abstract: OBJECTIVE: It has been suggested recently that cortical pathology in @entity15 ( @entity15 ) may, at least partly, be caused by factors in cerebrospinal fluid (CSF). We thus hypothesized that @entity15 -related tissue changes in compartments close to the CSF, such as @entity75 , might correlate with cortical pathology. METHODS: We investigated a cohort of 160 @entity1 , comprising 91 with a @entity922 ( @entity922 ) and 69 with relapsing-remitting @entity15 (RRMS; mean age: @entity922 : 31.4    9.0; RRMS: 33.0    8.7 years; mean disease duration: @entity922 : 7.2    15 months; RRMS: 8.0    6.5 years, Expanded Disability Status Scale (median, min-max): @entity922 : 1, 0-3.5; RRMS: 1.25, 0-4) with 3.0T magnetic resonance imaging. @entity15 lesions were segmented semiautomatically on fluid-attenuated inversion recovery images. To quantify periventricular lesion load (PV-LL), we generated ventricle masks and dilated them by a voxel factor of 3. Lesions within the dilated ventricle margin were classified as periventricular. Cortical thinning was assessed by @entity121 ( @entity121 ) and compared to data from 58 healthy controls (HCs; mean age: 29.1    7.4 years). RESULTS: Compared to HC, @entity922 and (even more so) RRMS @entity1 demonstrated significantly reduced @entity121 . Even after controlling for ventricular volume and total lesion load, increased periventricular lesion occupancy (percentage of PV-LL) significantly correlated with decreased @entity121 in RRMS (r = -0.295; p = 0.015), but not in @entity922 (r = 0.032; p = 0.768) @entity1 . INTERPRETATION: The correlation between increased periventricular lesion burden and decreased @entity121 indicative of subpial cortical pathology supports the concept that common CSF-mediated factors might play a role in the accumulation of @entity62 in @entity15 .

title: @entity75 correlate with cortical thinning in XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity121 :: ('MESH:D009135', 'Disease') :: ['CMT', 'cortical mean thickness']

entities_list: @entity75 :: ('MESH:D001927', 'Disease') :: ['periventricular lesions']

entities_list: @entity62 :: ('MESH:D056784', 'Disease') :: ['damage to gray and white matter']

entities_list: @entity15 :: ('MESH:D009103', 'Disease') :: ['multiple sclerosis', 'MS']

entities_list: @entity922 :: ('MESH:D013568', 'Disease') :: ['clinically isolated syndrome', 'CIS']

answer: @entity15 :: (MESH:D009103,Disease) :: ['multiple sclerosis']


abstract: OBJECTIVE: It has been suggested recently that cortical pathology in @entity15 ( @entity15 ) may, at least partly, be caused by factors in cerebrospinal fluid (CSF). We thus hypothesized that @entity15 -related tissue changes in compartments close to the CSF, such as @entity75 , might correlate with cortical pathology. METHODS: We investigated a cohort of 160 @entity1 , comprising 91 with a @entity922 ( @entity922 ) and 69 with relapsing-remitting @entity15 (RRMS; mean age: @entity922 : 31.4    9.0; RRMS: 33.0    8.7 years; mean disease duration: @entity922 : 7.2    15 months; RRMS: 8.0    6.5 years, Expanded Disability Status Scale (median, min-max): @entity922 : 1, 0-3.5; RRMS: 1.25, 0-4) with 3.0T magnetic resonance imaging. @entity15 lesions were segmented semiautomatically on fluid-attenuated inversion recovery images. To quantify periventricular lesion load (PV-LL), we generated ventricle masks and dilated them by a voxel factor of 3. Lesions within the dilated ventricle margin were classified as periventricular. Cortical thinning was assessed by @entity121 ( @entity121 ) and compared to data from 58 healthy controls (HCs; mean age: 29.1    7.4 years). RESULTS: Compared to HC, @entity922 and (even more so) RRMS @entity1 demonstrated significantly reduced @entity121 . Even after controlling for ventricular volume and total lesion load, increased periventricular lesion occupancy (percentage of PV-LL) significantly correlated with decreased @entity121 in RRMS (r = -0.295; p = 0.015), but not in @entity922 (r = 0.032; p = 0.768) @entity1 . INTERPRETATION: The correlation between increased periventricular lesion burden and decreased @entity121 indicative of subpial cortical pathology supports the concept that common CSF-mediated factors might play a role in the accumulation of @entity62 in @entity15 .

title: XXXX correlate with cortical thinning in @entity15 .

answer: @entity75 :: (MESH:D001927,Disease) :: ['Periventricular lesions']


abstract: OBJECTIVE: We previously demonstrated stimulation of collateral vessel formation in a @entity95 model of unilateral limb ischaemia after administration of endothelial cell growth factor ( @entity21349 ). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of @entity21349 . DESIGN: Ischaemia was produced in both hindlimbs of 11 @entity95 by femoral artery excision. Beginning 10 days later, @entity21349 (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses. OUTCOME MEASURES: @entity291 systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies. RESULTS: The mean @entity291 systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the @entity21349 -treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0.0001 for both comparisons). On day 50, collateral vessels were significantly more numerous in the @entity21349 -treated limb (17.2 +/- 1.6 versus 11.0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159.6 +/- 12.9 per mm2; p < 0.002). CONCLUSION: Local administration of @entity21349 enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.

title: Enhanced revascularisation after angiogenic stimulation in a XXXX model of bilateral limb ischaemia.

entities_list: @entity95 :: ('9986', 'Species') :: ['rabbits', 'rabbit']

answer: @entity95 :: (9986,Species) :: ['rabbit']


abstract: The clinical efficacy of COP-BLAM chemotherapy combined with @entity1 recombinant @entity1261 ( @entity1261 ) was evaluated in 104 previously untreated @entity1 with @entity1893 ( @entity1893 ). According to the method of Laurence et al., a modified COP-BLAM regimen was administered every 21 days. @entity1261 was added when the granulocyte count fell below 1000 x 10(9)/l. Ninety-eight of 104 (94.2%) @entity1 achieved a complete remission; the 4-year survival rate was 82.4% with a median duration of observation of 26 months. Survival was significantly longer in @entity1 with low serum LDH levels, B-cell type or low CRP or in earlier clinical stages, than in @entity1 with high serum LDH levels, T-cell type of higher CRP levels or in advanced clinical stages. The mean duration of administration of @entity1261 was 5.4 days. Twelve @entity1 developed @entity281 during treatment. The adverse effects of @entity1261 included @entity401 , @entity158 and @entity221 . @entity1 administered COP-BLAM combined with @entity1261 achieved a high rate of remission and had a low incidence of @entity281 . Nearly all the @entity1 could be treated in 21-day cycles. The results suggest that @entity1261 combined with COP-BLAM was effective in treating @entity1893 , because the @entity1 can tolerate a higher dose of the anticancer agents.

title: COP-BLAM regimen combined with @entity1261 and high-grade XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'human', 'patients']

entities_list: @entity1261 :: ('1440', 'Gene') :: ['G-CSF', 'granulocyte colony-stimulating factor']

entities_list: @entity401 :: ('MESH:D017563', 'Disease') :: ['interstitial pneumonia']

entities_list: @entity281 :: ('MESH:D007239', 'Disease') :: ['infection', 'infections']

entities_list: @entity158 :: ('MESH:D010146', 'Disease') :: ['bone pain']

entities_list: @entity1893 :: ('MESH:D008228', 'Disease') :: ["non-Hodgkin's lymphoma", 'NHL']

answer: @entity1893 :: (MESH:D008228,Disease) :: ['non-Hodgkin's lymphoma']


abstract: The clinical efficacy of COP-BLAM chemotherapy combined with @entity1 recombinant @entity1261 ( @entity1261 ) was evaluated in 104 previously untreated @entity1 with @entity1893 ( @entity1893 ). According to the method of Laurence et al., a modified COP-BLAM regimen was administered every 21 days. @entity1261 was added when the granulocyte count fell below 1000 x 10(9)/l. Ninety-eight of 104 (94.2%) @entity1 achieved a complete remission; the 4-year survival rate was 82.4% with a median duration of observation of 26 months. Survival was significantly longer in @entity1 with low serum LDH levels, B-cell type or low CRP or in earlier clinical stages, than in @entity1 with high serum LDH levels, T-cell type of higher CRP levels or in advanced clinical stages. The mean duration of administration of @entity1261 was 5.4 days. Twelve @entity1 developed @entity281 during treatment. The adverse effects of @entity1261 included @entity401 , @entity158 and @entity221 . @entity1 administered COP-BLAM combined with @entity1261 achieved a high rate of remission and had a low incidence of @entity281 . Nearly all the @entity1 could be treated in 21-day cycles. The results suggest that @entity1261 combined with COP-BLAM was effective in treating @entity1893 , because the @entity1 can tolerate a higher dose of the anticancer agents.

title: COP-BLAM regimen combined with XXXX and high-grade @entity1893 .

answer: @entity1261 :: (1440,Gene) :: ['granulocyte colony-stimulating factor']


abstract: BACKGROUND: @entity5149 ( @entity5149 )/clubfoot is the most common @entity558 . The success rate of Ponseti casting in the hands of the legend himself is not 100%. The prediction of difficult to correct foot and recurrences still remains a mystery to be solved. We all know that tarsal bones are @entity6349 in clubfoot and considering it; we hypothesize that the amount of @entity24185 can predict management duration and outcome. In literature we were not able to find studies that satisfactorily quantify the amount of @entity24185 . Hence, it was considered worthwhile to quantify the amount of @entity1141 in tarsal bone and to correlate these parameters with the duration and outcome of treatment by conventional method. METHODS: A total of 25 @entity1 with unilateral idiopathic clubfoot that have not taken any previous treatment were included in the study. An initial ultrasonography was done before start of treatment in 3 standard planes to measure the maximum length of 3 tarsal bones (talus, calcaneus, and navicular). Ponseti method of treatment was used; pirani scoring was done at each OPD (out @entity1 department) visit. Number of casts required for complete correction and need for any surgical intervention were taken as the outcome parameters. RESULTS: We found that there is a significant correlation between number of casts required and the @entity1141 of talus (a error=0.05). We also found a significant negative correlation between relative @entity1141 of talus and number of casts required (r=-0.629 sig=0.001, r=-0.552 sig=0.004). CONCLUSIONS: @entity18299 as quantified by using ultrasonography can be used as a prognostic indicator in @entity5149 . Although promising the method needs further studies and can be more useful after long-term follow-up where recurrences if any can be documented. LEVEL OF EVIDENCE: Level II.

title: @entity18299 in Clubfoot as Measured by Ultrasonography: Can It be Used as a Prognostic Indicator in XXXX ? A Prospective Observational Study.

