abstract: UNASSIGNED: A 48-year-old Japanese @entity0 experienced slow-onset @entity7 and @entity3 . Neurological examinations revealed @entity11 in the trunk and extremities, @entity12 and postural instability, although @entity2 and @entity4 symptoms were not apparent in the @entity1 stage. Neuroimaging revealed progressive bilateral frontotemporal lobe @entity5 with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as @entity13 or electromyogram findings. She eventually reached the @entity12 mutism state, and gastrostomy and tracheotomy were performed at 4   years after onset. A clinical diagnosis of @entity16 was made prior to her @entity6 , which occurred 6   years after onset. Post mortem examinations revealed that the brain weighed 1200   g and showed @entity5 . Severe @entity8 and @entity15 were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed @entity8 with @entity15 . Using hyperphosphorylated tau ( @entity10 ) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak @entity9 staining, thin and short threads were also extensively observed, but considerably fewer than those observed by @entity10 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15   nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of @entity18 -insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in @entity16 . No pathogenic mutations were found during the gene analysis of @entity14 . After completing our comprehensive investigation, we diagnosed this @entity0 with unclassifiable four-repeat @entity17 .

title: An autopsied case of unclassifiable sporadic four-repeat @entity17 presenting with @entity7 and XXXX .

answer: @entity3


abstract: UNASSIGNED: A 48-year-old Japanese @entity0 experienced slow-onset @entity7 and @entity3 . Neurological examinations revealed @entity11 in the trunk and extremities, @entity12 and postural instability, although @entity2 and @entity4 symptoms were not apparent in the @entity1 stage. Neuroimaging revealed progressive bilateral frontotemporal lobe @entity5 with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as @entity13 or electromyogram findings. She eventually reached the @entity12 mutism state, and gastrostomy and tracheotomy were performed at 4   years after onset. A clinical diagnosis of @entity16 was made prior to her @entity6 , which occurred 6   years after onset. Post mortem examinations revealed that the brain weighed 1200   g and showed @entity5 . Severe @entity8 and @entity15 were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed @entity8 with @entity15 . Using hyperphosphorylated tau ( @entity10 ) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak @entity9 staining, thin and short threads were also extensively observed, but considerably fewer than those observed by @entity10 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15   nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of @entity18 -insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in @entity16 . No pathogenic mutations were found during the gene analysis of @entity14 . After completing our comprehensive investigation, we diagnosed this @entity0 with unclassifiable four-repeat @entity17 .

title: An autopsied case of unclassifiable sporadic four-repeat @entity17 presenting with XXXX and @entity3 .

answer: @entity7


abstract: UNASSIGNED: A 48-year-old Japanese @entity0 experienced slow-onset @entity7 and @entity3 . Neurological examinations revealed @entity11 in the trunk and extremities, @entity12 and postural instability, although @entity2 and @entity4 symptoms were not apparent in the @entity1 stage. Neuroimaging revealed progressive bilateral frontotemporal lobe @entity5 with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as @entity13 or electromyogram findings. She eventually reached the @entity12 mutism state, and gastrostomy and tracheotomy were performed at 4   years after onset. A clinical diagnosis of @entity16 was made prior to her @entity6 , which occurred 6   years after onset. Post mortem examinations revealed that the brain weighed 1200   g and showed @entity5 . Severe @entity8 and @entity15 were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed @entity8 with @entity15 . Using hyperphosphorylated tau ( @entity10 ) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak @entity9 staining, thin and short threads were also extensively observed, but considerably fewer than those observed by @entity10 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15   nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of @entity18 -insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in @entity16 . No pathogenic mutations were found during the gene analysis of @entity14 . After completing our comprehensive investigation, we diagnosed this @entity0 with unclassifiable four-repeat @entity17 .

title: An autopsied case of unclassifiable sporadic four-repeat XXXX presenting with @entity7 and @entity3 .

answer: @entity17


abstract: BACKGROUND: Splenic vein ligation may result in sinistral (left-sided) portal @entity1 and @entity2 . The aim of this study was to analyse the pathogenesis of sinistral portal @entity1 following @entity6 in pancreaticoduodenectomy. METHODS: @entity0 who underwent pancreaticoduodenectomy for @entity4 between January 2005 and December 2012 were included in this retrospective study. The venous flow pattern from the spleen and @entity5 were examined after surgery. RESULTS: Of 103 @entity0 who underwent pancreaticoduodenectomy with portal vein resection, 43 had @entity6 . There were two predominant venous flow patterns from the spleen. In the varicose route (27 @entity0 ), flow from the spleen passed to @entity3 . In the non-varicose route, flow from the spleen passed through a splenocolonic collateral (14 @entity0 ) or a spontaneous splenorenal shunt (2 @entity0 ). The varicose route was associated with significantly greater @entity5 than the non-varicose route (median @entity5 ratio 1  52 versus 0  94; P   <   0  001). All @entity0 with the varicose route had colonic varices, and none had a right colic marginal vein at the hepatic flexure. CONCLUSION: Pancreaticoduodenectomy with @entity6 may lead to sinistral portal @entity1 . To avoid the development of varices, it is important to preserve the right colic marginal vein. Reconstruction of the splenic vein should be considered if the right colic marginal vein is divided.

title: Sinistral portal XXXX after pancreaticoduodenectomy with @entity6 .

answer: @entity1


abstract: BACKGROUND: Splenic vein ligation may result in sinistral (left-sided) portal @entity1 and @entity2 . The aim of this study was to analyse the pathogenesis of sinistral portal @entity1 following @entity6 in pancreaticoduodenectomy. METHODS: @entity0 who underwent pancreaticoduodenectomy for @entity4 between January 2005 and December 2012 were included in this retrospective study. The venous flow pattern from the spleen and @entity5 were examined after surgery. RESULTS: Of 103 @entity0 who underwent pancreaticoduodenectomy with portal vein resection, 43 had @entity6 . There were two predominant venous flow patterns from the spleen. In the varicose route (27 @entity0 ), flow from the spleen passed to @entity3 . In the non-varicose route, flow from the spleen passed through a splenocolonic collateral (14 @entity0 ) or a spontaneous splenorenal shunt (2 @entity0 ). The varicose route was associated with significantly greater @entity5 than the non-varicose route (median @entity5 ratio 1  52 versus 0  94; P   <   0  001). All @entity0 with the varicose route had colonic varices, and none had a right colic marginal vein at the hepatic flexure. CONCLUSION: Pancreaticoduodenectomy with @entity6 may lead to sinistral portal @entity1 . To avoid the development of varices, it is important to preserve the right colic marginal vein. Reconstruction of the splenic vein should be considered if the right colic marginal vein is divided.

title: Sinistral portal @entity1 after pancreaticoduodenectomy with XXXX .

answer: @entity6


abstract: UNASSIGNED: Several findings have pointed to the role of histaminergic neurotransmission in the modulation of @entity2 -like @entity1 . The elevated plus-maze (EPM) test has been widely used to investigate the process of @entity2 and also has been used to investigate the process of learning and memory. Visual cues are relevant to the formation of spatial maps, and as the hippocampus is involved in this task, experiment 1 explored this issue. Experiment 2 investigated the effects of intraperitoneal (i.p.) injections of l-histidine (LH, a precursor of histamine) and of intra-dorsal hippocampus (intra-DH) injections of chlorpheniramine (CPA, an H1 receptor antagonist) on @entity2 in @entity0 re-exposed to the EPM. @entity0 received saline (SAL) or LH i.p. and SAL or CPA (0.016, 0.052, and 0.16nmol/0.1 l) intra-DH prior to Trial 1 (T1) and Trial 2 (T2). No significant changes were observed in the number of enclosed-arm entries (EAE) in T1, an EPM index of general exploratory activity. LH had an anxiolytic-like effect that was reversed by intra-DH injections of CPA. T2 versus T1 analysis revealed that only the lower dose of CPA resulted in @entity3 . Combined injections of LH and CPA revealed that higher doses of CPA impair emotional memory. Taken together, these results suggest that LH and H1 receptors present in the dorsal hippocampus are involved in @entity2 -related @entity1 in @entity0 submitted to EPM.

title: Dorsal hippocampal microinjection of chlorpheniramine reverses the anxiolytic-like effects of l-histidine and impairs emotional memory in XXXX .

answer: @entity0


abstract: UNASSIGNED: We tested the antiproliferative activity and mechanism of the action of several novel @entity6 derivatives. Six different @entity0 cell lines were used to evaluate the potential cytotoxic effect of eleven @entity6 -based molecules. A standard @entity2 assay was used for cell bioavailability analysis. Additionally, the potential cytotoxic effect of the tested compounds on non- @entity0 cells was investigated in @entity1 skeletal @entity3 (L6) and in @entity4 aortic smooth muscle cells. In order to investigate whether the DNA binding activity of tested compounds correlated with their cytotoxic effect, circular dichroism (CD) measurement and DNA T4 ligase assay were performed. Finally, the potential mutagenic activity of the lead compound 5 was investigated. The cytotoxic effect of compound 5 in @entity0 cells was obtained in lower concentrations than the well-known: @entity6 based drug, @entity5 . The lead compound binds to DNA, but in a different mode than the parent molecules. Additionally, compound 5 was not cytotoxic in the effective range of concentrations in non- @entity0 cells. In identical concentrations, the parent compound ( @entity6 ) and @entity5 were extremely toxic for both types of these normal cells. Finally, based on CD measurement and T4 ligase assay, it was confirmed that 5 binds to DNA but in different from the parent compounds manner. Important to mention, that compound 5 might have increased mutagenic activity which must be verified in vivo. Based on these in vitro results, we conclude that 5 is a more potent and more selective antiprolifirative compound than @entity5 . Compound 5 was also more effective in HepG2 and P-12 cells. Thus, 5 is suitable for future in vivo biological evaluation and its structure might be used as a basis for developing novel anticancer drugs.

title: Antiproliferative Effect of Novel XXXX -based Compounds.

