abstract: UNASSIGNED: @entity2 -dependent haloperoxidases (VHPOs) perform two-electron oxidation of @entity4 using @entity0 . Their mechanism, including the factors determining the substrate specificity and the pH- @entity1 of the catalytic rates, is poorly understood. The @entity3 cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on @entity5 magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of @entity2 -dependent chloroperoxidases (VCPO). The cofactor environments in the wild type VCPO and its @entity6 / @entity7 / @entity8 mutant exhibiting 5-100 fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained owing to the fast MAS probe technologies enabled the assignment of the location and number of protons on the @entity3 as a function of pH. The @entity3 cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the @entity3 protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH dependent, could help explain the different reactivities of the wild type and mutant VCPO and their pH- @entity1 . This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of @entity2 centers in large biological molecules.

title: XXXX NMR Crystallography of @entity2 Chloroperoxidase and its Directed Evolution @entity6 / @entity7 / @entity8 Mutant: Protonation Environments of the Active Site.

answer: @entity5


abstract: UNASSIGNED: @entity2 -dependent haloperoxidases (VHPOs) perform two-electron oxidation of @entity4 using @entity0 . Their mechanism, including the factors determining the substrate specificity and the pH- @entity1 of the catalytic rates, is poorly understood. The @entity3 cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on @entity5 magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of @entity2 -dependent chloroperoxidases (VCPO). The cofactor environments in the wild type VCPO and its @entity6 / @entity7 / @entity8 mutant exhibiting 5-100 fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained owing to the fast MAS probe technologies enabled the assignment of the location and number of protons on the @entity3 as a function of pH. The @entity3 cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the @entity3 protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH dependent, could help explain the different reactivities of the wild type and mutant VCPO and their pH- @entity1 . This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of @entity2 centers in large biological molecules.

title: @entity5 NMR Crystallography of XXXX Chloroperoxidase and its Directed Evolution @entity6 / @entity7 / @entity8 Mutant: Protonation Environments of the Active Site.

answer: @entity2


abstract: UNASSIGNED: @entity2 -dependent haloperoxidases (VHPOs) perform two-electron oxidation of @entity4 using @entity0 . Their mechanism, including the factors determining the substrate specificity and the pH- @entity1 of the catalytic rates, is poorly understood. The @entity3 cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on @entity5 magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of @entity2 -dependent chloroperoxidases (VCPO). The cofactor environments in the wild type VCPO and its @entity6 / @entity7 / @entity8 mutant exhibiting 5-100 fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained owing to the fast MAS probe technologies enabled the assignment of the location and number of protons on the @entity3 as a function of pH. The @entity3 cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the @entity3 protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH dependent, could help explain the different reactivities of the wild type and mutant VCPO and their pH- @entity1 . This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of @entity2 centers in large biological molecules.

title: @entity5 NMR Crystallography of @entity2 Chloroperoxidase and its Directed Evolution XXXX / @entity7 / @entity8 Mutant: Protonation Environments of the Active Site.

answer: @entity6


abstract: UNASSIGNED: @entity2 -dependent haloperoxidases (VHPOs) perform two-electron oxidation of @entity4 using @entity0 . Their mechanism, including the factors determining the substrate specificity and the pH- @entity1 of the catalytic rates, is poorly understood. The @entity3 cofactor in the active site of VHPOs contains "spectroscopically silent" V(V), which does not change oxidation state during the reaction. We employed an NMR crystallography approach based on @entity5 magic angle spinning NMR spectroscopy and Density Functional Theory, to gain insights into the structure and coordination environment of the cofactor in the resting state of @entity2 -dependent chloroperoxidases (VCPO). The cofactor environments in the wild type VCPO and its @entity6 / @entity7 / @entity8 mutant exhibiting 5-100 fold improved catalytic activity are examined at various pH values. Optimal sensitivity attained owing to the fast MAS probe technologies enabled the assignment of the location and number of protons on the @entity3 as a function of pH. The @entity3 cofactor changes its protonation from quadruply protonated at pH 6.3 to triply protonated at pH 7.3 to doubly protonated at pH 8.3. In contrast, in the mutant, the @entity3 protonation is the same at pH 5.0 and 8.3, and the cofactor is doubly protonated. This methodology to identify the distinct protonation environments of the cofactor, which are also pH dependent, could help explain the different reactivities of the wild type and mutant VCPO and their pH- @entity1 . This study demonstrates that (51)V-based NMR crystallography can be used to derive the detailed coordination environments of @entity2 centers in large biological molecules.

title: @entity5 NMR Crystallography of @entity2 Chloroperoxidase and its Directed Evolution @entity6 / XXXX / @entity8 Mutant: Protonation Environments of the Active Site.

answer: @entity7


abstract: BACKGROUND: @entity5 (formerly known as @entity5 ) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between @entity6 polymorphism of @entity5 gene and decreased @entity4 ( @entity4 ) risk has been demonstrated. The aim of the current study was to test the hypothesis that @entity6 polymorphism can influence the prognosis of @entity4 @entity0 . METHODS: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on @entity2 -fixed and @entity3 -embedded @entity1 tissues. The influence of @entity0 ' genotype on overall survival and progression free survival were our main outcome measures. RESULTS: A total of 191 @entity4 @entity0 were included in the final analysis. Overall survival differed significantly (P   =   0.003) among genotypes. At multivariate analysis, a significant (P   <   0.05) effect on overall survival was detected for FIGO stage, and @entity6 polymorphism of @entity5 gene. After grouping @entity4 @entity0 according to adjuvant treatment, @entity6 polymorphism resulted significantly (P   <   0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P   =   0.014) interaction between @entity6 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P   =   0.090) towards significance was observed for @entity6 polymorphism effect on progression free survival. CONCLUSIONS: @entity6 polymorphism of @entity5 gene influences independently the prognosis of @entity4 @entity0 with a potential effect on @entity1 chemo-sensitivity.

title: XXXX polymorphism influences the prognosis of @entity4 @entity0 : a cohort study.

answer: @entity5


abstract: BACKGROUND: @entity5 (formerly known as @entity5 ) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between @entity6 polymorphism of @entity5 gene and decreased @entity4 ( @entity4 ) risk has been demonstrated. The aim of the current study was to test the hypothesis that @entity6 polymorphism can influence the prognosis of @entity4 @entity0 . METHODS: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on @entity2 -fixed and @entity3 -embedded @entity1 tissues. The influence of @entity0 ' genotype on overall survival and progression free survival were our main outcome measures. RESULTS: A total of 191 @entity4 @entity0 were included in the final analysis. Overall survival differed significantly (P   =   0.003) among genotypes. At multivariate analysis, a significant (P   <   0.05) effect on overall survival was detected for FIGO stage, and @entity6 polymorphism of @entity5 gene. After grouping @entity4 @entity0 according to adjuvant treatment, @entity6 polymorphism resulted significantly (P   <   0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P   =   0.014) interaction between @entity6 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P   =   0.090) towards significance was observed for @entity6 polymorphism effect on progression free survival. CONCLUSIONS: @entity6 polymorphism of @entity5 gene influences independently the prognosis of @entity4 @entity0 with a potential effect on @entity1 chemo-sensitivity.

title: @entity5 polymorphism influences the prognosis of XXXX @entity0 : a cohort study.

answer: @entity4


abstract: BACKGROUND: @entity5 (formerly known as @entity5 ) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between @entity6 polymorphism of @entity5 gene and decreased @entity4 ( @entity4 ) risk has been demonstrated. The aim of the current study was to test the hypothesis that @entity6 polymorphism can influence the prognosis of @entity4 @entity0 . METHODS: Retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on @entity2 -fixed and @entity3 -embedded @entity1 tissues. The influence of @entity0 ' genotype on overall survival and progression free survival were our main outcome measures. RESULTS: A total of 191 @entity4 @entity0 were included in the final analysis. Overall survival differed significantly (P   =   0.003) among genotypes. At multivariate analysis, a significant (P   <   0.05) effect on overall survival was detected for FIGO stage, and @entity6 polymorphism of @entity5 gene. After grouping @entity4 @entity0 according to adjuvant treatment, @entity6 polymorphism resulted significantly (P   <   0.001) related to overall survival only in subjects who received radiotherapy plus chemotherapy. A significant (P   =   0.014) interaction between @entity6 polymorphism and chemo-radiotherapy was also detected. Finally, only a trend (P   =   0.090) towards significance was observed for @entity6 polymorphism effect on progression free survival. CONCLUSIONS: @entity6 polymorphism of @entity5 gene influences independently the prognosis of @entity4 @entity0 with a potential effect on @entity1 chemo-sensitivity.

title: @entity5 polymorphism influences the prognosis of @entity4 XXXX : a cohort study.

answer: @entity0


abstract: INTRODUCTION: In a randomized controlled trial comparing tight @entity1 control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that @entity2 is associated with a poor outcome, even when controlling for initial severity. METHODS: We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) @entity2 , multiple hypoglycemic events (n >= 3) and the other main components of glycemic control (mean blood @entity1 level and blood @entity1 coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement). RESULTS: A total of 2,601 @entity0 were analyzed and divided into three groups: no @entity2 (n =1,474), moderate @entity2 (n =874, 34%) and severe @entity2 (n =253, 10%). @entity0 with moderate or severe @entity2 had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood @entity1 CV was not. Using multivariable matching, @entity0 with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality. CONCLUSION: In a large cohort of ICU @entity0 , severe @entity2 and multiple hypoglycemic events were associated with increased 90-day mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.

title: Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU XXXX .