entities_list: @entity1 :: ('9606', 'Species') :: ['patient', 'infants']

entities_list: @entity558 :: ('MESH:C536528', 'Disease') :: ['congenital orthopedic condition']

entities_list: @entity18299 :: ('MESH:D001848', 'Disease') :: ['Tarsal bone dysplasia']

entities_list: @entity5149 :: ('MESH:D003025', 'Disease') :: ['congenital idiopathic clubfoot', 'Congenital talipes equinovarus', 'CTEV']

entities_list: @entity24185 :: ('MESH:D013641', 'Disease') :: ['tarsal dysplasia']

entities_list: @entity6349 :: ('MESH:D004416', 'Disease') :: ['dysplastic']

entities_list: @entity1141 :: ('MESH:C535662', 'Disease') :: ['dysplasia']

answer: @entity5149 :: (MESH:D003025,Disease) :: ['Congenital Idiopathic Clubfoot']


abstract: BACKGROUND: @entity5149 ( @entity5149 )/clubfoot is the most common @entity558 . The success rate of Ponseti casting in the hands of the legend himself is not 100%. The prediction of difficult to correct foot and recurrences still remains a mystery to be solved. We all know that tarsal bones are @entity6349 in clubfoot and considering it; we hypothesize that the amount of @entity24185 can predict management duration and outcome. In literature we were not able to find studies that satisfactorily quantify the amount of @entity24185 . Hence, it was considered worthwhile to quantify the amount of @entity1141 in tarsal bone and to correlate these parameters with the duration and outcome of treatment by conventional method. METHODS: A total of 25 @entity1 with unilateral idiopathic clubfoot that have not taken any previous treatment were included in the study. An initial ultrasonography was done before start of treatment in 3 standard planes to measure the maximum length of 3 tarsal bones (talus, calcaneus, and navicular). Ponseti method of treatment was used; pirani scoring was done at each OPD (out @entity1 department) visit. Number of casts required for complete correction and need for any surgical intervention were taken as the outcome parameters. RESULTS: We found that there is a significant correlation between number of casts required and the @entity1141 of talus (a error=0.05). We also found a significant negative correlation between relative @entity1141 of talus and number of casts required (r=-0.629 sig=0.001, r=-0.552 sig=0.004). CONCLUSIONS: @entity18299 as quantified by using ultrasonography can be used as a prognostic indicator in @entity5149 . Although promising the method needs further studies and can be more useful after long-term follow-up where recurrences if any can be documented. LEVEL OF EVIDENCE: Level II.

title: XXXX in Clubfoot as Measured by Ultrasonography: Can It be Used as a Prognostic Indicator in @entity5149 ? A Prospective Observational Study.

answer: @entity18299 :: (MESH:D001848,Disease) :: ['Tarsal Bone Dysplasia']


abstract: Few studies have investigated the @entity2204 ( @entity2204 )   4 allele status of @entity303 @entity1 with severe @entity62 ( @entity195 ). In this study, we aimed to characterize the @entity2204 epsivlon genotypes and clinical features of @entity303 @entity1 with severe @entity195 . Four hundred and thirty nine @entity1 with @entity303 and 152 subjects with normal cognition (NC) were recruited from multiple centers in Korea, known as the Clinical Research Center for @entity303 of South Korea (CREDOS), since November 2005. The @entity195 were rated using the scale that had been developed by the CREDOS study. @entity303 @entity1 with minimal @entity195 were considered to have @entity195 ( @entity195 ) without @entity195 ( @entity195 - @entity195 : 325), and those with severe @entity195 were considered to have Subcortical @entity1294 (SIVD: 50) or @entity195 with severe @entity195 ( @entity195 ). Comparisons of @entity2204 allelic prevalence were performed using chi-square analysis. The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD and NC (p < 0.001). It was not more prevalent in those with SIVD than in those with NC (p = 0.169). @entity2204 allele status in @entity195 + @entity195 did not differ from that in @entity195 - @entity195 (p = 0.625). The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD. @entity2204 may not be associated with SIVD although it is one of the vascular risk factors.

title: @entity2204 allele status in korean @entity303 @entity1 with severe XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity2204 :: ('348', 'Gene') :: ['apolipoprotein E', 'APOE', 'APOE   4']

entities_list: @entity303 :: ('MESH:D003704', 'Disease') :: ['Dementia', 'dementia']

entities_list: @entity1294 :: ('MESH:D015140', 'Disease') :: ['Ischemic Vascular Dementia']

entities_list: @entity195 :: ('MESH:D000544', 'Disease') :: ['WMH', 'AD', "Alzheimer's disease", 'AD+WMH: 64']

entities_list: @entity62 :: ('MESH:D056784', 'Disease') :: ['white matter hyperintensities']

answer: @entity62 :: (MESH:D056784,Disease) :: ['white matter hyperintensities']


abstract: Few studies have investigated the @entity2204 ( @entity2204 )   4 allele status of @entity303 @entity1 with severe @entity62 ( @entity195 ). In this study, we aimed to characterize the @entity2204 epsivlon genotypes and clinical features of @entity303 @entity1 with severe @entity195 . Four hundred and thirty nine @entity1 with @entity303 and 152 subjects with normal cognition (NC) were recruited from multiple centers in Korea, known as the Clinical Research Center for @entity303 of South Korea (CREDOS), since November 2005. The @entity195 were rated using the scale that had been developed by the CREDOS study. @entity303 @entity1 with minimal @entity195 were considered to have @entity195 ( @entity195 ) without @entity195 ( @entity195 - @entity195 : 325), and those with severe @entity195 were considered to have Subcortical @entity1294 (SIVD: 50) or @entity195 with severe @entity195 ( @entity195 ). Comparisons of @entity2204 allelic prevalence were performed using chi-square analysis. The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD and NC (p < 0.001). It was not more prevalent in those with SIVD than in those with NC (p = 0.169). @entity2204 allele status in @entity195 + @entity195 did not differ from that in @entity195 - @entity195 (p = 0.625). The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD. @entity2204 may not be associated with SIVD although it is one of the vascular risk factors.

title: XXXX allele status in korean @entity303 @entity1 with severe @entity62 .

answer: @entity2204 :: (348,Gene) :: ['APOE   4']


abstract: Few studies have investigated the @entity2204 ( @entity2204 )   4 allele status of @entity303 @entity1 with severe @entity62 ( @entity195 ). In this study, we aimed to characterize the @entity2204 epsivlon genotypes and clinical features of @entity303 @entity1 with severe @entity195 . Four hundred and thirty nine @entity1 with @entity303 and 152 subjects with normal cognition (NC) were recruited from multiple centers in Korea, known as the Clinical Research Center for @entity303 of South Korea (CREDOS), since November 2005. The @entity195 were rated using the scale that had been developed by the CREDOS study. @entity303 @entity1 with minimal @entity195 were considered to have @entity195 ( @entity195 ) without @entity195 ( @entity195 - @entity195 : 325), and those with severe @entity195 were considered to have Subcortical @entity1294 (SIVD: 50) or @entity195 with severe @entity195 ( @entity195 ). Comparisons of @entity2204 allelic prevalence were performed using chi-square analysis. The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD and NC (p < 0.001). It was not more prevalent in those with SIVD than in those with NC (p = 0.169). @entity2204 allele status in @entity195 + @entity195 did not differ from that in @entity195 - @entity195 (p = 0.625). The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD. @entity2204 may not be associated with SIVD although it is one of the vascular risk factors.

title: @entity2204 allele status in korean XXXX @entity1 with severe @entity62 .

answer: @entity303 :: (MESH:D003704,Disease) :: ['dementia']


abstract: Few studies have investigated the @entity2204 ( @entity2204 )   4 allele status of @entity303 @entity1 with severe @entity62 ( @entity195 ). In this study, we aimed to characterize the @entity2204 epsivlon genotypes and clinical features of @entity303 @entity1 with severe @entity195 . Four hundred and thirty nine @entity1 with @entity303 and 152 subjects with normal cognition (NC) were recruited from multiple centers in Korea, known as the Clinical Research Center for @entity303 of South Korea (CREDOS), since November 2005. The @entity195 were rated using the scale that had been developed by the CREDOS study. @entity303 @entity1 with minimal @entity195 were considered to have @entity195 ( @entity195 ) without @entity195 ( @entity195 - @entity195 : 325), and those with severe @entity195 were considered to have Subcortical @entity1294 (SIVD: 50) or @entity195 with severe @entity195 ( @entity195 ). Comparisons of @entity2204 allelic prevalence were performed using chi-square analysis. The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD and NC (p < 0.001). It was not more prevalent in those with SIVD than in those with NC (p = 0.169). @entity2204 allele status in @entity195 + @entity195 did not differ from that in @entity195 - @entity195 (p = 0.625). The @entity2204 allele was more prevalent in those with @entity195 than in those with SIVD. @entity2204 may not be associated with SIVD although it is one of the vascular risk factors.

title: @entity2204 allele status in korean @entity303 XXXX with severe @entity62 .

answer: @entity1 :: (9606,Species) :: ['patients']


abstract: Between April 1993 and May 1994, 66 @entity1 were treated with @entity661 ( @entity661 ) for the relief of @entity1494 obstruction secondary to @entity1067 . @entity661 , with a urethral cooling system, employs a balloon catheter and irradiating laser through 360 degrees to produce @entity3459 and @entity39 of the prostatic tissue while preserving the urethral mucosa. The procedure was implemented under local topical anesthesia. Baseline AUA Symptom Scores, peak uroflow rates, postvoiding residual urine volumes (PVR), and prostatic volumes were measured before and at 1, 3, 6, and 12 months after treatment. The mean symptom score decreased from 18.8 preoperatively to 9.8, 6.9, 7.4, and 4.8 at 1, 3, 6, and 12 months, respectively. The mean peak uroflow rate increased from 6.4 mL/sec to 9.1, 11.2, 10.1, and 10.4 mL/sec at 1, 3, 6, and 12 months, respectively. As for the mean PVR, statistically significant reductions were clearly observed at 3 and 6 months after treatment. However, at 1 and 12 months, the difference was not statistically significant. In follow-up for as long as 12 months after the procedure, 23 of 26 @entity1 (88%) showed an improvement of 50% or more in the AUA Symptom Scores. Of 20 available @entity1 , 12 (60%) showed an improvement of 50% or higher in the peak uroflow rates, and 10 (50%) showed an improvement of 50% or higher in PVR. The mean prostatic volume reductions at 3, 6, and 9 months were 12%, 16%, and 14%, respectively. The serum @entity1486 concentration increased to four times the baseline concentration on the 7th day.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Transurethral balloon laser thermotherapy for symptomatic XXXX : preliminary clinical results.

entities_list: @entity1494 :: ('MESH:D001745', 'Disease') :: ['bladder outlet']