answer: @entity6


abstract: UNASSIGNED: Nuclear lamins are involved in many cellular functions due to their ability to bind numerous partners including chromatin and transcription factors, and affect their properties. @entity2 ( @entity1 ; OMIM#151660) is caused in most cases by the A-type lamin @entity4 mutation. We report here that the @entity4 mutation affects the regulatory activity of @entity3 , a transcription factor that regulates hundreds of genes involved in lipid metabolism and adipocyte differentiation. Using in situ proximity ligation assays, reporter assays and biochemical and transcriptomic approaches, we show that interactions of @entity3 with @entity1 ( @entity1 ) and @entity1 ( @entity1 ) occur at the nuclear periphery and in the nucleoplasm. These interactions involve the Ig-fold of A-type lamins and are favored upon @entity3 binding to its DNA target sequences. We show that @entity3 , @entity1 and sterol response DNA elements form ternary complexes in vitro. In addition, overexpression of A-type lamins reduces transcriptional activity of @entity3 . In contrast, both overexpression of @entity1 @entity4 in primary @entity0 preadipocytes and endogenous expression of A-type lamins @entity4 in @entity1 @entity0 fibroblasts, reduce A-type lamins- @entity3 in situ interactions and upregulates a large number of @entity3 target genes. As this @entity1 mutant was previously shown to inhibit adipogenic differentiation, we propose that deregulation of @entity3 by mutated A-type lamins constitutes one underlying mechanism of the physiopathology of @entity1 . Our data suggest that @entity3 targeting molecules could be considered in a therapeutic context.

title: The XXXX substitution in A-type lamins deregulates @entity3 activity in Dunnigan-type familial partial lipodystrophy.

answer: @entity4


abstract: UNASSIGNED: Nuclear lamins are involved in many cellular functions due to their ability to bind numerous partners including chromatin and transcription factors, and affect their properties. @entity2 ( @entity1 ; OMIM#151660) is caused in most cases by the A-type lamin @entity4 mutation. We report here that the @entity4 mutation affects the regulatory activity of @entity3 , a transcription factor that regulates hundreds of genes involved in lipid metabolism and adipocyte differentiation. Using in situ proximity ligation assays, reporter assays and biochemical and transcriptomic approaches, we show that interactions of @entity3 with @entity1 ( @entity1 ) and @entity1 ( @entity1 ) occur at the nuclear periphery and in the nucleoplasm. These interactions involve the Ig-fold of A-type lamins and are favored upon @entity3 binding to its DNA target sequences. We show that @entity3 , @entity1 and sterol response DNA elements form ternary complexes in vitro. In addition, overexpression of A-type lamins reduces transcriptional activity of @entity3 . In contrast, both overexpression of @entity1 @entity4 in primary @entity0 preadipocytes and endogenous expression of A-type lamins @entity4 in @entity1 @entity0 fibroblasts, reduce A-type lamins- @entity3 in situ interactions and upregulates a large number of @entity3 target genes. As this @entity1 mutant was previously shown to inhibit adipogenic differentiation, we propose that deregulation of @entity3 by mutated A-type lamins constitutes one underlying mechanism of the physiopathology of @entity1 . Our data suggest that @entity3 targeting molecules could be considered in a therapeutic context.

title: The @entity4 substitution in A-type lamins deregulates XXXX activity in Dunnigan-type familial partial lipodystrophy.

answer: @entity3


abstract: INTRODUCTION: @entity13 is a well-known complication of the anti- @entity9 @entity14 agent @entity11 , especially in peculiar but not rare clinical conditions. Attempts to reduce the incidence of this adverse reaction have been enforced by national agencies over the years. The Italian Medicines Agency recently released a safety recommendation on prescribing the drug and with regard to the existence of several conditions that contraindicate drug continuation, such as dehydration, @entity3 , @entity7 , surgery or hyperosmolar contrast agent infusion, but the recommendation does not mention the increased risk related to stoma. The present case report is, to our knowledge, the first in the literature of @entity11 -associated @entity13 in a @entity0 with a recently created ileostomy and low anterior resection for @entity1 . CASE PRESENTATION: A 70-year-old Caucasian @entity0 who had undergone low anterior resection with total mesorectal excision and temporary loop ileostomy creation at our institution returned to our department 30 days later because of @entity4 , @entity5 , diffuse @entity6 and @entity10 of about 24 hours' duration. During his physical examination, the @entity0 appeared dehydrated and had @entity12 and a reduced level of consciousness. His laboratory tests showed that he had @entity8 and severe @entity13 . CONCLUSION: An ileostomy puts @entity0 at high risk for output losses that can lead to dehydration and electrolyte abnormalities. The assessment of the losses through the stoma, especially the ileostomy, should be added to the recommendations issued by pharmacovigilance societies. The present clinical case illustrates the need for clinicians on surgical wards to carefully evaluate @entity0 before resuming @entity11 therapy and to provide appropriate information at discharge to @entity0 with @entity2 who have undergone ileostomy. Furthermore, this case report highlights the increasing need for more training of general physicians regarding both surgical and internal medicine problems that may arise in the post-operative course after major surgery in @entity0 with co-morbidities.

title: XXXX -associated @entity13 and temporary ileostomy: a case report.

answer: @entity11


abstract: INTRODUCTION: @entity13 is a well-known complication of the anti- @entity9 @entity14 agent @entity11 , especially in peculiar but not rare clinical conditions. Attempts to reduce the incidence of this adverse reaction have been enforced by national agencies over the years. The Italian Medicines Agency recently released a safety recommendation on prescribing the drug and with regard to the existence of several conditions that contraindicate drug continuation, such as dehydration, @entity3 , @entity7 , surgery or hyperosmolar contrast agent infusion, but the recommendation does not mention the increased risk related to stoma. The present case report is, to our knowledge, the first in the literature of @entity11 -associated @entity13 in a @entity0 with a recently created ileostomy and low anterior resection for @entity1 . CASE PRESENTATION: A 70-year-old Caucasian @entity0 who had undergone low anterior resection with total mesorectal excision and temporary loop ileostomy creation at our institution returned to our department 30 days later because of @entity4 , @entity5 , diffuse @entity6 and @entity10 of about 24 hours' duration. During his physical examination, the @entity0 appeared dehydrated and had @entity12 and a reduced level of consciousness. His laboratory tests showed that he had @entity8 and severe @entity13 . CONCLUSION: An ileostomy puts @entity0 at high risk for output losses that can lead to dehydration and electrolyte abnormalities. The assessment of the losses through the stoma, especially the ileostomy, should be added to the recommendations issued by pharmacovigilance societies. The present clinical case illustrates the need for clinicians on surgical wards to carefully evaluate @entity0 before resuming @entity11 therapy and to provide appropriate information at discharge to @entity0 with @entity2 who have undergone ileostomy. Furthermore, this case report highlights the increasing need for more training of general physicians regarding both surgical and internal medicine problems that may arise in the post-operative course after major surgery in @entity0 with co-morbidities.

title: @entity11 -associated XXXX and temporary ileostomy: a case report.

answer: @entity13


abstract: The Stannius bodies of @entity3 and @entity1 were ultrastructurally investigated after exposure of the fish to media of different osmolality and @entity0 content. In both species two structurally different secretory cell types are found. Type-1 cells predominate. They contain an extensive granular endoplasmic reticulum, some large Golgi areas, and secretory granules with a mean diameter of about 0.4 micron. These cells are activated by transfer of freshwater fish to seawater, but not by transfer to low- @entity0 seawater. Type-2 cells often contain cytoplasmic processes that penetrate between the type-1 cells and are ending on the basal lamina. In this contact area granule release takes place. Type-2 cells contain some strands of granular endoplasmic reticulum, several small Golgi areas, and secretory granules with a mean diameter between 0.15 and 0.20 micron. Type-2 cells are not activated after transfer of fish to seawater. In @entity3 seawater exposure leads to a reduction of type-2 cells. The differences between the reactions of both cell types to different media point to functional differences between their secretory products. Type-1 cells may produce @entity2 factor. It is concluded that type-2 cells are typical for freshwater fish or euryhaline fish spending part of their life cycle in freshwater. The proper function of these cells is unclear.

title: Evidence for two secretory cell types in the Stannius bodies of the teleosts @entity3 and XXXX .

answer: @entity1


abstract: The Stannius bodies of @entity3 and @entity1 were ultrastructurally investigated after exposure of the fish to media of different osmolality and @entity0 content. In both species two structurally different secretory cell types are found. Type-1 cells predominate. They contain an extensive granular endoplasmic reticulum, some large Golgi areas, and secretory granules with a mean diameter of about 0.4 micron. These cells are activated by transfer of freshwater fish to seawater, but not by transfer to low- @entity0 seawater. Type-2 cells often contain cytoplasmic processes that penetrate between the type-1 cells and are ending on the basal lamina. In this contact area granule release takes place. Type-2 cells contain some strands of granular endoplasmic reticulum, several small Golgi areas, and secretory granules with a mean diameter between 0.15 and 0.20 micron. Type-2 cells are not activated after transfer of fish to seawater. In @entity3 seawater exposure leads to a reduction of type-2 cells. The differences between the reactions of both cell types to different media point to functional differences between their secretory products. Type-1 cells may produce @entity2 factor. It is concluded that type-2 cells are typical for freshwater fish or euryhaline fish spending part of their life cycle in freshwater. The proper function of these cells is unclear.

title: Evidence for two secretory cell types in the Stannius bodies of the teleosts XXXX and @entity1 .

answer: @entity3


abstract: BACKGROUND: Maximum safe resection is the "gold standard" in surgical treatment of grade 2 @entity1 (G2Gs), aiming to achieve maximal survival benefit with minimal risk of functional deficit. OBJECTIVE: To investigate the attitude of @entity0 and experts towards more extensive surgery with a trade-off between neurological function and survival time. METHODS: Eight @entity0 and seven experts participated in semi-structured focus group interviews. RESULTS: Both @entity0 and experts accepted the premise of balancing neurological function versus longevity. Some @entity0 would accept an increased risk of permanent @entity2 in order to obtain a chance of increased survival. There was a significant variance in what constituted "quality of life" both between @entity0 and for the individual @entity0 over time. CONCLUSIONS: In important life-changing decisions there is no "one size fits all". We find that it is ethically acceptable to offer more extensive surgery than is possible within the concept of maximal safe surgery as a treatment option, when balancing the principles of beneficence, non-maleficience, autonomy and justice supports the decision. At the same time it must be remembered that even when the @entity0 have made a well-informed decision, some will regret it. In that situation it will be our job as healthcare professionals to support them and help carry some of this burden.