answer: @entity0


abstract: BACKGROUND: Large registries are important data sources in epidemiological studies of @entity3 , if these registries are valid. Therefore, we examined the positive predictive value ( @entity4 ) of diagnosis codes for @entity3 , the procedure codes for inotropic/vasopressor therapy among @entity0 with a diagnosis of @entity3 , and the combination of a @entity3 diagnosis and a code for inotropic/vasopressor therapy in the Danish National @entity0 Registry (DNPR). METHODS: We randomly selected 190 inpatients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis of @entity3 at Aarhus University Hospital from 2005-2012 using the DNPR; 50 @entity0 were diagnosed with @entity2 , 40 @entity0 with @entity3 , and 100 @entity0 with @entity1 . We used medical charts as the reference standard and calculated the @entity4 with 95% confidence intervals (CI) for overall @entity3 and for each type of @entity3 separately. We also examined the @entity4 for inotropic/vasopressor therapy and the @entity4 for @entity3 when a concurrent code for inotropic/vasopressor therapy was also registered. RESULTS: The @entity4 was 86.1% (95% CI: 79.7-91.1) for @entity3 overall, 93.5% (95% CI: 82.1-98.6) for @entity2 , 70.6% (95% CI: 52.5-84.9) for @entity3 , and 69.2% (95% CI: 57.7-79.2) for @entity1 . The @entity4 of use of inotropes/vasopressors among @entity3 @entity0 was 88.9% (95% CI: 79.3-95.1). When both a @entity3 code and a procedure code for inotropic/vasopressor therapy were used, the @entity4 for @entity3 overall was 93.1% (95% CI: 84.5-97.7). ICD-10 codes for subtypes of @entity3 and simultaneously registered use of inotropes/vasopressors provided PPVs of 96.0% (95% CI: 79.6-99.9) for @entity2 , 69.2% (95% CI: 38.6-90.9) for @entity3 , and 82.4% (95% CI: 65.5-93.2) for @entity1 . CONCLUSIONS: Overall, we found a moderately high @entity4 for @entity3 in the DNPR. The @entity4 was highest for @entity2 but lower for @entity5 and @entity1 . Combination diagnoses of @entity3 with codes for inotropic/vasopressor therapy further increased the @entity4 of @entity3 overall, and for cardiogenic and @entity1 diagnoses.

title: Positive predictive value of International Classification of Diseases, 10th revision, diagnosis codes for cardiogenic, XXXX , and @entity1 in the Danish National @entity0 Registry.

answer: @entity5


abstract: BACKGROUND: Large registries are important data sources in epidemiological studies of @entity3 , if these registries are valid. Therefore, we examined the positive predictive value ( @entity4 ) of diagnosis codes for @entity3 , the procedure codes for inotropic/vasopressor therapy among @entity0 with a diagnosis of @entity3 , and the combination of a @entity3 diagnosis and a code for inotropic/vasopressor therapy in the Danish National @entity0 Registry (DNPR). METHODS: We randomly selected 190 inpatients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis of @entity3 at Aarhus University Hospital from 2005-2012 using the DNPR; 50 @entity0 were diagnosed with @entity2 , 40 @entity0 with @entity3 , and 100 @entity0 with @entity1 . We used medical charts as the reference standard and calculated the @entity4 with 95% confidence intervals (CI) for overall @entity3 and for each type of @entity3 separately. We also examined the @entity4 for inotropic/vasopressor therapy and the @entity4 for @entity3 when a concurrent code for inotropic/vasopressor therapy was also registered. RESULTS: The @entity4 was 86.1% (95% CI: 79.7-91.1) for @entity3 overall, 93.5% (95% CI: 82.1-98.6) for @entity2 , 70.6% (95% CI: 52.5-84.9) for @entity3 , and 69.2% (95% CI: 57.7-79.2) for @entity1 . The @entity4 of use of inotropes/vasopressors among @entity3 @entity0 was 88.9% (95% CI: 79.3-95.1). When both a @entity3 code and a procedure code for inotropic/vasopressor therapy were used, the @entity4 for @entity3 overall was 93.1% (95% CI: 84.5-97.7). ICD-10 codes for subtypes of @entity3 and simultaneously registered use of inotropes/vasopressors provided PPVs of 96.0% (95% CI: 79.6-99.9) for @entity2 , 69.2% (95% CI: 38.6-90.9) for @entity3 , and 82.4% (95% CI: 65.5-93.2) for @entity1 . CONCLUSIONS: Overall, we found a moderately high @entity4 for @entity3 in the DNPR. The @entity4 was highest for @entity2 but lower for @entity5 and @entity1 . Combination diagnoses of @entity3 with codes for inotropic/vasopressor therapy further increased the @entity4 of @entity3 overall, and for cardiogenic and @entity1 diagnoses.

title: Positive predictive value of International Classification of Diseases, 10th revision, diagnosis codes for cardiogenic, @entity5 , and XXXX in the Danish National @entity0 Registry.

answer: @entity1


abstract: BACKGROUND: Large registries are important data sources in epidemiological studies of @entity3 , if these registries are valid. Therefore, we examined the positive predictive value ( @entity4 ) of diagnosis codes for @entity3 , the procedure codes for inotropic/vasopressor therapy among @entity0 with a diagnosis of @entity3 , and the combination of a @entity3 diagnosis and a code for inotropic/vasopressor therapy in the Danish National @entity0 Registry (DNPR). METHODS: We randomly selected 190 inpatients with an International Classification of Diseases, 10th revision (ICD-10) diagnosis of @entity3 at Aarhus University Hospital from 2005-2012 using the DNPR; 50 @entity0 were diagnosed with @entity2 , 40 @entity0 with @entity3 , and 100 @entity0 with @entity1 . We used medical charts as the reference standard and calculated the @entity4 with 95% confidence intervals (CI) for overall @entity3 and for each type of @entity3 separately. We also examined the @entity4 for inotropic/vasopressor therapy and the @entity4 for @entity3 when a concurrent code for inotropic/vasopressor therapy was also registered. RESULTS: The @entity4 was 86.1% (95% CI: 79.7-91.1) for @entity3 overall, 93.5% (95% CI: 82.1-98.6) for @entity2 , 70.6% (95% CI: 52.5-84.9) for @entity3 , and 69.2% (95% CI: 57.7-79.2) for @entity1 . The @entity4 of use of inotropes/vasopressors among @entity3 @entity0 was 88.9% (95% CI: 79.3-95.1). When both a @entity3 code and a procedure code for inotropic/vasopressor therapy were used, the @entity4 for @entity3 overall was 93.1% (95% CI: 84.5-97.7). ICD-10 codes for subtypes of @entity3 and simultaneously registered use of inotropes/vasopressors provided PPVs of 96.0% (95% CI: 79.6-99.9) for @entity2 , 69.2% (95% CI: 38.6-90.9) for @entity3 , and 82.4% (95% CI: 65.5-93.2) for @entity1 . CONCLUSIONS: Overall, we found a moderately high @entity4 for @entity3 in the DNPR. The @entity4 was highest for @entity2 but lower for @entity5 and @entity1 . Combination diagnoses of @entity3 with codes for inotropic/vasopressor therapy further increased the @entity4 of @entity3 overall, and for cardiogenic and @entity1 diagnoses.

title: Positive predictive value of International Classification of Diseases, 10th revision, diagnosis codes for cardiogenic, @entity5 , and @entity1 in the Danish National XXXX Registry.

answer: @entity0


abstract: BACKGROUND: @entity6 and @entity3 have been identified as the most common bacteria responsible for sub-clinical and overt @entity0 and their ability to form biofilm on the implant as been reported as the essential factor in the development of this type of @entity1 . Biofilm formation is a complex process with the participation of several distinct molecules, whose relative importance in different clinical settings has not yet been fully elucidated. To our knowledge this is the first study aimed at characterizing isolates causing @entity0 . RESULTS: Thirteen @entity3 and seven @entity6 causing @entity0 were studied. Using the broth microdilution method and the E-test, the majority of the strains were susceptible to all antibiotics tested. @entity4 resistance was detected in two @entity6 . All strains had different RAPD profiles and were able to produce biofilms in microtitre plate assays but, while all @entity3 carried and were able to express icaA and icaD genes, this was only true for one @entity6 . Biofilm development was @entity2 - and @entity5 -induced (5   @entity3 and 1   @entity6 ) or @entity2 -induced (the remaining strains). Proteinase K and @entity7 treatment had different effects on biofilms dispersion revealing that the strains studied were able to produce chemically different types of extracellular matrix mediating biofilm formation. All @entity3 strains harboured and expressed the atlA, clfA, FnA, eno and cna genes and the majority also carried and expressed the sasG (10/13), ebpS (10/13) genes. All @entity6 strains harboured and expressed the atlE, aae, embp genes, and the majority (six strains) also carried and expressed the fbe, aap genes. Genes for @entity3 capsular types 5 and 8 were almost equally distributed. The only leukotoxin genes detected were lukE/lukD (6/13). CONCLUSIONS: @entity3 and @entity6 @entity0 are caused by heterogeneous strains with different biofilm development mechanisms. Since the collagen adhesin (cna) gene is not ubiquitously distributed among @entity3 , this protein could have an important role in the cause of @entity0 .

title: Phenotypic and genotypic characterization of Staphylococci causing XXXX in oncologic patients.

answer: @entity0


abstract: BACKGROUND: Columnaris causes severe mortalities among many different wild and cultured freshwater fish species, but understanding of host resistance is lacking. Catfish, the primary aquaculture species in the United States, serves as a great model for the analysis of host resistance against @entity0 . @entity1 in general is highly resistant to the disease while blue catfish is highly susceptible. F2 generation of hybrids can be produced where phenotypes and genotypes are segregating, providing a useful system for QTL analysis. To identify genes associated with columnaris resistance, we performed a genome-wide association study (GWAS) using the catfish 250  K SNP array with 340 backcross progenies derived from crossing female @entity1 ( @entity1 ) with male F1 hybrid catfish (female @entity1 @entity1 * male blue catfish I. furcatus). RESULTS: A genomic region on linkage group 7 was found to be significantly associated with columnaris resistance. Within this region, five have known functions in immunity, including pik3r3b, cyld-like, adcyap1r1, adcyap1r1-like, and mast2. In addition, 3 additional suggestively associated QTL regions were identified on linkage groups 7, 12, and 14. The resistant genotypes on the QTLs of linkage groups 7 and 12 were found to be homozygous with both alleles being derived from @entity1 . The paralogs of the candidate genes in the suggestively associated QTL of linkage group 12 were found on the QTLs of linkage group 7. Many candidate genes on the four associated regions are involved in PI3K pathway that is known to be required by many bacteria for efficient entry into the host. CONCLUSION: The GWAS revealed four QTLs associated with columnaris resistance in catfish. Strikingly, the candidate genes may be arranged as functional hubs; the candidate genes within the associated QTLs on linkage groups 7 and 12 are not only co-localized, but also functionally related, with many of them being involved in the PI3K signal transduction pathway, suggesting its importance for columnaris resistance.

title: A genome-wide association study in catfish reveals the presence of functional hubs of related genes within QTLs for XXXX resistance.

