diff --git "a/test_predictions.txt" "b/test_predictions.txt"
new file mode 100644--- /dev/null
+++ "b/test_predictions.txt"
@@ -0,0 +1,32303 @@
+A O
+novel O
+SCN5A O
+mutation O
+manifests O
+as O
+a O
+malignant O
+form O
+of O
+long B
+QT I
+syndrome I
+with O
+perinatal O
+onset O
+of O
+tachycardia B
+/ O
+bradycardia I
+. O
+
+OBJECTIVE O
+: O
+Congenital B
+long I
+QT I
+syndrome I
+( O
+LQTS B
+) O
+with O
+in O
+utero O
+onset O
+of O
+the O
+rhythm O
+disturbances O
+is O
+associated O
+with O
+a O
+poor O
+prognosis O
+. O
+
+In O
+this O
+study O
+we O
+investigated O
+a O
+newborn O
+patient O
+with O
+fetal B
+bradycardia I
+, O
+2 O
+: O
+1 O
+atrioventricular B
+block I
+and O
+ventricular B
+tachycardia I
+soon O
+after O
+birth O
+. O
+
+METHODS O
+: O
+Mutational O
+analysis O
+and O
+DNA O
+sequencing O
+were O
+conducted O
+in O
+a O
+newborn O
+. O
+
+The O
+2 O
+: O
+1 O
+atrioventricular B
+block I
+improved O
+to O
+1 O
+: O
+1 O
+conduction O
+only O
+after O
+intravenous O
+lidocaine B
+infusion O
+or O
+a O
+high O
+dose O
+of O
+mexiletine B
+, O
+which O
+also O
+controlled O
+the O
+ventricular B
+tachycardia I
+. O
+
+RESULTS O
+: O
+A O
+novel O
+, O
+spontaneous O
+LQTS O
+- O
+3 O
+mutation O
+was O
+identified O
+in O
+the O
+transmembrane O
+segment O
+6 O
+of O
+domain O
+IV O
+of O
+the O
+Na O
+( O
+v O
+) O
+1 O
+. O
+5 O
+cardiac O
+sodium O
+channel O
+, O
+with O
+a O
+G O
+--> O
+A O
+substitution O
+at O
+codon O
+1763 O
+, O
+which O
+changed O
+a O
+valine O
+( O
+GTG O
+) O
+to O
+a O
+methionine O
+( O
+ATG O
+). O
+
+The O
+proband O
+was O
+heterozygous O
+but O
+the O
+mutation O
+was O
+absent O
+in O
+the O
+parents O
+and O
+the O
+sister O
+. O
+
+Expression O
+of O
+this O
+mutant O
+channel O
+in O
+tsA201 O
+mammalian O
+cells O
+by O
+site O
+- O
+directed O
+mutagenesis O
+revealed O
+a O
+persistent O
+tetrodotoxin B
+- O
+sensitive O
+but O
+lidocaine B
+- O
+resistant O
+current O
+that O
+was O
+associated O
+with O
+a O
+positive O
+shift O
+of O
+the O
+steady O
+- O
+state O
+inactivation O
+curve O
+, O
+steeper O
+activation O
+curve O
+and O
+faster O
+recovery O
+from O
+inactivation O
+. O
+
+We O
+also O
+found O
+a O
+similar O
+electrophysiological O
+profile O
+for O
+the O
+neighboring O
+V1764M O
+mutant O
+. O
+
+But O
+, O
+the O
+other O
+neighboring O
+I1762A O
+mutant O
+had O
+no O
+persistent O
+current O
+and O
+was O
+still O
+associated O
+with O
+a O
+positive O
+shift O
+of O
+inactivation O
+. O
+
+CONCLUSIONS O
+: O
+These O
+findings O
+suggest O
+that O
+the O
+Na O
+( O
+v O
+) O
+1 O
+. O
+5 O
+/ O
+V1763M O
+channel O
+dysfunction O
+and O
+possible O
+neighboring O
+mutants O
+contribute O
+to O
+a O
+persistent O
+inward O
+current O
+due O
+to O
+altered O
+inactivation O
+kinetics O
+and O
+clinically O
+congenital O
+LQTS B
+with O
+perinatal O
+onset O
+of O
+arrhythmias B
+that O
+responded O
+to O
+lidocaine B
+and O
+mexiletine B
+. O
+
+
+Allelic O
+expression O
+imbalance O
+of O
+human O
+mu O
+opioid O
+receptor O
+( O
+OPRM1 O
+) O
+caused O
+by O
+variant O
+A118G O
+. O
+
+As O
+a O
+primary O
+target O
+for O
+opioid B
+drugs O
+and O
+peptides O
+, O
+the O
+mu O
+opioid O
+receptor O
+( O
+OPRM1 O
+) O
+plays O
+a O
+key O
+role O
+in O
+pain B
+perception O
+and O
+addiction O
+. O
+
+Genetic O
+variants O
+of O
+OPRM1 O
+have O
+been O
+implicated O
+in O
+predisposition O
+to O
+drug B
+addiction I
+, O
+in O
+particular O
+the O
+single O
+nucleotide O
+polymorphism O
+A118G O
+, O
+leading O
+to O
+an O
+N40D O
+substitution O
+, O
+with O
+an O
+allele O
+frequency O
+of O
+10 O
+- O
+32 O
+%, O
+and O
+uncertain O
+functions O
+. O
+
+We O
+have O
+measured O
+allele O
+- O
+specific O
+mRNA O
+expression O
+of O
+OPRM1 O
+in O
+human O
+autopsy O
+brain O
+tissues O
+, O
+using O
+A118G O
+as O
+a O
+marker O
+. O
+
+In O
+8 O
+heterozygous O
+samples O
+measured O
+, O
+the O
+A118 O
+mRNA O
+allele O
+was O
+1 O
+. O
+5 O
+- O
+2 O
+. O
+5 O
+- O
+fold O
+more O
+abundant O
+than O
+the O
+G118 O
+allele O
+. O
+
+Transfection O
+into O
+Chinese O
+hamster O
+ovary O
+cells O
+of O
+a O
+cDNA O
+representing O
+only O
+the O
+coding O
+region O
+of O
+OPRM1 O
+, O
+carrying O
+adenosine O
+, O
+guanosine O
+, O
+cytidine O
+, O
+and O
+thymidine O
+in O
+position O
+118 O
+, O
+resulted O
+in O
+1 O
+. O
+5 O
+- O
+fold O
+lower O
+mRNA O
+levels O
+only O
+for O
+OPRM1 O
+- O
+G118 O
+, O
+and O
+more O
+than O
+10 O
+- O
+fold O
+lower O
+OPRM1 O
+protein O
+levels O
+, O
+measured O
+by O
+Western O
+blotting O
+and O
+receptor O
+binding O
+assay O
+. O
+
+After O
+transfection O
+and O
+inhibition O
+of O
+transcription O
+with O
+actinomycin B
+D I
+, O
+analysis O
+of O
+mRNA O
+turnover O
+failed O
+to O
+reveal O
+differences O
+in O
+mRNA O
+stability O
+between O
+A118 O
+and O
+G118 O
+alleles O
+, O
+indicating O
+a O
+defect O
+in O
+transcription O
+or O
+mRNA O
+maturation O
+. O
+
+These O
+results O
+indicate O
+that O
+OPRM1 O
+- O
+G118 O
+is O
+a O
+functional O
+variant O
+with O
+deleterious O
+effects O
+on O
+both O
+mRNA O
+and O
+protein O
+yield O
+. O
+
+Clarifying O
+the O
+functional O
+relevance O
+of O
+polymorphisms O
+associated O
+with O
+susceptibility O
+to O
+a O
+complex O
+disorder O
+such O
+as O
+drug B
+addiction I
+provides O
+a O
+foundation O
+for O
+clinical O
+association O
+studies O
+. O
+
+
+Genetic O
+polymorphisms O
+in O
+the O
+carbonyl O
+reductase O
+3 O
+gene O
+CBR3 O
+and O
+the O
+NAD O
+( O
+P O
+) O
+H O
+: O
+quinone O
+oxidoreductase O
+1 O
+gene O
+NQO1 O
+in O
+patients O
+who O
+developed O
+anthracycline B
+- O
+related O
+congestive B
+heart I
+failure I
+after O
+childhood O
+cancer B
+. O
+
+BACKGROUND O
+: O
+Exposure O
+to O