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis']

entities_list: @entity1067 :: ('MESH:D011470', 'Disease') :: ['benign prostatic hyperplasia']

entities_list: @entity3459 :: ('MESH:D025861', 'Disease') :: ['deep coagulation']

entities_list: @entity661 :: ('MESH:D054549', 'Disease') :: ['transurethral balloon laser thermotherapy', 'TUBAL-T']

entities_list: @entity1486 :: ('354', 'Gene') :: ['prostate specific antigen']

answer: @entity1067 :: (MESH:D011470,Disease) :: ['benign prostatic hyperplasia']


abstract: OBJECTIVES: To document the clinical and neurodevelopmental profiles of a cohort of @entity1 with neonatal-onset @entity19721 and to determine the efficacy of current therapy with respect to outcome. METHOD: The clinical, neurologic, and developmental status of six @entity1 was prospectively evaluated during a 15-month period. Previous clinical and biochemical data were ascertained from hospital records to determine longitudinal nutritional status, number of episodes of @entity3263 with @entity1270 , and developmental performance with respect to age. RESULTS: No deaths resulted from @entity19721 since the identification of the oldest @entity1 in the series in 1980. Therapeutic intervention (e.g., gastrostomy tube feeding) resulted in improved nutritional status and possibly contributed to improved survival. All @entity1 had @entity2421 , resulting in a significant effect on motor development; however, focal @entity51 and evidence of @entity302 were absent. Mild @entity194 was evident on cranial magnetic resonance imaging in four @entity1 . All @entity1 , including two @entity1 with no significant episodes of @entity3263 and normal growth since the neonatal period, had a mild to moderate degree of @entity73 . CONCLUSIONS: The results of our study suggest that current therapy for neonatal-onset @entity19721 is associated with improved survival and nutritional status, and an absence of focal @entity51 . However, @entity2421 and @entity73 were still present, even in @entity1 with "optimal" metabolic control. Additional therapeutic advances are required to improve the developmental and cognitive outcome.

title: Neonatal-onset XXXX : neurologic and developmental profiles, and implications for management.

entities_list: @entity1 :: ('9606', 'Species') :: ['children', 'patients', 'patient']

entities_list: @entity73 :: ('MESH:D003072', 'Disease') :: ['intellectual impairment', 'cognitive delay']

entities_list: @entity51 :: ('MESH:D009461', 'Disease') :: ['neurologic deficits']

entities_list: @entity2421 :: ('MESH:D009123', 'Disease') :: ['hypotonia']

entities_list: @entity194 :: ('MESH:D001284', 'Disease') :: ['cortical atrophy']

entities_list: @entity1270 :: ('MESH:D007662', 'Disease') :: ['ketoacidosis']

entities_list: @entity302 :: ('MESH:D004827', 'Disease') :: ['movement or seizure disorder']

entities_list: @entity19721 :: ('MESH:D056693', 'Disease') :: ['propionic acidemia']

entities_list: @entity3263 :: ('MESH:D022124', 'Disease') :: ['hyperammonemia']

answer: @entity19721 :: (MESH:D056693,Disease) :: ['propionic acidemia']


abstract: BACKGROUND: The lymphatic system contributes to fluid homeostasis in various tissues. Recent evidence suggests that lymphangiogenesis induced by a @entity1702 ( @entity1702 ) is associated with blood pressure regulation. Lymph nodes, located along lymphatic pathways, are not only important secondary lymphoid tissues for cancer @entity3 , @entity32 , and immune responses, but are also important for fluid homeostasis. Afferent lymphatics collect lymph from the pre-nodal area and efferent lymphatics drain lymph out of the lymph nodes. However, the difference in mechanical activity between afferent and efferent lymphatics and the effect of a @entity1702 on these vessels have not been shown. METHODS AND RESULTS: Changes in mechanical activity of isolated afferent and efferent lymphatics in @entity1702 ( @entity1702 ) and 4-week @entity1702 @entity19 in response to increases in intraluminal pressures from 3 to 7   cm @entity4358 were measured using video-microscopy. The higher intramural pressure equivalently decreased pumping activity of afferent and efferent lymphatics in @entity1702 @entity19 . A @entity1702 suppressed the amplitude, ejection fraction, and @entity64 volume of afferent lymphatics, leading to marked reductions in pumping activity. In contrast, the pumping activities of efferent lymphatics were resistant to a @entity1702 and were preserved by enhancing the contraction frequency. CONCLUSIONS: A @entity1702 differentially modulated the mechanical activity of afferent and efferent collecting lymphatics in @entity19 iliac lymph nodes.

title: A High-Salt Diet Differentially Modulates Mechanical Activity of Afferent and Efferent Collecting Lymphatics in XXXX Iliac Lymph Nodes.

entities_list: @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation']

entities_list: @entity1702 :: ('MESH:D013651', 'Disease') :: ['HSD', 'normal salt diet', 'NSD', 'high-salt diet']

entities_list: @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis']

answer: @entity19 :: (10090,Species) :: ['Murine']


abstract: The sarcomeres form the molecular motor of the cardiomyocyte and consist of a complex multi-protein of thick and thin filaments which are anchored to the cytoskeleton. The thick filament, composed of @entity3999 and associated proteins, and the thin filament composed of actin, tropomyosin and the troponins develop actinmyosin crossbridges which cycle in response to @entity460 resulting in sliding of the filaments and contraction. The thin filament in fixed to the cardiomyocyte cytoskeleton at the Z-disc, a complex of structural and regulatory proteins. A giant protein, @entity10484 , provides an external scaffold and regulates passive force in diastole. Both @entity74 and acquired conditions may affect proteins of the sarcomere. @entity74 of the thick and thin filament proteins are the predominant cause of @entity1121 . These mutations lead to abnormal sarcomere function, often an enhanced sensitivity to @entity460 , and impaired relaxation. This may result in secondary changes in @entity460 cycling and amplification of @entity1184 signaling cascades. Correcting the abnormal function of the sarcomere as well as intervening in later stages of the pathophysiologic cascades may ameliorate disease. In dilated @entity74 in the sarcomere, Z-disc, @entity460 regulatory and cytoskeletal proteins as well as the dystrophin complex may be causal for disease. In @entity384 , disturbances in post-translational modifications of the sarcomere my also play a prominent role. Experimental models indicate that altered phosphorylation of sarcomeric proteins may impair systolic and diastolic function as well as the response to heart rate and afterload. Thus correcting these post-translational changes are legitimate targets for future therapeutic strategies for @entity384 .

title: Molecular mechanisms of sarcomere dysfunction in dilated and XXXX .

entities_list: @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophic']

entities_list: @entity384 :: ('MESH:D002311', 'Disease') :: ['dilated cardiomyopathy']

entities_list: @entity74 :: ('MESH:D030342', 'Disease') :: ['genetic disorders', 'Genetic disorders', 'cardiomyopathy genetic abnormalities']

entities_list: @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']

entities_list: @entity1121 :: ('MESH:D002312', 'Disease') :: ['hypertrophic cardiomyopathy']

answer: @entity1121 :: (MESH:D002312,Disease) :: ['hypertrophic cardiomyopathy']


abstract: OBJECTIVE: To study the incidence, treatment, and outcomes of @entity420 of the nose and paranasal sinuses over the last 15 years. DESIGN: Retrospective chart review of 20 @entity1 identified and treated at the otolaryngology clinic of Zurich University Hospital between 1992 and 2007. MAIN OUTCOME MEASURES: Recurrence- and disease-free survival were the most important outcomes of interest. RESULTS: Twenty @entity1 (16 @entity1 ) with sinonasal @entity420 were found. The average age was 64 years. At the time of diagnosis, usually more than one sinus was involved and nasal obstruction was the most common symptom. In 57.9% of @entity1 , the initial treatment was endoscopic surgery. Two-year recurrence-free survival was 48.5%, and 5-year disease-specific survival was 77.8%. CONCLUSIONS: Surgical resection is difficult owing to anatomic restraints, and adjuvant therapy must be considered in most @entity1 . Endoscopic surgery was performed in a majority of @entity1 , with outcomes comparable to those in the general literature. SIGNIFICANCE: @entity420 of the paranasal sinuses was found to have almost 80% 5-year survival if adequately treated surgically and with adjuvant intensity-modulated radiotherapy.

title: XXXX and paranasal sinuses: single-institution review of diagnosis, histology, and outcome.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'men']

entities_list: @entity420 :: ('MESH:D000230', 'Disease') :: ['adenocarcinomas', 'Adenocarcinoma', 'adenocarcinoma']

answer: @entity420 :: (MESH:D000230,Disease) :: ['Adenocarcinoma of the nasal cavity']


abstract: PURPOSE: The aim of this study was to compare the clinical effect of graciloplasty using two different gracilis encircled loops for the treatment of @entity1241 after anoplasty for imperforate anus. METHODS: From January 2009 to January 2012, 38 @entity1 were treated by graciloplasty. The @entity1 were randomly divided into two groups, one group consisting of 18 cases underwent the "y-loop" and the other group consisting of 20 cases underwent the "  -loop." All @entity1 underwent postoperative defecation training and regular follow-up. All @entity1 were evaluated via Wexner score and anal manometry (including anal resting pressure, anal maximal squeeze pressure, duration of anal squeeze, and rectal maximum tolerable volume) before and after graciloplasty. In addition, it was assessed whether the @entity1 had difficulty defecating while squatting after surgery. RESULTS: The surgeries on the 38 @entity1 were accomplished successfully. There were no differences in postoperative complications between the two groups (P   >   0.05). The Wexner score and anal manometry parameters of the two groups were gradually improved after operation. The generalized estimating equation results of the Wexner score indicated that the difference of measurement time was statistically significant (P   <   0.05) but the difference of measurement group was not statistically significant (P   >   0.05). The results of anal manometry parameters using repeated measures ANOVA indicated that differences between different time points were statistically significant (all P   <   0.05) but differences between different surgery groups were not statistically significant (all P   >   0.05). Regarding the postoperative defecating @entity4764 while squatting, the probability of occurrence in the "y-loop" group was significantly higher than that in the "  -loop" group. The difference between the two groups was statistically significant (P   <   0.05). CONCLUSIONS: Graciloplasty with different gracilis loops can improve anal function in @entity1 . However, "  -loop" can significantly improve @entity4764 in defecating while squatting.