answer: @entity0


abstract: This study was performed to determine if differences in regional myocardial @entity3 clearance rates could differentiate salvaged from nonsalvaged myocardium after reperfusion. Twenty-one @entity1 underwent 2 hours of left anterior descending coronary artery ligation followed by reperfusion. @entity3 was administered 5 minutes later and serial images were acquired over 3 hours. Of the 21 @entity1 , 15 had @entity2 of which nine had initially reduced anterior wall @entity3 activity (group 1) and six had normal or increased activity (group 2). Six @entity1 did not have an @entity2 (group 3). All group 1 @entity1 demonstrated reduced clearance rates in the anterior wall (T1/2 = 15.0 +/- 4.7 hours, @entity0 ) compared to the posterior wall (T1/2 = 9.0 +/- 4.4 hours; p less than 0.001). Group 2 @entity1 demonstrated increased clearance rates in the anterior wall (T1/2 = 5.7 +/- 2.0 hours) compared to the posterior wall (T1/2 = 10.5 +/- 4.6 hours; p less than 0.001). Group 3 @entity1 demonstrated no difference in clearance rates. In conclusion, although @entity3 uptake is frequently reduced in nonsalvaged myocardium, tracer uptake can be normal or increased if perfusion has been completely restored. However, an increased clearance rate from the reperfused zone compared to the normal zone is a reliable indicator of nonsalvaged myocardium, despite normal initial @entity3 uptake.

title: Differentiation of viable and nonviable myocardium after acute reperfusion using serial XXXX -201 imaging.

answer: @entity3


abstract: @entity3 ( @entity3 ) is a progressive @entity2 that affects 36 million @entity0 worldwide, but currently has no effective treatment options. One of the original hallmarks of @entity3 are plaques comprised of beta amyloid (Ab) and neurofibrillary tangles comprised of phosphorylated Tau protein. However, it is soluble oligomeric Ab which is more closely correlated with @entity1 and is therefore considered to be the @entity4 species. Oligomeric Ab has recently been shown to form complexes with the @entity7 ( @entity9 )-anchored membrane protein, cellular @entity6 ( @entity6 ), and these complexes are believed to play an important role in the progression of @entity3 pathogenesis. @entity5 , the major excitatory neurotransmitter is responsible for mediating learning and memory under normal physiological conditions. However, the dysregulation of glutamatergic signaling has also been implicated in a number of @entity2 including @entity3 . @entity5 acts via both ionotropic @entity5 receptors (iGluR) and metabotropic @entity5 receptors (mGluR), each of which have been implicated in @entity3 . There is now growing evidence to suggest that @entity8 may contribute the @entity3 pathogenesis by acting as scaffolds for the @entity6 /Ab oligomer complex, enabling the propagation of @entity4 signaling in @entity3 . In addition, @entity6 and Ab oligomer signaling via NMDARs may also contribute to @entity3 pathology. The current review overviews our current understanding of the role of @entity6 and Ab oligomers in regulating @entity5 receptor signaling, as well as highlights the importance of understanding these signaling complexes to develop more effective therapeutic strategies to treat @entity3 .

title: @entity5 receptors function as scaffolds for the regulation of b-amyloid and cellular XXXX signaling complexes.

answer: @entity6


abstract: @entity3 ( @entity3 ) is a progressive @entity2 that affects 36 million @entity0 worldwide, but currently has no effective treatment options. One of the original hallmarks of @entity3 are plaques comprised of beta amyloid (Ab) and neurofibrillary tangles comprised of phosphorylated Tau protein. However, it is soluble oligomeric Ab which is more closely correlated with @entity1 and is therefore considered to be the @entity4 species. Oligomeric Ab has recently been shown to form complexes with the @entity7 ( @entity9 )-anchored membrane protein, cellular @entity6 ( @entity6 ), and these complexes are believed to play an important role in the progression of @entity3 pathogenesis. @entity5 , the major excitatory neurotransmitter is responsible for mediating learning and memory under normal physiological conditions. However, the dysregulation of glutamatergic signaling has also been implicated in a number of @entity2 including @entity3 . @entity5 acts via both ionotropic @entity5 receptors (iGluR) and metabotropic @entity5 receptors (mGluR), each of which have been implicated in @entity3 . There is now growing evidence to suggest that @entity8 may contribute the @entity3 pathogenesis by acting as scaffolds for the @entity6 /Ab oligomer complex, enabling the propagation of @entity4 signaling in @entity3 . In addition, @entity6 and Ab oligomer signaling via NMDARs may also contribute to @entity3 pathology. The current review overviews our current understanding of the role of @entity6 and Ab oligomers in regulating @entity5 receptor signaling, as well as highlights the importance of understanding these signaling complexes to develop more effective therapeutic strategies to treat @entity3 .

title: XXXX receptors function as scaffolds for the regulation of b-amyloid and cellular @entity6 signaling complexes.

answer: @entity5


abstract: The significance of elevated levels of the MB isomer of @entity2 kinase (CK-MB) when @entity2 kinase (CK) level is normal was studied in 400 @entity0 with suspected @entity1 ( @entity1 ). In 350 @entity0 both CK and CK-MB were elevated (group 1), in 21 only CK-MB was elevated (group 2), in 24 neither enzyme was elevated (group 3) and in 5 only CK was elevated (group 4). In 57% of @entity0 in group 2 the CK level was doubled, with a characteristic enzyme curve, within the normal range, suggesting that an increase in CK had been missed because arbitrary definitions of "normal" were used. The median CK increase (60 IU/liter) in group 2 was greater than that in group 3 (23 IU/liter) (p less than 0.001). @entity0 in group 1 with small AMIs had a relative increase in CK similar to that in group 2. However, @entity0 in group 2 had a lower baseline CK level so that peak CK did not become abnormally high despite a 5-fold increase in some @entity0 . In @entity0 in group 1 with small AMIs, CK was elevated in fewer samples than CK-MB. If only 2 samples were obtained in all @entity0 , elevation of CK levels would have been missed in 63 group 1 @entity0 , erroneously increasing the number of @entity0 in group 2 fourfold (to 84 of 400, or 21%, instead of 21 of 400, or only 5%). Conversely, if @entity0 in group 2 with a doubling of CK are excluded, the prevalence of elevated CK-MB with normal CK would be only 9 of 400 (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

title: Significance of elevated MB isoenzyme with normal XXXX kinase in @entity1 .

answer: @entity2


abstract: The significance of elevated levels of the MB isomer of @entity2 kinase (CK-MB) when @entity2 kinase (CK) level is normal was studied in 400 @entity0 with suspected @entity1 ( @entity1 ). In 350 @entity0 both CK and CK-MB were elevated (group 1), in 21 only CK-MB was elevated (group 2), in 24 neither enzyme was elevated (group 3) and in 5 only CK was elevated (group 4). In 57% of @entity0 in group 2 the CK level was doubled, with a characteristic enzyme curve, within the normal range, suggesting that an increase in CK had been missed because arbitrary definitions of "normal" were used. The median CK increase (60 IU/liter) in group 2 was greater than that in group 3 (23 IU/liter) (p less than 0.001). @entity0 in group 1 with small AMIs had a relative increase in CK similar to that in group 2. However, @entity0 in group 2 had a lower baseline CK level so that peak CK did not become abnormally high despite a 5-fold increase in some @entity0 . In @entity0 in group 1 with small AMIs, CK was elevated in fewer samples than CK-MB. If only 2 samples were obtained in all @entity0 , elevation of CK levels would have been missed in 63 group 1 @entity0 , erroneously increasing the number of @entity0 in group 2 fourfold (to 84 of 400, or 21%, instead of 21 of 400, or only 5%). Conversely, if @entity0 in group 2 with a doubling of CK are excluded, the prevalence of elevated CK-MB with normal CK would be only 9 of 400 (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

title: Significance of elevated MB isoenzyme with normal @entity2 kinase in XXXX .

answer: @entity1


abstract: BACKGROUND: Previous qualitative research has revealed that @entity0 with @entity4 use daytime napping as a coping strategy for managing symptoms against clinical advice. Yet there is no evidence to suggest whether daytime napping is beneficial or detrimental for @entity0 with @entity4 . The purpose of this study was to explore how @entity0 use daytime naps and to determine the links between daytime napping and symptom severity in @entity4 . METHODS: A community based sample of 1044 adults who had been diagnosed with @entity4 by a clinician completed an online questionnaire. Associations between napping behavior, sleep quality and @entity4 symptoms were explored using Spearman correlations, with possible predictors of napping behaviour entered into a logistic regression model. Differences between @entity0 who napped on a daily basis and those who napped less regularly, as well as nap duration were explored. RESULTS: Daytime napping was significantly associated with @entity3 , @entity5 , @entity2 , @entity1 . Sleep problems and fatigue explained the greatest amount of variance in napping behaviour, p < 0.010. Those who engaged in daytime naps for >30 minutes had higher memory difficulties (t = -3.45) and levels of @entity5 (t = -2.50) than those who napped for shorter periods (<30 mins) (p < 0.010). CONCLUSIONS: Frequent use and longer duration of daytime napping was linked with greater symptom severity in @entity0 with @entity4 . Given the common use of daytime napping in @entity0 with @entity4 evidence based guidelines on the use of daytime napping in @entity0 with @entity6 are urgently needed.

title: Daytime napping associated with increased symptom severity in XXXX .

answer: @entity4


abstract: BACKGROUND: Although numerous epidemiological studies on @entity4 have been conducted worldwide, only a few studies have paid attention to the effect of socioeconomic status on @entity4 , particularly studies focusing on the @entity1 ( @entity1 ). METHODS: We analyzed the epidemiological features of @entity4 in Taiwan using data from the National Health Insurance Research Database from 2003 to 2011. All cases diagnosed as @entity4 were enrolled. RESULTS: Between 2003 and 2011, 2,916 @entity0 from the @entity1 and 209,206 @entity0 from the normal population (NP) were diagnosed with @entity4 . Our finding revealed that the ratios of comorbidities, @entity2 , and readmissions in @entity1 @entity0 were slightly higher than those of NP @entity0 . @entity1 @entity0 were more likely to live in suburban and rural areas, and hence a higher proportion of them were hospitalized in a district or regional hospital compared with NP @entity0 . The crucially finding was that the overall incidence ratios of @entity4 , @entity3 , and @entity4 in the @entity1 were substantially higher than those in the NP (36.25%, 35.33%, and 37.28%, respectively). The mean LOS in @entity1 @entity0 was longer than that of NP @entity0 . The overall case-fatality ratio of appendectomy in the @entity1 was higher when compared with the NP (0.41% versus 0.12%, p < 0.05). We also observed that @entity4 was occurred frequently in male @entity0 , with a higher incidence for those aged 15-29 years in both the @entity1 and NP. The incidences of incidental appendectomy showed a decreasing trend in both the @entity1 and NP. Finally, a valuable discovery was that the total hospital cost was comparable between the laparoscopic appendectomy (LA) and @entity5 ( @entity5 ) (1,178    13 USD versus 1,191    19 USD, p < 0.05) in @entity1 @entity0 because they saved more hospitalization costs than NP @entity0 when the previous one chose the LA. CONCLUSION: This study confirmed that a lower socioeconomic status has significantly negative impact on the occurrence and treatment of @entity4 and appendectomy. In terms of hospital costs and LOS, @entity1 @entity0 benefit more from the LA approach than they do from the @entity5 approach in the treatment of @entity4 .