+anthracyclines B
+as O
+part O
+of O
+cancer B
+therapy O
+has O
+been O
+associated O
+with O
+the O
+development O
+of O
+congestive B
+heart I
+failure I
+( O
+CHF B
+). O
+
+The O
+potential O
+role O
+of O
+genetic O
+risk O
+factors O
+in O
+anthracycline B
+- O
+related O
+CHF O
+remains O
+to O
+be O
+defined O
+. O
+
+Thus O
+, O
+in O
+this O
+study O
+, O
+the O
+authors O
+examined O
+whether O
+common O
+polymorphisms O
+in O
+candidate O
+genes O
+involved O
+in O
+the O
+pharmacodynamics O
+of O
+anthracyclines B
+( O
+in O
+particular O
+, O
+the O
+nicotinamide O
+adenine O
+dinucleotide O
+phosphate O
+: O
+quinone O
+oxidoreductase O
+1 O
+gene O
+NQO1 O
+and O
+the O
+carbonyl O
+reductase O
+3 O
+gene O
+CBR3 O
+) O
+had O
+an O
+impact O
+on O
+the O
+risk O
+of O
+anthracycline B
+- O
+related O
+CHF B
+. O
+
+METHODS O
+: O
+A O
+nested O
+case O
+- O
+control O
+study O
+was O
+conducted O
+within O
+a O
+cohort O
+of O
+1979 O
+patients O
+enrolled O
+in O
+the O
+Childhood B
+Cancer I
+Survivor O
+Study O
+who O
+received O
+treatment O
+with O
+anthracyclines B
+and O
+had O
+available O
+DNA O
+. O
+
+Thirty O
+patients O
+with O
+CHF B
+( O
+cases O
+) O
+and O
+115 O
+matched O
+controls O
+were O
+genotyped O
+for O
+polymorphisms O
+in O
+NQO1 O
+( O
+NQO1 O
+* O
+2 O
+) O
+and O
+CBR3 O
+( O
+the O
+CBR3 O
+valine O
+[ O
+V O
+] O
+to O
+methionine O
+[ O
+M O
+] O
+substitution O
+at O
+position O
+244 O
+[ O
+V244M O
+]). O
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+Enzyme O
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+( O
+CBR3 O
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+CBR3 O
+M244 O
+) O
+and O
+the O
+anthracycline B
+substrate O
+doxorubicin B
+were O
+used O
+to O
+investigate O
+the O
+functional O
+impact O
+of O
+the O
+CBR3 O
+V244M O
+polymorphism O
+. O
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+RESULTS O
+: O
+Multivariate O
+analyses O
+adjusted O
+for O
+sex O
+and O
+primary O
+disease O
+recurrence O
+were O
+used O
+to O
+test O
+for O
+associations O
+between O
+the O
+candidate O
+genetic O
+polymorphisms O
+( O
+NQO1 O
+* O
+2 O
+and O
+CBR3 O
+V244M O
+) O
+and O
+the O
+risk O
+of O
+CHF B
+. O
+
+Analyses O
+indicated O
+no O
+association O
+between O
+the O
+NQO1 O
+* O
+2 O
+polymorphism O
+and O
+the O
+risk O
+of O
+anthracycline B
+- O
+related O
+CHF B
+( O
+odds O
+ratio O
+[ O
+OR O
+], O
+1 O
+. O
+4 O
+; O
+P O
+=. O
+97 O
+). O
+
+There O
+was O
+a O
+trend O
+toward O
+an O
+association O
+between O
+the O
+CBR3 O
+V244M O
+polymorphism O
+and O
+the O
+risk O
+of O
+CHF B
+( O
+OR O
+, O
+8 O
+. O
+16 O
+; O
+P O
+=. O
+56 O
+for O
+G O
+/ O
+G O
+vs O
+A O
+/ O
+A O
+; O
+OR O
+, O
+5 O
+. O
+44 O
+; O
+P O
+=. O
+92 O
+for O
+G O
+/ O
+A O
+vs O
+A O
+/ O
+A O
+). O
+
+In O
+line O
+, O
+recombinant O
+CBR3 O
+V244 O
+( O
+G O
+allele O
+) O
+synthesized O
+2 O
+. O
+6 O
+- O
+fold O
+more O
+cardiotoxic O
+doxorubicinol B
+per O
+unit O
+of O
+time O
+than O
+CBR3 O
+M244 O
+( O
+A O
+allele O
+; O
+CBR3 O
+V244 O
+[ O
+8 O
+. O
+26 O
++/- O
+3 O
+. O
+57 O
+nmol O
+/ O
+hour O
+. O
+mg O
+] O
+vs O
+CBR3 O
+M244 O
+[ O
+3 O
+. O
+22 O
++/- O
+0 O
+. O
+67 O
+nmol O
+/ O
+hour O
+. O
+mg O
+]; O
+P O
+=. O
+1 O
+). O
+
+CONCLUSIONS O
+: O
+The O
+functional O
+CBR3 O
+V244M O
+polymorphism O
+may O
+have O
+an O
+impact O
+on O
+the O
+risk O
+of O
+anthracycline B
+- O
+related O
+CHF B
+among O
+childhood B
+cancer I
+survivors O
+by O
+modulating O
+the O
+intracardiac O
+formation O
+of O
+cardiotoxic O
+anthracycline B
+alcohol I
+metabolites O
+. O
+
+Larger O
+confirmatory O
+case O
+- O
+control O
+studies O
+are O
+warranted O
+. O
+
+
+Debrisoquine B
+phenotype O
+and O
+the O
+pharmacokinetics O
+and O
+beta O
+- O
+2 O
+receptor O
+pharmacodynamics O
+of O
+metoprolol B
+and O
+its O
+enantiomers O
+. O
+
+The O
+metabolism O
+of O
+the O
+cardioselective O
+beta O
+- O
+blocker O
+metoprolol B
+is O
+under O
+genetic O
+control O
+of O
+the O
+debrisoquine O
+/ O
+sparteine O
+type O
+. O
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+The O
+two O
+metabolic O
+phenotypes O
+, O
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+( O
+EM O
+) O
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+poor O
+metabolizers O
+( O
+PM O
+), O
+show O
+different O
+stereoselective O
+metabolism O
+, O
+resulting O
+in O
+apparently O
+higher O
+beta O
+- O
+1 O
+adrenoceptor O
+antagonistic O
+potency O
+of O
+racemic O
+metoprolol B
+in O
+EMs O
+. O
+
+We O
+investigated O
+if O
+the O
+latter O
+also O
+applies O
+to O
+the O
+beta O
+- O
+2 O
+adrenoceptor O
+antagonism O
+by O
+metoprolol B
+. O
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+The O
+drug O
+effect O
+studied O
+was O
+the O
+antagonism O
+by O
+metoprolol B
+of O
+terbutaline B
+- O
+induced O
+hypokalemia B
+. O
+
+By O
+using O
+pharmacokinetic O
+pharmacodynamic O
+modeling O
+the O
+pharmacodynamics O
+of O
+racemic O
+metoprolol B
+and O
+the O
+active O
+S O
+- O
+isomer O
+, O
+were O
+quantitated O
+in O
+EMs O
+and O
+PMs O
+in O
+terms O
+of O
+IC50 O
+values O
+, O
+representing O
+metoprolol B
+plasma O
+concentrations O
+resulting O
+in O
+half O
+- O
+maximum O
+receptor O
+occupancy O
+. O
+
+Six O
+EMs O
+received O
+0 O
+. O
+5 O
+mg O
+of O
+terbutaline B
+s O
+. O
+c O
+. O
+
+on O
+two O
+different O
+occasions O
+: O
+1 O
+) O
+1 O
+hr O
+after O
+administration O
+of O
+a O
+placebo O
+and O
+2 O
+) O
+1 O
+hr O
+after O
+150 O
+mg O
+of O
+metoprolol B
+p O
+. O
+o O
+. O
+
+Five O
+PMs O
+were O
+studied O
+according O
+to O
+the O
+same O
+protocol O
+, O
+except O
+for O
+a O
+higher O
+terbutaline B
+dose O
+( O
+0 O
+. O
+75 O
+mg O
+) O
+on O
+day O
+2 O
+. O
+
+Blood O
+samples O
+for O
+the O