title: Two different gracilis loops in graciloplasty of XXXX : comparison of the therapeutic effects.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity1241 :: ('MESH:D005242', 'Disease') :: ['fecal incontinence']

entities_list: @entity4764 :: ('MESH:D051346', 'Disease') :: ['difficulties']

answer: @entity1241 :: (MESH:D005242,Disease) :: ['congenital fecal incontinence']


abstract: OBJECTIVE: Angiogenesis in the porcine heart can be induced by @entity296 following @entity432 . This process is characterised by increased numbers of monocytes/macrophages, known to be potent producers of various mitogens such as insulin-like growth factors (IGF) and interleukins (IL). The aim of the study was to examine gene expression of these factors by means of northern blot hybridisation, slot blot analysis, and in situ hybridisation in a porcine model of coronary angiogenesis. METHODS: Experimental ischaemia and subsequent focal @entity39 were induced by selective injection of 25 microns microspheres into the left circumflex artery. The hearts were excised after 3-168 h of microembolisation, and tissue was collected from a non-ischaemic control area and the circumflex region of the same heart for further analysis. RESULTS: @entity442 was constitutively transcribed in normal porcine myocardium mainly by myocytes. Following microembolisation, @entity442 mRNA expression was significantly increased in the experimental region (1.8-fold) after 72 h and to a lesser extent after 168 h. In the ischaemic region, characterised by capillary sprouting, numerous mononuclear cells contained @entity442 mRNA. In contrast, @entity5100 mRNA levels, constitutively produced by porcine myocytes, were not altered by microembolisation. @entity1192 , @entity1356 , and @entity3646 mRNA expression was undetectable in our animal model, whereas @entity650 was constitutively transcribed in normal and ischaemic heart and remained insensitive to microembolisation and focal @entity39 . CONCLUSION: After microembolisation, increased @entity442 mRNA expression occurred by infiltrating monocytes in areas of microsphere induced focal @entity39 , where capillary sprouting can be detected, suggesting that @entity442 is involved in @entity32 linked angiogenic processes.

title: Insulin-like growth factor I is involved in XXXX linked angiogenic processes after microembolisation in porcine heart.

entities_list: @entity296 :: ('MESH:D009202', 'Disease') :: ['myocardial ischaemia']

entities_list: @entity39 :: ('MESH:D009336', 'Disease') :: ['necrosis', 'necroses']

entities_list: @entity432 :: ('MESH:D001157', 'Disease') :: ['vascular occlusions']

answer: @entity32 :: (MESH:D007249,Disease) :: ['inflammation']


abstract: BACKGROUND: Mortality figures become available after some years. MATERIALS AND METHODS: Using the World Health Organization mortality and population data, we estimated numbers of @entity204 in 2011 from all @entity5 and selected sites for the European Union (EU) and six major countries, by fitting a joinpoint model to 5-year age-specific numbers of @entity204 . Age-standardized rates were computed using EUROSTAT population estimates. RESULTS: The predicted number of @entity5 @entity204 in the EU in 2011 was 1,281,436, with standardized rates of 143/100,000 @entity1 and 85/100,000 @entity1 . Poland had the highest rates, with smaller falls over recent periods. Declines in mortality for major sites including stomach, colorectum, breast, uterus, prostate and @entity1778 , plus @entity2 , will continue until 2011, and a trend reversal or a leveling off is predicted where upward trends were previously observed. @entity2 rates are increasing in all major EU countries except the UK, where it is the first cause of @entity5 death, as now in Poland. The increasing @entity788 trends in @entity1 observed up to 2004 have likely leveled off. CONCLUSIONS: Despite falls in rates, absolute numbers of @entity5 @entity204 are stable in Europe. The gap between Western and former nonmarket economy countries will likely persist.

title: XXXX mortality predictions for the year 2011.

entities_list: @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer']

entities_list: @entity2 :: ('MESH:D008175', 'Disease') :: ['male lung cancer', 'Female lung cancer']

entities_list: @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemias']

answer: @entity5 :: (MESH:D009369,Disease) :: ['European cancer']


abstract: Peripheral blood stem cells (PBSC) were collected from 24 @entity1 who were treated with high dose @entity2879 . Studied @entity1 included one with @entity981 , 4 with @entity3052 ( @entity3052 ), 1 with @entity2590 , 13 with @entity706 , 1 with @entity5 , 2 with @entity1582 , and 4 with @entity5 . @entity2879 was infused at a dose of 500 mg/m2 for 4 days, followed by subcutaneous injection of recombinant @entity1 @entity1261 from the nadir of leukocyte. PBSC were collected by processing 15-20 liters of blood apheresis in the recovery phase of chemotherapy. In all @entity1 , the number of CFU-GM collected per aphereresis ranged from 0.01 to 59.4 x 10(5)/kg, and more than 5 x 10(5)/kg CFU-GM were collected in 19 of the @entity1 (73%). All @entity1778 @entity1 treated along with our protocols have remained in complete remission, but one @entity1 with @entity3052 relapsed within 1 month after the treatment. @entity706 @entity1 were assessable for antitumor effect, and complete response (CR) was observed in 2, partial response (PR) was 7, and no change (NC) in one @entity1 . Two @entity1 with @entity1582 were classified to be NC. Three of the 4 @entity1 with @entity5 were PR, and the other one was NC. Eleven @entity1 subsequently underwent PBSCT. The number of days required to achieve an absolute granulocyte count of 0.5 x 10(9)/l was 7 to 11 days, with a mean of 8.6.

title: [Peripheral blood stem cell collection with high dose XXXX ].

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'human', 'patient']

entities_list: @entity981 :: ('MESH:D054198', 'Disease') :: ['acute lymphoblastic leukemia']

entities_list: @entity1261 :: ('1440', 'Gene') :: ['granulocyte-colony stimulating factor']

entities_list: @entity706 :: ('MESH:D008223', 'Disease') :: ['lymphoma', 'Ten lymphoma']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['malignant histiocytosis', 'testicular tumor']

entities_list: @entity2590 :: ('MESH:D009190', 'Disease') :: ['myelodysplastic syndrome']

entities_list: @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute myeloid leukemia', 'AML']

entities_list: @entity2879 :: ('MESH:D005047', 'Chemical') :: ['etoposide', 'Etoposide']

answer: @entity2879 :: (MESH:D005047,Chemical) :: ['etoposide']


abstract: The current study assesses hepatic and intestinal glucuronidation, sulfation, and @entity12325 (P450) metabolism of @entity441 , @entity3092 , @entity3045 , and @entity4506 using different in vitro systems. The fraction metabolized by conjugation and P450 metabolism was estimated in liver and intestine, and the importance of multiple metabolic pathways on accuracy of clearance prediction was assessed. In vitro intrinsic sulfation clearance (CL(int, SULT)) was determined in @entity1 intestinal and hepatic cytosol and compared with hepatic and intestinal microsomal glucuronidation (CL(int, @entity6900 )) and P450 clearance (CL(int, @entity13323 )) expressed per gram of tissue. Hepatic and intestinal cytosolic scaling factors of 80.7 mg/g liver and 18 mg/g intestine were estimated from published data. Scaled CL(int, SULT) ranged between 0.7 and 11.4 ml    @entity1009 )    g(-1) liver and 0.1 and 3.3 ml    @entity1009 )    g(-1) intestine ( @entity3045 and @entity3092 were the extremes). @entity3045 was the only compound with a high extent of sulfation (51 and 28% of total CL(int) for liver and intestine, respectively) and also significant renal clearance (26-57% of observed plasma clearance). In contrast, the clearance of @entity3092 was largely accounted for by glucuronidation. Drugs metabolized by multiple pathways ( @entity441 and @entity4506 ) demonstrated improved prediction of intravenous clearance using data from all hepatic pathways (44-86% of observed clearance) compared with predictions based only on the primary pathway (22-36%). The assumption of no intestinal first pass resulted in underprediction of oral clearance for @entity441 , @entity4506 , and @entity3092 (3-22% of observed, respectively). Accounting for the intestinal contribution to oral clearance via estimated intestinal availability improved prediction accuracy for @entity441 and @entity4506 (within 2.5-fold of observed). Current findings emphasize the importance of both hepatic and intestinal conjugation for in vitro-in vivo extrapolation of metabolic clearance.

title: Prediction of XXXX drug clearance by multiple metabolic pathways: integration of hepatic and intestinal microsomal and cytosolic data.

entities_list: @entity4506 :: ('MESH:C057693', 'Chemical') :: ['troglitazone']

entities_list: @entity3045 :: ('MESH:D000420', 'Chemical') :: ['salbutamol', 'Salbutamol']

entities_list: @entity3092 :: ('MESH:D011794', 'Chemical') :: ['quercetin']

entities_list: @entity441 :: ('MESH:D020849', 'Chemical') :: ['raloxifene']

answer: @entity1 :: (9606,Species) :: ['human']


abstract: UNASSIGNED: The exact time frame of @entity1230 -induced immunosuppression and the immune mechanisms mediating transition to @entity295 are largely unknown. Peripheral blood mononuclear cells were isolated from 69 @entity1 with @entity1230 within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of @entity295 onset. @entity1 had defective responses for @entity5 necrosis factor-alpha ( @entity310 ), @entity688 , @entity4155 and @entity379 (IFNy) using a broad-panel of bacterial stimuli. Production of IFNy was pronounced for @entity1 with @entity130 -related @entity881 ( @entity881 ). Thirty-six @entity1 developed @entity295 . At that time, production of @entity310 was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced @entity310 production on @entity295 onset was a main finding of @entity1 without @entity5694 . Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into @entity295 due to bacterial superinfection is accompanied by enhanced production of @entity310 and this is linked with unfavorable outcome.

title: Defective cytokine production early after @entity1230 : Modulation in XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'patients']

entities_list: @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis', 'severe sepsis']

entities_list: @entity5694 :: ('MESH:D019446', 'Disease') :: ['endotoxemia']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour']

entities_list: @entity1230 :: ('MESH:D009104', 'Disease') :: ['multiple trauma', 'multiple injuries']

entities_list: @entity379 :: ('3458', 'Gene') :: ['interferon-gamma']

entities_list: @entity881 :: ('MESH:D009102', 'Disease') :: ['MOF', 'multiple organ failure']

answer: @entity295 :: (MESH:D018805,Disease) :: ['severe sepsis']


abstract: UNASSIGNED: The exact time frame of @entity1230 -induced immunosuppression and the immune mechanisms mediating transition to @entity295 are largely unknown. Peripheral blood mononuclear cells were isolated from 69 @entity1 with @entity1230 within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of @entity295 onset. @entity1 had defective responses for @entity5 necrosis factor-alpha ( @entity310 ), @entity688 , @entity4155 and @entity379 (IFNy) using a broad-panel of bacterial stimuli. Production of IFNy was pronounced for @entity1 with @entity130 -related @entity881 ( @entity881 ). Thirty-six @entity1 developed @entity295 . At that time, production of @entity310 was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced @entity310 production on @entity295 onset was a main finding of @entity1 without @entity5694 . Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into @entity295 due to bacterial superinfection is accompanied by enhanced production of @entity310 and this is linked with unfavorable outcome.

title: Defective cytokine production early after XXXX : Modulation in @entity295 .