title: Epidemiology of @entity4 and appendectomy for the XXXX in Taiwan, 2003-2011.

answer: @entity1


abstract: BACKGROUND: Although numerous epidemiological studies on @entity4 have been conducted worldwide, only a few studies have paid attention to the effect of socioeconomic status on @entity4 , particularly studies focusing on the @entity1 ( @entity1 ). METHODS: We analyzed the epidemiological features of @entity4 in Taiwan using data from the National Health Insurance Research Database from 2003 to 2011. All cases diagnosed as @entity4 were enrolled. RESULTS: Between 2003 and 2011, 2,916 @entity0 from the @entity1 and 209,206 @entity0 from the normal population (NP) were diagnosed with @entity4 . Our finding revealed that the ratios of comorbidities, @entity2 , and readmissions in @entity1 @entity0 were slightly higher than those of NP @entity0 . @entity1 @entity0 were more likely to live in suburban and rural areas, and hence a higher proportion of them were hospitalized in a district or regional hospital compared with NP @entity0 . The crucially finding was that the overall incidence ratios of @entity4 , @entity3 , and @entity4 in the @entity1 were substantially higher than those in the NP (36.25%, 35.33%, and 37.28%, respectively). The mean LOS in @entity1 @entity0 was longer than that of NP @entity0 . The overall case-fatality ratio of appendectomy in the @entity1 was higher when compared with the NP (0.41% versus 0.12%, p < 0.05). We also observed that @entity4 was occurred frequently in male @entity0 , with a higher incidence for those aged 15-29 years in both the @entity1 and NP. The incidences of incidental appendectomy showed a decreasing trend in both the @entity1 and NP. Finally, a valuable discovery was that the total hospital cost was comparable between the laparoscopic appendectomy (LA) and @entity5 ( @entity5 ) (1,178    13 USD versus 1,191    19 USD, p < 0.05) in @entity1 @entity0 because they saved more hospitalization costs than NP @entity0 when the previous one chose the LA. CONCLUSION: This study confirmed that a lower socioeconomic status has significantly negative impact on the occurrence and treatment of @entity4 and appendectomy. In terms of hospital costs and LOS, @entity1 @entity0 benefit more from the LA approach than they do from the @entity5 approach in the treatment of @entity4 .

title: Epidemiology of XXXX and appendectomy for the @entity1 in Taiwan, 2003-2011.

answer: @entity4


abstract: BACKGROUND: There is conflicting evidence about the accuracy of estimates of @entity1 based on parent-reported data. We assessed accuracy of @entity0 height, weight, and overweight/ @entity1 classification in a pediatric clinic population based on parent data to learn whether accuracy differs by @entity0 age and race/ethnicity. METHODS: Parents of @entity0 ages 3-12 (n   =   1,119) completed a waiting room questionnaire that asked about their @entity0 's height and weight. @entity0 's height and weight was then measured and entered into the electronic health record (EHR) by clinic staff. The @entity0 's EHR and questionnaire data were subsequently linked. Accuracy of parent-reported height, weight, overweight/ @entity1 classification, and parent perception of @entity0 's weight status were assessed using EHR data as the gold standard. Statistics were calculated for the full sample, two age groups (3-5, 6-12), and four racial/ethnic groups (nonHispanic White, Black, Latino, Asian). RESULTS: A parent-reported height was available for 59.1% of the @entity0 , weight for 75.6%, and weight classification for 53.0%. Data availability differed by race/ethnicity but not age group. Parent-reported height was accurate for 49.2% of @entity0 and weight for 58.2%. Latino @entity0 were less likely than nonHispanic Whites to have accurate height and weight data, and weight data were less accurate for 6-12 year than 3-5 year olds. Concordance of parent- and EHR-based classifications of the @entity0 as overweight/ @entity1 and @entity1 was approximately 80% for all subgroups, with kappa statistics indicating moderate agreement. Parent-reported data significantly overestimated prevalence of overweight/ @entity1 (50.2% vs. 35.2%) and @entity1 (32.1% vs. 19.4%) in the full sample and across all age and racial/ethnic subgroups. However, the percentages of parents who perceived their @entity0 to be overweight or very overweight greatly underestimated actual prevalence of overweight/ @entity1 and @entity1 . Missing data did not bias parent-based overweight/ @entity1 estimates and was not associated with @entity0 's EHR weight classification or parental perception of @entity0 's weight. CONCLUSIONS: While the majority of parents of overweight or @entity1 @entity0 tend to be unaware that their @entity0 is overweight, use of parent-reported height and weight data for young @entity0 and pre-teens will likely result in overestimates of prevalence of youth overweight and @entity1 .

title: Accuracy of parent-reported information for estimating prevalence of overweight and XXXX in a race-ethnically diverse pediatric clinic population aged 3 to 12.

answer: @entity1


abstract: BACKGROUND: Systematic analysis of @entity2 gene-expression patterns using high-throughput transcriptional profiling technologies has led to the discovery and publication of hundreds of gene-expression signatures. However, few public signature values have been cross-validated over multiple studies for the prediction of @entity2 prognosis and chemosensitivity in the neoadjuvant setting. METHODS: To analyze the prognostic and predictive values of publicly available signatures, we have implemented a systematic method for high-throughput and efficient validation of a large number of datasets and gene-expression signatures. Using this method, we performed a meta-analysis including 351 publicly available signatures, 37,000 random signatures, and 31 @entity0 datasets. Survival analyses and pathologic responses were used to assess prediction of prognosis, chemoresponsiveness, and chemo-drug sensitivity. RESULTS: Among 31 @entity0 datasets and 351 public signatures, we identified 22 validation datasets, two robust prognostic signatures (BRmet50 and PMID18271932Sig33) in @entity0 and one signature (PMID20813035Sig137) specific for prognosis prediction in @entity1 with @entity2 . The 22 validation datasets demonstrated enhanced ability to distinguish @entity2 gene profiles from random gene profiles. Both prognostic signatures are composed of genes associated with @entity3 mutations and were able to stratify the good and poor prognostic groups successfully in 82%and 68% of the 22 validation datasets, respectively. We then assessed the abilities of the two signatures to predict treatment responses of @entity0 @entity1 treated with commonly used chemotherapeutic regimens. Both BRmet50 and PMID18271932Sig33 retrospectively identified those @entity1 with an insensitive response to neoadjuvant chemotherapy (mean positive predictive values 85%-88%). Among those @entity1 predicted to be treatment sensitive, distant relapse-free survival (DRFS) was improved (negative predictive values 87%-88%). BRmet50 was further shown to prospectively predict @entity4 - @entity5 sensitivity in @entity1 with @entity0 . CONCLUSIONS: We have developed and applied a high-throughput screening method for public @entity2 signature validation. Using this method, we identified appropriate datasets for cross-validation and two robust signatures that differentiate @entity3 mutation status and have prognostic and predictive value for @entity0 @entity1 .

title: Evaluation of public @entity2 datasets and signatures identifies XXXX mutant signatures with robust prognostic and predictive value.

answer: @entity3


abstract: BACKGROUND: Systematic analysis of @entity2 gene-expression patterns using high-throughput transcriptional profiling technologies has led to the discovery and publication of hundreds of gene-expression signatures. However, few public signature values have been cross-validated over multiple studies for the prediction of @entity2 prognosis and chemosensitivity in the neoadjuvant setting. METHODS: To analyze the prognostic and predictive values of publicly available signatures, we have implemented a systematic method for high-throughput and efficient validation of a large number of datasets and gene-expression signatures. Using this method, we performed a meta-analysis including 351 publicly available signatures, 37,000 random signatures, and 31 @entity0 datasets. Survival analyses and pathologic responses were used to assess prediction of prognosis, chemoresponsiveness, and chemo-drug sensitivity. RESULTS: Among 31 @entity0 datasets and 351 public signatures, we identified 22 validation datasets, two robust prognostic signatures (BRmet50 and PMID18271932Sig33) in @entity0 and one signature (PMID20813035Sig137) specific for prognosis prediction in @entity1 with @entity2 . The 22 validation datasets demonstrated enhanced ability to distinguish @entity2 gene profiles from random gene profiles. Both prognostic signatures are composed of genes associated with @entity3 mutations and were able to stratify the good and poor prognostic groups successfully in 82%and 68% of the 22 validation datasets, respectively. We then assessed the abilities of the two signatures to predict treatment responses of @entity0 @entity1 treated with commonly used chemotherapeutic regimens. Both BRmet50 and PMID18271932Sig33 retrospectively identified those @entity1 with an insensitive response to neoadjuvant chemotherapy (mean positive predictive values 85%-88%). Among those @entity1 predicted to be treatment sensitive, distant relapse-free survival (DRFS) was improved (negative predictive values 87%-88%). BRmet50 was further shown to prospectively predict @entity4 - @entity5 sensitivity in @entity1 with @entity0 . CONCLUSIONS: We have developed and applied a high-throughput screening method for public @entity2 signature validation. Using this method, we identified appropriate datasets for cross-validation and two robust signatures that differentiate @entity3 mutation status and have prognostic and predictive value for @entity0 @entity1 .

title: Evaluation of public XXXX datasets and signatures identifies @entity3 mutant signatures with robust prognostic and predictive value.