+analysis O
+of O
+plasma O
+potassium B
+, O
+terbutaline B
+, O
+metoprolol B
+( O
+racemic O
+, O
+R O
+- O
+and O
+S O
+- O
+isomer O
+), O
+and O
+alpha B
+- I
+hydroxymetoprolol I
+concentrations O
+were O
+taken O
+at O
+regular O
+time O
+intervals O
+, O
+during O
+8 O
+hr O
+after O
+metoprolol B
+. O
+
+In O
+PMs O
+, O
+metoprolol B
+increased O
+the O
+terbutaline B
+area O
+under O
+the O
+plasma O
+concentration O
+vs O
+. O
+
+time O
+curve O
+(+ O
+67 O
+%). O
+
+Higher O
+metoprolol B
+/ O
+alpha B
+- I
+hydroxymetoprolol I
+ratios O
+in O
+PMs O
+were O
+predictive O
+for O
+higher O
+R O
+-/ O
+S O
+- O
+isomer O
+ratios O
+of O
+unchanged O
+drug O
+. O
+
+There O
+was O
+a O
+difference O
+in O
+metoprolol B
+potency O
+with O
+higher O
+racemic O
+metoprolol B
+IC50 O
+values O
+in O
+PMs O
+( O
+72 O
++/- O
+7 O
+ng O
+. O
+ml O
+- O
+1 O
+) O
+than O
+EMs O
+( O
+42 O
++/- O
+8 O
+ng O
+. O
+ml O
+- O
+1 O
+, O
+P O
+less O
+than O
+. O
+1 O
+). O
+
+( O
+ABSTRACT O
+TRUNCATED O
+AT O
+250 O
+WORDS O
+) O
+
+
+The O
+first O
+founder O
+DGUOK O
+mutation O
+associated O
+with O
+hepatocerebral B
+mitochondrial B
+DNA I
+depletion I
+syndrome I
+. O
+
+Deoxyguanosine B
+kinase I
+( I
+dGK O
+) I
+deficiency I
+is O
+a O
+frequent O
+cause O
+of O
+mitochondrial B
+DNA I
+depletion I
+associated O
+with O
+a O
+hepatocerebral B
+phenotype O
+. O
+
+In O
+this O
+study O
+, O
+we O
+describe O
+a O
+new O
+splice O
+site O
+mutation O
+in O
+the O
+DGUOK O
+gene O
+and O
+the O
+clinical O
+, O
+radiologic O
+, O
+and O
+genetic O
+features O
+of O
+these O
+DGUOK B
+patients O
+. O
+
+This O
+new O
+DGUOK O
+homozygous O
+mutation O
+( O
+c O
+. O
+444 O
+- O
+62C O
+> O
+A O
+) O
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+identified O
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+- O
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+In O
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+anxiety B
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+Patients O
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+= O
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++ O
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++ O
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++ O
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+Identification O
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+novel O
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+family O
+with O
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+PURPOSE O
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+1 O
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+family O
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+The O
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+CONCLUSIONS O
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+Duchenne O
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+gene O
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+A1 O
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+medulla O
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+Targeting O
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+signaling O
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+0 O
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+WT O
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+urine O
+output O
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+
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+> O
+C O
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+or O
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+
+Cardioprotective O
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+= O
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+= O
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+= O
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+In O
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+These O
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+The O
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+= O
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+population O
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+
+Transgelin O
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+metastatic O
+potential O
+of O
+colorectal B
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+in O
+vivo O
+and O
+alters O
+expression O
+of O
+genes O
+involved O
+in O
+cell O
+motility O
+. O
+
+BACKGROUND O
+: O
+Transgelin O
+is O
+an O
+actin O
+- O
+binding O
+protein O
+that O
+promotes O
+motility O
+in O
+normal O
+cells O
+. O
+
+Although O
+the O
+role O
+of O
+transgelin O
+in O
+cancer B
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+controversial O
+, O
+a O
+number O
+of O
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+have O
+shown O
+that O
+elevated O
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+with O
+aggressive O
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+stage O
+, O
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+poor O
+prognosis O
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+
+Here O
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+sought O
+to O
+determine O
+the O
+role O
+of O
+transgelin O
+more O
+directly O
+by O
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+whether O
+experimental O
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+transgelin O
+levels O
+in O
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+CRC B
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+led O
+to O
+changes O
+in O
+metastatic O
+potential O
+in O
+vivo O
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+Isogenic O
+CRC B
+cell O
+lines O
+that O
+differ O
+in O
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+expression O
+were O
+characterized O
+using O
+in O
+vitro O
+assays O
+of O
+growth O
