TASK DEFINITION: Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.
PROBLEM: Evidence for an association between phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) and schizophrenia was recently obtained and replicated in several samples. PIP5K2A controls the function of KCNQ channels via phosphatidylinositol-4,5-bisphosphate (PIP2) synthesis. Interestingly, recent data suggest that KCNQ channels suppress basal activity of dopaminergic neurons and dopaminergic firing. Activation of KCNQ accordingly attenuates the central stimulating effects of dopamine, cocaine, methylphenidate, and phenylcyclidine.', 'The aim of this study was to explore the functional relevance of PIP5K2A, which might influence schizophrenic behavior.', 'Here, we study the effects of the neuronal PIP5K2A on KCNQ2, KCNQ5, KCNQ2/KCNQ3, and KCNQ3/KCNQ5 in the Xenopus expression system.', 'We find that wild-type PIP5K2A but not the schizophrenia-associated mutant (N251S)-PIP5K2A activates heteromeric KCNQ2/KCNQ3 and KCNQ3/KCNQ5, the molecular correlate of neuronal M channels. Homomeric KCNQ2 and KCNQ5 channels were not activated by the kinase indicating that the presence of KCNQ3 in the channel complex is required for the kinase-mediated effects. Acute application of PI(4,5)P2 and a PIP2 scavenger indicates that the mutation N251S renders the kinase PIP5K2A inactive.

SOLUTION: 1

PROBLEM: The evidence on the prognostic value of transthoracic echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary Embolism (PE) is limited.', 'To evaluate the prevalence of common echocardiographic signs of right ventricular (RV) dysfunction and their prognostic impact in hemodynamically stable patients aged 65years with acute PE in a prospective multicenter cohort.', 'TTE was performed by cardiologists. We defined RV dysfunction as a RV/left ventricular ratio >0.9 or RV hypokinesis (primary definition) or the presence of 1 or 2 of 6 predefined echocardiographic signs (secondary definitions). Outcomes were overall mortality and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30days, adjusting for the Pulmonary Embolism Severity Index risk score and highly sensitive troponin T values.', 'Of 400 patients, 36% had RV dysfunction based on our primary definition, and 81% (1 sign) and 53% (2 signs) based on our secondary definitions, respectively. Using our primary definition, there was no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI 0.31-2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40-2.98). Similarly, there was no statistically significant association between the presence of 1 or 2 echocardiographic signs (secondary definitions) and clinical outcomes.

SOLUTION: 1

PROBLEM: The canals of Hering (CoH), which are the most peripherally located bile drainage pathway, are considered a niche of hepatic progenitor cells. Recently, CoH loss has been described as an early feature of primary biliary cirrhosis (PBC). We investigated the correlation between CoH loss and the histopathological variables of PBC.', 'Liver biopsy specimens from 62 PBC patients (M:F=8:54, age=58 12 years) were evaluated prior to ursodeoxycholic acid treatment. Liver biopsies of patients with normal liver (n=11), chronic viral hepatitis (n=36) and non-alcoholic fatty liver disease (n=13) were used as controls. The number of CoH per definite area of hepatic parenchyma (c to p ratio) was calculated in individual cases. We compared the c to p ratios of PBC patients with that of controls and analysed the correlations with histological variables and clinical features.', 'The c to p ratios in PBC patients with mild and extensive fibrosis were lower than those in controls with each degree of fibrosis. The c to p ratios were negatively correlated with stage, fibrosis, bile duct loss, orcein-positive granule deposition and hepatitis activities in PBC (p<0.01) and with alkaline phosphatase and total bilirubin levels at liver biopsies (p<0.05).

SOLUTION:
1