answer: @entity2


abstract: OBJECTIVE: A literature review to evaluate quality of life and participation outcomes of individuals with earthquake-related @entity0 . DATA SOURCES: A systematic review was performed using National Health Service (NHS) @entity2 ( @entity2 ) guidelines. MEDLINE, Embase, PsychINFO, CINAHL and AMED electronic databases were searched from 1966 to January 2014. STUDY SELECTION: Studies that measured quality of life or participation outcomes among individuals who acquired a @entity1 as a result of an @entity0 were included, with no limits on research design. DATA EXTRACTION: The search yielded 961 potentially relevant articles after removal of duplicates. Of these, only 8 articles met the inclusion criteria. Studies were rated for quality using the Critical Appraisal Skills Programme (CASP) guidelines. DATA SYNTHESIS: A narrative synthesis was performed due to the heterogeneity of the included studies. RESULTS: Injured earthquake survivors in developing countries experience diminished participation and reduced quality of life. Small sample sizes and lack of uniformity in outcome measurement limit generalizability. No studies from developed countries were identified. CONCLUSION: To maximize our understanding of quality of life and participation in injured earthquake survivors, future research should consider both the functional consequences of the @entity0 . The research should be based on representative samples of the injured earthquake survivors and use validated condition-specific outcome measures that are clearly defined within the publications. In addition, research should include all countries that are affected by earthquakes.

title: Participation and quality of life outcomes among individuals with earthquake-related XXXX : A systematic review.

answer: @entity1


abstract: BACKGROUND: Evidence-based, guideline-recommended practices improve multiple outcomes in @entity0 admitted with acute exacerbation of @entity2 (AECOPD), but are incompletely implemented in actual practice. Admission order sets with evidence-based diagnostic and therapeutic guidance have enabled quality improvement and guideline implementation in other conditions. OBJECTIVE: To characterize the magnitude of care gaps and the effect of order sets on quality of care in @entity0 with AECOPD. METHODS: The authors prospectively designed a standardized chart review protocol to document process of care and health care utilization before and after implementation of AECOPD order sets at an academic hospital in Toronto, Ontario. RESULTS: A total of 243 total AECOPD admissions and multiple important care gaps were identified. There were 74 admissions in the pre-order set period (January to June 2009) and 169 in the order set period (October 2009 to September 2010). The order set was used in 78 of 169 (46.2%) admissions. In the order set period, we observed improvements in respiratory therapy educational referrals (five of 74 [6.8%] versus 48 of 169 [28.4%]; P<0.01); @entity3 prophylaxis prescriptions (when indicated) (15 of 68 [22.1%] versus 100 of 134 [74.6%]; P<0.01); systemic @entity1 prescriptions (55 of 74 (74.3%) versus 151 of 169 [89.4%]; P<0.01]); and appropriate antibiotic prescriptions (nine of 24 [37.5%] versus 61 of 88 [69.3%]; P<0.01). The mean (   SD) length of stay also decreased from 6.5  7.7 days before order sets to 4.1  5.0 days with order sets (P=0.017). CONCLUSIONS: Care gaps in inpatient AECOPD management were large and evidence-based order sets may improve guideline adherence at the point of care. Randomized trials including @entity0 outcomes are required to further evaluate this knowledge translation intervention.

title: Gaps in the inpatient management of XXXX and impact of an evidence-based order set.

answer: @entity2


abstract: Autophagy is an important component of the immune response. However, the functions of autophagy in @entity0 diseases are much less understood. We studied biological consequences of @entity6 in @entity1 lacking the essential autophagy gene @entity7 or @entity5 in myeloid cells. Surprisingly, these @entity1 presented with spontaneous @entity3 , characterized by marked recruitment of inflammatory cells, submucosal thickening, goblet cell metaplasia, and increased collagen content. @entity3 was associated with increase in several proinflammatory cytokines in the bronchoalveolar lavage and in serum. This @entity2 was largely driven by @entity4 as a result of constitutive inflammasome activation. Following i.p. LPS injection, autophagy-deficient @entity1 had higher levels of proinflammatory cytokines in lungs and in serum, as well as increased mortality, than control @entity1 . Intranasal bleomycin challenge exacerbated @entity3 in autophagy-deficient @entity1 and produced more severe fibrotic changes than in control @entity1 . These results uncover a new and important role for autophagy as negative regulator of @entity3 .

title: Critical role for XXXX in @entity3 caused by @entity6 .

answer: @entity4


abstract: Autophagy is an important component of the immune response. However, the functions of autophagy in @entity0 diseases are much less understood. We studied biological consequences of @entity6 in @entity1 lacking the essential autophagy gene @entity7 or @entity5 in myeloid cells. Surprisingly, these @entity1 presented with spontaneous @entity3 , characterized by marked recruitment of inflammatory cells, submucosal thickening, goblet cell metaplasia, and increased collagen content. @entity3 was associated with increase in several proinflammatory cytokines in the bronchoalveolar lavage and in serum. This @entity2 was largely driven by @entity4 as a result of constitutive inflammasome activation. Following i.p. LPS injection, autophagy-deficient @entity1 had higher levels of proinflammatory cytokines in lungs and in serum, as well as increased mortality, than control @entity1 . Intranasal bleomycin challenge exacerbated @entity3 in autophagy-deficient @entity1 and produced more severe fibrotic changes than in control @entity1 . These results uncover a new and important role for autophagy as negative regulator of @entity3 .

title: Critical role for @entity4 in XXXX caused by @entity6 .

answer: @entity3


abstract: Autophagy is an important component of the immune response. However, the functions of autophagy in @entity0 diseases are much less understood. We studied biological consequences of @entity6 in @entity1 lacking the essential autophagy gene @entity7 or @entity5 in myeloid cells. Surprisingly, these @entity1 presented with spontaneous @entity3 , characterized by marked recruitment of inflammatory cells, submucosal thickening, goblet cell metaplasia, and increased collagen content. @entity3 was associated with increase in several proinflammatory cytokines in the bronchoalveolar lavage and in serum. This @entity2 was largely driven by @entity4 as a result of constitutive inflammasome activation. Following i.p. LPS injection, autophagy-deficient @entity1 had higher levels of proinflammatory cytokines in lungs and in serum, as well as increased mortality, than control @entity1 . Intranasal bleomycin challenge exacerbated @entity3 in autophagy-deficient @entity1 and produced more severe fibrotic changes than in control @entity1 . These results uncover a new and important role for autophagy as negative regulator of @entity3 .

title: Critical role for @entity4 in @entity3 caused by XXXX .

answer: @entity6


abstract: @entity5 encodes the a subunit of nicotinic acetylcholine receptors (nAChRs) and is expressed at the neuromuscular junction. Moreover, it is one of the causative genes of @entity3 ( @entity3 ). @entity5 undergoes alternative splicing to produce two splice variants: P3A(-), without exon P3A, and P3A(+), with the exon P3A. Only P3A(-) forms functional @entity2 . Aberrant alternative splicing caused by intronic or exonic point mutations in @entity0 leads to an extraordinary increase in P3A(+) and a concomitant decrease in P3A(-). Consequently this resulted in a shortage of functional receptors. Aiming to restore the imbalance between the two splice products, antisense oligonucleotides (AONs) were employed to induce exon P3A skipping. Three AON sequences were designed to sterically block the putative binding sequences for splicing factors necessary for exon recognition. Herein, we show that AON @entity4 ' splice site of the exon was the most effective at exon skipping of the minigene with causative mutations, as well as endogenous wild-type @entity5 . We conclude that single administration of the AON against the 5' splice site is a promising therapeutic approach for @entity0 based on the dose-dependent effect of the AON and the additive effect of combined AONs. This conclusion is favorable to @entity0 with @entity1 of uncertain etiology that arise from aberrant splicing leading to a subsequent loss of functional translation products because our findings encourage the option of AON treatment as a therapeutic for these prospectively identified diseases.

title: Antisense oligonucleotide-mediated exon skipping of XXXX pre-mRNA as potential therapy for @entity3 .

answer: @entity5


abstract: @entity5 encodes the a subunit of nicotinic acetylcholine receptors (nAChRs) and is expressed at the neuromuscular junction. Moreover, it is one of the causative genes of @entity3 ( @entity3 ). @entity5 undergoes alternative splicing to produce two splice variants: P3A(-), without exon P3A, and P3A(+), with the exon P3A. Only P3A(-) forms functional @entity2 . Aberrant alternative splicing caused by intronic or exonic point mutations in @entity0 leads to an extraordinary increase in P3A(+) and a concomitant decrease in P3A(-). Consequently this resulted in a shortage of functional receptors. Aiming to restore the imbalance between the two splice products, antisense oligonucleotides (AONs) were employed to induce exon P3A skipping. Three AON sequences were designed to sterically block the putative binding sequences for splicing factors necessary for exon recognition. Herein, we show that AON @entity4 ' splice site of the exon was the most effective at exon skipping of the minigene with causative mutations, as well as endogenous wild-type @entity5 . We conclude that single administration of the AON against the 5' splice site is a promising therapeutic approach for @entity0 based on the dose-dependent effect of the AON and the additive effect of combined AONs. This conclusion is favorable to @entity0 with @entity1 of uncertain etiology that arise from aberrant splicing leading to a subsequent loss of functional translation products because our findings encourage the option of AON treatment as a therapeutic for these prospectively identified diseases.

title: Antisense oligonucleotide-mediated exon skipping of @entity5 pre-mRNA as potential therapy for XXXX .

answer: @entity3


abstract: BACKGROUND: @entity2 ( @entity2 ) has the worst survival of all periampullary @entity1 . This may relate to histopathological differences between @entity1 . Our aim was to examine the distribution and histopathologic features of @entity2 resected with a pancreaticoduodenectomy (PD) and to examine @entity1 resected with a PD. METHODS: A retrospective review of PD between January 2000 and December 2012 at a public metropolitan database was performed. The institutional ethics committee approved this study. RESULTS: There were 142 PDs during the study period, of which 70 cases were pre-2010 and 72 post-2010, corresponding to a recent increase in the number of cases. Of the 142 cases, 116 were for periampullary @entity1 . There were also proportionately more PD for @entity2 (26/60, 43% pre-2010 vs 39/56, 70% post-2010, P   =   0.005). There were 65/116 (56%) pancreatic, 29/116 (25%), ampullary, 17/116 (15%) biliary and 5/116 (4%) @entity1 . Nodal involvement occurred more frequently in @entity2 (78%) compared to ampullary (59%), biliary (47%) and @entity1 (20%), P   =   0.002. Perineural invasion was also more frequent in @entity2 (74%) compared to ampullary (34%), biliary (59%) and @entity1 (20%), P   =   0.002. @entity0 was seen in 57% pancreatic, 38% ampullary, 41% biliary and 20% @entity1 , P   =   0.222. Overall, clear margins (R0) were achieved in fewer @entity2 41/65 (63%) compared to ampullary 27/29 (93%; P   =   0.003) and @entity1 16/17 (94%; P   =   0.014). CONCLUSIONS: This study highlights that almost half of PD was performed for @entity1 other than @entity2 , mainly ampullary and @entity1 . The volume of PD has increased in recent years with an increased proportion being for @entity2 . @entity2 had higher rates of nodal and perineural invasion compared to ampullary, @entity1 .