+and O
+invasiveness O
+and O
+a O
+mouse O
+tail O
+vein O
+assay O
+of O
+experimental O
+metastasis B
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+
+Downstream O
+effects O
+of O
+transgelin O
+overexpression O
+were O
+investigated O
+by O
+gene O
+expression O
+profiling O
+and O
+quantitative O
+PCR O
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+
+RESULTS O
+: O
+Stable O
+overexpression O
+of O
+transgelin O
+in O
+RKO O
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+which O
+have O
+low O
+endogenous O
+levels O
+, O
+led O
+to O
+increased O
+invasiveness O
+, O
+growth O
+at O
+low O
+density O
+, O
+and O
+growth O
+in O
+soft O
+agar O
+. O
+
+Overexpression O
+also O
+led O
+to O
+an O
+increase O
+in O
+the O
+number O
+and O
+size O
+of O
+lung B
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+the O
+mouse O
+tail O
+vein O
+injection O
+model O
+. O
+
+Similarly O
+, O
+attenuation O
+of O
+transgelin O
+expression O
+in O
+HCT116 O
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+, O
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+high O
+endogenous O
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+, O
+decreased O
+metastases B
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+the O
+same O
+model O
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+
+Investigation O
+of O
+mRNA O
+expression O
+patterns O
+showed O
+that O
+transgelin O
+overexpression O
+altered O
+the O
+levels O
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+approximately O
+250 O
+other O
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+, O
+with O
+over O
+- O
+representation O
+of O
+genes O
+that O
+affect O
+function O
+of O
+actin O
+or O
+other O
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+proteins O
+. O
+
+Changes O
+included O
+increases O
+in O
+HOOK1 O
+, O
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+, O
+ENAH O
+/ O
+Mena O
+, O
+and O
+TNS1 O
+and O
+decreases O
+in O
+EMB O
+, O
+BCL11B O
+, O
+and O
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+CONCLUSIONS O
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+mRNAs O
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+
+Association O
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+4 O
+- O
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+'- O
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+region O
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+extracellular O
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+OBJECTIVE O
+: O
+Certain O
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+in O
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+, O
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+a O
+multiple O
+- O
+pass O
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+- O
+dominant O
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+for O
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+promote O
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+The O
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+specific O
+variants O
+on O
+expression O
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+markers O
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+transcription O
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+translation O
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+The O
+function O
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+variants O
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+in O
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+- O
+8 O
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+Sporadic O
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+a O
+G O
+- O
+to O
+- O
+A O
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+ANKH O
+5 O
+'- O
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+region O
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+6 O
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+0 O
+, O
+P O
+= O
+0 O
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+6 O
+; O
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+association O
+P O
+= O
+0 O
+. O
+2 O
+). O
+
+This O
+- O
+4 O
+- O
+bp O
+transition O
+, O
+as O
+well O
+as O
+2 O
+mutations O
+previously O
+linked O
+with O
+familial O
+and O
+sporadic O
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+(+ O
+14 O
+bp O
+C O
+- O
+to O
+- O
+T O
+and O
+C O
+- O
+terminal O
+GAG O
+deletion O
+, O
+respectively O
+), O
+but O
+not O
+the O
+French O
+familial O
+chondrocalcinosis B
+kindred O
+143 O
+- O
+bp O
+T O
+- O
+to O
+- O
+C O
+mutation O
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+reticulocyte O
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+transcription O
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+ANKH O
+translation O
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+the O
+- O
+4 O
+- O
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+protein O
+variant O
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+the O
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+PPi O
+and O
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+chondrocyte B
+hypertrophy I
+marker O
+, O
+type O
+X O
+collagen O
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+CONCLUSION O
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+A O
+subset O
+of O
+sporadic O
+chondrocalcinosis B
+appears O
+to O
+be O
+heritable O
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+a O
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+4 O
+- O
+bp O
+G O
+- O
+to O
+- O
+A O
+ANKH O
+5 O
+'- O
+UTR O
+transition O
+that O
+up O
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+expression O
+of O
+ANKH O
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+in O
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+Distinct O