title: Primo non nocere or maximum survival in grade 2 XXXX ? A medical ethical question.

answer: @entity1


abstract: 1. Glomerular filtration rate and effective renal blood-flow were normal in a series of @entity0 with sickle cell @entity1 . Fractional creatinine excretion and fractional @entity3 excretion were increased. 2. During @entity5 administration there were significant falls in glomerular filtration rate, effective renal blood-flow, @entity2 clearance and @entity3 clearance in the @entity0 with sickle cell @entity1 ; fractional @entity3 excretion also fell markedly. In control subjects none of these variables changed after @entity5 . 3. Serum concentration of @entity3 rose markedly during @entity5 administration in sickle cell @entity1 , owing to both the decrease in glomerular filtration rate and the increase in fractional @entity3 reabsorption. 4. We conclude that @entity4 have an important role in maintaining a normal glomerular filtration rate and effective renal blood-flow in sickle cell @entity1 . The abnormal @entity3 handling in @entity0 with this disease remains to be elucidated.

title: The influence of XXXX on renal haemodynamics in sickle cell @entity1 .

answer: @entity5


abstract: 1. Glomerular filtration rate and effective renal blood-flow were normal in a series of @entity0 with sickle cell @entity1 . Fractional creatinine excretion and fractional @entity3 excretion were increased. 2. During @entity5 administration there were significant falls in glomerular filtration rate, effective renal blood-flow, @entity2 clearance and @entity3 clearance in the @entity0 with sickle cell @entity1 ; fractional @entity3 excretion also fell markedly. In control subjects none of these variables changed after @entity5 . 3. Serum concentration of @entity3 rose markedly during @entity5 administration in sickle cell @entity1 , owing to both the decrease in glomerular filtration rate and the increase in fractional @entity3 reabsorption. 4. We conclude that @entity4 have an important role in maintaining a normal glomerular filtration rate and effective renal blood-flow in sickle cell @entity1 . The abnormal @entity3 handling in @entity0 with this disease remains to be elucidated.

title: The influence of @entity5 on renal haemodynamics in sickle cell XXXX .

answer: @entity1


abstract: We treated six @entity0 with @entity4 . They were all refractory to conventional chemotherapy or at an advanced stage when diagnosed. @entity0 were four males and two females aged 1 to 7 years old, with a mean age of 3.7 years. Total @entity9 dose ranged from 60 mg/m2 to 720 mg/m2, with a median dose of 240 mg/m2, and a mean dose of 260 mg/m2. Of the six @entity0 , two were PR, three were @entity7 , and one was NC. Of three non-responses, two cases were clinically improved. Two cases had @entity1 but this improved within 3 weeks. It is said that @entity9 induces irreversible @entity1 , especially @entity8 . Our two cases had progressively decreased @entity5 clearance, though values of BUN and @entity5 were normal. @entity2 was mild, so there was no need to discontinue or modify the @entity9 chemotherapy schedules. Two hypo-magnesemia were found, both cases being asymptomatic. Transient @entity3 occurred in one @entity0 , and @entity6 were observed in almost all cases.

title: [Effect of cis-platinum in XXXX ].

answer: @entity4


abstract: BACKGROUND: Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. PURPOSE: To evaluate a standardized clinical approach for distance measurement between benign @entity5 and eloquent cortex in terms of the ability to predict pre- and postoperative @entity3 after intraoperative neuronavigation-assisted surgery. MATERIAL AND METHODS: A retrospective study of 34 @entity0 . The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each @entity0 was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the @entity1 margin and fMRI activity could serve as a predictor for @entity3 . RESULTS: An odds ratio of 0.89   mm(-1) (P   =   0.03) was found between the risk of preoperative @entity2 and the @entity1 -fMRI distance. An odds ratio of 0.82   mm(-1) (P   =   0.04) was found between the risk of additional postoperative @entity2 and the @entity1 -fMRI distance. The @entity1 was radically removed in 10 cases; five @entity0 experienced @entity4 ( @entity1 -fMRI distance <18   mm) and five did not ( @entity1 -fMRI distance >18   mm) (P   =   0.008). CONCLUSION: This study indicates that the distance measured between the @entity1 margin and fMRI activation could serve as a valuable predictor of @entity2 .

title: Presurgical functional magnetic resonance imaging in @entity0 with XXXX .

answer: @entity5


abstract: BACKGROUND: Clinical functional magnetic resonance imaging (fMRI) is still an upcoming diagnostic tool because it is time-consuming to perform the post-scan calculations and interpretations. A standardized and easily used method for the clinical assessment of fMRI scans could decrease the workload and make fMRI more attractive for clinical use. PURPOSE: To evaluate a standardized clinical approach for distance measurement between benign @entity5 and eloquent cortex in terms of the ability to predict pre- and postoperative @entity3 after intraoperative neuronavigation-assisted surgery. MATERIAL AND METHODS: A retrospective study of 34 @entity0 . The fMRI data were reanalyzed using a standardized distance measurement procedure combining data from both fMRI and three-dimensional T1 MRI scans. The pre- and postoperative neurological status of each @entity0 was obtained from hospital records. Data analysis was performed using logistic regression analysis to determine whether the distance measured between the @entity1 margin and fMRI activity could serve as a predictor for @entity3 . RESULTS: An odds ratio of 0.89   mm(-1) (P   =   0.03) was found between the risk of preoperative @entity2 and the @entity1 -fMRI distance. An odds ratio of 0.82   mm(-1) (P   =   0.04) was found between the risk of additional postoperative @entity2 and the @entity1 -fMRI distance. The @entity1 was radically removed in 10 cases; five @entity0 experienced @entity4 ( @entity1 -fMRI distance <18   mm) and five did not ( @entity1 -fMRI distance >18   mm) (P   =   0.008). CONCLUSION: This study indicates that the distance measured between the @entity1 margin and fMRI activation could serve as a valuable predictor of @entity2 .

title: Presurgical functional magnetic resonance imaging in XXXX with @entity5 .

answer: @entity0


abstract: Symptoms related to menstruation are reported in 140 Swiss @entity0 according to postmenarcheal and chronological age. @entity2 were present in 9-28% of the @entity0 , depending on postmenarcheal age (i.e. years after menarche) (2-30% depending on chronological age). Dysmenorrhoea occurred in 44-64% of the @entity0 according to postmenarcheal age (51-67% according to chronological age). Occasional severe dysmenorrhoea was the type most often reported, by 20-35% of the @entity0 . Large intra-individual and inter-individual variabilities in the occurrence and severity of dysmenorrhoea were observed. The frequency of dysmenorrhoea increased in the first three postmenarcheal years and decreased thereafter. The prevalence of @entity1 was low, 0-5%. The frequency of @entity1 during menstruation was 2-11% according to postmenarcheal age (2-19% by chronological age) which was low in comparison with other studies. Severe @entity1 was more often reported than mild @entity1 . Frequency of severe @entity1 decreased in higher age groups. Other reported symptoms related to menstruation were general discomfort in 1-10% of the @entity0 and premenstrual vaginal discharge in 10-22% according to postmenarcheal age (3-17% according to chronological age). Severe vaginal discharge was more frequent than mild discharge, 8-20% versus 0-3%. The frequency of vaginal discharge increased from the first to the fourth year after menarche.

title: Symptoms related to menstruation in adolescent Swiss XXXX : a longitudinal study.

answer: @entity0


abstract: OBJECTIVES: This study sought to estimate the 2-year life expectancy (2YLE) (estimated survival rate >50% at  2  years) in @entity0 with @entity1 ( @entity1 ) using the risk score based on predictors of all-cause mortality within 2 years. BACKGROUND: It has been reported that 2YLE is one of the important factors in the decision making of the revascularization strategy. However, little is known about the probability and the prognostic factors of a 2YLE. METHOD: This study was performed as a multicenter retrospective analysis. Between March 2004 and December 2011, 995 @entity1 @entity0 with follow-up period >730 days undergoing endovascular therapy (EVT) were identified and analyzed. RESULTS: Within 2 years, 412 @entity0 (41%) died, and a cardiovascular cause accounted for 47% of @entity3 . On multivariate analysis, the independent prognostic factors were age 65 to 79 years (odds ratio [OR]: 1.9), 80 years of age or older (OR: 3.7), body mass index (BMI) 18.0 to 19.9 kg/m(2) (OR: 1.5), BMI  <18.0 kg/m(2) (OR: 2.9), nonambulatory status (OR: 2.4), hemodialysis (OR: 2.1), @entity2 (OR: 1.6), @entity4 ( @entity4 ) of 40% to 49% (OR: 1.8), @entity4  <40% (OR: 2.6), Rutherford class 5 (OR: 1.9), and Rutherford class 6 (OR: 3.4). The 2-year survival rate in each risk score was calculated based on each OR (full score: 15 points). After that, 2YLE was estimated based on the survival rate in each risk score, the probability of a 2YLE of  >= 8 points indicated a  <50% probability of 2-year survival. CONCLUSIONS: The independent prognostic factors for the 2YLE were age, BMI, nonambulatory status, hemodialysis, @entity2 , @entity4 , and tissue loss. A 2YLE score of  >= 8 points indicated a  <50% probability of 2-year survival. This score seemed to be helpful for identifying @entity1 @entity0 with a poor prognosis.

title: Two-year life expectancy in @entity0 with  XXXX .