title: Distribution and pathological features of XXXX resected with pancreaticoduodenectomy.

answer: @entity2


abstract: BACKGROUND: @entity0 and @entity3 are produced commercially by @entity1 . The production strains of @entity0 and @entity3 were both derivatives from mutagenesis. However, the exact metabolic and genetic factors affecting the productivity remain unknown. Genetic engineering may be a promising approach to identify and confirm these factors. RESULTS: With the deletion of the cdd and hom genes, and the deregulation of the pyr operon in @entity4 , the engineered strain produced 200.9  mg/L @entity0 , 14.9  mg/L @entity3 and 960.1  mg/L @entity2 . Then, the overexpressed prs gene led to a dramatic increase of @entity3 by 25.9 times along with a modest increase of @entity0 . Furthermore, the overexpressed pyrG gene improved the production of @entity0 , @entity3 and @entity2 by 259.5%, 11.2% and 68.8%, respectively. Moreover, the overexpression of the pyrH gene increasesd the yield of @entity0 by 40%, along with a modest augments of @entity3 and @entity2 . Lastly, the deletion of the nupC-pdp gene resulted in a doubled production of @entity3 up to 1684.6  mg/L, a 14.4% increase of @entity0 to 1423  mg/L, and a 99% decrease of @entity2 to only 14.2  mg/L. CONCLUSIONS: The deregulation of the pyr operon and the overexpression of the prs, pyrG and pyrH genes all contribute to the accumulation of @entity5 compounds in the medium. Among these factors, the overexpression of the pyrG and pyrH genes can particularly facilitate the production of @entity0 . Meanwhile, the deletion of the nupC-pdp gene can obviously reduce the production of @entity2 and simultaneously improve the production of @entity3 .

title: Metabolic and genetic factors affecting the productivity of XXXX in @entity1 .

answer: @entity5


abstract: BACKGROUND: @entity0 and @entity3 are produced commercially by @entity1 . The production strains of @entity0 and @entity3 were both derivatives from mutagenesis. However, the exact metabolic and genetic factors affecting the productivity remain unknown. Genetic engineering may be a promising approach to identify and confirm these factors. RESULTS: With the deletion of the cdd and hom genes, and the deregulation of the pyr operon in @entity4 , the engineered strain produced 200.9  mg/L @entity0 , 14.9  mg/L @entity3 and 960.1  mg/L @entity2 . Then, the overexpressed prs gene led to a dramatic increase of @entity3 by 25.9 times along with a modest increase of @entity0 . Furthermore, the overexpressed pyrG gene improved the production of @entity0 , @entity3 and @entity2 by 259.5%, 11.2% and 68.8%, respectively. Moreover, the overexpression of the pyrH gene increasesd the yield of @entity0 by 40%, along with a modest augments of @entity3 and @entity2 . Lastly, the deletion of the nupC-pdp gene resulted in a doubled production of @entity3 up to 1684.6  mg/L, a 14.4% increase of @entity0 to 1423  mg/L, and a 99% decrease of @entity2 to only 14.2  mg/L. CONCLUSIONS: The deregulation of the pyr operon and the overexpression of the prs, pyrG and pyrH genes all contribute to the accumulation of @entity5 compounds in the medium. Among these factors, the overexpression of the pyrG and pyrH genes can particularly facilitate the production of @entity0 . Meanwhile, the deletion of the nupC-pdp gene can obviously reduce the production of @entity2 and simultaneously improve the production of @entity3 .

title: Metabolic and genetic factors affecting the productivity of @entity5 in XXXX .

answer: @entity1


abstract: UNASSIGNED: Cry8Ka5 is a mutant protein from @entity4 (Bt) that has been proposed for developing transgenic plants due to promising activity against coleopterans, like Anthonomus grandis (the major pest of Brazilian @entity3 culture). Thus, an early food safety assessment of Cry8Ka5 protein could provide valuable information to support its use as a harmless biotechnological tool. This study aimed to evaluate the food safety of Cry8Ka5 protein following the two-tiered approach, based on weights of evidence, proposed by ILSI. Cry1Ac protein was used as a control Bt protein. The history of safe use revealed no convincing hazard reports for Bt pesticides and three-domain Cry proteins. The bioinformatics analysis with the primary @entity2 sequence of Cry8Ka5 showed no similarity to any known @entity1 , antinutritional or allergenic proteins. The mode of action of Cry proteins is well understood and their fine specificity is restricted to insects. Cry8Ka5 and Cry1Ac proteins were rapidly degraded in simulated gastric fluid, but were resistant to simulated intestinal fluid and heat treatment. The LD50 for Cry8Ka5 and @entity5 Ac was >5000   mg/kg body weight when administered by gavage in @entity0 . Thus, no expected relevant risks are associated with the consumption of Cry8Ka5 protein.

title: Food safety assessment of Cry8Ka5 mutant protein using XXXX Ac as a control Bt protein.

answer: @entity5


abstract: OBJECTIVE: To evaluate the outcomes after pylorus-preserving gastrectomy (PPG) for early @entity2 (EGC). METHODS: Clinicopathologic data of 52 @entity0 with EGC undergoing PPG between August 1995 and December 2005 were analyzed retrospectively. A total of 159 @entity0 of EGC who underwent distal gastrectomy with lymph node dissection(control group) were compared with those who received PPG. RESULTS: The lymph node @entity1 rate of EGC was 9.6% in PPG group, including 9.6% in No.3, 3.9% in No.4, 3.9% in No.6, and 3.9% in No.7. In the control group, the lymph node @entity1 rate was 17.0%, including N1(14.5%) and N2(2.5%). There were no significant differences between the PPG group and the control group (P>0.05). In the PPG group, D1 dissection was 25%, D1+a was 25%, D1+b was 34.6%, and D2 was 15.3%. In control group, 121 @entity0 (76.1%) had less than D2 dissection, while there were 33(20.7%) D2, and 5(3.1%) D3, and the difference was not statistically significant(P>0.05). There were no significant differences between the two groups in overall 5-year survival rate(92.3% vs. 93.1%, P=0.881). The 5-year survival rate in the PPG group was 100% for D1, 92.3% for D1+a, 88.9% for D1+b, and 85.7% for D2, while the 5-year survival rate in the control group was 92.3% for D1, 93.3% for D1+a, 91.7% for D1+b, and 93.9% for D2. The difference was not statistically significant(P>0.05). The recurrence rate was comparable (5.7% vs. 5.6%, P>0.05). CONCLUSION: Pylorus-preserving gastrectomy may provide long-term survival benefits for @entity0 with early @entity2 .

title: [Efficacy observation after pylorus-preserving gastrectomy for early XXXX ].

answer: @entity2


abstract: OBJECTIVE: To clinically study the antiviral effects of @entity8 and @entity9 on @entity0 with early-to-mid stage @entity5 related @entity3 ( @entity1 -ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of @entity6 analogues on @entity0 with early-to-mid stage @entity1 -ACLF. Three groups were set for controlled study, i. e. basic treatment group, @entity8 plus basic treatment group and @entity9 plus basic treatment group. RESULTS: One month after treatment, the improvement rates of @entity8 group and @entity9 group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of @entity0 with the antiviral treatments, i.e., @entity8 , @entity9 , were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in @entity0 with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the @entity0 with pretreatment @entity1 DNA > or = 10(7), the cumulative survival rate in @entity0 with @entity9 treatments group was higher than that of @entity0 in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either @entity8 or entecavia could significantly increase the improvement rate of @entity0 with early-to-mid stage @entity1 -ACLF. But severe complications, including @entity7 , electrolyte imbalance and @entity2 , medical history of @entity4 , and pretreatment @entity1 DNA > or = 10(7) had significant impacts on prognosis of this group patients. CONCLUSIONS: Antiviral therapy by using either @entity8 or entecavia could significantly increase the survival rate of @entity0 with early-to-mid stage @entity1 -ACLF.

title: [ XXXX and @entity9 significantly improved the prognosis of early-to-mid stage @entity5 related @entity3 ].

answer: @entity8


abstract: OBJECTIVE: To clinically study the antiviral effects of @entity8 and @entity9 on @entity0 with early-to-mid stage @entity5 related @entity3 ( @entity1 -ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of @entity6 analogues on @entity0 with early-to-mid stage @entity1 -ACLF. Three groups were set for controlled study, i. e. basic treatment group, @entity8 plus basic treatment group and @entity9 plus basic treatment group. RESULTS: One month after treatment, the improvement rates of @entity8 group and @entity9 group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of @entity0 with the antiviral treatments, i.e., @entity8 , @entity9 , were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in @entity0 with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the @entity0 with pretreatment @entity1 DNA > or = 10(7), the cumulative survival rate in @entity0 with @entity9 treatments group was higher than that of @entity0 in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either @entity8 or entecavia could significantly increase the improvement rate of @entity0 with early-to-mid stage @entity1 -ACLF. But severe complications, including @entity7 , electrolyte imbalance and @entity2 , medical history of @entity4 , and pretreatment @entity1 DNA > or = 10(7) had significant impacts on prognosis of this group patients. CONCLUSIONS: Antiviral therapy by using either @entity8 or entecavia could significantly increase the survival rate of @entity0 with early-to-mid stage @entity1 -ACLF.

title: [ @entity8 and XXXX significantly improved the prognosis of early-to-mid stage @entity5 related @entity3 ].

answer: @entity9


abstract: OBJECTIVE: To clinically study the antiviral effects of @entity8 and @entity9 on @entity0 with early-to-mid stage @entity5 related @entity3 ( @entity1 -ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of @entity6 analogues on @entity0 with early-to-mid stage @entity1 -ACLF. Three groups were set for controlled study, i. e. basic treatment group, @entity8 plus basic treatment group and @entity9 plus basic treatment group. RESULTS: One month after treatment, the improvement rates of @entity8 group and @entity9 group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of @entity0 with the antiviral treatments, i.e., @entity8 , @entity9 , were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in @entity0 with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the @entity0 with pretreatment @entity1 DNA > or = 10(7), the cumulative survival rate in @entity0 with @entity9 treatments group was higher than that of @entity0 in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either @entity8 or entecavia could significantly increase the improvement rate of @entity0 with early-to-mid stage @entity1 -ACLF. But severe complications, including @entity7 , electrolyte imbalance and @entity2 , medical history of @entity4 , and pretreatment @entity1 DNA > or = 10(7) had significant impacts on prognosis of this group patients. CONCLUSIONS: Antiviral therapy by using either @entity8 or entecavia could significantly increase the survival rate of @entity0 with early-to-mid stage @entity1 -ACLF.

