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: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies associated with mutations or copy number variations in over 70 genes encoding proteins with fundamental roles in the development and function of Schwann cells and peripheral axons. Here, we used iPSC-derived cells to identify common pathophysiological mechanisms in axonal CMT.', 'iPSC lines from patients with two distinct forms of axonal CMT (CMT2A and CMT2E) were differentiated into spinal cord motor neurons and used to study axonal structure and function and electrophysiological properties in vitro.', 'iPSC-derived motor neurons exhibited gene and protein expression, ultrastructural and electrophysiological features of mature primary spinal cord motor neurons. Cytoskeletal abnormalities were found in neurons from a CMT2E (NEFL) patient and corroborated by a mouse model of the same NEFL point mutation. Abnormalities in mitochondrial trafficking were found in neurons derived from this patient, but were only mildly present in neurons from a CMT2A (MFN2) patient. Novel electrophysiological abnormalities, including reduced action potential threshold and abnormal channel current properties were observed in motor neurons derived from both of these patients.

SOLUTION: 1

PROBLEM: Abnormalities of lung coagulation and fibrinolysis in sarcoidosis are thought to play a role in the pathogenesis of this disease.', 'We previously showed that bronchoalveolar lavage fluid (BALF) D dimer directly correlated with various measures of severity in sarcoidosis. Here, we analyze our observation that BALF D dimer was more frequently found at higher levels in African-American patients with pulmonary sarcoidosis.', 'BALF D dimer was measured in 55 subjects with pulmonary sarcoidosis and 31 healthy volunteers by enzyme immunoassay. The healthy group established a normal range of BALF D dimer with 71 ng/ml as the highest measured level. This was the cut point for comparisons among the patients with sarcoidosis.', 'High BALF D dimer levels (>71 ng/ml) were found in younger patients with sarcoidosis and were associated with a significantly lower percent predicted forced expiratory volume in 1 s and greater numbers of BAL lymphocytes. Black patients with sarcoidosis had higher BALF D dimer levels (median 131, range 0-2,040 ng/ml) than white patients (median 18, range 0-605 ng/ml; p = 0.011). Higher than normal BALF D dimer levels were found in 61% of the black subjects with sarcoidosis, but in only 20% of the white individuals (chi(2) = 5.539, p = 0.019). BALF D dimer was the only disease measure that discriminated black from white individuals with sarcoidosis.

SOLUTION: 1

PROBLEM: Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied.', 'We studied 136 patients (mean age 64+/-12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate).', 'Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5+/-2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P=.01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P=.004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model.

SOLUTION:
1