.gov", "NCT00478660", "and", "NCT00235885.", "Introduction", "Agents", "that", "target", "tumor", "necrosis", "factor", "(TNF)", "are", "highly", "effective", "in", "treating", "patients", "with", "active", "rheumatic", "disor-", "ders,", "such", "as", "rheumatoid", "arthritis", "(RA),", "ankylosing", "spon-", "dylitis", "(AS),", "or", "psoriatic", "arthritis", "(PsA)", "[1].", "Nevertheless,", "*", "Correspondence:", "publications@jkmed.com", "1", "Medical", "Department", "I,", "Rheumatology,", "Charité,", "Campus", "Benjamin", "Franklin", "Hospital,", "Hindenburgdamm", "30,", "12200", "Berlin,", "Germany", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "patients", "may", "not", "respond", "optimally", "to", "or", "may", "be", "intoler-", "ant", "of", "treatment", "with", "a", "given", "TNF", "antagonist.", "A", "practical", "question", "faced", "by", "clinicians", "and", "patients", "is", "whether", "switching", "to", "another", "TNF", "antagonist", "is", "likely", "to", "result", "in", "an", "improved", "therapeutic", "response.", "Treatment", "with", "a", "second", "or", "third", "TNF", "antagonist", "has", "been", "shown", "to", "be", "successful", "and", "well", "tolerated", "in", "a", "sub-", "stantial", "percentage", "of", "patients", "with", "RA,", "regardless", "of", "the", "order", "of", "subsequent", "therapies", "(etanercept", "(ETN),", "inflix-", "©", "2010", "Rudwaleit", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Chen", "et", "al.", "BMC", "Microbiology", "2010,", "10:198", "http://www.biomedcentral.com/1471-2180/10/198", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Chromosomal", "instability", "in", "Streptomyces", "avermitilis:", "major", "deletion", "in", "the", "central", "region", "and", "stable", "circularized", "chromosome", "Wei", "Chen,", "Fei", "He,", "Xiaojuan", "Zhang,", "Zhi", "Chen,", "Ying", "Wen*,", "Jilun", "Li", "Abstract", "Background:", "The", "chromosome", "of", "Streptomyces", "has", "been", "shown", "to", "be", "unstable,", "frequently", "undergoing", "gross", "chromosomal", "rearrangements.", "However,", "the", "mechanisms", "underlying", "this", "phenomenon", "remain", "unclear,", "with", "previous", "studies", "focused", "on", "two", "chromosomal", "ends", "as", "targets", "for", "rearrangements.", "Here", "we", "investigated", "chromosomal", "instability", "of", "Streptomyces", "avermitilis,", "an", "important", "producer", "of", "avermectins,", "and", "characterized", "four", "gross", "chromosomal", "rearrangement", "events,", "including", "a", "major", "deletion", "in", "the", "central", "region.", "The", "present", "findings", "provide", "a", "valuable", "contribution", "to", "the", "mechanistic", "study", "of", "genetic", "instability", "in", "Streptomyces.", "Results:", "Thirty", "randomly-selected", "“bald”", "mutants", "derived", "from", "the", "wild-type", "strain", "all", "contained", "gross", "chromosomal", "rearrangements", "of", "various", "types.", "One", "of", "the", "bald", "mutants,", "SA1-8,", "had", "the", "same", "linear", "chromosomal", "structure", "as", "the", "high", "avermectin-producing", "mutant", "76-9.", "Chromosomes", "of", "both", "strains", "displayed", "at", "least", "three", "independent", "chromosomal", "rearrangements,", "including", "chromosomal", "arm", "replacement", "to", "form", "new", "88-kb", "terminal", "inverted", "repeats", "(TIRs),", "and", "two", "major", "deletions.", "One", "of", "the", "deletions", "eliminated", "the", "36-kb", "central", "region", "of", "the", "chromosome,", "but", "surprisingly", "did", "not", "affect", "viability", "of", "the", "cells.", "The", "other", "deletion", "(74-kb)", "was", "internal", "to", "the", "right", "chromosomal", "arm.", "The", "chromosome", "of", "another", "bald", "mutant,", "SA1-6,", "was", "circularized", "with", "deletions", "at", "both", "ends.", "No", "obvious", "homology", "was", "found", "in", "all", "fusion", "sequences.", "Generational", "stability", "analysis", "showed", "that", "the", "chromosomal", "structure", "of", "SA1-8", "and", "SA1-6", "was", "stable.", "Conclusions:", "Various", "chromosomal", "rearrangements,", "including", "chromosomal", "arm", "replacement,", "interstitial", "deletions", "and", "chromosomal", "circularization,", "occurred", "in", "S.", "avermitilis", "by", "non-homologous", "recombination.", "The", "finding", "of", "an", "inner", "deletion", "involving", "in", "the", "central", "region", "of", "S.", "avermitilis", "chromosome", "suggests", "that", "the", "entire", "Streptomyces", "chromosome", "may", "be", "the", "target", "for", "rearrangements,", "which", "are", "not", "limited,", "as", "previously", "reported,", "to", "the", "two", "chromosomal", "ends.", "Background", "Streptomyces", "are", "a", "genus", "of", "Gram-positive,", "filamentous", "soil", "bacteria,", "which", "display", "complex", "morphological", "differ-", "entiation", "and", "produce", "a", "broad", "range", "of", "bioactive", "second-", "ary", "metabolites", "such", "as", "antibiotics,", "immunosuppressants", "and", "cholesterol-lowering", "agents.", "These", "bacteria", "thus", "pro-", "vide", "an", "important", "natural", "source", "of", "commercial", "products", "for", "the", "pharmaceutical", "and", "agricultural", "industries", "[1].", "The", "Streptomyces", "genome", "consists", "of", "an", "8-", "to", "9-Mb", "linear", "chromosome,", "characterized", "by", "terminal", "inverted", "repeats", "(TIRs)", "and", "a", "protein", "covalently", "attached", "to", "5’", "end", "[2-4].", "*", "Correspondence:", "wen@cau.edu.cn", "State", "Key", "Laboratories", "for", "Agro-biotechnology,", "College", "of", "Biological", "Sciences,", "China", "Agricultural", "University,", "Beijing", "100193,", "PR", "China", "This", "chromosome", "is", "inherently", "unstable,", "and", "frequently", "undergoes", "gross", "chromosomal", "rearrangements", "sponta-", "neously", "as", "well", "as", "under", "various", "mutagenic", "treatments", "[5,6],", "particularly", "in", "terminal", "regions", "where", "almost", "no", "essential", "genes", "reside.", "Gross", "chromosomal", "rearrangements", "include", "deletion,", "amplification,", "arm", "replacement,", "and", "cir-", "cularization", "[7-16].", "This", "chromosomal", "instability", "leads", "to", "genetic", "instability,", "which", "is", "ubiquitous", "among", "Strepto-", "myces,", "and", "affects", "nearly", "all", "life", "functions,", "e.g.,", "differentia-", "tion,", "secondary", "metabolism,", "and", "response", "to", "environmental", "changes", "[5].", "The", "chromosomal", "instability", "is", "not", "attributable", "to", "the", "linear", "chromosomal", "structure,", "since", "some", "mutants", "with", "circular", "chromosomes", "display", "even", "higher", "frequency", "of", "genetic", "instability", "[7,17,18].", "©", "2010", "Chen", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Bioinformation", "www.bioinformation.net", "by", "Biomedical", "Informatics", "Publishing", "Group", "open", "access", "Hypothesis", "Specific", "gene", "hypomethylation", "and", "cancer:", "New", "insights", "into", "coding", "region", "feature", "trends", "Elias", "Daura-Oller,", "Maria", "Cabre,", "Miguel", "A.", "Montero,", "Jose", "L.", "Paternain,", "Antoni", "Romeu*", "Biochemistry", "and", "Biotechnology", "Department,", "Faculty", "of", "Chemistry,", "Rovira", "i", "Virgili,", "University", "(URV),", "c/", "Marcel·li", "Domingo,", "s/n.", "Campus", "Sescelades,", "43007", "Tarragona,", "Spain,", "Antoni", "Romeu", "-", "E-mail:", "antoni.romeu@urv.cat;", "Phone:", "34977558188;", "Fax:", "34977558232;", "*Corresponding", "author", "received", "December", "02,", "2008;", "accepted", "January", "12,", "2009;", "published", "April", "21,", "2009", "Abstract:", "Giving", "coding", "region", "structural", "features", "a", "role", "in", "the", "hypomethylation", "of", "specific", "genes,", "the", "occurrence", "of", "G+C", "content,", "CpG", "islands,", "repeat", "and", "retrotransposable", "elements", "in", "demethylated", "genes", "related", "to", "cancer", "has", "been", "evaluated.", "A", "comparative", "analysis", "among", "different", "cancer", "types", "has", "also", "been", "performed.", "In", "this", "work,", "the", "inter-cancer", "coding", "region", "features", "comparative", "analysis", "carried", "out,", "show", "insights", "into", "what", "structural", "trends/patterns", "are", "present", "in", "the", "studied", "cancers.", "Keywords:", "epigenetics;", "cancer;", "CpG", "islands;", "hypomethylation", "Background:", "Alterations", "of", "DNA", "methylation", "have", "been", "recognized", "as", "an", "important", "component", "of", "cancer", "development", "[1].", "Hypomethylation", "generally", "arises", "earlier", "and", "is", "linked", "to", "chromosomal", "instability", "and", "loss", "of", "imprinting", "[2-6],", "whereas", "hypermethylation", "is", "associated", "with", "promoters", "and", "can", "arise", "secondary", "to", "gene", "silencing", "[7-9],", "but", "might", "be", "a", "target", "for", "epigenetic", "therapy", "[10].", "It", "is", "not", "currently", "known", "why", "certain", "CpG", "islands", "are", "hypermethylated", "or", "hyphometylated", "in", "specific", "cancers", "but", "not", "in", "others", "[1].", "Some", "of", "these", "events", "have", "been", "observed", "in", "vitro", "and", "using", "in", "vivo", "animal", "models", "[2-4,", "11,", "12]", "but", "their", "relative", "importance", "in", "human", "disease", "is", "not", "understood.", "Recent", "studies", "suggest", "that", "some", "methylation", "patterns", "are", "discernible", "in", "risk", "groups", "and", "certain", "diseases.", "Indications", "are", "that", "the", "hypomethylation", "of", "specific", "DNA", "repeat", "elements", "or", "genes", "can", "be", "disease-specific", "[13].", "These", "repeat", "sequences", "may", "be", "transposable", "elements", "found", "interspersed", "throughout", "the", "genome,", "or", "large", "repeat", "sequences", "and", "simple", "repeat", "ones,", "such", "as", "DNA", "satellites,", "that", "are", "found", "commonly", "in", "heterochromatin.", "Hypomethylation", "of", "satellites", "and", "retroelements", "together", "should", "account", "for", "the", "greater", "part", "of", "the", "decrease", "in", "methyl-cytosine", "content", "in", "cancer", "cells.", "Decreased", "methylation", "of", "single-copy", "genes", "does", "not", "contribute", "significantly", "to", "the", "decrease", "in", "quantity,", "but", "whether", "hypomethylation", "may", "lead", "to", "the", "reactivation", "of", "genes", "silenced", "in", "normal", "cells", "is", "an", "important", "issue.", "The", "site", "reported", "to", "be", "hypomethylated", "in", "several", "human", "cancers", "is", "located", "within", "the", "coding", "region.", "It", "may", "become", "demethylated", "in", "cancers", "as", "a", "consequence", "of", "global", "hypomethylation", "or", "may", "reflect", "increased", "transcriptional", "activity", "[14,", "15,", "16].", "The", "relationship", "between", "hypomethylation", "of", "specific", "genes", "and", "repeat", "elements", "within", "the", "genome", "may", "serve", "as", "useful", "diagnostic", "indicators", "for", "disease", "[13].", "Nowadays,", "more", "information", "is", "required", "with", "regard", "to", "what", "repeat", "elements", "are", "specific", "to", "what", "diseases", "and", "whether", "this", "information", "can", "be", "used", "to", "predict", "disease", "onset", "or", "progression.", "Thus,", "the", "occurrence", "of", "G+C", "content,", "CpG", "islands,", "repeat", "and", "retrotransposable", "elements", "in", "demethylated", "genes", "related", "to", "cancer", "has", "been", "evaluated", "in", "this", "work.", "Moreover,", "a", "comparative", "analysis", "among", "different", "cancer", "types", "has", "also", "been", "performed", "in", "ISSN", "0973-2063", "(online)", "0973-8894", "(print)", "Bioinformation", "3(8):", "340-343", "(2009)", "340", "order", "to", "elucidate", "what", "structural", "trends/patterns", "are", "present", "in", "the", "studied", "cancers.", "Methodology:", "All", "selected", "genes", "were", "compiled", "from", "the", "recent", "literature", "(see", "Table", "1", "in", "supplementary", "material)", "and", "were", "collected", "from", "the", "NCBI", "nucleotide", "database", "[21].", "The", "sequence", "characteristics", "of", "the", "coding", "regions", "of", "each", "gene", "were", "examined", "in", "the", "analysis.", "For", "CpG", "dinucleotide", "analysis,", "we", "used", "the", "NEWCPGREPORT", "program", "[17],", "and", "the", "total", "number", "of", "CpG", "islands", "was", "counted.", "For", "the", "repeat", "element", "analysis,", "the", "Repeat", "Masker", "program", "[18]", "was", "used", "and", "for", "tandem", "repeat", "analysis,", "the", "ETANDEM", "program", "[19]", "was", "used.", "All", "classes", "of", "repeat", "elements", "output", "from", "Repeat-Masker", "were", "collected.", "We", "used", "ETANDEM", "to", "obtain", "numbers", "of", "tandem", "repeat", "elements", "ranging", "from", "5", "bp", "to", "100", "bp.", "All", "the", "statistical", "calculations", "were", "performed", "using", "the", "Minitab", "software", "[20].", "Discussion:", "Firstly,", "a", "list", "of", "genes", "that", "are", "demethylated", "in", "cancer", "according", "to", "the", "recent", "existing", "literature", "was", "compiled", "(Table", "1", "in", "supplementary", "material).", "We", "observed", "that", "these", "genes", "are", "related", "with", "7", "different", "cancer", "types:", "breast,", "colon,", "lung,", "ovarian,", "pancreatic,", "prostate", "and", "testicular.", "As", "it", "can", "be", "seen", "in", "Table", "1,", "the", "ranges", "of", "genes", "affected", "by", "hypomethylation", "includes", "growth", "regulatory", "genes,", "enzymes,", "developmentally", "critical", "genes", "and", "tissue", "specific", "genes", "such", "as", "germ", "cell-specific", "tumour", "antigen", "genes,", "etc.", "Then,", "we", "selected", "6", "representative", "structural", "descriptors", "(variables)", "for", "the", "structural", "study:", "GC", "content,", "CpG", "islands,", "Simple", "Repeats", "(SR),", "Low", "Complexity", "(LC),", "Large", "Tandem", "Repeats", "(LTR)", "and", "SINE", "Alu.", "The", "[bp]%", "sequence", "characteristics", "of", "these", "descriptors", "were", "calculated", "for", "all", "gene", "coding", "regions.", "As", "it", "has", "stated", "before,", "the", "site", "reported", "to", "be", "hypomethylated", "in", "several", "human", "cancers", "is", "located", "within", "the", "coding", "region", "[13,", "15].", "For", "this", "reason,", "the", "structural", "information", "related", "with", "this", "region", "could", "be", "very", "useful", "in", "order", "to", "develop", "a", "first", "stage", "approximation.", 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[ "REVIEW", "ARTICLE", "published:", "02", "November", "2012", "doi:", "10.3389/fneur.2012.00144", "Biomarkers", "of", "hypoxic-ischemic", "encephalopathy", "in", "newborns", "Martha", "Douglas-Escobar", "1,2*", "and", "Michael", "D.", "Weiss", "1,2", "1", "Department", "of", "Pediatrics,", "University", "of", "Florida,", "Gainesville,", "FL,", "USA", "2", "McKnight", "Brain", "Institute,", "University", "of", "Florida,", "Gainesville,", "FL,", "USA", "Edited", "by:", "Stefania", "Mondello,", "University", "of", "Florida,", "USA", "Reviewed", "by:", "V.", "Wee", "Yong,", "University", "of", "Calgary,", "Canada", "Wolfgang", "J.", "Streit,", "University", "of", "Florida,", "USA", "*Correspondence:", "Martha", "Douglas-Escobar", ",", "Department", "of", "Pediatrics,", "University", "of", "Florida,", "PO", "Box", "100296,", "Gainesville,", "FL", "32610-0296,", "USA.", "e-mail:", "marthave@ufl.edu", "As", "neonatal", "intensive", "care", "has", "evolved,", "the", "focus", "has", "shifted", "from", "improving", "mortality", "alone", "to", "an", "effort", "to", "improve", "both", "mortality", "and", "morbidity.", "The", "most", "frequent", "source", "of", "neonatal", "brain", "injury", "occurs", "as", "a", "result", "of", "hypoxic-ischemic", "injury.", "Hypoxic-ischemic", "injury", "occurs", "in", "about", "2", "of", "1,000", "full-term", "infants", "and", "severe", "injured", "infants", "will", "have", "lifetime", "disabilities", "and", "neurodevelopmental", "delays.", "Most", "recently,", "remarkable", "efforts", "toward", "neu-", "roprotection", "have", "been", "started", "with", "the", "advent", "of", "therapeutic", "hypothermia", "and", "a", "key", "step", "in", "the", "evolution", "of", "neonatal", "neuroprotection", "is", "the", "discovery", "of", "biomarkers", "that", "enable", "the", "clinician-scientist", "to", "screen", "infants", "for", "brain", "injury,", "monitor", "progression", "of", "disease,", "identify", "injured", "brain", "regions,", "and", "assess", "efficacy", "of", "neuroprotective", "clinical", "trials.", "Lastly,", "biomark-", "ers", "offer", "great", "hope", "identifying", "when", "an", "injury", "occurred", "shedding", "light", "on", "the", "potential", "pathophysiology", "and", "the", "most", "effective", "therapy.", "In", "this", "article,", "we", "will", "review", "biomarkers", "of", "HIE", "including", "S100B,", "neuron", "specific", "enolase,", "umbilical", "cord", "IL-6,", "CK-BB,", "GFAP,", "myelin", "basic", "protein,", "UCHL-1,", "and", "pNF-H.", "We", "hope", "to", "contribute", "to", "the", "awareness,", "validation,", "and", "clinical", "use", "of", "established", "as", "well", "as", "novel", "neonatal", "brain", "injury", "biomarkers.", "Keywords:", "biomarkers,", "hypoxic-ischemic", "encephalopathy,", "brain", "injury", "INTRODUCTION", "Biomarkers", "are", "molecules", "released", "by", "or", "specific", "to", "a", "particular", "organ,", "can", "give", "a", "glimpse", "into", "the", "physiologic", "or", "pathologic", "status", "of", "that", "specific", "organ", "(Ling", "and", "Sylvester,", "2011).", "Biomarkers", "can", "be", "obtained", "from", "the", "blood,", "urine,", "cerebrospinal", "fluid", "(CSF),", "or", "any", "other", "bodily", "fluid.", "In", "neonates", "with", "brain", "injury,", "biomarkers", "may", "be", "able", "to", "predict", "the", "degree", "and", "location", "of", "injury", "shortly", "after", "the", "injury", "occurs.", "The", "discovery", "of", "neonatal", "brain", "injury", "biomarkers", "is", "a", "key", "step", "in", "neonatal", "neuroprotection.", "Biomarkers", "may", "enable", "the", "clinician-scientist", "to", "screen", "infants", "for", "brain", "injury,", "monitor", "the", "progression", "of", "disease,", "identify", "injured", "brain", "regions,", "and", "assess", "the", "efficacy", "of", "neuroprotective", "strategies", "procedures", "in", "clinical", "trials.", "In", "addition,", "large-scale", "validation", "of", "the", "poten-", "tial", "biomarkers", "is", "required,", "because", "the", "potential", "confounders", "(especially", "for", "biomarkers", "that", "are", "non-organ", "specific", "such", "as", "inflammatory", "mediators).", "Currently,", "clinicians", "do", "not", "routinely", "use", "biomarkers", "to", "care", "for", "neonates", "with", "brain", "injuries.", "This", "review", "will", "examine", "potential", "biomarkers", "the", "bedside", "clinician-scientist", "may", "use", "to", "hone", "the", "treatment", "of", "neonates", "with", "hypoxic-ischemic", "encephalopathy.", "HYPOXIC-ISCHEMIC", "ENCEPHALOPATHY", "Systemic", "asphyxia", "manifests", "in", "the", "brain", "as", "hypoxic-ischemic", "encephalopathy", "(HIE;", "Vannucci,", "1997).", "Systemic", "asphyxia", "occurs", "Abbreviations:", "aEEG,", "amplitude", "integrated", "electroencephalogram;", "BDNF,", "brain", "derived", "neurotrophic", "factor;", "CPK-BB,", "brain", "type", "creatine", "phosphokinase;", "CSF,", "cerebrospinal", "fluid;", "GFAP,", "glial", "fibrillary", "acidic", "protein;", "HIE,", "hypoxic-ischemic", "encephalopathy;", "IL-6,", "interleukin-6;", "NSE,", "neuron", "specific", "enolase;", "UCHL-1,", "ubiquitin", "carboxyl-terminal", "hydrolase", "L1.", "in", "about", "2%", "of", "full-term", "infants", "and", "in", "nearly", "60%", "of", "very", "low", "birth", "weight", "(premature)", "newborns", "(Mulligan", "et", "al.,", "1980;", "Gif-", "fard", "et", "al.,", "1990;", "Low", "et", "al.,", "1997).", "Twenty", "to", "fifty", "percent", "of", "asphyxiated", "babies", "who", "exhibit", "severe", "HIE", "die", "during", "the", "new-", "born", "period", "(MacDonald", "et", "al.,", "1980).", "Of", "the", "survivors", "of", "severe", "HIE,", "up", "to", "25%", "have", "permanent", "neuropsychological", "handicaps", "in", "the", "form", "of", "learning", "disabilities,", "epilepsy,", "cerebral", "palsy,", "with", "or", "without", "associated", "mental", "retardation,", "learning", "disabilities,", "or", "epilepsy", "(Finer", "et", "al.,", "1981;", "Robertson", "et", "al.,", "1989).", "Systemic", "asphyxia", "that", "causes", "HIE", "may", "occur", "prior", "to", "delivery", "(e.g.,", "placen-", "tal", "abruption,", "toxemia,", "maternal", "collagen", "vascular", "disease),", "during", "delivery", "(e.g.,", "prolonged", "labor,", "difficult", "delivery,", "abnormal", "presen-", "tation),", "or", "after", "delivery", "(e.g.,", "sepsis,", "shock,", "respiratory", "distress).", "Currently,", "hypoxic-ischemic", "injury", "is", "diagnosed", "based", "on", "clinical", "criteria.", "This", "review", "will", "use", "the", "term", "HIE", "although", "recently", "med-", "ical", "experts", "have", "proposed", "use", "the", "term", "neonatal", "encephalopathy", "instead", "of", "HIE.", "A", "clinician’s", "ability", "to", "predict", "the", "outcome", "of", "neonates", "with", "HIE", "is", "not", "straightforward.", "The", "Sarnat", "grading", "system", "(Sarnat", "and", "Sarnat,", "1976)", "stages", "HIE", "based", "on", "clinical", "criteria.", "This", "scoring", "system", "divides", "neonates", "into", "mild,", "moderate,", "or", "severe", "categories,", "and", "measures", "the", "progression", "of", "the", "neurologic", "insult", "to", "predict", "a", "neonate’s", "prognosis", "(Finer", "et", "al.,", "1981).", "Nevertheless,", "the", "Sarnat", "score", "system", "is", "subjective", "and", "changes", "over", "time.", "A", "new", "bedside", "tool,", "amplitude", "integrated", "electroencephalogram", "(aEEG),", "may", "help", "stage", "the", "severity", "of", "injury", "and", "predict", "prognosis", "(Hellstrom-", "Westas", "et", "al.,", "1995).", "Unfortunately,", "the", "Sarnat", "score", "and", "aEEG", "are", "not", "as", "effective", "in", "predicting", "outcomes", "in", "neonates", "during", "hypothermia", "(Thoresen", "et", "al.,", "2010)", "and", "do", "not", "provide", "informa-", "tion", "about", "the", "timing", "of", "the", "injury.", "Brain", "MRI", "can", "help", "determine", "www.frontiersin.org", "November", "2012", "|", "Volume", "3", "|", "Article", "144", "|", "1" ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Journal", "of", "Aging", "Research", "Volume", "2011,", "Article", "ID", "138015,", "10", "pages", "doi:10.4061/2011/138015", "Research", "Article", "Body", "Mass", "Index", "Is", "Associated", "with", "Dietary", "Patterns", "and", "Health", "Conditions", "in", "Georgia", "Centenarians", "Dorothy", "B.", "Hausman,1", "Mary", "Ann", "Johnson,1", "Adam", "Davey,2", "and", "Leonard", "W.", "Poon3", "1", "Department", "of", "Foods", "and", "Nutrition,", "University", "of", "Georgia,", "280", "Dawson", "Hall,", "Athens,", "GA", "30602,", "USA", "2", "Department", "of", "Public", "Health,", "Temple", "University,", "Philadelphia,", "PA", "19122,", "USA", "3", "Institute", "of", "Gerontology,", "University", "of", "Georgia,", "Athens,", "GA", "30602,", "USA", "Correspondence", "should", "be", "addressed", "to", "Dorothy", "B.", "Hausman,", "dhausman@uga.edu", "Received", "2", "March", "2011;", "Accepted", "4", "April", "2011", "Academic", "Editor:", "Bo", "A.", "Hagberg", "Copyright", "©", "2011", "Dorothy", "B.", "Hausman", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Associations", "between", "body", "mass", "index", "(BMI)", "and", "dietary", "patterns", "and", "health", "conditions", "were", "explored", "in", "a", "population-based", "multiethnic", "sample", "of", "centenarians", "from", "northern", "Georgia.", "BMI", "≤20", "and", "≥25", "was", "prevalent", "in", "30.9%", "and", "25.3%", "of", "study", "participants,", "respectively.", "In", "a", "series", "of", "logistic", "regression", "analyses", "controlled", "for", "gender", "and", "place", "of", "residence,", "the", "probability", "of", "having", "BMI", "≥25", "was", "increased", "by", "being", "black", "versus", "white", "and", "having", "a", "low", "citrus", "fruit,", "noncitrus", "fruit,", "orange/yellow", "vegetable", "or", "total", "fruit", "and", "vegetable", "intake.", "The", "probability", "of", "having", "BMI", "≤20", "was", "not", "associated", "with", "dietary", "intake.", "When", "controlled", "for", "race,", "gender,", "residence,", "and", "total", "fruit", "and", "vegetable", "intake,", "BMI", "≥25", "was", "an", "independent", "risk", "factor", "for", "diabetes", "or", "having", "a", "systolic", "blood", "pressure", "≥140", "mmHg", "or", "diastolic", "blood", "pressure", "≥90", "mmHg,", "whereas", "BMI", "≤20", "was", "a", "risk", "factor", "for", "anemia.", "Given", "the", "many", "potential", "adverse", "consequences", "of", "under-", "and", "overweight,", "efforts", "are", "needed", "to", "maintain", "a", "healthy", "weight,", "even", "in", "the", "oldest", "old.", "1.", "Introduction", "Body", "mass", "index", "is", "a", "simple", "index", "of", "weight", "for", "height", "that", "is", "frequently", "used", "in", "the", "assessment", "of", "nutritional", "status.", "A", "low", "BMI,", "or", "underweight", "status,", "is", "often", "associated", "with", "an", "increased", "risk", "of", "mortality", "in", "seriously", "ill", "or", "hospitalized", "older", "adults", "[1,", "2].", "Conversely,", "a", "high", "BMI,", "indicative", "of", "overweight", "or", "obesity,", "is", "associated", "with", "an", "exacerbation", "in", "age-related", "physical", "and", "cognitive", "decline", "[3,", "4]", "and", "with", "an", "increased", "prevalence", "or", "risk", "of", "many", "chronic", "health", "conditions", "common", "in", "older", "adults", "such", "as", "diabetes,", "hypertension,", "and", "cardiovascular", "disease", "[3–5].", "Such", "asso-", "ciations", "are", "typically", "determined", "across", "the", "entire", "spectrum", "of", "older", "adults", "(aged", "60+),", "with", "no", "further", "demarcation", "within", "this", "age", "classification.", "Our", "finding", "of", "a", "much", "higher", "prevalence", "of", "several", "nutritional", "deficiencies", "in", "centenarians", "as", "compared", "with", "octogenarians", "[6,", "7],", "suggests", "that", "there", "is", "considerable", "heterogeneity", "in", "nutrient", "status", "in", "the", "“older", "adult”", "age", "group.", "Likewise,", "there", "may", "also", "be", "considerable", "heterogeneity", "within", "the", "older", "adult", "age", "group", "with", "regard", "to", "chronic", "health", "conditions.", "Thus,", "it", "is", "not", "known", "whether", "the", "associations", "between", "underweight", "or", "overweight/obesity", "and", "chronic", "health", "conditions", "as", "observed", "in", "previous", "studies", "of", "older", "adults", "extend", "to", "the", "very", "old.", "Dietary", "intake", "patterns", "featuring", "a", "high", "intake", "of", "nutrient-dense", "foods", "such", "as", "cereals,", "fruits,", "vegetables,", "and", "low-fat", "meat", "and", "dairy", "products", "have", "been", "associated", "with", "a", "number", "of", "favorable", "health", "outcomes", "in", "adults", "including", "a", "decreased", "prevalence", "of", "obesity", "[8,", "9],", "lower", "rates", "of", "weight", "gain", "over", "time", "[10],", "and", "better", "quality", "of", "life", "and", "improved", "survival", "[11].", "In", "contrast,", "low-nutrient", "dense", "dietary", "patterns", "with", "high", "intakes", "of", "sweets,", "desserts,", "and", "high-fat", "dairy", "products", "have", "been", "associated", "with", "higher", "rates", "of", "obesity", "and", "poor", "nutritional", "status", "in", "older", "adults", "[9].", "Whether", "these", "observations", "extend", "to", "the", "very", "old", "is", "unknown.", "Studies", "comparing", "energy", "intakes", "and", "dietary", "intake", "patterns", "of", "centenarians", "to", "younger", "older", "adult", "cohorts", "have", "generally", "observed", "lower", "energy", "and/or", "fat", "intake", "in", "the", "centenarians,", "while", "dietary", "preferences", "of", "centenarians", "are", "considerably", "more", "varied", "and", "dependent", "of", "the", "region", "of", "study", "likely", "reflecting", "cultural", "patterns", "and", "cohort", "differences", "rather", "than", "longevity-related", "differences" ]

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[ "Zheng", "et", "al.", "Journal", "of", "Hematology", "&", "Oncology", "2011,", "4:21", "http://www.jhoonline.org/content/4/1/21", "S", "H", "O", "R", "T", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "HEMATOLOGY", "&", "ONCOLOGY", "Open", "Access", "Expression", "and", "distribution", "of", "PPP2R5C", "gene", "in", "leukemia", "Haitao", "Zheng1†,", "Yu", "Chen1,2†,", "Shaohua", "Chen1,", "Yuzhe", "Niu1,2,", "Lijian", "Yang1,", "Bo", "Li1,", "Yuhong", "Lu1,", "Suxia", "Geng3,", "Xin", "Du3", "and", "Yangqiu", "Li1,2*", "Abstract", "Background:", "Recently,", "we", "clarified", "at", "the", "molecular", "level", "novel", "chromosomal", "translocation", "t(14;14)(q11;q32)", "in", "a", "case", "of", "Sézary", "syndrome,", "which", "caused", "a", "rearrangement", "from", "TRAJ7", "to", "the", "PPP2R5C", "gene.", "PPP2R5C", "is", "one", "of", "the", "regulatory", "B", "subunits", "of", "protein", "phosphatase", "2A", "(PP2A).", "It", "plays", "a", "crucial", "role", "in", "cell", "proliferation,", "differentiation,", "and", "transformation.", "To", "characterize", "the", "expression", "and", "distribution", "of", "five", "different", "transcript", "variants", "of", "the", "PPP2R5C", "gene", "in", "leukemia,", "we", "analyzed", "the", "expression", "level", "of", "PPP2R5C", "in", "peripheral", "blood", "mononuclear", "cells", "from", "77", "patients", "with", "de", "novo", "leukemia,", "26", "patients", "with", "leukemia", "in", "complete", "remission", "(CR),", "and", "20", "healthy", "individuals", "by", "real-time", "PCR", "and", "identified", "the", "different", "variants", "of", "PPP2R5C", "by", "RT-PCR.", "Findings:", "Significantly", "higher", "expression", "of", "PPP2R5C", "was", "found", "in", "AML,", "CML,", "T-ALL,", "and", "B-CLL", "groups", "in", "comparison", "with", "healthy", "controls.", "High", "expression", "of", "PPP2R5C", "was", "detected", "in", "the", "B-ALL", "group;", "however,", "no", "significant", "difference", "was", "found", "compared", "with", "the", "healthy", "group.", "The", "expression", "level", "of", "PPP2R5C", "in", "the", "CML-CR", "group", "decreased", "significantly", "compared", "with", "that", "in", "the", "de", "novo", "CML", "group", "and", "was", "not", "significantly", "different", "from", "the", "level", "in", "the", "healthy", "group.", "By", "using", "different", "primer", "pairs", "that", "covered", "different", "exons,", "five", "transcript", "variants", "of", "PPP2R5C", "could", "be", "identified.", "All", "variants", "could", "be", "detected", "in", "healthy", "samples", "as", "well", "as", "in", "all", "the", "leukemia", "samples,", "and", "similar", "frequencies", "and", "distributions", "of", "PPP2R5C", "were", "indicated.", "Conclusions:", "Overexpression", "of", "PPP2R5C", "in", "T-cell", "malignancy", "as", "well", "as", "in", "myeloid", "leukemia", "cells", "might", "relate", "to", "its", "proliferation", "and", "differentiation.", "Investigation", "of", "the", "effect", "of", "target", "inhibition", "of", "this", "gene", "might", "be", "beneficial", "to", "further", "characterization", "of", "molecular", "mechanisms", "and", "targeted", "therapy", "in", "leukemia.", "Keywords:", "PPP2R5C", "leukemia,", "gene", "expression,", "transcript", "variant", "Background", "Molecular", "genetic", "aberrations", "could", "provide", "the", "basis", "for", "assays", "that", "can", "predict", "prognosis", "of", "individual", "patients", "as", "well", "as", "potential", "molecular", "targets", "for", "novel", "therapies", "[1-3].", "The", "process", "of", "malignant", "transformation", "in", "leukemia", "is", "complex,", "and", "many", "factors", "such", "as", "abnormal", "gene", "expression", "and", "mutation,", "chromosomal", "aberrations,", "deregulation", "of", "various", "cellular", "signaling", "pathways,", "and", "deregulation", "of", "epigenetic", "regulation", "are", "involved", "in", "the", "development", "of", "leukemia", "[1].", "Therefore,", "new", "data", "regarding", "molecular", "genetic", "aberrations", "in", "*", "Correspondence:", "yangqiuli@hotmail.com", "†", "Contributed", "equally", "1Institute", "of", "Hematology,", "Medical", "College,", "Jinan", "University,", "Guangzhou,", "P.R.", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "different", "types", "of", "leukemia", "are", "needed", "for", "further", "characterization.", "PPP2R5C", "is", "one", "of", "the", "regulatory", "B", "subunits", "of", "protein", "phosphatase", "2A", "(PP2A),", "which", "is", "a", "major", "cellu-", "lar", "serine/threonine", "phosphatase", "that", "affects", "the", "phos-", "phorylation", "status", "of", "many", "proteins", "[4].", "The", "PPP2R5C", "gene", "encodes", "five", "differentially", "spliced", "variants:", "B56g1,", "B56g2,", "B56g3,", "B56g5,", "and", "B56g6", "(Figure", "1),", "whereas", "B56g4", "is", "identified", "only", "in", "mice.", "The", "functional", "PPP2R5C", "gene", "locus", "resides", "at", "14q32.2,", "whereas", "a", "non-", "functional", "B56g1", "pseudogene", "PPP2R5C", "is", "present", "at", "3p21.3", "[4,5].", "PPP2R5C", "plays", "a", "crucial", "role", "in", "cell", "prolif-", "eration,", "differentiation,", "and", "transformation,", "based", "on", "its", "induction", "of", "dephosphorylation", "of", "P53", "at", "various", "resi-", "dues", "[6].", "It", "has", "been", "reported", "that", "the", "dynamic", "nuclear", "distribution", "of", "the", "B56g3", "regulatory", "subunit", "controls", "©", "2011", "Zheng", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "International", "Journal", "of", "Nephrology", "Volume", "2011,", "Article", "ID", "364890,", "5", "pages", "doi:10.4061/2011/364890", "Review", "Article", "Clinical", "Significance", "of", "FGF-23", "in", "Patients", "with", "CKD", "Domenico", "Russo", "and", "Yuri", "Battaglia", "Department", "of", "Nephrology,", "School", "of", "Medicine,", "University", "Federico", "II,", "Via", "Pansini", "5,", "80131", "Napoli,", "Italy", "Correspondence", "should", "be", "addressed", "to", "Domenico", "Russo,", "domenicorusso51@hotmail.com", "Received", "22", "December", "2010;", "Accepted", "24", "February", "2011", "Academic", "Editor:", "Angela", "Wang", "Copyright", "©", "2011", "D.", "Russo", "and", "Y.", "Battaglia.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "FGF23", "is", "a", "bone-derived", "hormone", "that", "plays", "an", "important", "role", "in", "the", "regulation", "of", "phosphate", "and", "1,25-dihydroxy", "vitamin", "D", "metabolism.", "FGF23", "principally", "acts", "in", "the", "kidney", "to", "induce", "urinary", "phosphate", "excretion", "and", "suppress", "1,25-dihydroxyvitamin", "D", "synthesis", "in", "the", "presence", "of", "FGF", "receptor", "1", "(FGFR1)", "and", "its", "coreceptor", "Klotho.", "In", "patients", "with", "chronic", "kidney", "disease", "(CKD),", "circulating", "FGF23", "levels", "are", "progressively", "increased", "to", "compensate", "for", "persistent", "phosphate", "retention,", "but", "this", "results", "in", "reduced", "renal", "production", "of", "1,25-dihydroxyvitamin", "D", "and", "leads", "to", "hypersecretion", "of", "parathyroid", "hormone.", "Furthermore,", "FGF23", "is", "associated", "with", "vascular", "dysfunction,", "atherosclerosis,", "and", "left", "ventricular", "hypertrophy.", "This", "paper", "summarizes", "the", "role", "of", "FGF23", "in", "the", "pathogenesis", "of", "mineral,", "bone,", "and", "cadiovascular", "disorders", "in", "CKD.", "1.", "Introduction", "Patients", "with", "chronic", "kidney", "disease", "(CKD)", "are", "at", "increased", "risk", "for", "cardiovascular", "events", "compared", "with", "individuals", "with", "normal", "kidney", "function", "[1].", "In", "addition", "to", "tradi-", "tional", "cardiovascular", "risk", "factors,", "disturbances", "in", "calcium-", "phosphate", "metabolism", "are", "regarded", "as", "strong", "contributing", "factors", "of", "higher", "cardiovascular", "mortality", "in", "CKD", "patients", "[2,", "3].", "Indeed,", "elevated", "serum", "phosphate,", "low", "calcitriol,", "and", "high", "PTH", "levels", "represent", "the", "classical", "triad", "that", "leads", "to", "secondary", "hyperparathyroidism,", "each", "factor", 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"acid", "synthesis", "[8];", "FGF-21", "stimulates", "insulin-", "independent", "glucose", "uptake", "in", "adipocytes", "and", "lowers", "triglyc-", "erides", "[9].", "Interestingly,", "FGF-19,", "FGF-21,", "and", "FGF-23", "con-", "tain", "a", "disulfide", "bond", "that", "is", "absent", "in", "most", "other", "subfamilies.", "This", "may", "explain", "why", "FGF-23", "can", "be", "distributed", "in", "the", "bloodstream", "to", "mediate", "its", "functions.", "FGF-23", "is", "a", "251-amino", "acid", "protein", "(MW", "26", "kDa)", "syn-", "thesized", "and", "secreted", "by", "bone", "cells,", "mainly", "osteoblast", "[10].", "It", "is", "composed", "of", "an", "amino-terminal", "signal", "peptide", "(residues", "1–24),", "followed", "by", "an", "“FGF-like", "sequence”", "(residues", "25–180)", "and", "a", "carboxyl-terminal", "extended", "sequence", "(residues", "181–", "251)", "that", "is", "unique", "compared", "with", "other", "members", "of", "the", "FGF", "family", "[7].", "The", "half-life", "of", "intact", "FGF-23", "in", "the", "circulation", "of", "healthy", "individuals", "has", "been", "estimated", "to", "be", "58", "min", "[11].", "FGF-23", "exerts", "its", "biological", "effects", "through", "activation", "of", "FGF", "receptors", "(FGF-Rs);", "this", "activation", "is", "Klotho", "dependent", "as", "a", "Klotho/FGF-R", "complex", "binds", "to", "FGF-23", "with", "higher", "affinity", "than", "does", "FGF-R", "or", "Klotho", "alone", "[12].", "Klotho", "is", "a", "130-", "kDa", "transmembrane", "b-glucuronidase", "capable", "of", "hydrolyzing" ]

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[ "Int.", "J.", "Mol.", "Sci.", "2009,", "10,", "2348-2366;", "doi:10.3390/ijms10052348", "OPEN", "ACCESS", "International", "Journal", "of", "Molecular", "Sciences", "ISSN", "1422-0067", "www.mdpi.com/journal/ijms", "Article", "Microscopic", "Investigation", "of", "Reversible", "Nanoscale", "Surface", "Size", "Dependent", "Protein", "Conjugation", "Kazushige", "Yokoyama", "1,*,", "Hyunah", "Cho", "1,", "Sean", "P.", "Cullen", "1,", "Matthew", "Kowalik", "1,", "Nicole", "M.", "Briglio", "1,", "Harold", "J.", "Hoops", "2,", "Zhouying", "Zhao", "3", "and", "Michael", "A.", "Carpenter", "3", "1", "Department", "of", "Chemistry,", "The", "State", "University", "of", "New", "York", "at", "Geneseo,", "1", "College", "Circle,", "Geneseo,", "NY", "14454,", "USA;", "E-Mails:", "hc7@geneseo.edu", "(H.C.);", "spc8@geneseo.edu", "(S.P.C.);", "mk16@geneseo.edu", "(M.K.);", "nmb11@geneseo.edu", "(N.M.B.)", "2", "Department", "of", "Biology,", "The", "State", "University", "of", "New", "York", "at", "Geneseo,", "1", "College", "Circle,", "Geneseo,", "NY", "14454,", "USA;", "E-Mail:", "hoops@geneseo.edu", "(H.J.H.)", "3", "College", "of", "Nanoscale", "Science", "and", "Engineering,", "University", "of", "Albany-SUNY,", "255", "Fuller", "Road,", "Albany,", "NY", "12203,", "USA;", "E-Mails:", "zzhao@uamail.albany.edu", "(Z.-Y.Z.);", "mcarpenter@uamail.albany.edu", "(M.A.C.)", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "yokoyama@geneseo.edu;", "Tel.", "+1-585-245-5320;", "Fax:", "+1-585-245-5288", "Received:", "3", "April", "2009;", "in", "revised", "form:", "14", "May", "2009", "/", "Accepted:", "18", "May", "2009", "/", "Published:", "20", "May", "2009", "Abstract:", "A1-40", "coated", "20", "nm", "gold", "colloidal", "nanoparticles", "exhibit", "a", "reversible", "color", "change", "as", "pH", "is", "externally", "altered", "between", "pH", "4", "and", "10.", "This", "reversible", "process", "may", "contain", "important", "information", "on", "the", "initial", "reversible", "step", "reported", "for", "the", "fibrillogenesis", "of", "Aa", "hallmark", "of", "Alzheimer’s", "disease).", "We", "examined", "this", "reversible", "color", "change", "by", "microscopic", "investigations.", "AFM", "images", "on", "graphite", "surfaces", "revealed", "the", "morphology", "of", "A", "aggregates", "with", "gold", "colloids.", "TEM", "images", "clearly", "demonstrate", "the", "correspondence", "between", "spectroscopic", "features", "and", "conformational", "changes", "of", "the", "gold", "colloid.", "Keywords:", "amyloid", "beta;", "fibrillogenesis;", "Alzheimer’s", "disease;", "ovalbumin;", "gold", "nanoparticles;", "AFM;", "TEM" ]

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[ "Nucleic", "Acids", "Research,", "2006,", "Vol.", "34,", "No.", "4", "e33", "doi:10.1093/nar/gkl003", "The", "use", "of", "biotin", "tagging", "in", "Saccharomyces", "cerevisiae", "improves", "the", "sensitivity", "of", "chromatin", "immunoprecipitation", "Folkert", "J.", "van", "Werven", "and", "H.", "Th.", "Marc", "Timmers*", "Department", "of", "Physiological", "Chemistry,", "Division", "of", "Biomedical", "Genetics,", "University", "Medical", "Centre", "Utrecht,", "Universiteitsweg", "100,", "3584", "CG", "Utrecht,", "The", "Netherlands", "Received", "January", "20,", "2006;", "Accepted", "February", "9,", "2006", "ABSTRACT", "Affinity", "tagging", "has", "been", "used", "in", "many", "global", "stu-", "dies", "towards", "protein", "function.", "We", "describe", "a", "highly", "efficient", "system", "for", "in", "vivo", "biotinylation", "of", "transcrip-", "tion", "factors", "in", "the", "yeast", "Saccharomyces", "cerevisiae,", "which", "is", "based", "on", "the", "bacterial", "BirA", "biotin", "ligase.", "The", "strength", "of", "the", "biotin–streptavidin", "interaction", "was", "exploited", "to", "improve", "detection", "of", "in", "vivo", "protein–DNA", "complexes", "in", "chromatin", "immunopre-", "cipitation", "(ChIP)", "experiments.", "In", "a", "test", "system", "using", "the", "biotin-tagged", "LexA", "DNA-binding", "protein,", "we", "found", "that", "stringent", "washing", "conditions", "resulted", "in", "a", "strong", "improvement", "of", "the", "signal-to-noise", "ratios.", "Yeast", "strains", "with", "chromosomally", "integrated", "ver-", "sions", "of", "tagged", "transcription", "factor", "genes", "were", "generated", "using", "N-", "or", "C-terminal", "biotin-tagging", "cas-", "settes.", "ChIP", "experiments", "with", "biotinylated", "Rbp3p,", "a", "RNA", "polymerase", "II", "subunit,", "showed", "that", "Rbp3p-", "binding", "could", "even", "be", "detected", "at", "weakly", "expressed", "genes.", "Other", "methods", "failed", "to", "detect", "RNA", "poly-", "merase", "II", "binding", "at", "such", "genes.", "Our", "results", "show", "that", "biotinylation", "of", "yeast", "transcription", "factors", "impr-", "oves", "the", "detection", "of", "in", "vivo", "protein–DNA", "complexes.", "INTRODUCTION", "Transcription", "regulation", "in", "eukaryotic", "cells", "requires", "the", "coordinated", "and", "sequential", "action", "of", "a", "plethora", "of", "gene-", "regulatory", "proteins,", "cofactor", "complexes", "and", "basal", "transcrip-", "tion", "factors", "(1–3).", "These", "proteins", "interact", "directly", "with", "the", "regulatory", "DNA", "sequences", "encompassing", "enhancers", "and", "pro-", "moter", "elements", "or", "indirectly", "via", "recruitment", "through", "DNA-", "specific", "gene", "regulators.", "Approaches", "depending", "on", "in", "vitro", "DNA-binding", "and", "transcription", "assays", "or", "on", "yeast", "genetic", "screens", "were", "instrumental", "in", "identification", "of", "transcription", "regulatory", "proteins.", "In", "many", "cases", "it", "remained", "uncertain,", "how-", "ever,", "whether", "the", "interaction", "between", "transcription", "regulators", "and", "promoter", "DNA", "occurred", "in", "living", "cells", "or", "whether", "the", "observed", "effects", "were", "indirect", "(4,5).", "This", "has", "motivated", "development", "of", "in", "vivo", "protein-DNA", "crosslinking", "methods", "(6,7).", "The", "so-called", "chromatin", "immuno-", "precipitation", "(ChIP)", "assay", "has", "found", "widespread", "use", "to", "study", "transcription", "and", "chromatin", "regulation.", "ChIP", "relies", "on", "fixation", "of", "protein–DNA", "interactions", "by", "crosslinking", "agents", "such", "as", "formaldehyde,", "immunopurification", "of", "the", "covalently", "cross-", "linked", "complexes", "and", "detection", "of", "the", "purified", "DNA", "(6,7).", "As", "formaldehyde", "instantly", "penetrates", "living", "cells,", "in", "vivo", "bind-", "ing", "of", "transcription", "factors", "to", "DNA", "can", "be", "determined", "in", "a", "time-resolved", "manner.", "This", "has", "been", "illustrated", "by", "several", "studies", "in", "yeast", "and", "human", "cells", "(8–11).", "In", "addition,", "sequential", "ChIP", "assays", "allow", "determination", "of", "simultaneous", "binding", "of", "transcription", "factors", "to", "the", "same", "DNA", "fragment", "(12).", "Com-", "bining", "ChIP", "experiments", "with", "DNA", "microarray", "detection", "allows", "determination", "of", "the", "genome-wide", "localization", "of", "transcription", "factors.", "Recent", "studies", "using", "tiling", "microarrays", "to", "determine", "histone", "modifications", "on", "yeast", "chromosomes", "showed", "that", "nearly", "all", "fragments", "can", "be", "mapped", "provided", "that", "the", "signal-to-noise", "ratios", "of", "the", "ChIP", "are", "acceptable", "(13).", "The", "immunoprecipitation", "step", "requires", "highly", "specific", "anti-", "bodies", "with", "high", "affinity", "for", "the", "antigen.", "In", "yeast,", "this", "can", "be", "often", "circumvented", "by", "fusing", "the", "gene", "of", "interest", "with", "one", "or", "more", "copies", "of", "generic", "epitopes", "like", "hemagglutinin", "(HA),", "Myc", "and", "Flag", "for", "which", "high", "quality", "antibodies", "are", "available.", "Alternative", "strategies", "involve", "modification", "with", "the", "tandem", "affinity", "purification", "(TAP)", "tag.", "However,", "all", "approaches", "suffer", "from", "low", "signal-to-noise", "ratios", "compromising", "the", "analysis", "of", "low-abundant", "and", "transient", "protein–DNA", "interactions.", "To", "increase", "signal-to-noise", "ratios", "we", "explored", "the", "use", "of", "in", "vivo", "biotinylation", "in", "the", "yeast", "Saccharomyces", "cerevisiae.", "The", "binding", "between", "biotin", "and", "streptavidin", "represents", "one", "of", "the", "strongest", "non-covalent", "interactions", "known", "(Kd", "¼", "10", "15", "M).", "Several", "in", "vivo", "protein", "biotinylation", "systems", "for", "bacterial", "and", "mammalian", "cells", "relying", "on", "the", "BirA", "biotin", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+31", "30", "2538981;", "Fax:", "+31", "30", "253", "9035;", "Email:", "h.t.m.timmers@med.uu.nl", "The", "Author", "2006.", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oxfordjournals.org" ]