+ANKH O
+mutations O
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+with O
+heritable O
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+PPi O
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+is O
+likely O
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+differences O
+in O
+the O
+clinical O
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+disease O
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+
+Contribution O
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+- O
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+the O
+Polish O
+population O
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+The O
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+found O
+to O
+be O
+a O
+susceptible O
+gene O
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+development O
+of O
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+erythematosus I
+( O
+SLE B
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+in O
+various O
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+. O
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+There O
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+evident O
+population O
+differences O
+in O
+the O
+context O
+of O
+clinical O
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+of O
+SLE B
+, O
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+we O
+investigated O
+the O
+prevalence O
+of O
+the O
+STAT4 O
+G O
+> O
+C O
+( O
+rs7582694 O
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+polymorphism O
+in O
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+with O
+SLE B
+( O
+n O
+= O
+253 O
+) O
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+controls O
+( O
+n O
+= O
+521 O
+) O
+in O
+a O
+sample O
+of O
+the O
+Polish O
+population O
+. O
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+We O
+found O
+that O
+patients O
+with O
+the O
+STAT4 O
+C O
+/ O
+G O
+and O
+CC O
+genotypes O
+exhibited O
+a O
+1 O
+. O
+583 O
+- O
+fold O
+increased O
+risk O
+of O
+SLE B
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+( O
+95 O
+% O
+CI O
+= O
+1 O
+. O
+168 O
+- O
+2 O
+. O
+145 O
+, O
+p O
+= O
+0 O
+. O
+3 O
+), O
+with O
+OR O
+for O
+the O
+C O
+/ O
+C O
+versus O
+C O
+/ O
+G O
+and O
+G O
+/ O
+G O
+genotypes O
+was O
+1 O
+. O
+967 O
+( O
+95 O
+% O
+CI O
+= O
+1 O
+. O
+152 O
+- O
+3 O
+. O
+358 O
+, O
+p O
+= O
+0 O
+. O
+119 O
+). O
+
+The O
+OR O
+for O
+the O
+STAT4 O
+C O
+allele O
+frequency O
+showed O
+a O
+1 O
+. O
+539 O
+- O
+fold O
+increased O
+risk O
+of O
+SLE B
+( O
+95 O
+% O
+CI O
+= O
+1 O
+. O
+209 O
+- O
+1 O
+. O
+959 O
+, O
+p O
+= O
+0 O
+. O
+4 O
+). O
+
+We O
+also O
+observed O
+an O
+increased O
+frequency O
+of O
+STAT4 O
+C O
+/ O
+C O
+and O
+C O
+/ O
+G O
+genotypes O
+in O
+SLE B
+patients O
+with O
+renal B
+symptoms I
+OR O
+= O
+2 O
+. O
+259 O
+( O
+1 O
+. O
+365 O
+- O
+3 O
+. O
+738 O
+, O
+p O
+= O
+0 O
+. O
+14 O
+), O
+( O
+p O
+( O
+corr O
+) O
+= O
+0 O
+. O
+238 O
+) O
+and O
+in O
+SLE B
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+with O
+neurologic O
+manifestations O
+OR O
+= O
+2 O
+. O
+867 O
+( O
+1 O
+. O
+467 O
+- O
+5 O
+. O
+604 O
+, O
+p O
+= O
+0 O
+. O
+16 O
+), O
+( O
+p O
+( O
+corr O
+) O
+= O
+0 O
+. O
+272 O
+). O
+
+Moreover O
+, O
+we O
+found O
+a O
+contribution O
+of O
+STAT4 O
+C O
+/ O
+C O
+and O
+C O
+/ O
+G O
+genotypes O
+to O
+the O
+presence O
+of O
+the O
+anti O
+- O
+snRNP O
+Ab O
+OR O
+= O
+3 O
+. O
+237 O
+( O
+1 O
+. O
+667 O
+- O
+6 O
+. O
+288 O
+, O
+p O
+= O
+0 O
+. O
+3 O
+), O
+( O
+p O
+( O
+corr O
+) O
+= O
+0 O
+. O
+51 O
+) O
+and O
+the O
+presence O
+of O
+the O
+anti O
+- O
+Scl O
+- O
+70 O
+Ab O
+OR O
+= O
+2 O
+. O
+665 O
+( O
+1 O
+. O
+380 O
+- O
+5 O
+. O
+147 O
+, O
+p O
+= O
+0 O
+. O
+28 O
+), O
+( O
+p O
+( O
+corr O
+) O
+= O
+0 O
+. O
+476 O
+). O
+
+Our O
+studies O
+confirmed O
+an O
+association O
+of O
+the O
+STAT4 O
+C O
+( O
+rs7582694 O
+) O
+variant O
+with O
+the O
+development O
+of O
+SLE B
+and O
+occurrence O
+of O
+some O
+clinical O
+manifestations O
+of O
+the O
+disease O
+. O
+
+
+Leukemia O
+inhibitory O
+factor O
+protects O
+the O
+lung O
+during O
+respiratory B
+syncytial I
+viral I
+infection I
+. O
+
+BACKGROUND O
+: O
+Respiratory O
+syncytial O
+virus O
+( O
+RSV O
+) O
+infects O
+the O
+lung O
+epithelium O
+where O
+it O
+stimulates O
+the O
+production O
+of O
+numerous O
+host O
+cytokines O
+that O
+are O
+associated O
+with O
+disease O
+burden O
+and O
+acute B
+lung I
+injury I
+. O
+
+Characterizing O
+the O
+host O
+cytokine O
+response O
+to O
+RSV B
+infection I
+, O
+the O
+regulation O
+of O
+host O
+cytokines O
+and O
+the O
+impact O
+of O
+neutralizing O
+an O
+RSV O
+- O
+inducible O
+cytokine O
+during O
+infection B
+were O
+undertaken O
+in O
+this O
+study O
+. O
+
+METHODS O
+: O
+A549 O
+, O
+primary O
+human O
+small O
+airway O
+epithelial O
+( O
+SAE O
+) O
+cells O
+and O
+wild O
+- O
+type O
+, O
+TIR O
+- O
+domain O
+- O
+containing O
+adapter O
+- O
+inducing O
+interferon O
+- O
+b O
+( O
+Trif O
+) O
+and O
+mitochondrial O
+antiviral O
+- O
+signaling O
+protein O
+( O
+Mavs O
+) O
+knockout O
+( O
+KO O
+) O
+mice O
+were O
+infected O
+with O
+RSV B
+and O
+cytokine O
+responses O
+were O
+investigated O
+by O
+ELISA O
+, O
+multiplex O
+analysis O
+and O
+qPCR O
+. O
+
+Neutralizing O
+anti O
+- O
+leukemia O
+inhibitory O
+factor O
+( O
+LIF O
+) O
+IgG O
+or O
+control O
+IgG O
+was O
+administered O
+to O
+a O
+group O
+of O
+wild O
+- O
+type O
+animals O
+prior O
+to O
+RSV B
+infection I
+. O
+
+RESULTS O
+AND O
+DISCUSSION O
+: O
+RSV O
+- O
+infected O
+A549 O
+and O
+SAE O
+cells O
+release O
+a O
+network O
+of O
+cytokines O
+, O
+including O
+newly O
+identified O
+RSV O
+- O
+inducible O
+cytokines O