title: [ @entity8 and @entity9 significantly improved the prognosis of early-to-mid stage XXXX related @entity3 ].

answer: @entity5


abstract: OBJECTIVE: To clinically study the antiviral effects of @entity8 and @entity9 on @entity0 with early-to-mid stage @entity5 related @entity3 ( @entity1 -ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of @entity6 analogues on @entity0 with early-to-mid stage @entity1 -ACLF. Three groups were set for controlled study, i. e. basic treatment group, @entity8 plus basic treatment group and @entity9 plus basic treatment group. RESULTS: One month after treatment, the improvement rates of @entity8 group and @entity9 group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of @entity0 with the antiviral treatments, i.e., @entity8 , @entity9 , were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in @entity0 with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the @entity0 with pretreatment @entity1 DNA > or = 10(7), the cumulative survival rate in @entity0 with @entity9 treatments group was higher than that of @entity0 in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either @entity8 or entecavia could significantly increase the improvement rate of @entity0 with early-to-mid stage @entity1 -ACLF. But severe complications, including @entity7 , electrolyte imbalance and @entity2 , medical history of @entity4 , and pretreatment @entity1 DNA > or = 10(7) had significant impacts on prognosis of this group patients. CONCLUSIONS: Antiviral therapy by using either @entity8 or entecavia could significantly increase the survival rate of @entity0 with early-to-mid stage @entity1 -ACLF.

title: [ @entity8 and @entity9 significantly improved the prognosis of early-to-mid stage @entity5 related XXXX ].

answer: @entity3


abstract: BACKGROUND: Mass spectrometry based phosphoproteomics emerged as advantageous approach for the analysis of @entity6 phosphorylation on proteins and @entity6 kinase signaling. Immunoaffinity purification is required for comprehensive analysis. Here we compared the performance of two antibodies for label-free @entity8 -based phosphoproteomics. METHODS: Phosphopeptide immunoprecipitation of six technical replicates corresponding to 10mg protein from HCT116 cells was performed using agarose bead-coupled @entity8 antibodies P-Tyr-1000 (N=3) and 4G10 (N=3). NanoLC-MS/MS was performed using a Q Exactive mass spectrometer. For relative quantitation of protein phosphorylation, spectral counts of phosphoproteins and ion intensities of phosphopeptides were determined using MaxQuant. RESULTS: From the 3 samples incubated with P-Tyr-1000 a total of 689 phosphopeptides were identified with 60% ID reproducibility. The phosphopeptide capture using 4G10 resulted in a total of 421 at 46% ID reproducibility. The P-Tyr-1000 was applied to @entity2 mutated U87 cells. @entity4 reduced @entity2 phosphorylation with 59% at y978, y1125, y1138, y1172, and y1197. @entity2 inhibition was accompanied by enhanced phosphorylation of @entity7 , MET, @entity3 , @entity10 , @entity5 and @entity9 . CONCLUSION: The P-Tyr-1000 @entity8 antibody performs superiorly when compared to 4G10 antibody for label-free @entity8 -based phosphoproteomics. This workflow allows evaluation of drug target phosphorylation and may give insights in the pharmacodynamic effects of @entity6 kinase inhibitors. CLINICAL SIGNIFICANCE: In the past decade multiple @entity6 kinase inhibitors (TKIs) have been implemented in standard treatment regimens for @entity0 with @entity1 . Unfortunately the majority of @entity0 develops resistance to these drugs. Reliable tools for analysis of pharmacodynamic effects and drug resistance mechanisms are therefore warranted. Phosphoproteomic analyses have meanwhile emerged as a sophisticated approach for the determination of protein phosphorylation. These analyses rely on antibodies for enrichment of @entity6 -phosphorylated peptides. Here we compared two commercially available @entity8 antibodies and show that P-Tyr-1000 yields 64% more phosphopeptides than 4G10 antibody, while including almost all 4G10 captured phosphopeptides. The workflow can be reproducibly performed at intermediate protein input levels of 10mg. Furthermore, application of the P-Tyr-1000 antibody in a standardized phosphoproteomics workflow allows relative quantitation of drug target inhibition and provides insights in alternative signaling pathways in @entity1 cells. This article is part of a Special Issue entitled: HUPO 2014.

title: Evaluation of different XXXX antibodies for label-free phosphoproteomics.

answer: @entity8


abstract: BACKGROUND: The recurrent @entity2 driver mutation @entity6 ( @entity2 ( @entity6 )) is currently one of the most clinically relevant mutations in @entity1 . However, the genome-wide transcriptional and epigenetic dysregulations induced by @entity2 ( @entity6 ) are still unclear. The investigation of this driver mutation's functional consequences is critical to the understanding of tumorigenesis and the development of therapeutic strategies. METHODS AND RESULTS: We performed an integrative analysis of transcriptomic and epigenomic changes disturbed by @entity2 ( @entity6 ) by comparing the gene expression and methylation profiles of 34 primary @entity1 harboring @entity2 ( @entity6 ) with those of 27 @entity2 ( @entity5 ) samples available from The @entity0 (TCGA). A total of 711 significantly differentially expressed genes were identified as putative @entity2 ( @entity6 ) target genes. Functional enrichment analyses revealed the transcription factor @entity4 (p   <   3.6 * 10(-16)) and growth factor @entity3 (p   <   3.1 * 10(-9)) were the most significantly enriched up-regulators, with @entity4 being significantly up-regulated, whereas @entity3 was significantly down-regulated in @entity2 ( @entity6 ), suggesting that they may mediate tumorigenesis driven by @entity2 ( @entity6 ). Further investigation using the @entity4 ChIP-Seq data confirmed that @entity2 ( @entity6 ) led to an overall increased level of gene expression for the @entity4 targets. Furthermore, DNA methylation analysis revealed a global DNA methylation loss in @entity2 ( @entity6 ) relative to @entity2 ( @entity5 ). This might be due to @entity2 dysregulation of @entity7 , which was identified as a potential target with significant down-regulation in @entity2 ( @entity6 ). Finally, we demonstrated that @entity2 ( @entity6 ) targets may play essential functional roles in cell growth and proliferation, measured by their effects on @entity1 growth using a short hairpin RNA silencing experimental dataset. CONCLUSIONS: Our integrative analysis identified a set of @entity2 ( @entity6 ) target genes. Further analyses suggested a complex mechanism driven by mutation @entity2 ( @entity6 ) on @entity1 that disturbs specific @entity0 -related genes, pathways, and methylation modifications.

title: In-depth genomic data analyses revealed complex transcriptional and epigenetic dysregulations of BRAFV600E in XXXX .

answer: @entity1


abstract: BACKGROUND: @entity3 are an extremely rare condition with only 17 cases described in the literature since 1980. They can reach enormous size and cause significant abdominal symptoms. The most important differential diagnosis is the well-differentiated @entity6 , which preoperatively often may not definitely be ruled out. CASE PRESENTATION: We present the case of a 73 year-old Caucasian @entity0 with a @entity3 of 9 kg measuring 55 cm in diameter. The @entity0 presented with @entity4 and swelling that had been slowly progressive for the last 15 years. On computerized tomography an immense @entity1 was revealed. Intraoperatively, the @entity1 did not show any signs of infiltrative growth, therefore sole @entity1 extirpation was performed. CONCLUSION: @entity3 are not clearly distinguishable from well-differentiated @entity6 on imaging and even biopsies may be misleading. Moreover, abdominal symptoms, i.e. @entity2 , obstipation and @entity5 may occur due to mechanical displacement. Therefore, surgical exploration with complete oncological resection is the therapy of choice if malignity cannot be ruled out.

title: En-bloc resection of a XXXX : a case report and review of the literature.

answer: @entity3


abstract: BACKGROUND: This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to measure @entity2 in @entity0 with @entity1 ( @entity1 ). A CAT can be used to precisely measure @entity0 -reported outcomes at an individual level as items are consequentially selected based on the @entity0 's previous answers. The item bank of the CAT Fatigue @entity1 has been developed from the @entity0 ' perspective and consists of 196 items pertaining to three @entity2 dimensions: severity, impact and variability of @entity2 . METHODS: The CAT Fatigue @entity1 was completed by fifteen @entity0 . To test the CAT's working mechanism, we applied the flowchart-check-method. The adaptive item selection procedure for each @entity0 was checked by the researchers. The estimated @entity2 levels and the measurement precision per dimension were illustrated with the selected items, answers and flowcharts. RESULTS: The CAT Fatigue @entity1 selected all items in a logical sequence and those items were selected which provided the most information about the @entity0 's individual @entity2 . Flowcharts further illustrated that the CAT reached a satisfactory measurement precision, with less than 20 items, on the dimensions severity and impact and to somewhat lesser extent also for the dimension variability. @entity0 ' @entity2 scores varied across the three dimensions; sometimes severity scored highest, other times impact or variability. The CAT's ability to display different @entity2 experiences can improve communication in daily clinical practice, guide interventions, and facilitate research into possible predictors of @entity2 . CONCLUSIONS: The results indicate that the CAT Fatigue @entity1 measures precise and comprehensive. Once it is examined in more detail in a consecutive, elaborate validation study, the CAT will be available for implementation in daily clinical practice and for research purposes.

title: Working mechanism of a multidimensional computerized adaptive test for XXXX in @entity1 .

answer: @entity2


abstract: BACKGROUND: This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to measure @entity2 in @entity0 with @entity1 ( @entity1 ). A CAT can be used to precisely measure @entity0 -reported outcomes at an individual level as items are consequentially selected based on the @entity0 's previous answers. The item bank of the CAT Fatigue @entity1 has been developed from the @entity0 ' perspective and consists of 196 items pertaining to three @entity2 dimensions: severity, impact and variability of @entity2 . METHODS: The CAT Fatigue @entity1 was completed by fifteen @entity0 . To test the CAT's working mechanism, we applied the flowchart-check-method. The adaptive item selection procedure for each @entity0 was checked by the researchers. The estimated @entity2 levels and the measurement precision per dimension were illustrated with the selected items, answers and flowcharts. RESULTS: The CAT Fatigue @entity1 selected all items in a logical sequence and those items were selected which provided the most information about the @entity0 's individual @entity2 . Flowcharts further illustrated that the CAT reached a satisfactory measurement precision, with less than 20 items, on the dimensions severity and impact and to somewhat lesser extent also for the dimension variability. @entity0 ' @entity2 scores varied across the three dimensions; sometimes severity scored highest, other times impact or variability. The CAT's ability to display different @entity2 experiences can improve communication in daily clinical practice, guide interventions, and facilitate research into possible predictors of @entity2 . CONCLUSIONS: The results indicate that the CAT Fatigue @entity1 measures precise and comprehensive. Once it is examined in more detail in a consecutive, elaborate validation study, the CAT will be available for implementation in daily clinical practice and for research purposes.