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"and", "terminators?", "Are", "translation", "efficiency", "measures,", "e.g.", "codon", "adaptation", "index", "and", "RBS", "score", "related", "to", "gene", "expression?", "We", "used", "the", "whole", "transcriptome", "shotgun", "sequen-", "cing", "of", "a", "bacterial", "pathogen", "Bacillus", "anthracis", "to", "assess", "correlation", "of", "gene", "expression", "level", "with", "promoter,", "termi-", "nator", "and", "RBS", "scores,", "codon", "adaptation", "index,", "as", "well", "as", "with", "a", "new", "measure", "of", "gene", "translational", "efficiency,", "average", "translation", "speed.", "We", "compared", "computational", "predictions", "of", "operon", "topologies", "with", "the", "transcript", "bor-", "ders", "inferred", "from", "RNA-Seq", "reads.", "Transcriptome", "mapping", "may", "also", "improve", "existing", "gene", "annotation.", "Upon", "assessment", "of", "accuracy", "of", "current", "annotation", "of", "protein-coding", "genes", "in", "the", "B.", 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"License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Perspective", "Prognostic", "Significance", "of", "Subtype", "Classification", "for", "Short-", "and", "Long-Term", "Survival", "in", "Breast", "Cancer:", "Survival", "Time", "Holds", "the", "Key", "Stefan", "Ambs*", "Laboratory", "of", "Human", "Carcinogenesis", "(LHC),", "Center", "for", "Cancer", "Research", "(CCR),", "National", "Cancer", "Institute", "(NCI),", "Bethesda,", "Maryland,", "United", "States", "of", "America", "‘‘We", "still", "lack", "the", "ability", "to", "accurately", "predict", "survival", "among", "breast", "cancer", "patients", "with", "early-stage", "disease’’", "Advances", "in", "hormone", "therapy", "and", "com-", "bination", "chemotherapy", "have", "led", "to", "signifi-", "cant", "declines", "in", "disease", "recurrence", "and", "mortality", "due", "to", "breast", "cancer", "[1,2].", "How-", "ever,", "the", "burden", "of", "developing", "a", "deadly", "disease", "remains", "unequal.", "A", "disease", "diagnosis", "at", "age", "50", "or", "younger", "is", "still", "more", "likely", "to", "have", "a", "fatal", "outcome", "than", "the", "same", "diagnosis", "at", "an", "older", "age.", "Moreover,", "African-American", "women", "and", "women", "di-", "agnosed", "with", "estrogen,", "progesterone,", "and", "HER2", "receptor–negative", "disease", "(termed", "triple-negative", "breast", "cancer)", "continue", "to", "experience", "an", "excessive", "mortality", "and", "have", "not", "benefited", "from", "the", "advances", "in", "breast", "cancer", "therapy", "as", "much", "as", "other", "patient", "groups", "[3,4].", "Currently,", "about", "10%", "of", "breast", "cancer", "patients", "will", "succumb", "to", "the", "disease", "within", "the", "first", "5", "years", "following", "the", "initial", "diagnosis", "[5],", "despite", "many", "being", "diagnosed", "with", "an", "early-stage", "disease.", "The", "relative", "risk", "of", "dying", "from", "breast", "cancer", "has", "a", "peak", "between", "2", "and", "4", "years", "post-diagnosis", "[2],", "and", "we", "can", "only", "speculate", "why", "so", "many", "women", "die", "in", "that", "period.", "It", "remains", "a", "great", "challenge", "to", "prospectively", "identify", "those", "breast", "cancer", "patients", "who", "have", "been", "diagnosed", "with", "a", "primary", "disease", "but", "have", "a", "low", "chance", "of", "surviving", "when", "treated", "with", "current", "standard", "therapy.", "A", "study", "by", "Paul", "Pharoah", "and", "colleagues", "[6]", "published", "in", "this", "week’s", "PLoS", "Medicine", "evaluated", "immunohistochemistry-based", "subtype", "classification", "of", "breast", "tumors", "for", "prediction", "of", "disease", "outcome.", "The", "au-", "thors", "recommend", "that", "this", "method", "is", "being", "used", "in", "clinical", "practice.", "Yet,", "questions", "remain", "of", "how", "useful", "subtype", "classification", "will", "be", "in", "the", "management", "of", "breast", "cancer.", "The", "Perspective", "section", "is", "for", "experts", "to", "discuss", "the", "clinical", "practice", "or", "public", "health", "implications", "of", "a", "published", "study", "that", "is", "freely", "available", "online.", "Linked", "Research", "Article", "This", "Perspective", "discusses", "the", "fol-", "lowing", "new", "study", "published", "in", "PLoS", "Medicine:", "Blows", "FM,", "Driver", "KE,", "Schmidt", "MK,", "Broeks", "A,", "van", "Leeuwen", "FE,", "et", "al.", "(2010)", "Subtyping", "of", "Breast", "Cancer", "by", "Immunohistochemistry", "to", "Inves-", "tigate", "a", "Relationship", "between", "Sub-", "type", "and", "Short-", "and", "Long-Term", "Survival:", "A", "Collaborative", "Analysis", "of", "Data", "for", "10,159", "Cases", "from", "12", "Studies.", "PLoS", "Med", "7(5):", "e1000279.", "doi:10.1371/journal.pmed.1000279", "Paul", "Pharoah", "and", "colleagues", "evalu-", "ate", "the", "prognostic", "significance", "of", "immunohistochemical", "subtype", "clas-", "sification", "in", "more", "than", "10,000", "breast", "cancer", "cases", "with", "early", "dis-", "ease,", "and", "examine", "the", "influence", "of", "a", "patient’s", "survival", "time", "on", "the", "prediction", "of", "future", "survival.", "Breast", "Cancer", "Molecular", "Subtypes", "Are", "Biologically", "Distinct", "and", "Have", "Different", "Outcomes", "Landmark", "studies", "by", "Perou", "et", "al.", "and", "by", "Sorlie", "et", "al.", "identified", "five", "distinct", "sub-", "types,", "which", "are", "different", "from", "one", "another", "in", "their", "gene", "expression", "charac-", "teristics", "[7,8].", "They", "include", "two", "estrogen", "receptor", "(ER)-positive", "subtypes,", "termed", "luminal", "A", "and", "B,", "and", "three", "ER-negative", "subtypes,", "termed", "basal-like,", "HER2-posi-", "tive,", "and", "normal", "breast-like", "tumors.", "Lu-", "minal", "tumors", "develop", "more", "frequently", "than", "the", "other", "subtypes", "and", "share", "many", "features", "with", "luminal", "epithelial", "cells", "lining", "the", "mammary", "ducts,", "but", "tumors", "in", "the", "luminal", "B", "subgroup", "also", "aberrantly", "over-", "express", "the", "HER2", "receptor", "or", "prolifera-", "tion", "marker", "genes", "that", "distinguish", "them", "from", "the", "HER2-negative", "luminal", "A", "tu-", "mors.", "Basal-like", "breast", "cancer", "has", "similar-", "ities", "with", "normal", "breast", "basal", "epithelial", "cells", "and", "is", "commonly", "identified", "by", "a", "lack", "of", "ER", "and", "HER2", "receptor", "expression", "and", "by", "the", "expression", "of", "either", "cytokeratin", "5/6", "or", "epidermal", "growth", "factor", "receptor", "(EGFR).", "This", "group", "of", "tumors", "is", "charac-", "terized", "by", "a", "high", "proliferation", "rate,", "pushing", "border", "of", "invasion,", "and", "the", "frequent", "expression", "of", "cancer", "stem", "cell", "markers", "[9].", "Basal-like", "breast", "tumors", "share", "many", "features", "with", "triple-negative", "tumors", "although", "the", "overlap", "is", "not", "complete,", "raising", "the", "question", "of", "whether", "they", "should", "be", "treated", "as", "two", "different", "entities", "in", "clinical", "practice.", "A", "diagnosis", "of", "either", "the", "basal-like", "or", "triple", "negative", "disease", "signals", "a", "diminished", "chance", "of", "survival", "because", "of", "high", "relapse", "rates", "within", "the", "first", "three", "years", "after", "diagnosis,", "mainly", "affecting", "patients", "with", "residual", "disease", "despite", "the", "use", "of", "adjuvant", "chemotherapy.", "Citation:", "Ambs", "S", "(2010)", "Prognostic", "Significance", "of", "Subtype", "Classification", "for", "Short-", "and", "Long-Term", "Survival", "in", "Breast", "Cancer:", "Survival", "Time", "Holds", "the", "Key.", "PLoS", "Med", "7(5):", "e1000281.", "doi:10.1371/journal.pmed.1000281", "Published", "May", "25,", "2010", "Copyright:", "2010", "Stefan", "Ambs.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "No", "specific", "funding", "was", "received", "for", "this", "piece.", "Competing", "Interests:", "The", "author", "has", "declared", "that", "no", "competing", "interests", "exist.", "Abbreviations:", "ER,", "estrogen", "receptor;", "EGFR,", "epidermal", "growth", "factor", "receptor", "*", "E-mail:", "ambss@mail.nih.gov", "Stefan", "Ambs", "is", "a", "Principal", "Investigator", "at", "LHC.", "He", "is", "supported", "by", "the", "Intramural", "Research", "Program", "of", "the", "National", "Institute", "of", "Health,", "NCI,", "CCR.", "Provenance:", "Commissioned;", "not", "externally", "peer", "reviewed.", "PLoS", "Medicine", "|", "www.plosmedicine.org", "1", "May", "2010", "|", "Volume", "7", "|", "Issue", "5", "|", "e1000281" ]

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[ "J", "Gastrointest", "Surg", "(2011)", "15:304–310", "DOI", "10.1007/s11605-010-1376-7", "ORIGINAL", "ARTICLE", "The", "Use", "of", "a", "Compression", "Device", "as", "an", "Alternative", "to", "Hand-Sewn", "and", "Stapled", "Colorectal", "Anastomoses:", "Is", "Three", "a", "Crowd?", "Brian", "S.", "Buchberg", "&", "Hossein", "Masoomi", "&", "Herlinda", "Bergman", "&", "Steven", "D.", "Mills", "&", "Michael", "J.", "Stamos", "Received:", "10", "September", "2010", "/", "Accepted:", "19", "October", "2010", "/", "Published", "online:", "10", "November", "2010", "#", "2010", "The", "Author(s).", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Background", "The", "NiTi", "CAR™", "27", "is", "a", "newer", "device", "that", "uses", "compression", "to", "create", "an", "anastomosis.", "An", "analysis", "of", "this", "device", "in", "the", "creation", "of", "colorectal", "anastomoses", "in", "humans", "has", "yet", "to", "be", "reported", "in", "the", "USA.", "Methods", "A", "non-randomized,", "prospective", "pilot", "study", "of", "the", "NiTi", "CAR™", "27", "device", "in", "patients", "undergoing", "a", "left-sided", "colectomy", "between", "March", "2008", "and", "August", "2009", "was", "performed.", "Results", "Twenty-three", "patients", "(9", "men", "and", "14", "women)", "underwent", "a", "left-sided", "colectomy", "and", "compression", "anastomosis", "with", "the", "CAR™", "27", "device.", "Minor", "morbidities,", "3", "of", "23", "(13%)", "patients,", "included", "one", "small", "postoperative", "abscess", "requiring", "antibiotics", "alone", "and", "two", "postoperative", "anastomotic", "strictures", "requiring", "balloon", "dilation.", "Major", "morbidities,", "1", "of", "23", "(4%)", "patients,", "included", "a", "partial", "anastomotic", "dehiscence/leak", "requiring", "surgical", "dismantling", "of", "the", "anastomosis", "and", "diversion.", "Conclusion", "The", "CAR™", "27", "device", "shows", "promise", "as", "a", "safe", "and", "effective", "alternative", "for", "the", "creation", "of", "colorectal", "anastomoses.", "However,", "studies", "in", "a", "larger", "patient", "population", "are", "warranted", "to", "demonstrate", "equivalence", "of", "this", "device.", "Keywords", "Anastomosis", ".", "Anastomotic", "leak", ".", "Compression", ".", "Colorectal", ".", "Stricture", ".", "Nitinol", "Introduction", "Currently,", "the", "two", "available", "methods", "used", "for", "the", "creation", "of", "colorectal", "anastomoses", "include", "hand", "suturing", "and", "stapling", "devices.", "Although", "both", "are", "well", "established,", "they", "are", "not", "without", "their", "faults.", "Neither", "provides", "an", "immediately", "“sealed”", "anastomosis", "and", "both", "are", "prone", "to", "uncommon", "but", "serious", "complications", "such", "as", "anastomotic", "bleeding,", "strictures,", "or", "leaks.", "After", "colorectal", "resection,", "the", "incidence", "Presented", "as", "part", "of", "an", "oral", "presentation", "session", "at", "the", "62nd", "Annual", "Meeting", "of", "The", "Southwestern", "Surgical", "Congress", "held", "March", "21-24,", "2010,", "at", "the", "Loews", "Ventana", "Canyon", "Resort", "in", "Tucson,", "AZ.", "B.", "S.", "Buchberg", ":", "H.", "Masoomi", ":", "H.", "Bergman", ":", "S.", "D.", "Mills", ":", "M.", "J.", "Stamos", "(*)", "Department", "of", "Surgery,", "University", "of", "California-Irvine", "Medical", "Center,", "333", "City", "Blvd.", "West,", "Suite", "700,", "Orange,", "CA", "92868,", "USA", "e-mail:", "mstamos@uci.edu", "of", "anastomotic", "leak", "ranges", "from", "2.9%", "to", "15.3%,1", "while", "the", "incidence", "of", "subsequent", "stenosis", "or", "stricture", "ranges", "from", "1.2%", "to", "4.2%.2", "These", "complications", "may", "require", "further", "surgical", "intervention", "and", "can", "lead", "to", "significant", "morbidity", "and", "mortality.", "As", "a", "result,", "the", "concept", "of", "tissue", "compression", "during", "colorectal", "anastomoses", "has", "been", "revisited.", "This", "idea", "is", "not", "new", "and", "previous", "attempts", "have", "included", "the", "Murphy", "button,", "the", "biofragmentable", "anastomotic", "ring,", "and", "AKA-2", "devices.3–11", "Drawbacks", "of", "these", "devices", "included", "retained", "foreign", "material", "within", "the", "tissue,", "narrowing", "of", "the", "lumen,", "necrosis", "at", "the", "anastomotic", "site,", "and", "problems", "with", "passage", "of", "the", "deployment", "device.3", "As", "a", "result,", "the", "use", "of", "these", "devices", "became", "extremely", "limited", "and", "was", "eventually", "replaced", "with", "the", "more", "reliable", "stapling", "devices.", "Recently,", "the", "FDA-approved", "NiTi", "CAR™", "27", "(endolu-", "minal", "compression", "anastomosis", "ring)", "device", "has", "been", "introduced", "and", "may", "overcome", "many", "limitations", "of", "the", "previous", "compression", "devices.", "The", "device", "is", "intended", "for", "use", "in", "the", "colon", "and", "rectum", "for", "the", "creation", "of", "end-to-end,", "end-to-side,", "and", "side-to-side", "anastomoses", "in", "both", "open", "and", "laparoscopic", "surgeries.", "This", "novel", "device", "consists", "of", "two", "disposable", "rings", "that", "trap", "the", "ends", "of", "transected", "bowel," ]

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[ "CASE", "REPORT", "http://dx.doi.org/10.4306/pi.2011.8.3.269", "Print", "ISSN", "1738-3684", "/", "On-line", "ISSN", "1976-3026", "OPEN", "ACCESS", "Duloxetine-Induced", "Liver", "Injury", "in", "Patients", "with", "Major", "Depressive", "Disorder", "Seung-Gul", "Kang1,", "Young-Min", "Park2", ",", "Heon-Jeong", "Lee3", "and", "Byungmun", "Yoon4", "1Department", "of", "Psychiatry,", "Catholic", "University", "of", "Daegu", "School", "of", "Medicine,", "Daegu,", "Korea", "2Department", "of", "Neuropsychiatry,", "Ilsan", "Paik", "Hospital,", "Inje", "University", "College", "of", "Medicine,", "Goyang,", "Korea", "3Department", "of", "Psychiatry,", "Korea", "University", "College", "of", "Medicine,", "Seoul,", "Korea", "4Department", "of", "Psychiatry,", "Maumtomaum", "Clinic,", "Yongin,", "Korea", "Duloxetine", "is", "a", "balanced", "serotonin-norepinephrine", "reuptake", "inhibitor.", "Duloxetine-induced", "liver", "injury", "in", "patients", "with", "preexisting", "liver", "disease", "or", "chronic", "alcohol", "use", "is", "known.", "However,", "we", "have", "found", "that", "duloxetine", "can", "also", "induce", "liver", "injury", "in", "cases", "without", "those", "risk", "factors.", "We", "recommend", "that", "clinicians", "should", "monitor", "liver", "function", "carefully", "following", "duloxetine", "treatment.", "Psychiatry", "Investig", "2011;8:269-271", "Key", "WordsaaDuloxetine,", "Liver", "injury,", "Major", "depressive", "disorder.", "INTRODUCTION", "Drug-induced", "liver", "injury", "(DILI)", "is", "a", "term", "that", "describes", "ab-", "normalities", "in", "liver", "function", "tests", "(LFTs)", "that", "are", "attributable", "to", "medication", "intake.1", "DILI", "accounts", "for", "more", "than", "50%", "of", "acu-", "te", "liver", "failures", "and", "is", "the", "most", "common", "cause", "of", "the", "withdra-", "wal", "of", "drugs", "from", "the", "pharmaceutical", "market.2,3", "Eli", "Lilly", "and", "Company", "informed", "healthcare", "professionals", "that", "there", "had", "been", "some", "postmarketing", "reports", "of", "cholestatic", "jaundice", "and", "hepatitis", "in", "patients", "with", "chronic", "liver", "disease", "or", "cirrhosis", "receiving", "duloxetine", "in", "late", "2005.", "In", "addition,", "the", "pro-", "duct", "labeling", "was", "modified", "by", "stating", "that", "duloxetine", "should", "not", "ordinarily", "be", "prescribed", "to", "patients", "with", "chronic", "alcohol", "use", "or", "evidence", "of", "chronic", "liver", "disease.", "Duloxetine", "was", "approved", "in", "Korea", "for", "major", "depressive", "dis-", "order", "(MDD),", "generalized", "anxiety", "disorder,", "and", "diabetic", "pe-", "ripheral", "neuropathic", "pain", "(DPNP)", "in", "2009.", "It", "is", "a", "balanced", "and", "potent", "serotonin-norepinephrine", "reuptake", "inhibitor,", "and", "has", "been", "prescribed", "increasingly", "in", "Korea.", "However,", "data", "regard-", "Received:", "January", "19,", "2011", "Revised:", "May", "8,", "2011", "Accepted:", "May", "8,", "2011", "Available", "online:", "August", "10,", "2011", "", "Correspondence:", "Young-Min", "Park,", "MD,", "PhD", "Department", "of", "Neuropsychiatry,", "Ilsan", "Paik", "Hospital,", "Inje", "University", "College", "of", "Medicine,", "2240", "Daehwa-dong,", "Ilsansu-ku,", "Goyang", "411-706,", "Korea", "Tel:", "+82-31-910-7260,", "Fax:", "+82-31-910-7268,", "E-mail:", "medipark@hanmail.net", "cc", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-", "nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduc-", "tion", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "ing", "its", "effects", "on", "the", "liver", "are", "not", "well", "known", "in", "this", "country.", "We", "have", "previously", "reported", "a", "case", "of", "duloxetine-induced", "liver", "injury", "in", "a", "patient", "with", "MDD.4", "We", "have", "now", "experienced", "another", "three", "cases", "involving", "duloxetine-induced", "liver", "injury.", "Thus,", "we", "describe", "herein", "a", "case", "series", "of", "liver", "injury", "in", "patients", "with", "MDD.", "A", "MEDLINE", "se-", "arch", "revealed", "no", "other", "report", "related", "to", "duloxetine-induced", "liver", "injury", "in", "Asian", "patients;", "this", "therefore", "appears", "to", "be", "the", "first", "reported", "case", "thereof", "in", "Asia.", "CASES", "Case", "1", "A", "22-year-old", "Korean", "male", "visited", "our", "clinic", "due", "to", "depres-", "sion.", "The", "patient", "had", "no", "relevant", "medical", "history", "and", "no", "his-", "tory", "of", "substance", "abuse;", "his", "laboratory", "tests", "were", "also", "normal.", "He", "was", "diagnosed", "with", "MDD,", "and", "initially", "treated", "with", "duloxe-", "tine", "at", "30", "mg/day.", "After", "3", "weeks,", "the", "dosage", "was", "increased", "to", "60", "mg/day.", "However,", "the", "patient", "had", "only", "a", "partial", "response", "and", "complained", "of", "fatigue.", "Laboratory", "tests", "were", "performed,", "and", "his", "total", "bilirubin", "was", "1.8", "mg/dL", "and", "alanine", "transaminase", "(ALT)", "was", "60", "U/L", "(See", "Table", "1", "for", "normal", "range", "in", "our", "hospi-", "tal).", "Thus,", "duloxetine", "was", "immediately", "discontinued", "and", "re-", "placed", "by", "escitalopram.", "Liver", "function", "had", "normalized", "by", "4", "months", "after", "the", "discontinuation", "of", "duloxetine,", "at", "which", "time", "the", "patient’s", "total", "bilirubin", "and", "ALT", "levels", "were", "1.2", "mg/dL", "and", "7", "U/L,", "respectively.", "Copyright", "©", "2011", "Korean", "Neuropsychiatric", "Association", "269" ]

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[ "Vet.", "Res.", "(2009)", "40:29", "DOI:", "10.1051/vetres/2009011", "INRA,", "EDP", "Sciences,", "2009", "www.vetres.org", "Review", "article", "Ecological", "fitness", "and", "strategies", "of", "adaptation", "of", "Bartonella", "I", "species", "to", "their", "hosts", "and", "vectors", "Bruno", "B.", "CHOMEL1*,", "Henri-Jean", "BOULOUIS", "2", ",", "Edward", "B.", "BREITSCHWERDT", "3", ",", "1", "2", "4", "Rickie", "W.", "KASTEN", ",", "Muriel", "VAYSSIER-TAUSSAT", ",", "Richard", "J.", "BIRTLES", ",", "Jane", "E.", "KOEHLER5,", "Christoph", "DEHIO6", "1", "Department", "of", "Population", "Health", "and", "Reproduction,", "School", "of", "Veterinary", "Medicine,", "University", "of", "California,", "Davis,", "CA", "95616,", "USA", "2", "UMR", "BIPAR", "ENVA/AFSSA/INRA/UPVM,", "E´", "cole", "Nationale", "Ve´te´rinaire", "d’Alfort,", "7", "avenue", "du", "Ge´ne´ral", "de", "Gaulle,", "94704", "Maisons-Alfort,", "France", "3", "Center", "for", "Comparative", "Medicine", "and", "Transitional", "Research,", "College", "of", "Veterinary", "Medicine,", "North", "Carolina", "State", "University,", "4700", "Hillsborough", "St.,", "Raleigh,", "NC", "27606,", "USA", "4", "Department", "of", "Veterinary", "Pathology,", "Faculty", "of", "Veterinary", "Science,", "University", "of", "Liverpool,", "Leahurst,", "CH64", "7TE,", "United", "Kingdom", "5", "Division", "of", "Infectious", "Diseases,", "University", "of", "California,", "San", "Francisco,", "513", "Parnassus", "Avenue,", "Room", "S-380,", "San", "Francisco,", "CA,", "94143-0654,", "USA", "6", "Focal", "Area", "of", "Infection", "Biology", "Biozentrum,", "University", "of", "Basel,", "Klingelbergstrasse", "50/70,", "CH-4056", "Basel,", "Switzerland", "(Received", "12", "November", "2008;", "accepted", "12", "March", "2009)", "Abstract", "–", "Bartonella", "spp.", "are", "facultative", "intracellular", "bacteria", "that", "cause", "characteristic", "host-", "restricted", "hemotropic", "infections", "in", "mammals", "and", "are", "typically", "transmitted", "by", "blood-sucking", "arthropods.", "In", "the", "mammalian", "reservoir,", "these", "bacteria", "initially", "infect", "a", "yet", "unrecognized", "primary", "niche,", "which", "seeds", "organisms", "into", "the", "blood", "stream", "leading", "to", "the", "establishment", "of", "a", "long-lasting", "intra-erythrocytic", "bacteremia", "as", "the", "hall-mark", "of", "infection.", "Bacterial", "type", "IV", "secretion", "systems,", "which", "are", "supra-molecular", "transporters", "ancestrally", "related", "to", "bacterial", "conjugation", "systems,", "represent", "crucial", "pathogenicity", "factors", "that", "have", "contributed", "to", "a", "radial", "expansion", "of", "the", "Bartonella", "lineage", "in", "nature", "by", "facilitating", "adaptation", "to", "unique", "mammalian", "hosts.", "On", "the", "molecular", "level,", "the", "type", "IV", "secretion", "system", "VirB/VirD4", "is", "known", "to", "translocate", "a", "cocktail", "of", "different", "effector", "proteins", "into", "host", "cells,", "which", "subvert", "multiple", "cellular", "functions", "to", "the", "benefit", "of", "the", "infecting", "pathogen.", "Furthermore,", "bacterial", "adhesins", "mediate", "a", "critical,", "early", "step", "in", "the", "pathogenesis", "of", "the", "bartonellae", "by", "binding", "to", "extracellular", "matrix", "components", "of", "host", "cells,", "which", "leads", "to", "firm", "bacterial", "adhesion", "to", "the", "cell", "surface", "as", "a", "prerequisite", "for", "the", "efficient", "translocation", "of", "type", "IV", "secretion", "effector", "proteins.", "The", "best-", "studied", "adhesins", "in", "bartonellae", "are", "the", "orthologous", "trimeric", "autotransporter", "adhesins,", "BadA", "in", "Bartonella", "henselae", "and", "the", "Vomp", "family", "in", "Bartonella", "quintana.", "Genetic", "diversity", "and", "strain", "variability", "also", "appear", "to", "enhance", "the", "ability", "of", "bartonellae", "to", "invade", "not", "only", "specific", "reservoir", "hosts,", "but", "also", "accidental", "hosts,", "as", "shown", "for", "B.", "henselae.", "Bartonellae", "have", "been", "identified", "in", "many", "different", "blood-sucking", "arthropods,", "in", "which", "they", "are", "typically", "found", "to", "cause", "extracellular", "infections", "of", "the", "mid-gut", "epithelium.", "Adaptation", "to", "specific", "vectors", "and", "reservoirs", "seems", "to", "be", "a", "common", "strategy", "of", "bartonellae", "for", "transmission", "and", "host", "diversity.", "However,", "knowledge", "regarding", "arthropod", "specificity/", "I", "This", "manuscript", "is", "dedicated", "to", "the", "memory", "of", "Professor", "Yves", "Piemont", "(1951–2009)", "from", "Strasbourg", "University", "(France)", "whose", "significant", "contribution", "to", "the", "field", "of", "Bartonella", "knowlegde", "expended", "the", "number", "of", "known", "species", "and", "its", "epidemiology.", "*", "Corresponding", "author:", "bbchomel@ucdavis.edu", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution-Noncommercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0/),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "noncommercial", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Quinoxalin-2-yl", "p-tolyl", "ether", "Nor", "Duha", "Hassan,", "Hairul", "Anuar", "Tajuddin,", "Zanariah", "Abdullah", "and", "Seik", "Weng", "Ng*", "Department", "of", "Chemistry,", "University", "of", "Malaya,", "50603", "Kuala", "Lumpur,", "Malaysia", "Correspondence", "e-mail:", "seikweng@um.edu.my", "Received", "12", "August", "2008;", "accepted", "19", "August", "2008", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "100", "K;", "mean", "(C–C)", "=", "0.002", "A˚;", "R", "factor", "=", "0.036;", "wR", "factor", "=", "0.100;", "data-to-parameter", "ratio", "=", "12.4.", "The", "dihedral", "angle", "between", "the", "two", "aromatic", "ring", "systems", "in", "the", "title", "compound,", "C15H12N2O,", "is", "42.6", "(1)", ".", "The", "angle", "at", "the", "O", "atom", "is", "widened", "to", "117.7", "(1)", ".", "Related", "literature", "The", "title", "compound", "exhibits", "fluorescence;", "see:", "Abdullah", "(2005);", "Kawai", "et", "al.", "(2001);", "Mohd", "Salleh", "et", "al.", "(2007).", "Experimental", "Crystal", "data", "C15H12N2O", "Mr", "=", "236.27", "Triclinic,", "P1", "a", "=", "5.2655", "(1)", "A˚", "b", "=", "9.1713", "(2)", "A˚", "c", "=", "12.8112", "(2)", "A˚", "=", "74.660", "(1)", "=", "81.163", "(1)", "=", "89.095", "(1)", "V", "=", "589.35", "(2)", "A˚", "3", "Data", "collection", "Bruker", "SMART", "APEX", "diffractometer", "Absorption", "correction:", "none", "2828", "measured", "reflections", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.035", "wR(F", "2)", "=", "0.099", "S", "=", "0.99", "2030", "reflections", "organic", "compounds", "Z", "=", "2", "Mo", "K", "radiation", "=", "0.09", "mm", "1", "T", "=", "100", "(2)", "K", "0.25", "0.25", "0.25", "mm", "2030", "independent", "reflections", "1764", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.012", "164", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.15", "e", "A˚", "3", "min", "=", "0.23", "e", "A˚", "3", "Data", "collection:", "APEX2", "(Bruker,", "2007);", "cell", "refinement:", "SAINT", "(Bruker,", "2007);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "X-", "SEED", "(Barbour,", "2001);", "software", "used", "to", "prepare", "material", "for", "publication:", "publCIF", "(Westrip,", "2008).", "We", "thank", "the", "University", "of", "Malaya", "for", "supporting", "this", "study", "(grant", "No.", "358/2008", "A).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "BT2771).", "References", "Abdullah,", "Z.", "(2005).", "Int.", "J.", "Chem.", "Sci.", "3,", "9–15.", "Barbour,", "L.", "J.", "(2001).", "J.", "Supramol.", "Chem.", "1,", "189–191.", "Bruker", "(2007).", "APEX2", "and", "SAINT.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Kawai,", "M.,", "Lee,", "M.", "J.,", "Evans,", "K.", "O.", "&", "Norlund,", "T.", "(2001).", "J.", "Fluoresc.", "11,", "23–32.", "Mohd", "Salleh,", "N.,", "Ling,", "L.", "P.,", "Abdullah,", "Z.", "M.", "A.", "A.", "&", "Aiyub,", "Z.", "(2007).", "Malays.", "J.", "Anal.", "Sci.", "11,", "229–236.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Westrip,", "S.", "P.", "(2008).", "publCIF.", "In", "preparation.", "Acta", "Cryst.", "(2008).", "E64,", "o1823", "doi:10.1107/S1600536808026834", "Hassan", "et", "al.", "o1823" ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "International", "Journal", "of", "Inflammation", "Volume", "2010,", "Article", "ID", "954051,", "9", "pages", "doi:10.4061/2010/954051", "Review", "Article", "The", "Bowel", "Microbiota", "and", "Inflammatory", "Bowel", "Diseases", "Gerald", "W.", "Tannock", "Department", "of", "Microbiology", "and", "Immunology,", "University", "of", "Otago,", "P.O.", "Box", "56,", "Dunedin", "9054,", "New", "Zealand", "Correspondence", "should", "be", "addressed", "to", "Gerald", "W.", "Tannock,", "gerald.tannock@stonebow.otago.ac.nz", "Received", "29", "April", "2010;", "Accepted", "4", "July", "2010", "Academic", "Editor:", "Gerhard", "Rogler", "Copyright", "©", "2010", "Gerald", "W.", "Tannock.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "The", "human", "bowel", "contains", "a", "large", "and", "biodiverse", "bacterial", "community", "known", "as", "the", "microbiota", "or", "microbiome.", "It", "seems", "likely", "that", "the", "microbiota,", "fractions", "of", "the", "microbiota,", "or", "specific", "species", "comprising", "the", "microbiota", "provide", "the", "antigenic", "fuel", "that", "drives", "the", "chronic", "immune", "inflammation", "of", "the", "bowel", "mucosa", "that", "is", "characteristic", "of", "Crohn’s", "disease", "and", "ulcerative", "colitis.", "At", "least", "twenty", "years", "of", "microbiological", "research", "have", "been", "expended", "on", "analysis", "of", "the", "composition", "of", "the", "bowel", "microbiota", "of", "inflammatory", "bowel", "disease", "patients", "in", "comparison", "to", "that", "of", "control", "subjects.", "Despite", "extensive", "speculations", "about", "the", "aetiological", "role", "of", "dysbiosis", "in", "inflammatory", "bowel", "diseases,", "knowledge", "that", "can", "be", "easily", "translated", "into", "effective", "remedies", "for", "patients", "has", "not", "eventuated.", "The", "causes", "of", "this", "failure", "may", "be", "due", "to", "poorly", "defined", "and", "executed", "bacteriological", "studies,", "as", "well", "as", "the", "overwhelming", "complexity", "of", "a", "biome", "that", "contains", "hundreds", "of", "bacterial", "species", "and", "trillions", "of", "bacterial", "cells.", "1.", "Introduction", "The", "large", "bowels", "of", "mammals", "comprise", "a", "biome", "(ecosystem)", "that", "includes", "a", "bacterial", "community", "that", "is", "biodiverse", "and", "numerous.", "It", "can", "be", "estimated", "that", "there", "are", "a", "total", "of", "twenty", "trillion", "bacterial", "cells", "per", "human", "colon", "if", "it", "is", "assumed", "that", "the", "colonic", "contents", "weigh", "on", "average", "about", "200", "grams.", "The", "majority", "of", "these", "bacteria", "are", "obligate", "anaerobes.", "They", "are", "commonly", "referred", "to", "as", "commensals", "or", "symbionts", "because", "they", "form", "long-lasting,", "interactive", "associations", "with", "their", "animal", "hosts", "[1,", "2].", "These", "associations", "are", "generally", "regarded", "to", "involve", "mutually", "beneficial", "interactions,", "although", "some", "commensals", "are", "opportunistic", "pathogens", "when", "appropriate", "predisposing", "events", "occur", "[3].", "The", "bacterial", "communities", "(microbiota,", "microbiome)", "of", "human", "bowels", "contain", "pre-", "dominantly", "representatives", "of", "four", "phyla:", "Actinobacteria,", "Proteobacteria,", "Bacteroidetes,", "and", "Firmicutes", "(Table", "1).", "The", "Firmicutes", "and", "Bacteroidetes", "are", "numerically", "dominant", "in", "the", "community.", "Numerous", "genera", "and", "species", "of", "bacteria", "are", "represented", "in", "each", "of", "these", "broad", "phylogenetic", "groups", "and,", "at", "least", "in", "the", "case", "of", "humans,", "there", "is", "person-to-person", "variation", "in", "the", "composition", "of", "the", "bowel", "microbiota", "[4–", "6].", "Descriptions", "of", "a", "“normal", "range”", "of", "bowel", "inhabitants", "of", "humans", "in", "terms", "of", "genera", "and", "species", "has", "recently", "begun", "to", "emerge,", "sometimes", "referred", "to", "as", "the", "“core”", "microbiota", "(5,", "6;", "Table", "2).", "The", "bowel", "microbiota", "is,", "like", "bacterial", "communities", "in", "general,", "self-regulating", "and", "this", "provides", "temporal", "stability", "in", "composition.", "At", "least", "in", "health,", "the", "proportions", "of", "broad", "phylogenetic", "groups", "of", "bacteria", "within", "the", "community", "remain", "much", "the", "same", "over", "time", "[4].", "Inducible", "biochemical", "pathways", "that", "mediate", "hydrolysis", "of", "exogenous", "(dietary", "plant", "cell", "wall", "polysaccharides)", "and", "endogenous", "(mucins)", "substrates", "enable", "the", "bacteria", "to", "obtain", "an", "uninterrupted", "supply", "of", "carbon", "and", "energy", "despite", "daily", "changes", "in", "the", "composition", "of", "the", "human", "diet", "[7,", "8].", "The", "fermentation", "of", "hydrolytic", "products", "by", "the", "bacteria", "produces", "short", "chain", "fatty", "acids,", "amines,", "phenols,", "indoles,", "and", "gases", "[9].", "Knowledge", "of", "the", "nutritional", "niches", "of", "specific", "bacterial", "groups", "is", "sparse", "but", "a", "detailed", "description", "and", "importance", "of", "the", "butyrate-producing", "species", "in", "the", "ecology", "of", "the", "bowel", "is", "emerging", "due", "to", "work", "at", "the", "Rowett", "Institute,", "Scotland", "[10,", "11].", "Partitioning", "of", "bacteria", "within", "the", "contents", "of", "the", "bowel", "occurs.", "Some", "bacterial", "types", "are", "more", 