answer: @entity1230 :: (MESH:D009104,Disease) :: ['multiple traumas']


abstract: BACKGROUND: The identification of @entity1 for targeted antineoplastic therapies requires accurate measurement of therapeutic targets and associated signaling complexes. @entity7514 signaling through heterodimerization is an important growth-promoting mechanism in several @entity5 types and may be a principal resistance mechanism by which @entity470 and @entity1722 expressing @entity5 elude targeted therapies. Current methods that can study these interactions are inadequate for @entity406 -fixed, @entity982 -embedded (FFPE) @entity5 samples. METHODOLOGY AND PRINCIPAL FINDINGS: Herein, we describe a panel of proximity-directed assays capable of measuring protein-interactions and phosphorylation in FFPE samples in the @entity7514 / @entity10412 / @entity584 pathway and examine the capability of these assays to inform on the functional state of the pathway. We used FFPE @entity0 cell line and @entity5 models for this study. In @entity0 cell lines we observe both ligand-dependent and independent activation of the pathway and strong correlations between measured activation of key analytes. When selected cell lines are treated with @entity1722 inhibitors, we not only observe the expected molecular effects based on mechanism of action knowledge, but also novel effects of @entity1722 inhibition on key targets in the HER receptor pathway. Significantly, in a xenograft model of delayed @entity5 fixation, @entity7514 phosphorylation is unstable, while alternate measures of pathway activation, such as formation of the HER3PI3K complex is preserved. Measurements in @entity0 samples showed correlations between @entity7514 phosphorylation and receptor interactions, obviating the need to use phosphorylation as a surrogate for @entity7514 activation. SIGNIFICANCE: This assay system is capable of quantitatively measuring therapeutically relevant responses and enables molecular profiling of receptor networks in both preclinical and @entity5 models.

title: Profiling the XXXX / @entity10412 pathway in @entity0 using proximity-directed assays identifies correlations between protein complexes and phosphoproteins.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast tumor']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors']

entities_list: @entity406 :: ('MESH:D005557', 'Chemical') :: ['formalin']

entities_list: @entity982 :: ('MESH:D010232', 'Chemical') :: ['paraffin']

answer: @entity7514 :: (2065,Gene) :: ['HER3']


abstract: BACKGROUND: The identification of @entity1 for targeted antineoplastic therapies requires accurate measurement of therapeutic targets and associated signaling complexes. @entity7514 signaling through heterodimerization is an important growth-promoting mechanism in several @entity5 types and may be a principal resistance mechanism by which @entity470 and @entity1722 expressing @entity5 elude targeted therapies. Current methods that can study these interactions are inadequate for @entity406 -fixed, @entity982 -embedded (FFPE) @entity5 samples. METHODOLOGY AND PRINCIPAL FINDINGS: Herein, we describe a panel of proximity-directed assays capable of measuring protein-interactions and phosphorylation in FFPE samples in the @entity7514 / @entity10412 / @entity584 pathway and examine the capability of these assays to inform on the functional state of the pathway. We used FFPE @entity0 cell line and @entity5 models for this study. In @entity0 cell lines we observe both ligand-dependent and independent activation of the pathway and strong correlations between measured activation of key analytes. When selected cell lines are treated with @entity1722 inhibitors, we not only observe the expected molecular effects based on mechanism of action knowledge, but also novel effects of @entity1722 inhibition on key targets in the HER receptor pathway. Significantly, in a xenograft model of delayed @entity5 fixation, @entity7514 phosphorylation is unstable, while alternate measures of pathway activation, such as formation of the HER3PI3K complex is preserved. Measurements in @entity0 samples showed correlations between @entity7514 phosphorylation and receptor interactions, obviating the need to use phosphorylation as a surrogate for @entity7514 activation. SIGNIFICANCE: This assay system is capable of quantitatively measuring therapeutically relevant responses and enables molecular profiling of receptor networks in both preclinical and @entity5 models.

title: Profiling the @entity7514 / @entity10412 pathway in XXXX using proximity-directed assays identifies correlations between protein complexes and phosphoproteins.

answer: @entity0 :: (MESH:D001943,Disease) :: ['breast tumors']


abstract: BACKGROUND: The identification of @entity1 for targeted antineoplastic therapies requires accurate measurement of therapeutic targets and associated signaling complexes. @entity7514 signaling through heterodimerization is an important growth-promoting mechanism in several @entity5 types and may be a principal resistance mechanism by which @entity470 and @entity1722 expressing @entity5 elude targeted therapies. Current methods that can study these interactions are inadequate for @entity406 -fixed, @entity982 -embedded (FFPE) @entity5 samples. METHODOLOGY AND PRINCIPAL FINDINGS: Herein, we describe a panel of proximity-directed assays capable of measuring protein-interactions and phosphorylation in FFPE samples in the @entity7514 / @entity10412 / @entity584 pathway and examine the capability of these assays to inform on the functional state of the pathway. We used FFPE @entity0 cell line and @entity5 models for this study. In @entity0 cell lines we observe both ligand-dependent and independent activation of the pathway and strong correlations between measured activation of key analytes. When selected cell lines are treated with @entity1722 inhibitors, we not only observe the expected molecular effects based on mechanism of action knowledge, but also novel effects of @entity1722 inhibition on key targets in the HER receptor pathway. Significantly, in a xenograft model of delayed @entity5 fixation, @entity7514 phosphorylation is unstable, while alternate measures of pathway activation, such as formation of the HER3PI3K complex is preserved. Measurements in @entity0 samples showed correlations between @entity7514 phosphorylation and receptor interactions, obviating the need to use phosphorylation as a surrogate for @entity7514 activation. SIGNIFICANCE: This assay system is capable of quantitatively measuring therapeutically relevant responses and enables molecular profiling of receptor networks in both preclinical and @entity5 models.

title: Profiling the @entity7514 / XXXX pathway in @entity0 using proximity-directed assays identifies correlations between protein complexes and phosphoproteins.

answer: @entity10412 :: (5293,Gene) :: ['PI3K']


abstract: PURPOSE: p53 protein has been reported as frequently overexpressed in esophageal and @entity356 . However, the correlation between p53 protein expression and clinico-pathological features of the @entity5 is debated in this heterogeneous group of @entity5 . The aim of this study was to establish the prevalence of p53 protein overexpression in a series of resected @entity1721 (n = 78), @entity420 developed on Barrett's esophagus (n = 20), @entity420 (n = 36), and @entity420 of the antrum (n = 30), and to correlate this expression with the clinico-pathological and flow-cytometric characteristics of the @entity5 . METHODS: Immunohistochemical staining was performed on frozen sections with a monoclonal antibody directed against wild type and mutated p53 protein (Pab 1801). An adjacent frozen specimen was used for flow cytometric determination of the DNA-ploidy and S phase fraction. RESULTS: p53 protein nuclear expression was detected in 76% of @entity1721 , in 75% of @entity420 developed in Barretts esophagus, in 56% of @entity420 , and in 27% of @entity420 of the antrum. Only the number of positive @entity420 of the antrum was significantly lower when compared to the other three types of @entity5 (p = 0.001). No significant correlation was observed between p53 protein expression and most of the clinico-pathological and flow-cytometric parameters (sex, age, @entity286 smoking, chronic alcohol consumption, size of the @entity5 , grade of differentiation, depth of infiltration, presence of lymph node metastases, UICC stage, DNA-ploidy, S phase fraction). p53 protein expression was more frequent in Lauren's intestinal @entity420 (67%) when compared to the @entity5 (24%) (p = 0.002). CONCLUSIONS: Our results confirm that overexpression of p53 protein is a common feature of esophageal and @entity356 . The high prevalence of p53 protein overexpression found in cardiac @entity420 when compared to antral @entity420 reinforces the hypothesis of distinct carcinogenetic mechanisms in these two @entity5 . In particular the lack of correlation between p53 expression and @entity5 stage suggests that p53 protein overexpression is an early event in these @entity5 .

title: Overexpression of the p53 @entity5 suppressor gene product in esophageal and XXXX .

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'diffuse type tumors', 'cancers', 'tumors']

entities_list: @entity1721 :: ('MESH:C562729', 'Disease') :: ['esophageal squamous carcinomas']

entities_list: @entity420 :: ('MESH:D000230', 'Disease') :: ['adenocarcinomas', 'adenocarcinomas of the cardia', 'adenocarcinoma']

entities_list: @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric carcinomas']

answer: @entity356 :: (MESH:D013274,Disease) :: ['gastric carcinomas']


abstract: PURPOSE: p53 protein has been reported as frequently overexpressed in esophageal and @entity356 . However, the correlation between p53 protein expression and clinico-pathological features of the @entity5 is debated in this heterogeneous group of @entity5 . The aim of this study was to establish the prevalence of p53 protein overexpression in a series of resected @entity1721 (n = 78), @entity420 developed on Barrett's esophagus (n = 20), @entity420 (n = 36), and @entity420 of the antrum (n = 30), and to correlate this expression with the clinico-pathological and flow-cytometric characteristics of the @entity5 . METHODS: Immunohistochemical staining was performed on frozen sections with a monoclonal antibody directed against wild type and mutated p53 protein (Pab 1801). An adjacent frozen specimen was used for flow cytometric determination of the DNA-ploidy and S phase fraction. RESULTS: p53 protein nuclear expression was detected in 76% of @entity1721 , in 75% of @entity420 developed in Barretts esophagus, in 56% of @entity420 , and in 27% of @entity420 of the antrum. Only the number of positive @entity420 of the antrum was significantly lower when compared to the other three types of @entity5 (p = 0.001). No significant correlation was observed between p53 protein expression and most of the clinico-pathological and flow-cytometric parameters (sex, age, @entity286 smoking, chronic alcohol consumption, size of the @entity5 , grade of differentiation, depth of infiltration, presence of lymph node metastases, UICC stage, DNA-ploidy, S phase fraction). p53 protein expression was more frequent in Lauren's intestinal @entity420 (67%) when compared to the @entity5 (24%) (p = 0.002). CONCLUSIONS: Our results confirm that overexpression of p53 protein is a common feature of esophageal and @entity356 . The high prevalence of p53 protein overexpression found in cardiac @entity420 when compared to antral @entity420 reinforces the hypothesis of distinct carcinogenetic mechanisms in these two @entity5 . In particular the lack of correlation between p53 expression and @entity5 stage suggests that p53 protein overexpression is an early event in these @entity5 .

title: Overexpression of the p53 XXXX suppressor gene product in esophageal and @entity356 .