answer: @entity1


abstract: OBJECTIVES: This study sought to estimate the 2-year life expectancy (2YLE) (estimated survival rate >50% at  2  years) in @entity0 with @entity1 ( @entity1 ) using the risk score based on predictors of all-cause mortality within 2 years. BACKGROUND: It has been reported that 2YLE is one of the important factors in the decision making of the revascularization strategy. However, little is known about the probability and the prognostic factors of a 2YLE. METHOD: This study was performed as a multicenter retrospective analysis. Between March 2004 and December 2011, 995 @entity1 @entity0 with follow-up period >730 days undergoing endovascular therapy (EVT) were identified and analyzed. RESULTS: Within 2 years, 412 @entity0 (41%) died, and a cardiovascular cause accounted for 47% of @entity3 . On multivariate analysis, the independent prognostic factors were age 65 to 79 years (odds ratio [OR]: 1.9), 80 years of age or older (OR: 3.7), body mass index (BMI) 18.0 to 19.9 kg/m(2) (OR: 1.5), BMI  <18.0 kg/m(2) (OR: 2.9), nonambulatory status (OR: 2.4), hemodialysis (OR: 2.1), @entity2 (OR: 1.6), @entity4 ( @entity4 ) of 40% to 49% (OR: 1.8), @entity4  <40% (OR: 2.6), Rutherford class 5 (OR: 1.9), and Rutherford class 6 (OR: 3.4). The 2-year survival rate in each risk score was calculated based on each OR (full score: 15 points). After that, 2YLE was estimated based on the survival rate in each risk score, the probability of a 2YLE of  >= 8 points indicated a  <50% probability of 2-year survival. CONCLUSIONS: The independent prognostic factors for the 2YLE were age, BMI, nonambulatory status, hemodialysis, @entity2 , @entity4 , and tissue loss. A 2YLE score of  >= 8 points indicated a  <50% probability of 2-year survival. This score seemed to be helpful for identifying @entity1 @entity0 with a poor prognosis.

title: Two-year life expectancy in XXXX with  @entity1 .

answer: @entity0


abstract: Experiments were performed to determine whether serum concentrations of total @entity2 (TC) undergo cyclic changes during the estrous cycle of dairy heifers and to assess the relationship between serum concentrations of TC and ovarian @entity1 hormones. The effects of a hypercholesterolemic diet upon luteal @entity4 secretion also were determined. Experiment 1 involved five dairy heifers exhibiting normal estrous cycles. Serum concentrations of TC, @entity4 , @entity3 and @entity0 -17 beta were determined in blood samples collected throughout a complete estrous cycle. A transient decline in TC was observed during the luteal phase of all heifers beginning on d 2 and reached a nadir 6 d after estrus. Highest mean concentrations of TC occurred between d -2 and +2 (96.3 +/- 8.2 mg/dl), which were markedly higher (P less than .05) than the lowest mean concentrations (76.3 +/- 10.3 mg/dl) observed on d 6. Concentrations of serum TC were negatively correlated (r = -.40; P less than .01) with @entity4 between d 2 and 9. Serum TC was not correlated with @entity3 or @entity0 -17 beta. In Exp. 2, seven cycling Holstein heifers were fed a control diet for 70 d (Stage I), a diet containing 15% whole sunflower seed as a source of supplemental dietary lipid for 70 d (Stage II) and then the control diet for 70 d (Stage III). Diets were isocaloric and isonitrogenous. All heifers were synchronized with @entity5 after wk 5 in each of the three feeding stages.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Relationships among dietary lipid intake, serum XXXX and ovarian function in Holstein heifers.

answer: @entity2


abstract: BACKGROUND: @entity0 with chronic severe @entity3 (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these @entity0 due to major methodologic drawbacks, findings with low-dose @entity5 ( @entity6 ) are encouraging. However, larger and well-designed clinical trials are required to establish the beneficial role of @entity6 in CSA, and for the detection of the key characteristics of those who are going to respond to this drug.Methods/design: @entity0 will be recruited from the accessible @entity4 @entity0 lists of tertiary referral centers. All @entity0 will meet the stringent diagnostic criteria for CSA, including the requirement for the regular use of Global Initiative for @entity3 (GINA) Global Strategy for @entity3 Management and Prevention Step 5 medications (oral @entity1 and/or omalizumab). The experimental design of the proposed study will take the form of a double-blind parallel-randomized placebo-controlled trial consisting of a @entity2 , including run-in and run-out periods. @entity0 will be randomly allocated to receive either @entity6 or a matched placebo once a week as an add-on therapy to their existing medication after run-in. Physiological, laboratory and clinical assessments will be measured regularly throughout the study and compared with baseline assessments. DISCUSSION: We expect that @entity6 will reduce Step 5 medications dosage in @entity0 with CSA without compromising the overall disease control. Improvement in several indicators of @entity3 severity and control will be also investigated.Trial registration: ClinicalTrials.gov Identifier: NCT02124226 (assigned 25 April 2014).

title: Weekly low-dose XXXX for reduction of Global Initiative for @entity3 Step 5 treatment in severe refractory @entity3 : study protocol for a randomized controlled trial.

answer: @entity5


abstract: BACKGROUND: @entity0 with chronic severe @entity3 (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these @entity0 due to major methodologic drawbacks, findings with low-dose @entity5 ( @entity6 ) are encouraging. However, larger and well-designed clinical trials are required to establish the beneficial role of @entity6 in CSA, and for the detection of the key characteristics of those who are going to respond to this drug.Methods/design: @entity0 will be recruited from the accessible @entity4 @entity0 lists of tertiary referral centers. All @entity0 will meet the stringent diagnostic criteria for CSA, including the requirement for the regular use of Global Initiative for @entity3 (GINA) Global Strategy for @entity3 Management and Prevention Step 5 medications (oral @entity1 and/or omalizumab). The experimental design of the proposed study will take the form of a double-blind parallel-randomized placebo-controlled trial consisting of a @entity2 , including run-in and run-out periods. @entity0 will be randomly allocated to receive either @entity6 or a matched placebo once a week as an add-on therapy to their existing medication after run-in. Physiological, laboratory and clinical assessments will be measured regularly throughout the study and compared with baseline assessments. DISCUSSION: We expect that @entity6 will reduce Step 5 medications dosage in @entity0 with CSA without compromising the overall disease control. Improvement in several indicators of @entity3 severity and control will be also investigated.Trial registration: ClinicalTrials.gov Identifier: NCT02124226 (assigned 25 April 2014).

title: Weekly low-dose @entity5 for reduction of Global Initiative for XXXX Step 5 treatment in severe refractory @entity3 : study protocol for a randomized controlled trial.

answer: @entity3


abstract: BACKGROUND: @entity0 with chronic severe @entity3 (CSA) have a crippling disease and current available treatments are not satisfactory. Thus, management of CSA remains a major unmet need. Although the evidence from existing randomized controlled trials fails to support a definite role for immunomodulatory drugs in these @entity0 due to major methodologic drawbacks, findings with low-dose @entity5 ( @entity6 ) are encouraging. However, larger and well-designed clinical trials are required to establish the beneficial role of @entity6 in CSA, and for the detection of the key characteristics of those who are going to respond to this drug.Methods/design: @entity0 will be recruited from the accessible @entity4 @entity0 lists of tertiary referral centers. All @entity0 will meet the stringent diagnostic criteria for CSA, including the requirement for the regular use of Global Initiative for @entity3 (GINA) Global Strategy for @entity3 Management and Prevention Step 5 medications (oral @entity1 and/or omalizumab). The experimental design of the proposed study will take the form of a double-blind parallel-randomized placebo-controlled trial consisting of a @entity2 , including run-in and run-out periods. @entity0 will be randomly allocated to receive either @entity6 or a matched placebo once a week as an add-on therapy to their existing medication after run-in. Physiological, laboratory and clinical assessments will be measured regularly throughout the study and compared with baseline assessments. DISCUSSION: We expect that @entity6 will reduce Step 5 medications dosage in @entity0 with CSA without compromising the overall disease control. Improvement in several indicators of @entity3 severity and control will be also investigated.Trial registration: ClinicalTrials.gov Identifier: NCT02124226 (assigned 25 April 2014).

title: Weekly low-dose @entity5 for reduction of Global Initiative for @entity3 Step 5 treatment in severe refractory XXXX : study protocol for a randomized controlled trial.

answer: @entity3


abstract: The prevalence of @entity4 in Veterans Administration Hospitals has been well documented. Several methods have been proposed to assess nutritional status including prognostic nutritional index (PNI) and instant nutritional assessment (INA). A prospective study was done to evaluate the currently used nutritional assessments and determine their efficacy based on sensitivity and specificity in predicting surgical morbidity and mortality. Data on 46 @entity0 were evaluated for the multiparameter index of PNI, total lymphocyte count and serum albumin for INA, and @entity3 alone. In this analysis, intermediate and high risk PNI were combined as positive predictor of complications. Any abnormal value in INA was considered positive as was @entity3 of greater than 6% of usual body weight. Sensitivity and specificity of each assessment method were determined by 2 X 2 contingency table, and significance of observed differences between methods was determined by chi 2 analysis. There were no complications or @entity1 in @entity0 with less than 6% @entity3 . All three @entity0 with abnormal albumin and total lymphocyte count had complications as compared to only three of 32 @entity0 when both of these parameters were normal. The PNI was also able to predict complications with an increasing incidence as the PNI increased. Only the difference between specificity of @entity3 alone vs INA was statistically significant, p less than 0.05. Thus, @entity3 alone can be used as a rapid, inexpensive assessment of nutritional status for predicting @entity2 .

title: The value of nutritional assessment in the surgical XXXX .

answer: @entity0


abstract: UNASSIGNED: Obesity has reached epidemic proportions worldwide. This condition, and its related diseases such as @entity0 and @entity3 , have become major public health challenges. Fruits are important dietary components, and bioactive constituents from fruits are considered to be a promising source for developing effective and safe anti- @entity1 drugs. Garcinia mangostana Linn. (Clusiaceae) is a tropical evergreen tree, and its fruit, mangosteen, is called 'Queen of Fruit'. The pericarp of G. mangostana has been used for centuries in Southeast Asia as a medicinal agent for treatment of @entity4 . Products derived from mangosteen are widely consumed to ameliorate @entity5 and resultant @entity5 . However, the chemical principles and mechanisms underlying these effects are unclear. This review summarizes the recent chemical and pharmacological studies related to G. mangostana, including weight reduction, anti-adipogenesis, anti- @entity2 and anti-oxidation activity. The aim of this review is to shed light on the role of G. mangostana and its constituents in preventing and treating @entity1 , which should encourage more interest in the development of relevant therapeutic methods.