title: Working mechanism of a multidimensional computerized adaptive test for @entity2 in XXXX .

answer: @entity1


abstract: BACKGROUND: Cone-beam computed tomography (CBCT) image-guided radiotherapy (IGRT) systems are widely used tools to verify and correct the target position before each fraction, allowing to maximize treatment accuracy and precision. In this study, we evaluate automatic three-dimensional intensity-based rigid registration (RR) methods for prostate setup correction using CBCT scans and study the @entity1 on registration quality. METHODS: We retrospectively analyzed 115 CBCT scans of 10 prostate @entity0 . CT-to-CBCT registration was performed using (a) global RR, (b) bony RR, or (c) bony RR refined by a local prostate RR using the CT clinical target volume (CTV) expanded with 1-to-20-mm varying margins. After propagation of the manual CT contours, automatic CBCT contours were generated. For evaluation, a radiation oncologist manually delineated the CTV on the CBCT scans. The propagated and manual CBCT contours were compared using the Dice similarity and a measure based on the bidirectional local distance (BLD). We also conducted a blind visual assessment of the quality of the propagated segmentations. Moreover, we automatically quantified @entity2 between the CT and CBCT scans without using the manual CBCT contours and we investigated its correlation with the registration failures. To improve the registration quality, the air in the rectum was replaced with soft tissue using a filter. The results with and without filtering were compared. RESULTS: The statistical analysis of the Dice coefficients and the BLD values resulted in highly significant differences (p<10(-6)) for the 5-mm and 8-mm local RRs vs the global, bony and 1-mm local RRs. The 8-mm local RR provided the best compromise between accuracy and robustness (Dice median of 0.814 and 97% of success with filtering the air in the rectum). We observed that all failures were due to high @entity2 . Moreover, the visual assessment confirmed the superiority of the 8-mm local RR over the bony RR. CONCLUSION: The most successful CT-to-CBCT RR method proved to be the 8-mm local RR. We have shown the correlation between its registration failures and @entity2 . Furthermore, we have provided a simple (easily applicable in routine) and automatic method to quantify @entity2 and to predict registration failure using only the manual CT contours.

title: Development of CBCT-based prostate setup correction strategies and XXXX .

answer: @entity1


abstract: Adult intussusception is rare and usually caused by a @entity1 acting as the lead point. Therefore, laparotomy should be considered for the treatment. Laparoscopic procedures for use in cases of adult intussusception have been recently reported; however, there is no consensus regarding the safety and efficacy. Here, we describe a successful case of laparoscopic management of an octogenarian adult intussusception caused by an @entity2 , which was preoperatively suspected. An 87-year-old male presented with progressive @entity3 . Contrast radiography of the small intestine showed an @entity1 , and magnetic resonance imaging indicated a target-like mass, consistent with an ileal intussusception. The @entity0 was suspected with an intussusception due to an @entity2 , and laparoscopic surgery was performed. An approximately 10-cm-long ileal intussusception with a preceding @entity1 was present, and partial resection of the ileum, including the @entity1 , was performed. Macroscopic examination of the excised specimen showed a pedunculated @entity1 measuring 4.0   *   3.5   *   1.9  cm with an uneven surface, yielding a histological diagnosis of @entity2 . The @entity0 had an uneventful recovery and was discharged on postoperative day 8. This successful case showed that laparoscopic surgery can be a useful, safe, and efficacious procedure for adult intussusception, even in octogenarians.

title: Laparoscopic management of an octogenarian adult intussusception caused by an XXXX suspected preoperatively: a case report.

answer: @entity2


abstract: BACKGROUND: Primary umbilical @entity3 is an uncommon @entity2 that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary @entity2 affecting the umbilicus require a different and more radical surgical approach compared with other @entity3 . CASE PRESENTATION: In this report, we describe a series of three @entity0 of Caucasian ethnicity who presented with primary umbilical @entity3 at the National @entity2 Institute of Naples, Italy. All @entity0 underwent wide excision of the @entity2 including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the @entity0 . Sentinel lymph node biopsy was negative in two cases. Two of the @entity0 developed @entity1 and died after systemic medical therapy. The other @entity0 is currently in follow-up, and remains disease-free after 21 months. CONCLUSIONS: The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical @entity3 . As such, @entity2 resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.

title: Clinicopathologic features and surgical management of primary umbilical XXXX : a case series.

answer: @entity3


abstract: The glomerular filtration rate (GFR) can be estimated by an equation that incorporates @entity0 ' age, gender, @entity4 and weight or, ideally, lean body mass (LBM). However, measuring LBM is not easy if the @entity0 is @entity2 . The aim was to determine an acceptable bedside method for GFR estimation in @entity2 @entity0 . In 82 @entity2 Caucasian outpatients, anthropometric and other characteristics were collected including LBM by impedance analysis. Estimates of GFR were compared with a reference equation (CCGLBM) using Bland-Altman plots, correlation analysis and an independent sample t-test. The @entity0 (72% female) were aged 43.1  12.7 years with BMI 47.0  8.0kg/m(2), height 168.4  9.4cm and serum @entity4 70.3  25.7 M. The GFR estimated by the CCGLBM equation was 98.2  33.6ml/min compared to other equations which ranged from 100.0  22.8 to 218.4  85.5ml/min. Any equation incorporating actual body weight overestimated the GFR by >120ml/min (p<0.001) with a significant fixed proportional bias (p<0.001). For GFRs between 20 and 180ml/min, an equation using ideal body weight (CCGIBW) equated to the CCGLBM estimate. The Modified Diet in @entity1 and @entity3 Epidemiology Collaboration equations performed as well as the CCGLBM in estimating GFR but with proportional bias (p<0.001). Considering the ease of calculation of the CCGIBW at the bedside, it has a role in GFR estimation of @entity2 inpatients.

title: Estimating glomerular filtration rate in XXXX subjects.

answer: @entity2


abstract: BACKGROUND: Little is known about health outcomes in severe @entity4 reflected by Global Initiative for @entity4 and  5. OBJECTIVE: To analyze control, risk, economic, and @entity3 ( @entity3 ) outcomes associated with treatment escalation to Global Initiative for @entity4 and  5. METHODS: This was a before-vs-after retrospective cohort study of @entity0 (12-75 years old) with @entity4 newly @entity5 , high-intensity corticosteroids (HICS; >= 1,000  g/day of inhaled @entity6 equivalent or oral @entity2 ), or high-dose inhaled corticosteroid (HDICS; >= 500 to <1,000  g/day of @entity6 equivalent) using 2002 to 2011 MarketScan data. Poisson regression was used to model @entity3 outcomes; Tobit regression was used to model medical expenditures. RESULTS: Of 19,227 @entity0 , 856 @entity5 , 6,926 initiated HICS, and 11,445 initiated HDICS. Use of b-agonist increased for the HDICS and HICS cohorts and decreased for the omalizumab cohort; acute care visits and oral @entity1 use decreased during follow-up for the HDICS and omalizumab cohorts. Annual health care expenditures, polypharmacy burden, and outpatient visits were high for all cohorts and increased in the follow-up year (baseline to follow-up; general health care expenditures: omalizumab  14,071 to  34,887, HICS  12,030 to  15,557, HDICS  7,570 to  9,826; annual number of @entity4 prescriptions: omalizumab 11.74 to 19.46, HICS 7.8 to 12.44, HDICS 5.17 to 9.69; outpatient visits: omalizumab 26.79 to 34.06, HICS 18.78 to 21.37, HDICS 15.06 to 16.64). CONCLUSION: Omalizumab use was associated with improvements in risk and control accompanied by large increases in expenditures per @entity3 . @entity0 on HDICS and HICS showed improvements in risk but worsening control and increased expenditures per @entity3 . Innovations in disease management and available treatment options are needed to more optimally achieve treatment goals.

title: Outcomes before and after treatment escalation to Global Initiative for XXXX and 5 in severe @entity4 .

answer: @entity4


abstract: BACKGROUND: Little is known about health outcomes in severe @entity4 reflected by Global Initiative for @entity4 and  5. OBJECTIVE: To analyze control, risk, economic, and @entity3 ( @entity3 ) outcomes associated with treatment escalation to Global Initiative for @entity4 and  5. METHODS: This was a before-vs-after retrospective cohort study of @entity0 (12-75 years old) with @entity4 newly @entity5 , high-intensity corticosteroids (HICS; >= 1,000  g/day of inhaled @entity6 equivalent or oral @entity2 ), or high-dose inhaled corticosteroid (HDICS; >= 500 to <1,000  g/day of @entity6 equivalent) using 2002 to 2011 MarketScan data. Poisson regression was used to model @entity3 outcomes; Tobit regression was used to model medical expenditures. RESULTS: Of 19,227 @entity0 , 856 @entity5 , 6,926 initiated HICS, and 11,445 initiated HDICS. Use of b-agonist increased for the HDICS and HICS cohorts and decreased for the omalizumab cohort; acute care visits and oral @entity1 use decreased during follow-up for the HDICS and omalizumab cohorts. Annual health care expenditures, polypharmacy burden, and outpatient visits were high for all cohorts and increased in the follow-up year (baseline to follow-up; general health care expenditures: omalizumab  14,071 to  34,887, HICS  12,030 to  15,557, HDICS  7,570 to  9,826; annual number of @entity4 prescriptions: omalizumab 11.74 to 19.46, HICS 7.8 to 12.44, HDICS 5.17 to 9.69; outpatient visits: omalizumab 26.79 to 34.06, HICS 18.78 to 21.37, HDICS 15.06 to 16.64). CONCLUSION: Omalizumab use was associated with improvements in risk and control accompanied by large increases in expenditures per @entity3 . @entity0 on HDICS and HICS showed improvements in risk but worsening control and increased expenditures per @entity3 . Innovations in disease management and available treatment options are needed to more optimally achieve treatment goals.

title: Outcomes before and after treatment escalation to Global Initiative for @entity4 and 5 in severe XXXX .

answer: @entity4