answer: @entity5 :: (MESH:D009369,Disease) :: ['tumor']


abstract: In the intrinsic death pathway, @entity4674 (CC) released from mitochondria to the cytosol triggers @entity3437 apoptosome formation and subsequent caspase activation. This process can be recapitulated using recombinant @entity3437 and CC in the presence of @entity2036 @entity855 or @entity17699 [(d) @entity855 ] or using fresh cytosol and CC without the need of exogenous @entity2036 . Surprisingly, we found that stored cytosols failed to support CC-initiated caspase activation. Storage of cytosols at different temperatures led to the loss of all (deoxy) @entity2036 including (d) @entity855 . Addition of @entity17699 to such stored cytosols partially restored CC-initiated caspase activation. Nevertheless, CC could not induce complete @entity8187 /3 activation in stored cytosols, even with the addition of @entity17699 , despite robust @entity3437 oligomerization. The @entity3437 apoptosome, which functions as a proteolytic-based molecular timer appeared to be defective as auto-processing of recruited procaspase-9 was inhibited. Far Western analysis revealed that procaspase-9 directly interacted with @entity3437 and this interaction was reduced in the presence of physiological levels of @entity855 . Co-incubation of recombinant @entity3437 and procaspase-9 prior to CC and @entity855 addition inhibited CC-induced caspase activity. These findings suggest that in the absence of @entity377 such as @entity855 , direct association of procaspase-9 with @entity3437 leads to defective molecular timer, and thus, inhibits apoptosome-mediated caspase activation. Altogether, our results provide novel insight on @entity377 regulation of apoptosome.

title: Defective molecular timer in the absence of XXXX leads to inefficient caspase activation.

entities_list: @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides']

entities_list: @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide']

answer: @entity2036 :: (MESH:D009711,Chemical) :: ['nucleotides']


abstract: IMPORTANCE: Facial @entity425 from @entity912 or @entity3986 can significantly affect lip strength and function. Lip @entity425 may result in articulation difficulties and spillage of food, both of which are socially and functionally disruptive for @entity1 . There are few quantitative data on the effect of @entity3541 on lip strength. OBJECTIVES: To quantify the effect of @entity3541 and @entity3986 on lip strength and evaluate the effectiveness of targeted lip injection augmentation. DESIGN, SETTING, AND @entity1 : Analysis of @entity1 at the Johns Hopkins Hospital between January 1, 2008, and July 31, 2014, presenting for treatment of @entity3384 due to @entity3541 and @entity3986 was prospectively undertaken. @entity1 who had undergone direct surgical lip procedures were excluded. MAIN OUTCOMES AND MEASURES: Lip pressure measurements, anterior bolus spillage, and articulation of bilabial sounds before and after treatment were assessed by a single speech pathologist. Lip pressures were measured with the Iowa Oral Performance Instrument. RESULTS: Twenty-two @entity1 with unilateral @entity3541 were evaluated for this study. Three @entity1 with @entity3986 were also evaluated. In unilateral @entity3541 , central lip strength was reduced in all @entity1 compared with sex-corrected normative data (mean [SD] central lip strength, 5.5   [2.5] kPa in females and 9.6   [4.6] kPa in males). Compared with the nonparalyzed side, labial strength on the paralyzed sided was reduced by 69%. After injection augmentation of the paralyzed side, labial strength improved across the entire lip. Mean lip strength improved by 0.7-fold in the central lip from 5.60 to 9.30 kPa (P   =   .009), by 1.4-fold on the paralyzed side from 2.2 to 5.33 kPa (P   =   .006), and by 0.4-fold on the unaffected side from 7.11 to 9.56 kPa (P   =   .12). Lip strength in the 3 @entity1 with @entity3986 were uniformly reduced across the entire lip and improved by 6- to 7-fold after injection augmentation. All @entity1 were noted by the speech pathologist to have improved articulation of plosive sounds and @entity1347 after the injection. CONCLUSIONS AND RELEVANCE: Labial strength is reduced across the lip in @entity1 with unilateral @entity3541 . The Iowa Oral Performance Instrument is an effective tool for measuring labial strength and can be use to evaluate the effectiveness of facial reanimation procedures. Injection augmentation of the lip is a simple and effective means of improving labial strength, bilabial sounds, and @entity1347 in @entity1 with @entity3541 or @entity3986 . LEVEL OF EVIDENCE: 3.

title: Quantifying Labial Strength and Function in XXXX : Effect of Targeted Lip Injection Augmentation.

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'PARTICIPANTS']

entities_list: @entity1347 :: ('MESH:C537775', 'Disease') :: ['decreased anterior bolus spillage', 'anterior spillage']

entities_list: @entity3986 :: ('MESH:D009136', 'Disease') :: ['muscular dystrophy', 'facioscapulohumeral muscular dystrophy', 'muscle dystrophy', 'facial muscular dystrophy']

entities_list: @entity425 :: ('MESH:D018908', 'Disease') :: ['muscle weakness']

entities_list: @entity3541 :: ('MESH:D005158', 'Disease') :: ['facial paralysis']

entities_list: @entity3384 :: ('MESH:D002971', 'Disease') :: ['lip incompetence']

entities_list: @entity912 :: ('MESH:D010243', 'Disease') :: ['paralysis']

answer: @entity3541 :: (MESH:D005158,Disease) :: ['Facial Paralysis']


abstract: BACKGROUND: The development of insulin resistance (IR) in @entity19 models of @entity28 and @entity6 ( @entity6 ) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue @entity32 via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose @entity32 and investigated the role of Tregs in IR/ @entity28 through coordinated studies in @entity19 and @entity1 . METHODS AND FINDINGS: @entity403 -green fluorescent protein (GFP) "knock-in" @entity19 were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese @entity1 without overt type 2 @entity6 (n=13) and lean controls (n=7) were recruited prospectively for assessment of @entity32 . DIO resulted in increased CD3(+)CD4(+), and CD3(+)CD8(+) cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with @entity9536 (+) @entity2935 (+) adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors @entity366 and @entity9350 and marker of activation @entity1759 . In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. @entity1 visceral adipose in morbid @entity28 was characterized by an increase in @entity2935 (+) ATMs and a decrease in @entity403 expression. CONCLUSIONS: Our experiments indicate that @entity28 in @entity19 and @entity1 results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose @entity32 .

title: @entity32 in XXXX is associated with critical alterations in tregulatory cell numbers.

entities_list: @entity1 :: ('9606', 'Species') :: ['humans', 'Human']

entities_list: @entity32 :: ('MESH:D007249', 'Disease') :: ['visceral adipose inflammation', 'inflammation']

entities_list: @entity6 :: ('MESH:D003920', 'Disease') :: ['DM', 'type 2 diabetes mellitus']

entities_list: @entity28 :: ('MESH:D009765', 'Disease') :: ['obesity']

answer: @entity28 :: (MESH:D009765,Disease) :: ['obesity']


abstract: BACKGROUND: The development of insulin resistance (IR) in @entity19 models of @entity28 and @entity6 ( @entity6 ) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue @entity32 via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose @entity32 and investigated the role of Tregs in IR/ @entity28 through coordinated studies in @entity19 and @entity1 . METHODS AND FINDINGS: @entity403 -green fluorescent protein (GFP) "knock-in" @entity19 were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese @entity1 without overt type 2 @entity6 (n=13) and lean controls (n=7) were recruited prospectively for assessment of @entity32 . DIO resulted in increased CD3(+)CD4(+), and CD3(+)CD8(+) cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with @entity9536 (+) @entity2935 (+) adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors @entity366 and @entity9350 and marker of activation @entity1759 . In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. @entity1 visceral adipose in morbid @entity28 was characterized by an increase in @entity2935 (+) ATMs and a decrease in @entity403 expression. CONCLUSIONS: Our experiments indicate that @entity28 in @entity19 and @entity1 results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose @entity32 .

title: XXXX in @entity28 is associated with critical alterations in tregulatory cell numbers.

answer: @entity32 :: (MESH:D007249,Disease) :: ['Visceral adipose inflammation']


abstract: INTRODUCTION: @entity3799 ( @entity3799 ) represents a spectrum of pathologies with progressive compression of the spinal cord. The clinical signs and symptoms play a key role in diagnosis. The characteristic hand @entity602 signs are of significant clinical importance. The aim of this descriptive study was to report a relatively easy to elicit new hand @entity602 sign. The basis for this is finger and wrist flexor disinhibition, which is used for the spinal specificity of @entity1745 at or above the C5/6 level. METHODS: The new clinical test was conducted in 68 @entity1 with a mean age of 62 (range 54-68) years. The @entity1 were divided into two groups according to their level of @entity850 . Group 1 (n is 58) @entity1 had @entity850 at or above the C5/6 level, while Group 2 (n is 10) @entity1 had @entity850 at or below the C6/7 level. All these @entity1 were clinically evaluated and their level of @entity850 was confirmed using magnetic resonance imaging. RESULTS: The Wazir sign was observed and well reproducible in 54 (93%) @entity1 (Group 1); the @entity602 signs of three @entity1 were positive (Hoffman's sign, finger escape and ten-second test). In Group 2, the Wazir sign was not reproducible, but the @entity602 signs were also positive in three @entity1 . CONCLUSION: The Wazir hand @entity602 sign was found to be consistently present in our @entity1 , in addition to the other hand @entity602 signs.

title: New clinical sign of cervical @entity602 : Wazir hand XXXX sign.

entities_list: @entity1 :: ('9606', 'Species') :: ['patients']

entities_list: @entity602 :: ('MESH:D013118', 'Disease') :: ['myelopathy']

entities_list: @entity3799 :: ('MESH:D002575', 'Disease') :: ['Cervical spondylotic myelopathy', 'CSM']

entities_list: @entity1745 :: ('MESH:D013117', 'Disease') :: ['cord compression']

entities_list: @entity850 :: ('MESH:D003251', 'Disease') :: ['stenosis']

answer: @entity602 :: (MESH:D013118,Disease) :: ['myelopathy']


abstract: INTRODUCTION: @entity3799 ( @entity3799 ) represents a spectrum of pathologies with progressive compression of the spinal cord. The clinical signs and symptoms play a key role in diagnosis. The characteristic hand @entity602 signs are of significant clinical importance. The aim of this descriptive study was to report a relatively easy to elicit new hand @entity602 sign. The basis for this is finger and wrist flexor disinhibition, which is used for the spinal specificity of @entity1745 at or above the C5/6 level. METHODS: The new clinical test was conducted in 68 @entity1 with a mean age of 62 (range 54-68) years. The @entity1 were divided into two groups according to their level of @entity850 . Group 1 (n is 58) @entity1 had @entity850 at or above the C5/6 level, while Group 2 (n is 10) @entity1 had @entity850 at or below the C6/7 level. All these @entity1 were clinically evaluated and their level of @entity850 was confirmed using magnetic resonance imaging. RESULTS: The Wazir sign was observed and well reproducible in 54 (93%) @entity1 (Group 1); the @entity602 signs of three @entity1 were positive (Hoffman's sign, finger escape and ten-second test). In Group 2, the Wazir sign was not reproducible, but the @entity602 signs were also positive in three @entity1 . CONCLUSION: The Wazir hand @entity602 sign was found to be consistently present in our @entity1 , in addition to the other hand @entity602 signs.

title: New clinical sign of cervical XXXX : Wazir hand @entity602 sign.