title: New insights into the anti- XXXX activity of xanthones from Garcinia mangostana.

answer: @entity1


abstract: UNASSIGNED: This study aims to determine the incidence of @entity4 and @entity3 after @entity1 . Records of all @entity0 treated for traumatic @entity5 or microhyphema admitted to a district hospital throughout a 10-year period were retrospectively reviewed. @entity0 with @entity2 were excluded. The following clinical features were recorded during @entity0 ' initial presentation and follow-up visits: Snellen visual acuity, examination with slit-lamp biomicroscopy, intraocular pressure (IOP), dilated fundoscopic examination, gonioscopic examination and treatment. For @entity0 with IOP  >  21  mmHg and requiring @entity3 medications, visual field tests were performed. A total of 97 @entity0 met the study criteria, of which 62 had microhyphema and 35 had gross @entity5 . Among the @entity1 @entity0 , 47 (75.8  %) had @entity4 and 4 (6.5  %) had @entity3 with mean follow-up of 49  months (range 6-98  months). A statistically significant association was found between @entity4 greater than 180   and the occurrence of @entity3 (p  <  0.01). No statistically significant differences were found between groups of @entity0 with microhyphema or gross @entity5 regarding the incidence of @entity4 and @entity3 . The complications of @entity4 and @entity3 in @entity0 after @entity1 appear similar to those found in @entity0 after gross @entity5 .

title: Angle-recession glaucoma: long-term clinical outcomes over a 10-year period in XXXX .

answer: @entity1


abstract: OBJECTIVE: This preliminary study aims to verify the effectiveness of the additional information provided by spectral computed tomography (CT) with the proposed @entity2 ( @entity2 ) @entity8 ( @entity3 ) from mucinous @entity1 of @entity7 . MATERIALS AND METHODS: This study was conducted from January 2010 to October 2013. Twenty-three @entity0 (5 @entity0 and 18 @entity0 ; mean age, 43.96 years old) with SOA and 19 @entity0 (3 @entity0 and 16 @entity0 ; mean age, 41.74 years old) with MCN were included in this retrospective study. Two types of features were collected by dual-energy spectral CT imaging as follows: conventional and additional quantitative spectral CT features. Classification results of the @entity2 scheme were compared using the conventional features and full feature data set. Important features were selected using support vector machine classification method combined with feature-selection technique. The optimal cutoff values of selected features were determined through receiver-operating characteristic curve analyses. RESULTS: Combining conventional features with additional spectral CT features improved the overall accuracy from 88.37% to 93.02%. The selected features of the proposed @entity2 scheme were @entity1 size, contour, location, and low-energy CT values (43 keV). @entity6 -water basis material pair densities in both arterial phase (AP) and portal venous phase (PP) were important factors for differential diagnosis of SOA and MCN. The optimal cutoff values of @entity5 , @entity4 , 40 keV monochromatic CT value in AP, @entity6 (water) density in AP, 43 keV monochromatic CT value in PP, and @entity6 (water) density in PP were 3.4 mm, 3.1 mm, 35.7 Hu, 0.32533 mg/mL, 39.4 Hu, and 0.348 mg/mL, respectively. CONCLUSION: The combination of conventional features and additional information provided by dual-energy spectral CT shows a high accuracy in the @entity2 scheme. The quantitative information of spectral CT may prove useful in the diagnosis and classification of @entity3 and MCNs with machine learning algorithms.

title: Computer-Aided Diagnosis for Distinguishing Pancreatic Mucinous Cystic Neoplasms From XXXX in Spectral CT Images.

answer: @entity3


abstract: Age-related changes in the intake of food and water, and the output of faeces and urine were investigated in C57BL/Icrfat @entity0 of 6 and 24 months of age. Animals were singly housed in a metabolic cage for a period of 30 days. 14 days were allowed for acclimatization before the animals were dehydrated for 24 hours. 10 days of rehydration were allowed prior to a hyperosmotic challenge with 3% @entity4 in the drinking water. The animals were then observed for 5 more days of rehydration. Urine was collected and analysed with regard to @entity3 , @entity1 , @entity2 and vasopressin output/24 hours (/100g body weight), and the osmotic pressure of the urine was determined. Data were analysed by a 2 factor analysis of variance with repeated measures on one factor. Significant changes were detected in the control of body weight, @entity1 , @entity3 and @entity2 outputs. No age-differences were detected in the intake of food or water, the output of faeces or urine, the urine osmotic pressure or the excretion of vasopressin. However, significant changes in these variables were detected in both age groups on the days of physiological challenge. The conclusion drawn is that in the @entity0 studied, and for the period of the lifespan investigated, there is no age related defect in the secretion of vasopressin. However, there are trends in the data suggesting a decreased responsiveness of the kidney with age.

title: The effect of age on the control of water conservation in the laboratory XXXX --metabolic studies.

answer: @entity0


abstract: BACKGROUND: @entity3 is a @entity4 characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is @entity1 ( @entity1 ), which is caused by @entity1 and decreased bone formation. The @entity7 ( @entity7 ) is a pro-inflammatory protein and chemokine that stimulates osteoclasts in @entity1 . However, little is known about the effect of @entity7 on osteoblasts (OB). METHODS: The OBs are induced from @entity0 with @entity1 and healthy donors, cultured in vitro, and identified by histochemistry. The effects of @entity7 and @entity7 antibody on the OBs in vitro are observed. The @entity7 receptor ( @entity9 ), @entity8 ( @entity8 ), @entity5 ( @entity5 ), and @entity6 ( @entity6 ) are detected using flow cytometry, enzyme-linked immunosorbent assay, and real-time PCR. RESULTS: Proliferation and osteogenic potential of the OB in @entity0 with @entity1 are suppressed. Moreover, the @entity9 expression is significantly higher in @entity0 with @entity1 than in normal controls. The @entity8 level, quantity of @entity2 nodules, and @entity5 and @entity6 levels decrease after @entity7 stimulation, which indicates that @entity7 inhibits OB function. Furthermore, @entity7 antibody partially restores OB activity through the upregulation of the @entity8 , @entity5 , and @entity6 . CONCLUSIONS: @entity7 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in @entity1 .

title: Osteoblast inhibition by chemokine cytokine ligand3 in XXXX -induced @entity1 .

answer: @entity3


abstract: BACKGROUND: @entity3 is a @entity4 characterized by the accumulation of monoclonal plasma cells in the bone marrow. A common manifestation of the disease is @entity1 ( @entity1 ), which is caused by @entity1 and decreased bone formation. The @entity7 ( @entity7 ) is a pro-inflammatory protein and chemokine that stimulates osteoclasts in @entity1 . However, little is known about the effect of @entity7 on osteoblasts (OB). METHODS: The OBs are induced from @entity0 with @entity1 and healthy donors, cultured in vitro, and identified by histochemistry. The effects of @entity7 and @entity7 antibody on the OBs in vitro are observed. The @entity7 receptor ( @entity9 ), @entity8 ( @entity8 ), @entity5 ( @entity5 ), and @entity6 ( @entity6 ) are detected using flow cytometry, enzyme-linked immunosorbent assay, and real-time PCR. RESULTS: Proliferation and osteogenic potential of the OB in @entity0 with @entity1 are suppressed. Moreover, the @entity9 expression is significantly higher in @entity0 with @entity1 than in normal controls. The @entity8 level, quantity of @entity2 nodules, and @entity5 and @entity6 levels decrease after @entity7 stimulation, which indicates that @entity7 inhibits OB function. Furthermore, @entity7 antibody partially restores OB activity through the upregulation of the @entity8 , @entity5 , and @entity6 . CONCLUSIONS: @entity7 contributes to the OB/OC imbalance by inhibiting OB differentiation and function in @entity1 .

title: Osteoblast inhibition by chemokine cytokine ligand3 in @entity3 -induced XXXX .

answer: @entity1


abstract: We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFkB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic @entity2 (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary @entity3 /9 (scAAV2/9) delivery in the adult @entity0 cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, @entity3 /9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFkB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the @entity4 marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or @entity1 models. However, further improvements are required to enhance viral particles penetration into the brain.

title: Intracisternal delivery of NFkB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic XXXX treatment.

answer: @entity2


abstract: @entity2 ( @entity2 ) is an @entity1 leading to the loss inter alia of @entity4 positive medium spiny projection neurons ("MSNs") in the striatum. There is no known cure for @entity2 but the relative specificity of cell loss early in the disease has made cell replacement by neural transplantation an attractive therapeutic possibility. Transplantation of @entity0 fetal striatal precursor cells has shown "proof-of-principle" in clinical trials; however, the practical and ethical difficulties associated with sourcing fetal tissues have stimulated the need to identify alternative source(s) of donor cells that are more readily available and more suitable for standardization. We now have available the first generation of protocols to generate @entity4 positive @entity3 -like neurons from pluripotent stem cells and these have been successfully grafted into animal models of @entity2 . However, whether these grafts can provide stable functional recovery to the level that can regularly be achieved with primary fetal striatal grafts remains to be demonstrated. Of particular concern, primary fetal striatal grafts are not homogenous; they contain not only the @entity3 subpopulation of striatal projection neurons but also include all the different cell types that make up the mature striatum, such as the multiple populations of striatal interneurons and striatal glia, and which certainly contribute to normal striatal function. By contrast, present protocols for pluripotent stem cell differentiation are almost entirely targeted at specifying just neurons of an @entity3 lineage. So far, evidence for the functionality and integration of stem-cell derived grafts is correspondingly limited. Indeed, consideration of the features of full striatal reconstruction that is achieved with primary fetal striatal grafts suggests that optimal success of the next generations of stem cell-derived replacement therapy in @entity2 will require that graft protocols be developed to allow inclusion of multiple striatal cell types, such as interneurons and/or glia. Almost certainly, therefore, more sophisticated differentiation protocols will be necessary, over and above replacement of a specific population of MSNs. A rational solution to this technical challenge requires that we re-address the underlying question-what constitutes a functional striatal graft?