+LIF O
+, O
+migration O
+inhibitory O
+factor O
+( O
+MIF O
+), O
+stem O
+cell O
+factor O
+( O
+SCF O
+), O
+CCL27 O
+, O
+CXCL12 O
+and O
+stem O
+cell O
+growth O
+factor O
+beta O
+( O
+SCGF O
+- O
+b O
+). O
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+These O
+RSV O
+- O
+inducible O
+cytokines O
+were O
+also O
+observed O
+in O
+the O
+airways O
+of O
+mice O
+during O
+an O
+infection B
+. O
+
+To O
+identify O
+the O
+regulation O
+of O
+RSV O
+inducible O
+cytokines O
+, O
+Mavs O
+and O
+Trif O
+deficient O
+animals O
+were O
+infected O
+with O
+RSV O
+. O
+
+In O
+vivo O
+induction O
+of O
+airway O
+IL O
+- O
+1b O
+, O
+IL O
+- O
+4 O
+, O
+IL O
+- O
+5 O
+, O
+IL O
+- O
+6 O
+, O
+IL O
+- O
+12 O
+( O
+p40 O
+), O
+IFN O
+- O
+g O
+, O
+CCL2 O
+, O
+CCL5 O
+, O
+CCL3 O
+, O
+CXCL1 O
+, O
+IP O
+- O
+10 O
+/ O
+CXCL10 O
+, O
+IL O
+- O
+22 O
+, O
+MIG O
+/ O
+CXCL9 O
+and O
+MIF O
+were O
+dependent O
+on O
+Mavs O
+expression O
+in O
+mice O
+. O
+
+Loss O
+of O
+Trif O
+expression O
+in O
+mice O
+altered O
+the O
+RSV O
+induction O
+of O
+IL O
+- O
+1b O
+, O
+IL O
+- O
+5 O
+, O
+CXCL12 O
+, O
+MIF O
+, O
+LIF O
+, O
+CXCL12 O
+and O
+IFN O
+- O
+g O
+. O
+
+Silencing O
+of O
+retinoic O
+acid O
+- O
+inducible O
+gene O
+- O
+1 O
+( O
+RIG O
+- O
+I O
+) O
+expression O
+in O
+A549 O
+cells O
+had O
+a O
+greater O
+impact O
+on O
+RSV O
+- O
+inducible O
+cytokines O
+than O
+melanoma O
+differentiation O
+- O
+associated O
+protein O
+5 O
+( O
+MDA5 O
+) O
+and O
+laboratory O
+of O
+genetics O
+and O
+physiology O
+2 O
+( O
+LGP2 O
+), O
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+reported O
+in O
+a O
+zonular O
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+gene O
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+CONCLUSION O
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+MCM8 O
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+Rb O
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+phosphorylation O
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+4 O
+in O
+vitro O
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+in O
+vivo O
+. O
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+The O
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+D1 O
+/ O
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+interaction O
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+required O
+for O
+Rb O
+phosphorylation O
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+S O
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+As O
+a O
+result O
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+number O
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+loci O
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+Complete O
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+Animals O
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+RESULTS O
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+control O
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+However O
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+GAP43 O
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+band O
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+= O
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+compared O
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+Pilo B
+group O
+. O
+
+CONCLUSIONS O
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+Our O
+current O
+finding O
+that O
+animals O
+in O
+the O
+CHX O
++ O
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+group O
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+a O
+GAP43 O
+- O
+ir O
+band O
+in O
+the O
+IML O
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+to O
+that O
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+controls O
+, O
+reinforces O
+prior O
+data O
+on O
+the O
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+The O
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+a O
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+the O
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+of O
+hilar O
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+projections O
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+express O
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+- O
+43 O
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+Daidzein B
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+choline O
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+- O
+IXC O
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+and O
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+drug O
+- O
+induced O
+amnesia B
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+
+The O
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+acetyltransferase O
+( O
+ChAT O
+) O
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+enhances O
+cholinergic B
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+via O
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+augmentation O
+of O
+the O
+enzymatic O
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+acetylcholine B
+( O
+ACh B
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+factor O
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+Alzheimer B
+' I
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+disease I
+( O
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+). O
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+from O
+Pueraria O
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+activation O
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+vitro O
+. O
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+Via O
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+Pueraria O
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+daidzein B
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+4 B
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+- I