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[ "Published:", "11", "February", "2010", "©", "2010", "Medicine", "Reports", "Ltd", "Recent", "advances", "in", "management", "of", "bladder", "overactivity", "Ariana", "L", "Smith*", "and", "Alan", "J", "Wein", "Address:", "Division", "of", "Urology,", "University", "of", "Pennsylvania,", "School", "of", "Medicine,", "3400", "Spruce", "Street,", "9", "Penn", "Tower,", "Philadelphia,", "PA", "19104,", "USA", "*", "Corresponding", "author:", "Ariana", "L", "Smith", "(ariana.smith@uphs.upenn.edu)", "F1000", "Medicine", "Reports", "2010,", "2:9", "(doi:10.3410/M2-9)", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution-NonCommercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0/legalcode),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "for", "non-commercial", "purposes", "provided", "the", "original", "work", "is", "properly", "cited.", "You", "may", "not", "use", "this", "work", "for", "commercial", "purposes.", "The", "electronic", "version", "of", "this", "article", "is", "the", "complete", "one", "and", "can", "be", "found", "at:", "http://f1000.com/reports/medicine/content/2/9", "Abstract", "Pharmacologic", "therapies,", "primarily", "antimuscarinic", "agents,", "have", "been", "the", "mainstay", "of", "treatment", "for", "overactive", "bladder.", "These", "drugs", "produce", "variable", "efficacy,", "a", "moderate", "rate", "of", "side", "effects,", "and", "rare", "occurrences", "of", "cure.", "The", "search", "for", "newer", "and", "better", "formulations", "and", "derivatives", "of", "this", "class", "of", "medication", "as", "well", "as", "novel", "therapies", "is", "ongoing", "and", "primarily", "fueled", "by", "the", "high", "prevalence", "of", "overactive", "bladder", "and", "the", "tremendous", "number", "of", "health", "care", "dollars", "spent", "on", "current", "therapy.", "Surgical", "options", "for", "overactive", "bladder", "have", "evolved", "slowly", "and", "are", "currently", "reserved", "for", "medical", "treatment", "failures", "and", "drug", "intolerance.", "This", "article", "will", "highlight", "the", "new", "drugs", "and", "therapies", "brought", "into", "clinical", "use", "for", "the", "treatment", "of", "overactive", "bladder", "over", "the", "last", "few", "years", "as", "well", "as", "a", "promising", "new", "agent", "in", "the", "advanced", "stages", "of", "development.", "Introduction", "and", "context", "Overactive", "bladder", "(OAB)", "affects", "between", "8.0-13.9%", "of", "the", "population", "in", "Western", "nations", "[1].", "This", "variation", "in", "prevalence", "is", "thought", "to", "be", "due", "primarily", "to", "differences", "in", "the", "definition", "of", "OAB", "used", "across", "different", "study", "populations.", "The", "International", "Continence", "Society", "has", "defined", "OAB", "as", "‘urgency,", "with", "or", "without", "urge", "incon-", "tinence,", "usually", "with", "frequency", "and", "nocturia’", "[2]", "in", "attempts", "to", "standardize", "reporting", "of", "this", "highly", "prevalent", "and", "bothersome", "condition.", "The", "drugs", "most", "commonly", "prescribed", "for", "the", "treatment", "of", "OAB", "are", "the", "antimuscari-", "nics;", "these", "drugs", "are", "proven", "efficacious", "and", "safe", "and", "are", "the", "mainstay", "of", "treatment", "for", "OAB", "[3].", "These", "agents", "produce", "symptomatic", "improvement", "by", "reducing", "urgency", "and", "therefore", "urge", "urinary", "incontinence", "(UI)", "and", "frequency,", "decreasing", "detrusor", "overactivity", "and", "increas-", "ing", "bladder", "capacity", "[4].", "There", "are", "several", "drugs", "available", "for", "use", "today,", "with", "some", "variability", "based", "on", "country", "of", "residence.", "As", "newer", "antimuscarinic", "agents", "have", "become", "available,", "some", "progress", "has", "been", "made", "in", "maximizing", "therapeutic", "efficacy", "while", "minimizing", "bothersome", "side", "effects;", "however,", "a", "large", "number", "of", "patients", "remain", "dissatisfied", "with", "the", "mix", "of", "efficacy", "and", "tolerability", "and", "discontinue", "therapy.", "Nevertheless,", "most", "physicians", "prescribe", "a", "trial", "of", "antimuscarinic", "therapy", "and", "behavioral", "modification", "in", "patients", "with", "bothersome", "OAB,", "and", "if", "it", "is", "not", "effective,", "a", "second", "trial", "using", "a", "different", "drug", "or", "formulation", "is", "often", "instituted.", "When", "these", "drugs", "fail,", "the", "side", "effects", "become", "intolerable,", "or", "the", "category", "of", "drug", "is", "contraindicated,", "physicians", "have", "limited", "ther-", "apeutic", "options,", "including", "off-label", "use", "of", "other", "cate-", "gories", "of", "drug", "or", "more", "invasive", "treatment", "options", "such", "as", "neuromodulatory", "agents", "or", "devices.", "With", "recent", "advances", "in", "the", "science", "of", "OAB,", "it", "has", "become", "clear", "that", "the", "functioning", "and", "malfunctioning", "of", "the", "urinary", "bladder", "are", "much", "more", "complex", "than", "previously", "appreciated", "and", "that", "other", "targets", "besides", "the", "muscarinic", "receptors", "should", "be", "addressed.", "The", "contin-", "uous", "evolution", "and", "development", "of", "innovative", "agents", "for", "the", "treatment", "of", "OAB", "stem", "from", "the", "fact", "that", "the", "ideal", "agent", "–", "one", "that", "is", "lower", "urinary", "tract", "(LUT)-selective,", "easily", "administered,", "and", "relatively", "inexpensive", "–", "has", "yet", "to", "be", "found.", "This", "search", "continues", "and", "therapies", "with", "different", "mechanisms", "of", "action", "are", "currently", "being", "studied", "with", "some", "promise.", "Recent", "advances", "Several", "new", "therapies", "have", "been", "added", "to", "the", "armamen-", "tarium", "of", "treatment", "options", "for", "OAB", "over", "the", "last", "couple", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "ORIGINAL", "RESEARCH", "Prognostic", "Significance", "of", "in", "situ", "Phenotypic", "Marker", "Expression", "in", "Diffuse", "Large", "B-cell", "Lymphomas", "Alexandar", "Tzankov,", "Philip", "Went", "and", "Stephan", "Dirnhofer", "Department", "of", "Pathology,", "University", "Hospital", "Basel,", "Switzerland.", "Abstract:", "Diffuse", "large", "B-cell", "lymphomas", "(DLBCL)", "are", "the", "most", "common", "lymphoid", "malignancies,", "and", "encompass", "all", "malignant", "lymphomas", "characterized", "by", "large", "neoplastic", "cells", "and", "B-cell", "derivation.", "In", "the", "last", "decade,", "DLBCL", "has", "been", "subjected", "to", "intense", "clinical,", "phenotypic", "and", "molecular", "studies,", "and", "were", "found", "to", "represent", "a", "heterogeneous", "group", "of", "tumors.", "These", "studies", "suggested", "new", "disease", "subtypes", "and", "variants", "with", "distinct", "clinical", "characteristics,", "morphologies,", "immunophe-", "notypes,", "genotypes", "or", "gene", "expression", "profiles,", "associated", "with", "distinct", "prognoses", "or", "unique", "sensitivities", "to", "particular", "therapy", "regimens.", "Unfortunately,", "the", "reliability", "and", "reproducibility", "of", "the", "molecular", "results", "remains", "unclear", "due", "to", "contra-", "dictory", "reports", "in", "the", "literature", "resulting", "from", "small", "sample", "sizes,", "referral", "and", "selection", "biases,", "and", "variable", "methodologies", "and", "cut-off", "levels", "used", "to", "determine", "positivity.", "Here,", "we", "review", "phenotypic", "studies", "on", "the", "prognostic", "significance", "of", "protein", "expression", "profiles", "in", "DLBCL", "and", "reconsider", "our", "own", "retrospective", "data", "on", "301", "primary", "DLBCL", "cases", "obtained", "on", "a", "pre-", "viously", "validated", "tissue", "microarray", "in", "light", "of", "powerful", "statistical", "methods", "of", "determining", "optimal", "cut-off", "values", "of", "pheno-", "typic", "factors", "for", "prediction", "of", "outcome.", "Keywords:", "Diffuse", "large", "B-cell", "lymphoma,", "Phenotype,", "Prognosis,", "Tissue", "microarray,", "Receiver", "operating", "characteristic", "(ROC)", "curves", "Introduction", "Diffuse", "large", "B-cell", "lymphomas", "(DLBCL)", "are", "the", "most", "common", "lymphoid", "malignancies,", "comprising", "35%", "to", "40%", "of", "all", "adult", "non-Hodgkin", "lymphomas.", "This", "category", "encompasses", "all", "malignant", "lymphomas", "characterized", "by", "large", "neoplastic", "cells", "and", "B-cell", "derivation", "(Gatter", "and", "Warnke,", "2001;", "Lossos,", "2005;", "Mitterlechner", "et", "al.", "2006).", "DLBCL", "may", "develop", "de", "novo", "(primary", "DLBCL)", "or", "arise", "from", "a", "previously", "indolent", "lymphoma", "(secondary,", "transformed", "DLBCL)", "at", "virtually", "every", "nodal", "or", "extranodal", "location.", "It", "is", "most", "commonly", "observed", "in", "cervical,", "axillar", "and", "mediastinal", "nodes,", "the", "stomach", "and", "the", "ileo-coecal", "region", "(Gatter", "and", "Warnke,", "2001).", "DLBCL", "are", "accompanied", "by", "an", "aggressive", "clinical", "presentation", "with", "the", "need", "for", "highly", "effective", "chemotherapy", "regimens", "(e.g.", "Coiffier,", "2005).", "Only", "about", "60%", "of", "patients", "can", "be", "cured", "by", "rituximab,", "cyclophosphamide,", "doxorubicin,", "vincristine,", "prednisone", "(R-CHOP)", "and", "equivalent", "treatment", "regimens", "(Coiffier,", "2005;", "Mitterlchner", "et", "al.", "2006).", "The", "gold", "standard", "of", "predicting", "survival", "and", "stratifying", "patients", "for", "risk-adjusted", "therapy", "is", "the", "international", "prognostic", "index", "(IPI)", "(Shipp", "et", "al.", "1993),", "which", "consists", "of", "easily", "assessable", "clinical", "and", "laboratory", "parameters:", "age,", "serum", "lactate", "dehydrogenase", "(LDH),", "stage,", "performance", "status", "and", ">1", "extranodal", "sites", "involved.", "No", "such", "histopathologically-defined", "parameters", "exist", "and", "although", "the", "current", "World", "Health", "Organization", "(WHO)", "classification", "(Gatter", "and", "Warnke,", "2001)", "accepts", "different", "morphologic", "variants", "and", "subtypes", "of", "DLBCL,", "their", "prognostic", "utility", "is", "hampered", "by", "a", "high", "rate", "of", "interobserver", "variation,", "which", "generally", "minimizes", "their", "influence", "in", "therapy.", "In", "the", "last", "decade,", "extensive", "studies", "of", "the", "clinical,", "phenotypic", "and", "molecular", "aspects", "of", "DLBCL", "have", "identified", "them", "as", "a", "heterogeneous", "group", "of", "tumors.", "These", "studies", "suggested", "new", "disease", "subtypes", "and", "variants", "with", "distinct", "clinical", "characteristics,", "morphology,", "immunophenotypes,", "genotypes", "or", "gene", "expression", "profiles", "associated", "with", "distinct", "prognoses", "or", "unique", "sensitivities", "to", "specific", "therapy", "regimens", "(Pileri", "et", "al.", "2002;", "de", "Leval", "and", "Harris,", "2003;", "Wright", "et", "al.", "2003;", "Rosenwald", "and", "Staudt,", "2003;", "Lossos,", "2005;", "Morgensztern", "and", "Lossos,", "2005;", "de", "Paepe", "and", "de", "Wolf-Peeters,", "2006;", "Muris", "et", "al.", "2006a).", "Unfortunately,", "the", "reliability", "and", "reproducibility", "of", "the", "molecular", "results", "remains", "unclear,", "and", "consequently", "translation", "into", "generally", "accepted", "standards", "to", "predict", "survival", "and", "stratify", "patients", "for", "risk-adjusted", "therapy", "has", "not", "taken", "place", "(for", "critical", "remarks", "see", "e.g.", "Hsi,", "2001;", "de", "Leval", "and", "Harris,", "2003;", "Gascoyne,", "2004).", "Technical", "issues", "(antibody", "affinity),", "lack", "of", "standardization", "of", "Correspondence:", "Stephan", "Dirnhofer,", "MD,", "Department", "of", "Pathology,", "University", "Hospital", "Basel,", "Schoenbeinstr.", "40,", "CH-4031", "Basel,", "Switzerland;", "Tel:", "0041", "61", "265", "2789;", "Fax:", "0041", "61", "265", "3194;", "Email:", "sdirnhofer@uhbs.ch", "Please", "note", "that", "this", "article", "may", "not", "be", "used", "for", "commercial", "purposes.", "For", "further", "information", "please", "refer", "to", "the", "copyright", "statement", "at", "http://www.la-press.com/copyright.htm", "Biomarker", "Insights", "2007:", "2", "403–417", "403" ]