title: Differentiation of pluripotent stem cells into striatal projection neurons: a pure XXXX fate may not be sufficient.

answer: @entity3


abstract: Neuropsychological and neuroimaging studies have shown that facial recognition and emotional expressions are dissociable. However, it is unknown if a single system supports the processing of emotional and non-emotional facial expressions. We aimed to understand if individuals with impairment in face recognition from birth ( @entity2 , @entity1 ) can use non-emotional facial expressions to recognize a face as an already seen one, and thus, process this facial dimension independently from features (which are impaired in @entity1 ), and basic emotional expressions. To this end, we carried out a behavioral study in which we compared the performance of 6 @entity1 individuals to that of typical development individuals, using upright and inverted faces. Four avatar faces with a neutral expression were presented in the initial phase. The target faces presented in the recognition phase, in which a recognition task was requested (2AFC paradigm), could be identical (neutral) to those of the initial phase or present biologically plausible changes to features, non-emotional expressions, or emotional expressions. After this task, a second task was performed, in which the @entity0 had to detect whether or not the recognized face exactly matched the study face or showed any difference. The results confirmed the CPs' impairment in the configural processing of the invariant aspects of the face, but also showed a spared configural processing of non-emotional facial expression ( @entity4 ). Interestingly and unlike the non-emotional expressions, the configural processing of emotional expressions was compromised in CPs and did not improve their change detection ability ( @entity3 ). These new results have theoretical implications for face perception models since they suggest that, at least in CPs, non-emotional expressions are processed configurally, can be dissociated from other facial dimensions, and may serve as a compensatory strategy to achieve face recognition.

title: Behavioral dissociation between emotional and non-emotional facial expressions in XXXX .

answer: @entity2


abstract: This study was designed to evaluate airway dysfunction in relation to duration of disease in @entity0 with @entity8 for less than two years. Twenty four subjects with @entity2 were compared with nine subjects with disease of more than two years' duration. They underwent lung function testing (lung volumes, lung transfer factor for CO and pulmonary mechanics). Small airway function was assessed using frequency dependence of compliance, closing volume, @entity7 single breath test and flow-volume curves breathing air and helium- @entity1 mixture. @entity4 was seen in @entity8 even in some @entity0 with @entity2 and it became more evident in disease of longer duration. The results suggest small airway involvement. The frequency of airway dysfunction is difficult to evaluate, varying from estimates of 0% using flow-volume curves to 79% with frequency dependence of compliance. This apparent discrepancy could be explained by the consequences of parenchymal involvement leading to inhomogeneities in distribution of compliance, and of elastic lung recoil. We conclude that @entity0 with recent @entity3 are probably affected by @entity6 , but an increase in elastic recoil often conceals its consequences. The @entity5 may not be apparent using conventional function tests and published predicted values.

title: Respiratory function in recent XXXX with special reference to small airways.

answer: @entity8


abstract: @entity1 plays an essential role in plants' growth and development and in their response to various abiotic and biotic stresses despite its leachability and its very low abundance in the only form that plant roots can uptake ( @entity0 ). It is part of @entity3 , @entity4 ( @entity5 ), @entity2 of proteins and peptides, membrane sulfolipids, cell walls and secondary products, so reduced availability can drastically alter plant growth and development. The nutritional benefits of symbiotic interactions can help the plant in case of @entity7 . In particular the arbuscular mycorrhizal (AM) interaction improves N, P, and S plant nutrition, but the mechanisms behind these exchanges are not fully known yet. Although the transcriptional changes in the leguminous model plant @entity6 have been already assessed in several biotic and/or abiotic conditions, @entity7 has not been considered so far. The aim of this work is to get a first overview on S-deficiency responses in the leaf and root tissues of plants interacting with the AM fungus @entity8 . Several hundred genes displayed significantly different transcript accumulation levels. Annotation and GO ID association were used to identify biological processes and molecular functions affected by @entity1 starvation. Beside the beneficial effects of AM interaction, plants were greatly affected by the nutritional status, showing various differences in their transcriptomic footprints. Several pathways in which S plays an important role appeared to be differentially affected according to mycorrhizal status, with a generally reduced responsiveness to @entity7 in mycorrhized plants.

title: Transcriptional responses of @entity6 upon XXXX deficiency stress and arbuscular mycorrhizal symbiosis.

answer: @entity1


abstract: @entity1 plays an essential role in plants' growth and development and in their response to various abiotic and biotic stresses despite its leachability and its very low abundance in the only form that plant roots can uptake ( @entity0 ). It is part of @entity3 , @entity4 ( @entity5 ), @entity2 of proteins and peptides, membrane sulfolipids, cell walls and secondary products, so reduced availability can drastically alter plant growth and development. The nutritional benefits of symbiotic interactions can help the plant in case of @entity7 . In particular the arbuscular mycorrhizal (AM) interaction improves N, P, and S plant nutrition, but the mechanisms behind these exchanges are not fully known yet. Although the transcriptional changes in the leguminous model plant @entity6 have been already assessed in several biotic and/or abiotic conditions, @entity7 has not been considered so far. The aim of this work is to get a first overview on S-deficiency responses in the leaf and root tissues of plants interacting with the AM fungus @entity8 . Several hundred genes displayed significantly different transcript accumulation levels. Annotation and GO ID association were used to identify biological processes and molecular functions affected by @entity1 starvation. Beside the beneficial effects of AM interaction, plants were greatly affected by the nutritional status, showing various differences in their transcriptomic footprints. Several pathways in which S plays an important role appeared to be differentially affected according to mycorrhizal status, with a generally reduced responsiveness to @entity7 in mycorrhized plants.

title: Transcriptional responses of XXXX upon @entity1 deficiency stress and arbuscular mycorrhizal symbiosis.

answer: @entity6


abstract: BACKGROUND: @entity8 ( @entity8 ) is an independent risk factor for @entity1 , such as @entity4 and @entity5 . However, the mechanisms underlying this pro-oxidative effect of @entity3 ( @entity9 ) in hepatocytes remain largely unknown. Thus, we investigated the effect of @entity9 on the gene expression of @entity11 ( @entity11 ), the primary rate-limiting enzyme in heme catabolism and a key anti-oxidant detoxification enzyme in maintaining cellular redox homeostasis. METHODS: In vivo, twenty male C57BL/6 @entity0 at 8  weeks of age were randomly divided into two groups. One group was fed a chow diet (chow group; n   =   10), the other group of @entity0 was fed a @entity6 -supplemented diet (Met group, 1  mg  kg(-1)  day(-1)  @entity6 in drinking water; n   =   10) for 4  weeks. In vitro, HepG2 cells were stimulated with different doses of @entity3 ( @entity9 ). RESULTS: Four weeks' @entity6 supplementation caused a significant increase of plasma @entity9 concentration and a decrease of @entity11 expression in the liver of C57BL/6 @entity0 than @entity0 received chow diet. Besides, SOD enzyme activities were impaired and the level of oxidative stress markers, such as @entity2 ( @entity7 ) were elevated in the liver from @entity0 supplemented with @entity6 compared with control @entity0 . In cultured hepatocytes, @entity9 treatment reduced both the mRNA and protein levels of @entity11 dose-dependently. However, @entity9 had no effect on the gene expression of @entity10 , the major transcriptional regulator of @entity11 . Instead, @entity9 induced the expression of @entity12 , a transcriptional repressor of @entity11 . In addition, @entity9 stimulated the nuclear localization of @entity12 but prevented that of @entity10 . Furthermore, we found that knockdown of @entity12 attenuated the suppression of the @entity11 expression by @entity9 . CONCLUSIONS: Collectively, our results demonstrated that @entity12 plays an important role in @entity9 -triggered ROS generations through inhibiting @entity11 expression, likely, resulting from the disturbed interplay between @entity12 and @entity10 .

title: XXXX downregulates gene expression of @entity11 in hepatocytes.

answer: @entity3


abstract: BACKGROUND: @entity8 ( @entity8 ) is an independent risk factor for @entity1 , such as @entity4 and @entity5 . However, the mechanisms underlying this pro-oxidative effect of @entity3 ( @entity9 ) in hepatocytes remain largely unknown. Thus, we investigated the effect of @entity9 on the gene expression of @entity11 ( @entity11 ), the primary rate-limiting enzyme in heme catabolism and a key anti-oxidant detoxification enzyme in maintaining cellular redox homeostasis. METHODS: In vivo, twenty male C57BL/6 @entity0 at 8  weeks of age were randomly divided into two groups. One group was fed a chow diet (chow group; n   =   10), the other group of @entity0 was fed a @entity6 -supplemented diet (Met group, 1  mg  kg(-1)  day(-1)  @entity6 in drinking water; n   =   10) for 4  weeks. In vitro, HepG2 cells were stimulated with different doses of @entity3 ( @entity9 ). RESULTS: Four weeks' @entity6 supplementation caused a significant increase of plasma @entity9 concentration and a decrease of @entity11 expression in the liver of C57BL/6 @entity0 than @entity0 received chow diet. Besides, SOD enzyme activities were impaired and the level of oxidative stress markers, such as @entity2 ( @entity7 ) were elevated in the liver from @entity0 supplemented with @entity6 compared with control @entity0 . In cultured hepatocytes, @entity9 treatment reduced both the mRNA and protein levels of @entity11 dose-dependently. However, @entity9 had no effect on the gene expression of @entity10 , the major transcriptional regulator of @entity11 . Instead, @entity9 induced the expression of @entity12 , a transcriptional repressor of @entity11 . In addition, @entity9 stimulated the nuclear localization of @entity12 but prevented that of @entity10 . Furthermore, we found that knockdown of @entity12 attenuated the suppression of the @entity11 expression by @entity9 . CONCLUSIONS: Collectively, our results demonstrated that @entity12 plays an important role in @entity9 -triggered ROS generations through inhibiting @entity11 expression, likely, resulting from the disturbed interplay between @entity12 and @entity10 .