+dihydroxy I
+- I
+isoflavone I
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+In O
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+Administration O
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+/ O
+kg O
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+reverse O
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+Injections O
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+role O
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+it O
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+Effect O
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+free O
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+- I
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+/ O
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+alpha B
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+kg O
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+kg O
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+activity O
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+The O
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+- I
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+
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+trial O
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+contrast B
+- O
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+nephropathy B
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+patients O
+with O
+chronic B
+kidney I
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+- O
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+: O
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+Serum O
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+/ O
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+/ O
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+= O
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+= O
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+2 O
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+SCr O
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+= O
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+4 O
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+4 O
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+204 O
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+6 O
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+= O
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+9 O
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+= O
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+In O
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+= O
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+5 O
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+1 O
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+78 O
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+13 O
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+0 O
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+= O
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+= O
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+10 O
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+3 O
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+= O
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+Mean O
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+iopamidol B
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+7 O
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+0 O
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+/ O
+dL O
+, O
+6 O
+. O
+2 O
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+10 O
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+6 O
+micromol O
+/ O
+L O
+, O
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+= O
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+0 O
+. O
+16 O
+mg O
+/ O
+dL O
+, O
+6 O
+. O
+2 O
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+14 O
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+1 O
+micromol O
+/ O
+L O
+, O
+P O
+= O
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+CONCLUSIONS O
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+, O
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+by O
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+, O
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+not O
+statistically O
+different O
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+the O
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+high O
+- O
+risk O
+patients O
+, O
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+Any O
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+and O
+not O
+likely O
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+be O
+clinically O
+significant O
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+
+Estrogen B
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+cholesteryl B
+ester I
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+macrophages O
+induced O
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+
+Individuals O
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+live O
+long O
+lives O
+with O
+drug O
+therapy O
+that O
+often O
+includes O
+protease O
+inhibitors O
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+ritonavir B
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+Many O
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+, O
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+, O
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+long O
+- O
+term O
+side O
+effects O
+such O
+as O
+premature O
+atherosclerosis B
+. O
+
+We O
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+male O
+mice O
+to O
+a O
+greater O
+extent O
+than O
+in O
+female O
+mice O
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+Furthermore O
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+In O
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+model O