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[ "World", "Journal", "of", "Surgical", "Oncology", "Review", "Guidelines,", "guidelines", "and", "more", "guidelines:", "And", "we", "still", "do", "not", "know", "how", "to", "follow-up", "patients", "with", "breast", "cancer", "Steven", "D", "Heys*,", "Shailesh", "Chaturvedi,", "Andrew", "W", "Hutcheon", "and", "Tarun", "K", "Sarkar", "BioMed", "Central", "Open", "Access", "Address:", "Section", "of", "Surgical", "Oncology,", "Department", "of", "Surgery,", "University", "of", "Aberdeen,", "Medical", "School,", "Foresterhill,", "Aberdeen,", "Scotland,", "AB25", "2ZD,", "UK", "Email:", "Steven", "D", "Heys*", "-", "s.d.heys@abdn.ac.uk;", "Shailesh", "Chaturvedi", "-", "shailesh.chaturvedi@arh.grampian.scot.nhs.uk;", "Andrew", "W", "Hutcheon", "-", "Andrew.Hutcheon@arh.grampian.scot.nhs.uk;", "Tarun", "K", "Sarkar", "-", "Dr.Tarun.Sarkar@arh.grampian.scot.nhs.uk", "*", "Corresponding", "author", "Published:", "23", "August", "2005", "World", "Journal", "of", "Surgical", "Oncology", "2005,", "3:54", "doi:10.1186/1477-7819-3-54", "This", "article", "is", "available", "from:", "http://www.wjso.com/content/3/1/54", "Received:", "02", "May", "2005", "Accepted:", "23", "August", "2005", "©", "2005", "Heys", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "A", "major", "challenge", "facing", "us", "is", "the", "provision", "of", "health", "care", "and", "appropriate", "allocation", "of", "available", "resources", "for", "the", "treatment", "of", "patients", "with", "breast", "cancer.", "This", "is", "of", "particular", "concern", "in", "the", "provision", "of", "follow-up", "care.", "With", "the", "increasing", "incidence", "of", "breast", "cancer", "and", "the", "improvements", "in", "survival", "which", "have", "resulted", "in", "up", "to", "75%", "of", "patients", "surviving", "for", "more", "than", "five", "years,", "an", "increasing", "resource", "is", "required.", "However,", "there", "is", "controversy", "as", "to", "the", "most", "appropriate", "schedule", "for", "follow-up", "of", "these", "patients.", "This", "brief", "review", "has", "focused", "on", "the", "evidence-base", "and", "guidelines", "that", "currently", "exist", "in", "the", "United", "Kingdom", "for", "the", "follow-up", "of", "patients", "who", "have", "been", "treated", "for", "breast", "cancer.", "Methods:", "A", "review", "of", "the", "current", "guidelines", "published", "in", "the", "United", "Kingdom", "for", "the", "follow-up", "of", "patients", "with", "breast", "cancer", "(National", "Institute", "for", "Clinical", "Excellence,", "Scottish", "Intercollegiate", "Guidelines", "Network,", "British", "Association", "of", "Surgical", "Oncology)", "and", "the", "randomised", "controlled", "trials", "evaluating", "the", "follow-up", "of", "patients", "with", "breast", "cancer", "was", "undertaken.", "Results:", "The", "results", "have", "demonstrated", "the", "different", "follow-up", "protocols", "currently", "indicated", "in", "these", "guidelines", "within", "the", "same", "country.", "Furthermore,", "the", "lack", "of", "well", "designed,", "randomised", "controlled", "trials", "on", "which", "to", "base", "a", "follow-up", "protocol", "for", "patients", "with", "breast", "cancer", "is", "apparent.", "Conclusion:", "The", "evidence-base", "on", "which", "these", "guidelines", "have", "been", "developed", "is", "lacking.", "It", "is", "apparent", "that", "well", "designed", "randomised", "controlled", "trials", "are", "needed", "urgently", "if", "we", "are", "to", "understand", "the", "most", "appropriate", "and", "effective", "ways", "of", "following", "up", "patients", "with", "breast", "cancer.", "Background", "A", "major", "challenge", "in", "the", "provision", "of", "healthcare", "through-", "out", "the", "world", "in", "the", "21st", "century", "is", "trying", "to", "ensure", "that", "the", "resources", "that", "are", "available", "meet", "the", "demand.", "Nowhere", "is", "the", "situation", "more", "acute", "than", "in", "the", "provision", "of", "care", "for", "patients", "with", "cancer.", "Whilst", "current", "statistics", "show", "that", "one", "in", "three", "people", "in", "the", "world", "will", "develop", "a", "malignant", "disease,", "this", "figure", "is", "the", "projected", "to", "increase", "dramatically", "during", "the", "next", "10", "years.", "Of", "particular", "concern", "has", "been", "the", "continual", "rise", "in", "the", "incidence", "of", "breast", "cancer.", "Each", "year", "the", "incidence", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Iriarte1*.", "Abstract", "Brucella", "abortus", "Ornithine", "Lipids", "Are", "Dispensable", "Outer", "Membrane", "Components", "Devoid", "of", "a", "Marked", "Pathogen-", "Associated", "Molecular", "Pattern", "Leyre", "Palacios-Chaves1,", "Raquel", "Conde-A´", "lvarez1,2,", "Yolanda", "Gil-Ramı´rez1,", "Amaia", "Zu´", "n˜", "iga-Ripa1,", "Elı´as", "Barquero-Calvo", "4", ",", "Carlos", "Chaco´", "n-Dı´az3,4,", "Esteban", "Chaves-Olarte3,4,", "Vilma", "Arce-Gorvel5,", "Jean-Pierre", "Gorvel5,", "Edgardo", "Moreno3,6,", "Marı´a-Jesu´", "s", "de", "Miguel7,", "Marı´a-Jesu´", "s", "Grillo´", "8,", "Ignacio", "Moriyo´", "n1.,", "Maite", "1", "Departamento", "de", "Microbiolog´ıa", "y", "Parasitolog´ıa,", "Universidad", "de", "Navarra,", "Pamplona,", "Spain,", "2", "Focal", "Area", "Infection", "Biology,", "Biozentrum", "of", "the", "University", "of", "Basel,", "Basel,", "Switzerland,", "3", "Centro", "de", "Investigacio´", "n", "en", "Enfermedades", "Tropicales,", "Facultad", "de", "Microbiolog´ıa,", "Universidad", "de", "Costa", "Rica,", "San", "Jose´,", "Costa", "Rica,", "4", "Programa", "de", "Investigacio´", "n", "en", "Enfermedades", "Tropicales,", "Escuela", "de", "Medicina", "Veterinaria,", "Universidad", "Nacional,", "Heredia,", "Costa", "Rica,", "5", "Centre", "d’Immunologie", "de", "Marseille-Luminy,", "Aix", "Marseille", "Universite´,", "Faculte´", "de", "Sciences", "de", "Luminy,", "Marseille,", "INSERM", "U631,", "CNRS", "UMR6102,", "Marseille,", "France,", "6", "Instituto", "Clodomiro", "Picado,", "Facultad", "de", "Microbiolog´ıa,", "Universidad", "de", "Costa", "Rica,", "San", "Pedro,", "Costa", "Rica,", "7", "Centro", "de", "Investigacio´", "n", "y", "Tecnolog´ıa", "Agroalimentaria", "(CITA),", "Unidad", "de", "Sanidad", "Animal,", "Gobierno", "de", "Arago´", "n,", "Zaragoza,", "Spain,", "8", "Instituto", "de", "Agrobiotecnolog´ıa,", "CSIC-UPNA-Gobierno", "de", "Navarra,", "Pamplona,", "Spain", "The", "brucellae", "are", "a-Proteobacteria", "facultative", "intracellular", "parasites", "that", "cause", "an", "important", "zoonosis.", "These", "bacteria", "escape", "early", "detection", "by", "innate", "immunity,", "an", "ability", "associated", "to", "the", "absence", "of", "marked", "pathogen-associated", "molecular", "patterns", "in", "the", "cell", "envelope", "lipopolysaccharide,", "lipoproteins", "and", "flagellin.", "We", "show", "here", "that,", "in", "contrast", "to", "the", "outer", "membrane", "ornithine", "lipids", "(OL)", "of", "other", "Gram", "negative", "bacteria,", "Brucella", "abortus", "OL", "lack", "a", "marked", "pathogen-associated", "molecular", "pattern", "activity.", "We", "identified", "two", "OL", "genes", "(olsB", "and", "olsA)", "and", "by", "generating", "the", "corresponding", "mutants", "found", "that", "olsB", "deficient", "B.", "abortus", "did", "not", "synthesize", "OL", "or", "their", "lyso-OL", "precursors.", "Liposomes", "constructed", "with", "B.", "abortus", "OL", "did", "not", "trigger", "IL-6", "or", "TNF-a", "release", "by", "macrophages", "whereas", "those", "constructed", "with", "Bordetella", "pertussis", "OL", "and", "the", "olsB", "mutant", "lipids", "as", "carriers", "were", "highly", "active.", "The", "OL", "deficiency", "in", "the", "olsB", "mutant", "did", "not", "promote", "proinflammatory", "responses", "or", "generated", "attenuation", "in", "mice.", "In", "addition,", "OL", "deficiency", "did", "not", "increase", "sensitivity", "to", "polymyxins,", "normal", "serum", "or", "complement", "consumption,", "or", "alter", "the", "permeability", "to", "antibiotics", "and", "dyes.", "Taken", "together,", "these", "observations", "indicate", "that", "OL", "have", "become", "dispensable", "in", "the", "extant", "brucellae", "and", "are", "consistent", "within", "the", "trend", "observed", "in", "a-Proteobacteria", "animal", "pathogens", "to", "reduce", "and", "eventually", "eliminate", "the", "envelope", "components", "susceptible", "of", "recognition", "by", "innate", "immunity.", "Citation:", "Palacios-Chaves", "L,", "Conde-A´", "lvarez", "R,", "Gil-Ram´ırez", "Y,", "Zu´", "n˜", "iga-Ripa", "A,", "Barquero-Calvo", "E,", "et", "al.", "(2011)", "Brucella", "abortus", "Ornithine", "Lipids", "Are", "Dispensable", "Outer", "Membrane", "Components", "Devoid", "of", "a", "Marked", "Pathogen-Associated", "Molecular", "Pattern.", "PLoS", "ONE", "6(1):", "e16030.", "doi:10.1371/journal.pone.0016030", "Editor:", "David", "M.", "Ojcius,", "University", "of", "California", "Merced,", "United", "States", "of", "America", "Received", "October", "28,", "2010;", "Accepted", "December", "3,", "2010;", "Published", "January", "7,", "2011", "Copyright:", "2011", "Palacios-Chaves", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Research", "at", "the", "laboratories", "of", "the", "authors", "is", "supported", "by", "the", "Ministerio", "de", "Ciencia", "y", "Tecnolog´ıa", "of", "Spain", "(AGL2008-04514-C03);", "FIDA,", "Universidad", "Nacional", "de", "Costa", "Rica;", "FS-Conare", "UNA/UCR", "IFEG29", "Costa", "Rica;", "NeTropica", "P00059", "and", "F00013-02;", "MICIT/CONICIT", "IFDG12;", "Fundacio´", "n", "CRUSA-CSIC", "(CR2008-0006);", "Centre", "National", "de", "la", "Recherche", "Scientifique,", "Institut", "National", "de", "la", "Sante´", "et", "de", "la", "Recherche", "Me´dicale", "and", "the", "Ministry", "of", "Education", "in", "France.", "Fellowship", "support", "for", "L.P.-C.,", "Y.G.-R.", "and", "A.Z.-R", "from", "the", "Ministerio", "de", "Ciencia", "y", "Tecnolog´ıa", "of", "Spain,", "Gobierno", "de", "Navarra", "and", "Friends", "of", "the", "University", "of", "Navarra", "is", "also", "acknowledged.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "miriart@unav.es", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "The", "members", "of", "the", "genus", "Brucella", "are", "a-2", "Proteobacteria", "that", "cause", "brucellosis,", "an", "important", "disease", "affecting", "livestock", "and", "wild", "life", "as", "well", "as", "human", "beings.", "These", "bacteria", "trigger", "only", "low", "proinflammatory", "responses", "in", "the", "initial", "stages", "of", "infection", "and,", "accordingly,", "they", "follow", "a", "stealthy", "behavior", "that", "allows", "them", "to", "reach", "sheltered", "intracellular", "niches", "before", "effective", "immunity", "activation.", "The", "outer", "membranes", "(OM)", "of", "brucellae", "are", "of", "critical", "importance", "in", "this", "strategy.", "Whereas", "most", "gram-negative", "have", "OM", "molecules", "bearing", "the", "pathogen-associated", "molecular", "pat-", "terns", "(PAMP)", "recognized", "by", "innate", "immunity,", "at", "least", "the", "Brucella", "OM", "lipopolysaccharide", "(LPS),", "lipoproteins", "and", "flagellin", "display", "a", "reduced", "PAMP", "[1,2].", "Moreover,", "smooth", "(S)", "brucellae", "such", "as", "B.", "abortus", "and", "B.", "melitensis", "have", "OMs", "that", "are", "unusually", "resistant", "to", "the", "disrupting", "action", "of", "bactericidal", "peptides", "and", "complement.", "Thus,", "periplasmic", "and", "internal", "PAMP-bearing", "molecules", "like", "peptido-", "glycan", "or", "DNA", "are", "not", "readily", "accessible", "to", "pathogen", "recognition", "receptors", "[1,3–8].", "The", "Brucella", "LPS", "is", "clearly", "implicated", "in", "these", "properties", "and", "there", "is", "evidence", "that", "other", "lipid", "molecules", "also", "contribute.", "Brucella", "OMs", "contain", "large", "amounts", "of", "phosphatidyl-", "choline", "(PC)", "and", "blockage", "of", "the", "synthesis", "of", "PC", "with", "the", "subsequent", "replacement", "by", "phosphatidylethanolamine", "(PE)", "gen-", "erates", "attenuation", "[9,10].", "Ornithine", "lipids", "(OLs)", "are", "present", "in", "relatively", "large", "amounts", "in", "Brucella", "[11]", "and,", "although", "they", "have", "interesting", "properties", "in", "other", "bacteria,", "have", "not", "been", "investigated.", "PLoS", "ONE", "|", "www.plosone.org", "1", "January", "2011", "|", "Volume", "6", "|", "Issue", "1", "|", "e16030" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "tert-Butyl", "(2S)-2-{3-[(R)-bis(tert-butoxy-", "carbonyl)amino]-2-oxopiperidin-1-yl}-", "1", "3-methylbutanoate", "Michael", "J.", "Kangas,", "Frank", "R.", "Fronczek*", "and", "Steven", "F.", "Watkins", "Department", "of", "Chemistry,", "Louisiana", "State", "University,", "Baton", "Rouge,", "LA", "70803-1804,", "USA", "Correspondence", "e-mail:", "ffroncz@lsu.edu", "Received", "13", "October", "2011;", "accepted", "18", "October", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "86", "K,", "P", "=", "0.0", "kPa;", "mean", "(C–C)", "=", "0.002", "A˚;", "R", "factor", "=", "0.026;", "wR", "factor", "=", "0.071;", "data-to-parameter", "ratio", "=", "15.6.", "The", "title", "compound,", "C24H42N2O7,", "is", "a", "chiral", "lactam-", "constrained", "amino", "acid", "with", "a", "six-membered", "ring", "backbone", "and", "isopropyl", "and", "tert-butyl", "ester", "side", "chains.", "The", "conforma-", "tion", "of", "the", "six-membered", "ring", "can", "be", "described", "as", "a", "half", "chair,", "with", "two", "CH2", "C", "atoms", "lying", "0.443", "(1)", "and", "0.310", "(1)", "A˚", "out", "of", "the", "best", "plane", "of", "the", "other", "four", "atoms", "(mean", "deviation", "=", "0.042", "A˚", ").", "Both", "N", "atoms", "are", "sp2", "hybridized,", "lying", "0.0413", "(9)", "and", "0.067", "(1)", "A˚", "out", "of", "the", "planes", "defined", "by", "the", "three", "C", "atoms", "bonded", "to", "them.", "The", "absolute", "configuration", "was", "determined,", "based", "on", "resonant", "scattering", "of", "light", "atoms", "in", "Cu", "K", "radiation.", "Related", "literature", "For", "synthesis", "and", "chemical", "interest,", "see:", "Oguz", "(2003);", "Oguz", "et", "al.", "(2001).", "For", "a", "similar", "structure,", "see:", "Valle", "et", "al.", "(1989).", "For", "absolute", "configuration", "parameters,", "see:", "Hooft", "et", "al.", "(2008).", "Experimental", "Crystal", "data", "C24H42N2O7", "Mr", "=", "470.6", "Monoclinic,", "C2", "a", "=", "27.282", "(3)", "A˚", "b", "=", "9.4315", "(10)", "A˚", "c", "=", "11.5884", "(10)", "A˚", "=", "110.729", "(1)", "Data", "collection", "Bruker", "Kappa", "APEXII", "CCD", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Sheldrick,", "2004)", "Tmin", "=", "0.800,", "Tmax", "=", "0.878", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.026", "wR(F", "2)", "=", "0.071", "S", "=", "1.01", "4844", "reflections", "310", "parameters", "1", "restraint", "organic", "compounds", "V", "=", "2788.7", "(5)", "A˚", "3", "Z", "=", "4", "Cu", "K", "radiation", "=", "0.67", "mm", "1", "T", "=", "86", "K", "0.35", "0.25", "0.20", "mm", "10823", "measured", "reflections", "4844", "independent", "reflections", "4782", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.023", "H-atom", "parameters", "constrained", "max", "=", "0.19", "e", "A˚", "3", "min", "=", "0.12", "e", "A˚", "3", "Absolute", "structure:", "Flack", "(1983),", "2174", "Friedel", "pairs", "Flack", "parameter:", "0.02", "(10)", "Data", "collection:", "APEX2", "(Bruker,", "2006);", "cell", "refinement:", "APEX2;", "data", "reduction:", "APEX2;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "for", "Windows", "(Farrugia,", "1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "WinGX", "(Farrugia,", "1999).", "We", "are", "grateful", "to", "Dr", "Umut", "Oguz", "for", "providing", "the", "crys-", "talline", "sample.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "PV2462).", "References", "Bruker", "(2006).", "APEX2.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Farrugia,", "L.", "J.", "(1999).", "J.", "Appl.", "Cryst.", "32,", "837–838.", "Flack,", "H.", "D.", "(1983).", "Acta", "Cryst.", "A39,", "876–881.", "Hooft,", "R.", "W.", "W.,", "Straver,", "L.", "H.", "&", "Spek,", "A.", "L.", "(2008).", "J.", "Appl.", "Cryst.", "41,", "96–103.", "Oguz,", "U.", "(2003).", "PhD", "dissertation,", "Louisiana", "State", "University,", "Baton", "Rouge,", "LA,", "USA.", "Oguz,", "U.,", "Gauthier,", "T.", "J.", "&", "McLaughlin,", "M.", "L.", "(2001).", "Peptides:", "the", "Wave", "of", "the", "Future.", "Proceedings", "of", "the", "2nd", "International", "and", "the", "17th", "American", "Peptide", "Symposium,", "San", "Diego,", "CA,", "USA,", "June", "9-14,", "2001,", "pp.", "46–47.", "San", "Diego:", "The", "American", "Peptide", "Society", "Sheldrick,", "G.", "(2004).", "SADABS.", "University", "of", "Go¨", "ttingen,", "Germany.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Valle,", "G.,", "Crisma,", "M.,", "Toniolo,", "C.,", "Yu,", "K.-L.", "&", "Johnson,", "R.", "L.", "(1989).", "J.", "Chem.", "Soc.", "Perkin", "Trans.", "2,", "pp.", "83–87.", "1", "CAS", "Registry", "Number", "500222-63-9.", "Acta", "Cryst.", "(2011).", "E67,", "o3057", "doi:10.1107/S1600536811043212", "Kangas", "et", "al.", "o3057" ]