answer: @entity602 :: (MESH:D013118,Disease) :: ['myelopathy']


abstract: The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules @entity2071 ( @entity2071 ), @entity4105 , and @entity4725 ( @entity4725 ) were studied in the serum of @entity1 with @entity30 , @entity31 , and healthy controls. A second blood sample was taken from @entity1 with @entity66 after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating @entity4725 concentrations were significantly higher in @entity1 with active @entity31 (n = 11, median = 165 U/ml) compared with @entity1 with inactive @entity31 (n = 10, median = 117 U/ml, p < 0.005), active @entity30 (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in @entity4105 or @entity2071 concentrations between the active and inactive states, however, @entity1 with active @entity30 had significantly higher @entity2071 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). @entity4725 concentrations fell significantly from pretreatment values to remission in active @entity31 (p < 0.01). In @entity30 there was a significant fall in @entity2071 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of @entity2071 occurred more often and was more intense in inflamed tissue sections from @entity1 with @entity31 and @entity30 than from controls. Vascular labelling with antibody to @entity4105 also occurred more often in @entity1 with active @entity29 . In conclusion, increased circulating concentrations of selected adhesion molecules are associated with @entity29 . There is also evidence of local upregulation, particularly of @entity2071 . Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local @entity32 ; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.

title: Adhesion molecules in XXXX .

entities_list: @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation']

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['active disease']

entities_list: @entity4725 :: ('7412', 'Gene') :: ['vascular cell adhesion molecule 1', 'VCAM-1']

entities_list: @entity31 :: ('MESH:D003093', 'Disease') :: ['ulcerative colitis']

entities_list: @entity29 :: ('MESH:D015212', 'Disease') :: ['inflammatory bowel disease']

entities_list: @entity2071 :: ('3383', 'Gene') :: ['ICAM-1', 'intercellular adhesion molecule 1']

entities_list: @entity30 :: ('MESH:D003424', 'Disease') :: ["Crohn's disease"]

answer: @entity29 :: (MESH:D015212,Disease) :: ['inflammatory bowel disease']


abstract: @entity5125 is a food-borne pathogen of significant threat to public health. @entity101 ( @entity101 ) treatment can be used to control @entity5125 in food. The CtsR (class three stress gene repressor) protein negatively regulates the expression of class III heat shock genes. A spontaneous pressure-tolerant ctsR mutant 2-1 that was able to survive under @entity101 treatment has been identified previously. So far, there is only limited information about the mechanisms of survival and adaptation of this mutant to high pressure. Microarray technology was used to monitor the gene expression profiles of the ctsR mutant 2-1 under @entity101 treatment. Compared to pressure-treated @entity5125 Scott A wild type, 17 genes were up-regulated (>2-fold increase) in the ctsR mutant 2-1, whereas 58 genes were down-regulated (<-2-fold decrease). The entire clpC operon was up-regulated in the ctsR mutant 2-1, indicating that the mutant CtsR protein was not a functional repressor. The increased levels of expression of stress-related genes in ctsR mutant 2-1 may contribute to its survival under high pressure. The reduced expression levels of the genes related to virulence, flagella synthesis, and cell division in the ctsR mutant 2-1 correlate with its characteristics (elongated cells, reduced virulence, and @entity2048 ). The gene expression changes determined by microarray assays were confirmed by real-time reverse transcriptase PCR analyses. This study enhances our understanding of how @entity5125 survives under @entity101 and may contribute to the design of effective and economically feasible @entity101 treatment in food processing.

title: Gene expression profiling of a pressure-tolerant XXXX Scott A ctsR deletion mutant.

entities_list: @entity5125 :: ('1639', 'Species') :: ['Listeria monocytogenes', 'L. monocytogenes']

entities_list: @entity101 :: ('MESH:D006973', 'Disease') :: ['HHP', 'High hydrostatic pressure']

entities_list: @entity2048 :: ('MESH:D004832', 'Disease') :: ['absence of flagella']

answer: @entity5125 :: (1639,Species) :: ['Listeria monocytogenes']


abstract: Contraction-induced activation of a skeletal muscle specific @entity141 and calmodulin dependent myosin light chain kinase (skMLCK) catalyzes phosphorylation of the @entity56825 , a reaction that potentiates twitch force. The purpose of this study was to test the effect of skMLCK gene ablation on the fatigability of @entity19 extensor digitorum longus (EDL) muscle (in vitro at 25  C). Muscles were isolated from wildtype (WT, n = 10-12) and skeletal @entity23452 knockout (skMLCK KO, n = 10-12) @entity19 and fatigued using a protocol consisting of 5 min of repeated tetanic stimulation (150 Hz for 1000 ms every 5 s). Both twitch (P(t)) and tetanic (P(o)) force as well as unloaded shortening velocity (V(o)) were assessed before, during and after fatiguing stimulation. Fatiguing stimulation increased @entity56825 phosphorylation in WT but not skMLCK KO muscles (16    0.01-0.63    0.02 and 0.07    0.02-0.08    0.02 mol phos mol @entity56825 , respectively). Although P(t) was potentiated above baseline in both WT and KO muscles, this increase was greater in WT than in KO muscles (to 1.37    0.05 vs. 1.14    0.02 of unpotentiated values, respectively). The difference in P(t) persisted until P(o) had been diminished to ~60% of baseline and thereafter P(t) declined to similar levels in both WT and KO muscles (to ~35% of initial). Overall, the time-course and decline in P(o) for WT and KO was similar (reduced to 0.20    0.01 and 0.20    0.01 of baseline, respectively) (P < 0.05). Initial values for V(o) were similar between WT and KO muscles and, moreover, the fatigue related decline in Vo was similar for both muscle genotypes (P < 0.05). Thus, our results demonstrate that skMLCK--catalyzed @entity56825 phosphorylation augments isometric twitch force during moderate, but not severe, levels of fatigue.

title: The effect of skeletal myosin light chain kinase gene ablation on the fatigability of XXXX fast muscle.

entities_list: @entity56825 :: ('68813(Tax:10090)', 'Gene') :: ['RLC', 'myosin regulatory light chain (RLC)']

answer: @entity19 :: (10090,Species) :: ['mouse']


abstract: BACKGROUND: Autologous peripheral-blood progenitor cells can restore @entity1210 after high-dose chemotherapy in @entity1 with solid @entity5 or @entity1583 . We investigated the ability of peripheral-blood progenitor cells generated ex vivo to restore @entity1210 in @entity1 with @entity5 who have undergone high-dose chemotherapy. METHODS: Ten @entity1 who had received high-dose chemotherapy were given transplants of autologous progenitor cells that had been generated ex vivo. We used 11 million @entity2280 + hematopoietic progenitor cells as the starting population for the cell growth. This number corresponds to less than 10 percent of the usual preparation of peripheral-blood @entity2280 + mononuclear cells used in leukapheresis. The @entity2280 + cells were grown in medium containing autologous plasma, recombinant @entity1 @entity6826 , @entity1356 , @entity2772 , @entity650 , and erythropoietin. RESULTS: No toxic effects were observed with the infusion of the generated cells. The cells promoted a rapid and sustained hemopoietic recovery when transplanted after treatment with high-dose @entity2879 (1500 mg per square meter of body-surface area), @entity1260 (12 g per square meter), @entity3003 (750 mg per square meter), and @entity1259 (150 mg per square meter). The pattern of hematopoietic reconstitution was identical to that in historical controls treated with unseparated mononuclear cells or positively selected @entity2280 + cells. CONCLUSIONS: A small number of peripheral-blood @entity2280 + cells, when grown ex vivo, can supply a population of hematopoietic precursors that have the ability to restore blood formation in @entity1 treated with high doses of chemotherapy. This method, which requires only a small volume of the @entity1 's blood, may reduce the risk of @entity5 -cell contamination, circumvent the need for leukapheresis, and allow repeated cycles of high-dose chemotherapy.

title: Reconstitution of XXXX after high-dose chemotherapy by autologous progenitor cells generated ex vivo.

entities_list: @entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors']

entities_list: @entity3003 :: ('MESH:D016190', 'Chemical') :: ['carboplatin']

entities_list: @entity1259 :: ('MESH:D015251', 'Chemical') :: ['epirubicin']

entities_list: @entity2879 :: ('MESH:D005047', 'Chemical') :: ['etoposide']

entities_list: @entity1583 :: ('MESH:D019337', 'Disease') :: ['hematologic cancers']

entities_list: @entity1260 :: ('MESH:D007069', 'Chemical') :: ['ifosfamide']

entities_list: @entity1210 :: ('MESH:C536227', 'Disease') :: ['hematopoiesis']

answer: @entity1210 :: (MESH:C536227,Disease) :: ['hematopoiesis']


abstract: BACKGROUND: @entity5202 ( @entity5202 ) is defined by a minimum of 15 eosinophils (eos) per @entity2194 ( @entity2194 ) on esophageal biopsy, along with esophageal symptoms and the exclusion of @entity354 ( @entity354 ). The clinical significance of fewer eosinophils is unknown. METHODS: Fifty-nine adult @entity1 without a previous diagnosis of @entity5202 with esophageal biopsies containing 1-14 eos per @entity2194 (low grade @entity1712 ) and 418 adult @entity1 with >= 15 eos per @entity2194 were identified by retrospective review. @entity1 were divided into group A (1-9 eos per @entity2194 ), group B (10-14 eos per @entity2194 ), and group C (>= 15 eos per @entity2194 ) with a chart review of clinical and demographic data. RESULTS: While @entity1282 and @entity402 ( @entity565 and @entity2023 ) were more common in @entity1 with >= 15 eos per @entity2194 (group C) than those with low grade esophageal @entity1712 (groups A and B) (93 vs. 88%, P  =  0.02), food impaction and heartburn occurred at an equal frequency across all @entity1 groups. Endoscopic findings were likewise similar between groups. Of the 14 @entity1 with low grade esophageal @entity1712 who underwent repeat endoscopy a mean interval of 42  weeks (range 8-118  weeks) later, five (36%) met conventional diagnostic criteria for @entity5202 of 15 or greater eos per @entity2194 . Follow-up in ten @entity1 treated with topical corticosteroids noted improvement in nine, with mean follow-up of 8  weeks (range 4-12  weeks). CONCLUSION: Some adult @entity1 with @entity1282 and less than 15 eos per @entity2194 have similar endoscopic findings and clinical course to @entity1 meeting the consensus definition of @entity5202 . Further evaluation of @entity1 with low grade esophageal @entity1712 is needed.

title: Low grade esophageal @entity1712 in adults: an unrecognized part of the spectrum of XXXX ?