title: @entity3 downregulates gene expression of XXXX in hepatocytes.

answer: @entity11


abstract: The pathophysiology of reflexes mediated by the fifth and seventh @entity1 has been studied in 16 @entity0 with @entity5 and oromandibular @entity3 compared with normal age-matched subjects. The EMG activity of the @entity4 in the periocular and jaw muscles was similar to that described in other muscles in @entity0 with generalized @entity6 . The latency of the R1 and R2 components of the blink reflex and of the corneal reflex was normal. However, the amplitude and the duration of the R1 and R2 and the duration of the corneal reflex were increased. In some @entity0 the R1 component was also present on the side contralateral to the stimulus, while in normal subjects it was present only on the ipsilateral side. The excitability cycle of recovery of the R2 component of the blink reflex after a prior conditioning shock was enhanced in the @entity0 . There were no EEG potentials preceding @entity5 in the @entity0 , although a Bereitschaftspotential was seen beginning some 500 ms prior to @entity2 in the same individuals. Exteroceptive suppression in the contracting masseter and orbicularis oculi muscles was absent in 40 to 50 per cent of the @entity0 . The jaw jerk was present in all the @entity0 with normal latency. These results indicate that the neuronal arcs of the facial reflexes in @entity5 and oromandibular @entity3 are normal. However, there is an abnormal excitatory drive, perhaps from the basal ganglia, to the facial motoneurons and the interneurons which mediate the facial reflexes in the brainstem.

title: Pathophysiology of XXXX and oromandibular @entity3 .

answer: @entity5


abstract: The pathophysiology of reflexes mediated by the fifth and seventh @entity1 has been studied in 16 @entity0 with @entity5 and oromandibular @entity3 compared with normal age-matched subjects. The EMG activity of the @entity4 in the periocular and jaw muscles was similar to that described in other muscles in @entity0 with generalized @entity6 . The latency of the R1 and R2 components of the blink reflex and of the corneal reflex was normal. However, the amplitude and the duration of the R1 and R2 and the duration of the corneal reflex were increased. In some @entity0 the R1 component was also present on the side contralateral to the stimulus, while in normal subjects it was present only on the ipsilateral side. The excitability cycle of recovery of the R2 component of the blink reflex after a prior conditioning shock was enhanced in the @entity0 . There were no EEG potentials preceding @entity5 in the @entity0 , although a Bereitschaftspotential was seen beginning some 500 ms prior to @entity2 in the same individuals. Exteroceptive suppression in the contracting masseter and orbicularis oculi muscles was absent in 40 to 50 per cent of the @entity0 . The jaw jerk was present in all the @entity0 with normal latency. These results indicate that the neuronal arcs of the facial reflexes in @entity5 and oromandibular @entity3 are normal. However, there is an abnormal excitatory drive, perhaps from the basal ganglia, to the facial motoneurons and the interneurons which mediate the facial reflexes in the brainstem.

title: Pathophysiology of @entity5 and oromandibular XXXX .

answer: @entity3


abstract: The temporal contrast sensitivity function and temporal frequency discrimination have been studied in normals and in 7 cases of @entity1 or @entity3 . Sinusoidal gratings of two spatial frequencies (0.2 and 2.0 cycles/deg) were used. The abnormalities demonstrated in the @entity0 varied between individuals but overall a picture has emerged of four @entity2 . The temporal transfer function of the 2 cycles/deg medium spatial frequency grating has a band-pass appearance, whereas it is low-pass in normal subjects (5 out of 8 eyes). The peak of temporal frequency discrimination function (i.e. the temporal frequency at which discrimination is most acute) occurs at a lower temporal frequency in the @entity0 than in normal subjects particularly at the higher spatial frequency (5 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). It was found that normal subjects were able to discriminate between the maximum temporal frequency used as a standard in the discrimination experiments (16 Hz) and a higher temporal frequency. In the @entity0 , however, a cut-off in the discrimination function occurred at a temporal frequency well below this (8 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). Further to the above result, in a number of @entity0 an attempt was made to ascertain how the gratings were perceived in this abnormally extensive region of ambiguity in the high temporal frequency range. It was found that high temporal frequencies, at a constant contrast level above threshold and constant apparent contrast, were perceived either as flickering at a slower rate than did an intermediate temporal frequency or even appeared stationary. This effect was rare at the lower spatial frequency (1 out of 8 eyes) but was demonstrated in 4 out of 8 eyes at the spatial frequency of 2.0 cycles/deg. It was not specifically sought in all individuals. These results are discussed in the context of an information channelling model of temporal frequency processing in the visual system.

title: Temporal frequency discrimination in @entity3 and XXXX .

answer: @entity1


abstract: The temporal contrast sensitivity function and temporal frequency discrimination have been studied in normals and in 7 cases of @entity1 or @entity3 . Sinusoidal gratings of two spatial frequencies (0.2 and 2.0 cycles/deg) were used. The abnormalities demonstrated in the @entity0 varied between individuals but overall a picture has emerged of four @entity2 . The temporal transfer function of the 2 cycles/deg medium spatial frequency grating has a band-pass appearance, whereas it is low-pass in normal subjects (5 out of 8 eyes). The peak of temporal frequency discrimination function (i.e. the temporal frequency at which discrimination is most acute) occurs at a lower temporal frequency in the @entity0 than in normal subjects particularly at the higher spatial frequency (5 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). It was found that normal subjects were able to discriminate between the maximum temporal frequency used as a standard in the discrimination experiments (16 Hz) and a higher temporal frequency. In the @entity0 , however, a cut-off in the discrimination function occurred at a temporal frequency well below this (8 out of 8 eyes for a spatial frequency of 2.0 cycles/deg; 2 out of 8 eyes for a spatial frequency of 0.2 cycles/deg). Further to the above result, in a number of @entity0 an attempt was made to ascertain how the gratings were perceived in this abnormally extensive region of ambiguity in the high temporal frequency range. It was found that high temporal frequencies, at a constant contrast level above threshold and constant apparent contrast, were perceived either as flickering at a slower rate than did an intermediate temporal frequency or even appeared stationary. This effect was rare at the lower spatial frequency (1 out of 8 eyes) but was demonstrated in 4 out of 8 eyes at the spatial frequency of 2.0 cycles/deg. It was not specifically sought in all individuals. These results are discussed in the context of an information channelling model of temporal frequency processing in the visual system.

title: Temporal frequency discrimination in XXXX and @entity1 .

answer: @entity3


abstract: Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a @entity1 (DA)-denervated caudate nucleus can reverse a number of the @entity0 induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of @entity2 (K+) from DA-depleted, SN transplant-reinnervated striatum. Animals were injected unilaterally with @entity3 ( @entity3 ) into the SN and screened by measuring @entity4 -induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. @entity7 -coated @entity6 epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from @entity5 or acidic DA metabolites. The GEC electrode was fixed to a K+-filled micropipette and this assembly was used to map the caudate nucleus of control, @entity3 -treated, and @entity3 -treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Monoamine release from XXXX -depleted rat caudate nucleus reinnervated by substantia nigra transplants: an in vivo electrochemical study.

answer: @entity1


abstract: Preclinical compounds tested in animal models often show limited efficacy when transitioned into @entity0 clinical trials. As a result, many @entity0 are stratified into treatment regimens that have little impact on their disease. In order to create preclinical models that can more accurately predict @entity1 responses, we established @entity0 -derived xenograft (PDX) models of @entity2 ( @entity2 ). Surgically resected @entity1 specimens from @entity2 @entity0 were implanted subcutaneously into athymic @entity3 . Following successful establishment, fourteen models underwent further evaluation to determine whether these models exhibit heterogeneity, both at the cellular and genetic level. Histological review revealed properties not found in @entity2 cell lines, most notably in overall architecture (predominantly columnar epithelium with evidence of gland formation) and the presence of mucin-producing cells. Custom @entity2 gene panels identified somatic driver mutations in each model, and therapeutic efficacy studies in @entity1 -bearing @entity3 were designed to determine how models with known mutations respond to PI3K, @entity4 , or MAPK inhibitors. Interestingly, MAPK pathway inhibition drove @entity1 responses across most models tested. Noteworthy, the MAPK inhibitor @entity6 alone did not significantly mediate @entity1 response in the context of a KRAS( @entity5 ) model, and improved @entity1 responses resulted when combined with @entity4 inhibition. As a result, these genetically diverse models represent a valuable resource for preclinical efficacy and drug discovery studies.

title: Establishment of genetically diverse @entity0 -derived xenografts of XXXX .

answer: @entity2


abstract: Preclinical compounds tested in animal models often show limited efficacy when transitioned into @entity0 clinical trials. As a result, many @entity0 are stratified into treatment regimens that have little impact on their disease. In order to create preclinical models that can more accurately predict @entity1 responses, we established @entity0 -derived xenograft (PDX) models of @entity2 ( @entity2 ). Surgically resected @entity1 specimens from @entity2 @entity0 were implanted subcutaneously into athymic @entity3 . Following successful establishment, fourteen models underwent further evaluation to determine whether these models exhibit heterogeneity, both at the cellular and genetic level. Histological review revealed properties not found in @entity2 cell lines, most notably in overall architecture (predominantly columnar epithelium with evidence of gland formation) and the presence of mucin-producing cells. Custom @entity2 gene panels identified somatic driver mutations in each model, and therapeutic efficacy studies in @entity1 -bearing @entity3 were designed to determine how models with known mutations respond to PI3K, @entity4 , or MAPK inhibitors. Interestingly, MAPK pathway inhibition drove @entity1 responses across most models tested. Noteworthy, the MAPK inhibitor @entity6 alone did not significantly mediate @entity1 response in the context of a KRAS( @entity5 ) model, and improved @entity1 responses resulted when combined with @entity4 inhibition. As a result, these genetically diverse models represent a valuable resource for preclinical efficacy and drug discovery studies.