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+address O
+this O
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+Briefly O
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+h O
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+100 O
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+of O
+CD36 O
+at O
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+in O
+monocyte O
+- O
+derived O
+macrophages O
+resulting O
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+Clinical O
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+of O
+cardiorespiratory O
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+conventional O
+spinal O
+anaesthesia O
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+in O
+clinical O
+practice O
+but O
+has O
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+main O
+drawback O
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+post O
+- O
+spinal O
+block O
+hypotension B
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+Efforts O
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+be O
+made O
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+setback O
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+: O
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+and O
+respiratory O
+changes O
+during O
+unilateral O
+and O
+conventional O
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+anaesthesia O
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+METHODS O
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+approval O
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+we O
+studied O
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+Society O
+of O
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+( O
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+), O
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+and O
+2 O
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+scheduled O
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+unilateral O
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+Patients O
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+allocated O
+into O
+one O
+of O
+two O
+groups O
+: O
+lateral O
+and O
+conventional O
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+anaesthesia O
+groups O
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+In O
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+lateral O
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+1 O
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+( O
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+CONCLUSION O
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+Also O
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+The O
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+activity O
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+( O
+glutamate B
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+-( I
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+side O
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+The O
+primary O
+objective O
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+cohort O
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+units O
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+two O
+academic O
+medical O
+centers O
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+board O
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+certified O
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+PATIENTS O
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+matched O
+1 O
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+1 O
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+propensity O
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+characteristics O
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+INTERVENTIONS O
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+sedation O
+with O
+dexmedetomidine B
+or O
+propofol B
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+MEASUREMENTS O
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+of O
+342 O
+patients O
+( O
+105 O
+dexmedetomidine B
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+237 O
+propofol B
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+were O
+included O
+in O
+the O
+analysis O
+, O
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+190 O
+matched O
+( O
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+group O
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+by O
+propensity O
+score O
+. O
+
+The O
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+outcome O
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+this O
+study O
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+a O
+composite O
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+severe O
+hypotension B
+( O
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+arterial O
+pressure O
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+bradycardia B
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+rate O
+< O
+50 O
+beats O
+/ O
+min O
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+during O
+sedative O
+infusion O
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+
+No O
+difference O
+in O
+the O
+primary O
+composite O
+outcome O
+in O
+both O
+the O
+unmatched O
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+%, O
+p O
+= O
+0 O
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+or O
+matched O
+cohorts O
+( O
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+% O
+vs O
+34 O
+%, O
+p O
+= O
+0 O
+. O
+35 O
+) O
+could O
+be O
+found O
+. O
+
+When O
+analyzed O
+separately O
+, O
+no O
+differences O
+could O
+be O
+found O
+in O
+the O
+prevalence O
+of O
+severe O
+hypotension B
+or O
+bradycardia B
+in O
+either O
+the O
+unmatched O
+or O
+matched O
+cohorts O
+. O
+
+CONCLUSIONS O
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