entities_list: @entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'patient']

entities_list: @entity1712 :: ('MESH:D004802', 'Disease') :: ['eosinophilia']

entities_list: @entity2194 :: ('MESH:D005128', 'Disease') :: ['HPF', 'high-powered field']

entities_list: @entity5202 :: ('MESH:D057765', 'Disease') :: ['Eosinophilic esophagitis', 'EoE']

entities_list: @entity2023 :: ('MESH:D006255', 'Disease') :: ['allergic rhinitis']

entities_list: @entity354 :: ('MESH:D005764', 'Disease') :: ['gastroesophageal reflux', 'GERD']

entities_list: @entity1282 :: ('MESH:D003680', 'Disease') :: ['dysphagia']

answer: @entity5202 :: (MESH:D057765,Disease) :: ['eosinophilic esophagitis']


abstract: BACKGROUND: @entity5202 ( @entity5202 ) is defined by a minimum of 15 eosinophils (eos) per @entity2194 ( @entity2194 ) on esophageal biopsy, along with esophageal symptoms and the exclusion of @entity354 ( @entity354 ). The clinical significance of fewer eosinophils is unknown. METHODS: Fifty-nine adult @entity1 without a previous diagnosis of @entity5202 with esophageal biopsies containing 1-14 eos per @entity2194 (low grade @entity1712 ) and 418 adult @entity1 with >= 15 eos per @entity2194 were identified by retrospective review. @entity1 were divided into group A (1-9 eos per @entity2194 ), group B (10-14 eos per @entity2194 ), and group C (>= 15 eos per @entity2194 ) with a chart review of clinical and demographic data. RESULTS: While @entity1282 and @entity402 ( @entity565 and @entity2023 ) were more common in @entity1 with >= 15 eos per @entity2194 (group C) than those with low grade esophageal @entity1712 (groups A and B) (93 vs. 88%, P  =  0.02), food impaction and heartburn occurred at an equal frequency across all @entity1 groups. Endoscopic findings were likewise similar between groups. Of the 14 @entity1 with low grade esophageal @entity1712 who underwent repeat endoscopy a mean interval of 42  weeks (range 8-118  weeks) later, five (36%) met conventional diagnostic criteria for @entity5202 of 15 or greater eos per @entity2194 . Follow-up in ten @entity1 treated with topical corticosteroids noted improvement in nine, with mean follow-up of 8  weeks (range 4-12  weeks). CONCLUSION: Some adult @entity1 with @entity1282 and less than 15 eos per @entity2194 have similar endoscopic findings and clinical course to @entity1 meeting the consensus definition of @entity5202 . Further evaluation of @entity1 with low grade esophageal @entity1712 is needed.

title: Low grade esophageal XXXX in adults: an unrecognized part of the spectrum of @entity5202 ?

answer: @entity1712 :: (MESH:D004802,Disease) :: ['eosinophilia']


abstract: BACKGROUND: The aim of this study was to evaluate the technical feasibility and safety of a hybrid surgical approach of video-assisted minithoracotomy (hybrid VATS) sleeve lobectomy for @entity1149 ( @entity1149 ), using success rate as the primary end point. METHODS: Between February 1996 and December 2006, @entity1 with @entity5 were prospectively registered to undergo hybrid VATS sleeve resection in a single institution. Hybrid VATS involved performing the main procedures via rib spreading and minithoracotomy using a monitor and direct vision. A successful procedure was defined as a @entity1 who had a sleeve lobectomy via hybrid VATS without conversion to thoracotomy and without significant perioperative morbidity or mortality. RESULTS: A total of 148 @entity1 (108 @entity1 and 40 @entity1 ; median age = 58 years) who underwent hybrid VATS sleeve lobectomy for @entity1149 were identified in our database. The median duration of the successfully completed procedures was 190 min (range = 145-305 min). The median length of time of chest tube in place was 3 days (range = 1-12 days). Hybrid VATS sleeve lobectomy was performed successfully in 134 of 148 @entity1 for a success rate of 90.5%. The median follow-up period was 65.1 months (range = 34.5-154.8 months). The overall 5-year disease-free survival and overall survival of all @entity1 were 36.7% (95% CI = 27.9-45.5%) and 54.2% (95% CI = 44.8-63.6%), respectively. CONCLUSION: Hybrid VATS sleeve lobectomy is feasible for selected @entity1 with @entity1149 in specialized centers.

title: Long-term outcome of hybrid surgical approach of video-assisted minithoracotomy sleeve lobectomy for XXXX .

entities_list: @entity1 :: ('9606', 'Species') :: ['women', 'patients', 'patient', 'men']

entities_list: @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer']

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['bronchogenic tumors']

answer: @entity1149 :: (MESH:D002289,Disease) :: ['non-small-cell lung cancer']


abstract: Activation of the phosphoinositide (PI) pathway has been shown to be involved in the compaction of blastomeres in @entity19 embryos and in @entity2085 formation in @entity1238 and in @entity3392 embryos. Here we investigate @entity141 signals in individual blastomeres of @entity3392 embryos with the goal to better understand the role of PI and @entity141 signaling for early vertebrate embryogenesis. Initial studies showed that the @entity671 (IP3) concentration increases after the 32-cell stage of development, suggesting that IP3-mediated @entity141 signals may be present during the blastula stage. @entity141 signals were measured by identifying individual cells using confocal imaging of a nuclear localized @entity141 indicator. Using this in situ indicator, changes in @entity141 concentration were measured over several hours in each cell of a series of sections through the developing embryo. Transient increases in @entity141 concentration that lasted 20-50 sec ( @entity141 spikes) were first triggered during the 32- to 128-cell stage in cells of the outer embryonic cell layer. These cells develop epithelial characteristics and specialize into the enveloping layer (EVL). No @entity141 activity was observed during the earlier cleavage cycles or in deep blastomeres. @entity141 spikes remained restricted to the EVL until the end of the blastula stage. @entity141 spikes in neighboring EVL cells often occurred in the same short time interval, indicating that small groups of EVL cells can synchronize their activity. When averaged over several cell cycles, @entity141 activity showed an even distribution in the EVL and did not indicate future polarities.

title: Localized calcium signals in early XXXX development.

entities_list: @entity671 :: ('MESH:D015544', 'Chemical') :: ['inositol 1,4,5-trisphosphate']

entities_list: @entity2085 :: ('MESH:D020964', 'Disease') :: ['embryonic axis']

answer: @entity3392 :: (7955,Species) :: ['zebrafish']


abstract: Recent experimental and clinical studies suggest that @entity5 -induced angiogenesis may be an important step in the evolution of @entity5 , and may be related to prognosis. In our study we examined 42 cases of @entity0 (mean age: 56.76 +/- 13.5), 21 with lymph node @entity3 and 21 without. Angiogenesis was evaluated after immunohistochemical staining of @entity5 vessels, using polyclonal antibody to factor VIII related antigen (VIIIR-Ag) and counting of the three most active areas of neovascularization. In the same manner we counted the microvessels in lymph node @entity3 . The mean vessel count of node-negative cases (51.16 +/- 19.32) did not differ significantly from node-positive cases (45.66 +/- 17.44). In contrast @entity1 younger than 50 years had much higher mean vessel counts (54.04 +/- 16.47) than did @entity1 older than 70 years (38.03 +/- 16.73) producing a P value of < or = 0.05. No association was found between @entity5 size and mean vessel count, nor was there any significant difference between grade I (45.94 +/- 16.54), grade II (53.13 +/- 23.22) and @entity5 (51.71 +/- 20.64). When we compared the mean vessel count of primary @entity5 with those of node @entity3 , we found much lower counts in the latter (P < or = 0.01). The differences in our results from previous studies, probably reflect the heterogeneity which exists between different @entity5 in their ability to induce angiogenesis. Additionally, there is some evidence in our study that angiogenesis is possibly related to @entity1 age and probably depends on differences in the @entity5 stroma.

title: Angiogenesis in XXXX : is it associated with parameters of prognostic significance?

entities_list: @entity5 :: ('MESH:D009369', 'Disease') :: ['malignant tumours', 'grade III tumours', 'tumours', 'tumour']

entities_list: @entity1 :: ('9606', 'Species') :: ['patients', 'patient']

entities_list: @entity0 :: ('MESH:D001943', 'Disease') :: ['breast carcinoma']

entities_list: @entity3 :: ('MESH:D009362', 'Disease') :: ['metastases']

answer: @entity0 :: (MESH:D001943,Disease) :: ['invasive breast carcinoma']


abstract: STUDY DESIGN: Expression of light chain 3 ( @entity22227 ), a characteristic marker of autophagy, was examined by immunohistochemistry and Western blot using a @entity1566 ( @entity1566 ) model in @entity19 . Electron microscopic analysis was also performed to examine the anatomic formation of autophagy and autophagic cell @entity204 in the injured spinal cord. OBJECTIVE: To examine both biochemically and anatomically the activity of autophagy in the damaged neural tissue after @entity1566 . SUMMARY OF BACKGROUND DATA: Autophagy is the bulk degradation of intracellular proteins and organelles, and it is involved in a number of diseases. Autophagy can lead to nonapoptotic programmed cell @entity204 , which is called autophagic cell @entity204 . Recent researches have revealed the increased expression of @entity22227 and the anatomic formation of autophagy and autophagic cell @entity204 in damaged tissues of @entity66 models. However, previous studies have focused on apoptotic process but not autophagic activity as mechanism of @entity3145 after @entity1566 . To date, there has been no study to examine the expression of @entity22227 and the anatomic formation of autophagy after @entity1566 . METHODS: The spinal cord was hemitransected at T10 in adult female C57BL/6J @entity19 . The @entity22227 expression was examined by immunohistochemistry and Western blot. The anatomic formation of autophagic activity was investigated using electron microscopy. RESULTS: Immunohistochemistry showed that the number of the @entity22227 -positive cells significantly increased at the lesion site after hemisection. The increase of @entity22227 -positive cells was observed from 4 hours and peaked at 3 days, and it lasted for at least 21 days after hemisection. The @entity22227 -positive cells were observed in neurons, astrocytes, and oligodendrocytes. Western blot analysis demonstrated that the level of @entity22227 -II protein expression significantly increased in the injured spinal cord. Electron microscopy showed the formation of autophagic vacuoles to increase in the damaged cells. Furthermore, the nuclei in the transferase-mediated @entity1977 nick end labeling-positive cells expressed @entity22227 were round, which is consistent with autophagic cell @entity204 , and they were neither shrunken nor fragmented as is observed in apoptotic nuclei. CONCLUSION: This study suggested both biochemically and anatomically that autophagy was clearly activated and autophagic cell @entity204 was induced in the damaged neural tissue after @entity1566 .

title: Induction of autophagy and autophagic cell XXXX in damaged neural tissue after acute @entity1566 in @entity19 .

entities_list: @entity66 :: ('MESH:D004194', 'Disease') :: ['various disease']

entities_list: @entity3145 :: ('MESH:D017695', 'Disease') :: ['neural tissue damage']

entities_list: @entity1566 :: ('MESH:D013119', 'Disease') :: ['spinal cord injury', 'SCI']

answer: @entity204 :: (MESH:D003643,Disease) :: ['death']