title: Establishment of genetically diverse XXXX -derived xenografts of @entity2 .

answer: @entity0


abstract: Constipation has many definitions and is often described differently depending on the population queried. Many physicians define @entity5 as a reduction in the frequency of bowel movements to fewer than three times per week while @entity0 identify more with the symptoms associated with @entity5 such as difficulty passing stool, hard stool consistency, feelings of abdominal cramping, and feelings of incomplete stool passage. Causes of @entity5 may be primary (idiopathic) or secondary to other factors such as diet, medication, or medical conditions. Constipation can affect anyone as a minor annoyance but up to a quarter of the population experiences it chronically or severely. It can substantially affect quality of life and be debilitating. It is estimated that between 2% to 27% of the population are affected depending upon the definition of @entity5 used. Chronic @entity5 is a significant problem in the elderly,, in @entity0 with chronic conditions,    and in @entity0 receiving opioids as part of a treatment regimen.    Up to 20% suffer from chronic @entity5 in the community-dwelling elderly population while this number increases to approximately 50% to 75% in institutionalized elderly @entity0 . Approximately 90% of @entity0 treated with opioids for non- @entity1 suffer from @entity5 with this number rising to 95% in @entity0 treated for @entity1 . Chronic @entity5 can be defined using any one of three options: the Rome III criteria for functional @entity5 , the American College of Gastroenterology definition, or the American Gastroenterological Association definition. Current treatment options include dietary or bulking agents (i.e. psyllium seed husk), osmotic laxatives (i.e. @entity8 , @entity6 , @entity3 [ @entity4 ]), stimulant laxatives (i.e. @entity7 , @entity9 , @entity11 ), and stool softeners (i.e. @entity10 or @entity2 )., In North America, docusate and a stimulant laxative such as @entity7 are commonly used in bowel treatment protocols associated with institutionalized elderly and oncology treatments. A paucity of evidence is available to support the use of the stool softener docusate yet it continues to be prescribed in everyday clinical practice for the aforementioned populations.    While the actual cost of docusate is low, additional costs associated with its administration (i.e. nursing time) and its widespread use can be significant. Therefore, this review was undertaken to determine the clinical effectiveness of docusate for the prevention or management of @entity5 .

title: @entity10 or @entity10 ( XXXX or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness

answer: @entity2


abstract: Constipation has many definitions and is often described differently depending on the population queried. Many physicians define @entity5 as a reduction in the frequency of bowel movements to fewer than three times per week while @entity0 identify more with the symptoms associated with @entity5 such as difficulty passing stool, hard stool consistency, feelings of abdominal cramping, and feelings of incomplete stool passage. Causes of @entity5 may be primary (idiopathic) or secondary to other factors such as diet, medication, or medical conditions. Constipation can affect anyone as a minor annoyance but up to a quarter of the population experiences it chronically or severely. It can substantially affect quality of life and be debilitating. It is estimated that between 2% to 27% of the population are affected depending upon the definition of @entity5 used. Chronic @entity5 is a significant problem in the elderly,, in @entity0 with chronic conditions,    and in @entity0 receiving opioids as part of a treatment regimen.    Up to 20% suffer from chronic @entity5 in the community-dwelling elderly population while this number increases to approximately 50% to 75% in institutionalized elderly @entity0 . Approximately 90% of @entity0 treated with opioids for non- @entity1 suffer from @entity5 with this number rising to 95% in @entity0 treated for @entity1 . Chronic @entity5 can be defined using any one of three options: the Rome III criteria for functional @entity5 , the American College of Gastroenterology definition, or the American Gastroenterological Association definition. Current treatment options include dietary or bulking agents (i.e. psyllium seed husk), osmotic laxatives (i.e. @entity8 , @entity6 , @entity3 [ @entity4 ]), stimulant laxatives (i.e. @entity7 , @entity9 , @entity11 ), and stool softeners (i.e. @entity10 or @entity2 )., In North America, docusate and a stimulant laxative such as @entity7 are commonly used in bowel treatment protocols associated with institutionalized elderly and oncology treatments. A paucity of evidence is available to support the use of the stool softener docusate yet it continues to be prescribed in everyday clinical practice for the aforementioned populations.    While the actual cost of docusate is low, additional costs associated with its administration (i.e. nursing time) and its widespread use can be significant. Therefore, this review was undertaken to determine the clinical effectiveness of docusate for the prevention or management of @entity5 .

title: XXXX or @entity10 ( @entity2 or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness

answer: @entity10


abstract: Constipation has many definitions and is often described differently depending on the population queried. Many physicians define @entity5 as a reduction in the frequency of bowel movements to fewer than three times per week while @entity0 identify more with the symptoms associated with @entity5 such as difficulty passing stool, hard stool consistency, feelings of abdominal cramping, and feelings of incomplete stool passage. Causes of @entity5 may be primary (idiopathic) or secondary to other factors such as diet, medication, or medical conditions. Constipation can affect anyone as a minor annoyance but up to a quarter of the population experiences it chronically or severely. It can substantially affect quality of life and be debilitating. It is estimated that between 2% to 27% of the population are affected depending upon the definition of @entity5 used. Chronic @entity5 is a significant problem in the elderly,, in @entity0 with chronic conditions,    and in @entity0 receiving opioids as part of a treatment regimen.    Up to 20% suffer from chronic @entity5 in the community-dwelling elderly population while this number increases to approximately 50% to 75% in institutionalized elderly @entity0 . Approximately 90% of @entity0 treated with opioids for non- @entity1 suffer from @entity5 with this number rising to 95% in @entity0 treated for @entity1 . Chronic @entity5 can be defined using any one of three options: the Rome III criteria for functional @entity5 , the American College of Gastroenterology definition, or the American Gastroenterological Association definition. Current treatment options include dietary or bulking agents (i.e. psyllium seed husk), osmotic laxatives (i.e. @entity8 , @entity6 , @entity3 [ @entity4 ]), stimulant laxatives (i.e. @entity7 , @entity9 , @entity11 ), and stool softeners (i.e. @entity10 or @entity2 )., In North America, docusate and a stimulant laxative such as @entity7 are commonly used in bowel treatment protocols associated with institutionalized elderly and oncology treatments. A paucity of evidence is available to support the use of the stool softener docusate yet it continues to be prescribed in everyday clinical practice for the aforementioned populations.    While the actual cost of docusate is low, additional costs associated with its administration (i.e. nursing time) and its widespread use can be significant. Therefore, this review was undertaken to determine the clinical effectiveness of docusate for the prevention or management of @entity5 .

title: @entity10 or XXXX ( @entity2 or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness

answer: @entity10


abstract: Early reperfusion after a @entity4 may reduce @entity1 size, but late reperfusion into necrotic myocardium may alter post- @entity3 healing. In @entity0 , we compared 1- or 3-week-old scars resulting from permanent @entity4 to those resulting from a 1- or 3-hour occlusion followed by reperfusion. Reperfusion at 1 hour post-occlusion did not affect scar mechanical properties assessed at 1 week post- @entity3 , but at 3 weeks post- @entity3 , these scars had a tensile strength significantly lower than those not reperfused (78 +/- 11 vs. 158 +/- 15 g/mm2, P less than 0.001). They also were composed of a mixture of fibrous tissue (58 +/- 8%) and myocytes (43 +/- 8%) with a @entity2 content of 23 +/- 2.5 mg/g dry weight. The nonreperfused scars had a higher proportion of fibrous tissue (73 +/- 3%) by histological evaluation and a 35% higher @entity2 content (31 +/- 2 mg/g dry weight, P less than 0.001) than the scars reperfused after 1 hour. In contrast, 3-week-old scars resulting from "late" reperfusion at 3 hours post-occlusion were similar to nonreperfused scars in fibrous tissue composition and @entity2 content. Nonetheless, the tensile strength of these scars reperfused 3 hours post-occlusion was significantly less than that of the nonreperfused scars (72 +/- 5 vs. 158 +/- 15 g/mm2, P less than 0.001). The lower tensile strength was associated with a lower collagen cross-link density in this reperfused group of scars. At physiological stress levels (approximately 3 g/mm2), all groups of reperfused and nonreperfused scars had similar mechanical properties in terms of natural strain, stiffness, creep, and stress relaxation. Thus, although the reperfused scars ruptured more easily at high stresses, when assessed at physiological stresses their mechanical properties were not significantly different from those of nonreperfused scars.

title: Effects of reperfusion after coronary artery occlusion on post- XXXX scar tissue.

answer: @entity3


abstract: Eighteen volunteers with a mean age of 63.3 years, who were asymptomatic and without significant @entity1 , were investigated with standard electrophysiological tests, performed before and after inhibition of autonomous neural tone with @entity2 (0.1 mg . kg-1) and @entity6 (0.02 mg . kg-1). In addition heart rate responses to maximal exercise, carotid sinus pressure and bolus injection of @entity4 (0.01 microgram . kg-1) were studied to evaluate the relation between different functional qualities of the cardiac conduction system. Autonomous tone inhibition (ATI) caused significant reductions in the mean PP-interval, sinus code recovery time (SNRT) and corrected sinus node recovery time (CSNRT). Furthermore, the precision of CSNRT determinations increased after ATI. In contrast, the AV-node effective refractory period and conduction time ( @entity5 ) did not change after ATI. A significant correlation existed between CSNRT and heart rate after ATI, both variables reflecting sinus node @entity7 , while no covariation was found between CSNRT and the response to @entity4 stimulation. AV-node refractoriness and conduction time showed covariation after, but not before, autonomous inhibition. As elderly asymptomatic non- @entity0 were examined the use of the presented group characteristics as reference values for diagnostic investigations is suggested. For example pre-drug CSNRT above 545 ms (mean + 2 SD) or above 505 ms after ATI, indicates @entity3 .

title: Autonomous influence on sinus node and AV node function in the elderly without significant XXXX : assessment with electrophysiological and autonomic tests.

answer: @entity1