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[ "Research", "|", "Children’s", "Health", "Lead", "Exposure", "and", "Behavior", "among", "Young", "Children", "in", "Chennai,", "India", "Ananya", "Roy,1", "David", "Bellinger,2,3", "Howard", "Hu,1,2,4", "Joel", "Schwartz,2,4", "Adrienne", "S.", "Ettinger,1,2,4", "Robert", "O.", "Wright,2,4,5", "Maryse", "Bouchard,2", "Kavitha", "Palaniappan,6", "and", "Kalpana", "Balakrishnan", "6", "1Department", "of", "Environmental", "Health", "Sciences,", "University", "of", "Michigan", "School", "of", "Public", "Health,", "Ann", "Arbor,", "Michigan,", "USA;", "2Depart-", "ment", "of", "Environmental", "Health,", "Harvard", "School", "of", "Public", "Health,", "Boston,", "Massachusetts,", "USA;", "3Department", "of", "Neurology,", "Children’s", "Hospital", "Boston,", "Boston,", "Massachusetts,", "USA;", "4Channing", "Laboratory,", "Brigham", "and", "Women’s", "Hospital,", "Boston,", "Massachusetts,", "USA;", "5Department", "of", "Medicine,", "Children’s", "Hospital", "Boston,", "Boston,", "Massachusetts,", "USA;", "6Department", "of", "Environmental", "Health", "Engineering,", "Sri", "Ramachandra", "Medical", "College", "and", "Research", "Institute,", "Chennai,", "Tamil", "Nadu,", "India", "Bdnuorgkca", ":", "Lead", "exposure", "has", "long", "been", "associated", "with", "deficits", "in", "IQ", "among", "children.", "However,", "few", "studies", "have", "assessed", "the", "impact", "of", "lead", "on", "specific", "domains", "of", "behavior", "and", "cognition.", "o", "Bjectiv", ":", "We", "evaluated", "the", "associations", "between", "lead", "and", "different", "domains", "of", "neurobehavior", "and", "their", "relative", "sensitivity", "to", "lead.", "Msdohte", ":", "We", "determined", "blood", "lead", "levels", "using", "a", "LeadCare", "instrument", "in", "756", "children", "3–7", "years", "of", "age", "attending", "pre-", "and", "elementary", "schools", "in", "Chennai,", "India.", "Anxiety,", "social", "problems,", "inatten-", "tion,", "hyperactivity,", "and", "attention", "deficit", "hyperactivity", "disorder", "(ADHD),", "as", "well", "as", "executive", "function", "were", "assessed", "in", "children", "by", "their", "schoolteachers", "using", "Conners’", "Teacher", "Rating", "Scales-39,", "Conners’", "ADHD/Diagnostic", "and", "Statistical", "Manual", "for", "Mental", "Disorders,", "4th", "Edition", "Scales", "(CADS),", "and", "the", "Behavior", "Rating", "Inventory", "of", "Executive", "Function", "questionnaires,", "with", "higher", "scores", "denoting", "worse", "behavior.", "Analyses", "were", "carried", "out", "using", "multivariate", "generalized", "estimating", "equations", "with", "com-", "parisons", "of", "outcome", "Z-scores", "to", "assess", "the", "relative", "strengths", "of", "the", "associations", "between", "log-blood", "lead", "and", "the", "different", "domains", "of", "behavior.", "r", "tluse", ":", "Mean", "blood", "lead", "level", "was", "11.4", "±", "5.3", "µg/dL.", "Blood", "lead", "was", "associated", "with", "higher", "anxiety", "(β", "=", "0.27,", "p", "=", "0.01),", "social", "problems", "(β", "=", "0.20,", "p", "=", "0.02),", "and", "higher", "scores", "in", "the", "ADHD", "index", "(β", "=", "0.17;", "p", "=", "0.05).", "The", "effect", "estimate", "was", "highest", "for", "global", "executive", "function", "(β", "=", "0.42;", "p", "<", "0.001).", "c", "onclusi", ":", "Higher", "blood", "lead", "levels", "in", "this", "population", "of", "young", "children", "is", "associated", "with", "increased", "risk", "of", "neurobehavioral", "deficits", "and", "ADHD,", "with", "executive", "function", "and", "attention", "being", "particularly", "vulnerable", "domains", "to", "the", "effects", "of", "lead.", "k", "ey", "words", ":", "ADHD,", "anxiety,", "blood", "lead,", "children,", "executive", "function,", "India,", "sociability.", "Environ", "Health", "Perspect", "117:1607–1611", "(2009).", "doi:10.1289/ehp.0900625", "available", "via", "http://dx.doi.org/", "[Online", "26", "June", "2009]", "The", "removal", "of", "lead", "from", "sources", "in", "the", "environment,", "such", "as", "gasoline", "and", "residential", "paint,", "have", "resulted", "in", "declines", "in", "blood", "lead", "levels", "in", "many", "countries", "[Centers", "for", "Disease", "Control", "and", "Prevention", "(CDC)", "1997,", "2005a].", "In", "India,", "leaded", "gasoline", "was", "phased", "out", "in", "early", "2001.", "Nichani", "et", "al.", "(2006)", "reported", "that", "37%", "of", "children", "in", "Mumbai", "in", "2002", "had", "blood", "lead", "levels", ">", "10", "µg/dL,", "the", "CDC", "level", "of", "concern", "for", "blood", "lead", "(CDC", "2005b),", "down", "from", "60%", "in", "1997.", "Other", "studies", "describe", "continued", "elevations", "in", "blood", "lead", "levels", "among", "children", "in", "other", "parts", "of", "the", "country", "(Ahamed", "et", "al.", "2006;", "Bellinger", "et", "al.", "2005).", "Many", "studies", "have", "shown", "that", "lead", "exposure", "is", "associated", "with", "significant", "defi-", "cits", "in", "intelligence", "quotient", "(IQ)", "of", "children", "(Lanphear", "et", "al.", "2005).", "However,", "IQ", "is", "a", "global", "construct", "of", "cognition,", "and", "fewer", "studies", "have", "assessed", "the", "impact", "of", "lead", "on", "specific", "domains", "of", "behavior", "and", "cognition,", "such", "as", "executive", "function", "(Canfield", "et", "al.", "2003,", "2004;", "Froehlich", "et", "al.", "2007),", "attention", "(Bellinger", "et", "al.", "1994;", "Stiles", "and", "Bellinger", "1993),", "and", "internaliz-", "ing", "behaviors.", "Recent", "evidence", "suggests", "that", "increased", "lead", "exposure", "is", "associated", "with", "atten-", "tion", "deficit", "hyperactivity", "disorder", "(ADHD)", "(Braun", "et", "al.", "2006;", "Nigg", "2008)", "and", "conduct", "disorder", "(Needleman", "et", "al.", "2002;", "Nevin", "2000).", "Currently,", "relatively", "little", "is", "known", "about", "the", "shape", "of", "the", "dose–response", "relationships", "or", "the", "relative", "sensitivity", "of", "behavioral", "domains", "to", "lead", "toxicity.", "Only", "one", "study", "has", "reported", "on", "the", "relationship", "between", "lead", "exposure", "and", "behav-", "ior,", "as", "well", "as", "other", "cognitive", "outcomes", "among", "children", "in", "India", "(Bellinger", "et", "al.", "2005).", "The", "objective", "of", "this", "study", "was", "to", "explore", "the", "associations", "between", "lead", "and", "specific", "neurobehavioral", "outcomes", "such", "as", "ADHD-", "like", "behaviors,", "executive", "function,", "and", "inter-", "nalizing", "problems", "(anxiety", "and", "sociability)", "in", "a", "cohort", "of", "children", "3–7", "years", "of", "age", "in", "Chennai,", "India.", "In", "addition,", "we", "investigated", "the", "shape", "of", "the", "dose–response", "relationships", "and", "the", "relative", "sensitivity", "of", "the", "different", "behavioral", "outcomes", "to", "lead", "exposure.", "Methods", "Study", "population.", "This", "cross-sectional", "study", "of", "814", "children", "was", "carried", "out", "during", "2005–2006", "in", "Chennai,", "India.", "Four", "traffic", "and", "industry", "zones", "were", "selected", "on", "the", "basis", "of", "industrial", "zoning", "information", "provided", "by", "the", "Tamil", "Nadu", "State", "Pollution", "Control", "Board", "and", "the", "Chennai", "traffic", "police", "department.", "Children", "3–7", "years", "of", "age", "were", "recruited", "from", "12", "schools", "(three", "schools", "within", "each", "zone).", "Informed", "consent", "was", "obtained", "from", "each", "child’s", "primary", "caregiver.", "Venous", "blood", "was", "collected", "from", "each", "child,", "and", "questionnaires", "Environmental", "Health", "Perspectives", "•", "volume", "117", "|", "number", "10", "|", "October", "2009", "were", "administered", "in", "Tamil", "(the", "regional", "lan-", "guage)", "to", "the", "teachers", "and", "primary", "caregivers", "(usually", "the", "mothers)", "of", "the", "children.", "A", "semi-", "quantitative", "food", "frequency", "questionnaire", "was", "used", "to", "assess", "nutritional", "status.", "Information", "was", "collected", "on", "a", "family’s", "average", "monthly", "income,", "educational", "attainment", "and", "occupa-", "tion", "of", "the", "parents,", "and", "type", "of", "housing.", "Data", "on", "family", "size,", "maternal", "age", "at", "birth", "of", "child,", "and", "child’s", "age,", "birth", "weight,", "and", "birth", "rank", "were", "also", "collected.", "This", "investigation", "was", "conducted", "as", "part", "of", "a", "collaborative", "study", "between", "the", "Harvard", "School", "of", "Public", "Health", "(HSPH),", "Boston,", "Massachusetts", "(USA),", "and", "Sri", "Ramachandra", "Medical", "College", "and", "Research", "Institute", "(SRMC),", "Chennai,", "India,", "on", "lead", "genetics", "and", "neurotoxicity.", "The", "study", "was", "approved", "by", "institutional", "review", "boards", "at", "HSPH,", "SRMC,", "the", "University", "of", "Michigan,", "and", "the", "Indian", "Council", "for", "Medical", "Research,", "New", "Delhi,", "India,", "and", "complied", "with", "U.S.", "federal", "and", "Indian", "regulations", "and", "laws", "regarding", "research", "on", "human", "subjects.", "Blood", "lead", "measurement.", "Blood", "was", "col-", "lected", "from", "the", "cubital", "vein", "of", "each", "child", "into", "lead-free", "tubes", "(royal", "blue", "top", "tubes", "#369736;", "Becton-Dickinson,", "Franklin", "Lakes,", "NJ,", "USA)", "by", "a", "trained", "phlebotomist", "during", "a", "school", "day.", "The", "blood", "was", "transferred", "to", "the", "laboratory", "at", "SRMC,", "and", "blood", "lead", "was", "measured", "using", "Anodic", "Stripping", "Voltammetry", "by", "a", "LeadCare", "Analyzer", "(ESA", "Laboratories,", "Chelmsford,", "MA,", "USA),", "which", "is", "a", "well-validated", "field", "instru-", "ment", "with", "sensitivity", "of", "1", "µg/dL", "blood", "lead", "(Shannon", "and", "Rifai", "1997).", "Duplicates", "and", "controls", "were", "run", "with", "every", "20", "samples,", "every", "new", "batch,", "and", "kit", "lot.", "Fifty-eight", "children", "Address", "correspondence", "to", "A.", "Roy,", "University", "of", "Michigan", "School", "of", "Public", "Health,", "Department", "of", "Environmental", "Health", "Sciences,", "109", "South", "Observatory", "St.,", "Building", "1,", "Ann", "Arbor,", "MI", "48109", "USA.", "Telephone:", "(617)", "642-1376.", "Fax:", "(734)", "936-", "7283.", "E-mail:", "aroyk@umich.edu", "This", "study", "was", "supported", "by", "U.S.", "National", "Institutes", "of", "Health", "(NIH)", "grants", "1R03TW005914", "and", "R01ES007821.", "This", "work", "was", "carried", "out", "as", "a", "part", "of", "the", "Sc.D.", "thesis", "of", "A.R.", "at", "the", "Harvard", "School", "of", "Public", "Health,", "where", "she", "was", "supported", "by", "the", "training", "core", "of", "NIH", "P42-ES05947.", "The", "contents", "of", "this", "study", "are", "solely", "the", "responsi-", "bility", "of", "the", "authors", "and", "do", "not", "necessarily", "represent", "the", "official", "views", "of", "the", "NIH.", "The", "authors", "declare", "they", "have", "no", "competing", "financial", "interests.", "Received", "28", "January", "2009;", "accepted", "26", "June", "2009.", "1607" ]

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[ "Takuma", "et", "al.", "World", "Journal", "of", "Surgical", "Oncology", "2011,", "9:153", "http://www.wjso.com/content/9/1/153", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "WORLD", "JOURNAL", "OF", "SURGICAL", "ONCOLOGY", "Open", "Access", "Main-duct", "intraductal", "papillary", "mucinous", "adenoma", "of", "the", "pancreas", "Kensuke", "Takuma1,", "Terumi", "Kamisawa1*,", "Taku", "Tabata1,", "Masanao", "Kurata2,", "Goro", "Honda2", "and", "Shin-ichiro", "Horiguchi3", "Abstract", "Background:", "The", "prevalence", "of", "carcinoma", "in", "main-duct", "intraductal", "papillary", "mucinous", "neoplasm", "(IPMN)", "is", "high,", "and", "surgical", "resection", "is", "recommended", "for", "all", "patients", "with", "a", "main-duct", "IPMN.", "Results:", "A", "main-duct", "IPMN", "with", "typical", "imagings", "including", "protruding", "lesions", "in", "the", "dilated", "main", "pancreatic", "duct", "was", "resected,", "but", "the", "histology", "was", "intraductal", "papillary", "mucinous", "adenoma", "of", "the", "pancreas.", "Discussion:", "It", "has", "been", "reported", "that", "the", "presence", "of", "mural", "nodules", "and", "dilatation", "of", "MPD", "are", "significantly", "higher", "in", "malignant", "IPMNs.", "The", "presented", "case", "had", "protruding", "lesions", "in", "the", "dilated", "main", "pancreatic", "duct", "on", "endoscopic", "ultrasonography,", "but", "the", "histology", "was", "adenoma.", "Conclusion:", "Preoperative", "distinction", "between", "benign", "and", "malignant", "IPMNs", "is", "difficult.", "Keywords:", "intraductal", "papillary", "mucinous", "neoplasm,", "main", "duct,", "mural", "nodule,", "IPMN", "Background", "Intraductal", "papillary", "mucinous", "neoplasm", "(IPMN)", "of", "the", "pancreas", "is", "a", "distinct", "entity", "characterized", "by", "intraductal", "papillary", "growth", "and", "thick", "mucus", "secretion.", "Copious", "mucous", "fills", "the", "main", "and", "branch", "pancreatic", "ducts", "and", "causes", "ductal", "dilation.", "Thus,", "IPMNs", "of", "the", "pancreas", "are", "being", "diagnosed", "with", "increasing", "frequency", "by", "radiologic", "findings.", "IPMNs", "are", "pathologically", "classified", "into", "two", "types", "based", "on", "site", "of", "tumor", "involvement,", "that", "is,", "main-duct", "type", "or", "branch", "type.", "The", "histology", "is", "classified", "into", "intraductal", "adenocarcinoma,", "intraductal", "adenoma,", "and", "hyperplasia.", "It", "has", "been", "suggested", "that", "these", "lesions", "have", "the", "capacity", "to", "progress", "from", "hyperplasia", "to", "adenoma,", "to", "noninvasive", "car-", "cinoma,", "and", "ultimately", "to", "invasive", "carcinoma.", "The", "preva-", "lence", "of", "carcinoma", "in", "main-duct", "IPMN", "is", "as", "high", "as", "60%", "[1]", "to", "92%", "[2],", "and", "international", "consensus", "guidelines", "[3]", "recommend", "surgical", "resection", "for", "all", "patients", "with", "a", "main-", "duct", "IPMN.", "In", "preoperative", "diagnosis,", "it", "is", "evaluated", "the", "existence", "of", "mural", "nodule", "increase", "the", "risk", "of", "malignancy", "[3-5].", "Whereas,", "there", "are", "various", "unanswered", "problems", "about", "the", "conditions", "of", "main-duct", "type", "IPMNs.", "It", "is", "*", "Correspondence:", "kamisawa@cick.jp", "1Departments", "of", "Internal", "Medicine,", "Tokyo", "Metropolitan", "Komagome", "Hospital,", "Tokyo,", "Japan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "unknown", "whether", "all", "IPMNs", "have", "malignant", "potential", "or", "what", "the", "time", "course", "of", "progression", "may", "be.", "Case", "presentation", "A", "56-year-old", "man", "presented", "with", "mild", "abdominal", "pain.", "Physical", "examination", "and", "laboratory", "data", "were", "unremark-", "able.", "Abdominal", "symptoms", "were", "relieved", "with", "conservative", "medical", "management", "within", "a", "few", "days.", "Abdominal", "ultra-", "sonography", "showed", "dilation", "of", "the", "main", "pancreatic", "duct", "(MPD).", "Subsequent", "computed", "tomography", "scan", "showed", "dilatation", "of", "the", "MPD", "and", "several", "small", "cysts", "in", "the", "pancreatic", "tail,", "with", "no", "findings", "of", "mural", "nodules,", "mass", "formation,", "metastasis,", "or", "lymph", "node", "swelling.", "Magnetic", "resonance", "cholangiopancreatography", "(MRCP)", "showed", "an", "irregular", "dilatation", "(10", "mm)", "of", "the", "MPD", "of", "the", "tail", "[Figure", "1].", "On", "duodenoscopy,", "mucin", "was", "secreted", "from", "a", "patulous", "orifice", "of", "the", "papilla", "of", "Vater.", "On", "endoscopic", "retrograde", "pancreatography,", "a", "filling", "defect", "equivalent", "to", "mucus", "was", "shown", "in", "the", "dilated", "MPD.", "Cytological", "examination", "of", "the", "pancreatic", "fluid", "was", "negative,", "and", "CEA", "level", "in", "the", "pan-", "creatic", "fluid", "was", "2.3", "ng/ml.", "Endoscopic", "ultrasonography", "(EUS)", "revealed", "hyperplastic", "or", "polypoid", "growth", "of", "the", "epithelial", "layer", "and", "hyperechoic", "ductal", "margin", "of", "the", "irre-", "gularly", "dilated", "MPD", "[Figure", "2].", "Under", "a", "diagnosis", "of", "main-", "duct", "IPMN,", "laparoscopy-assisted", "distal", "pancreatectomy", "was", "performed.", "Cut", "surface", "of", "the", "resected", "specimen", "©", "2011", "Takuma", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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