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The American Academy of Family Physicians and NIH identify the following clinical manifestations: Fatigue and generalized weakness Megaloblastic anemia (abnormally large, immature red blood cells) Tingling or numbness in the hands and feet (peripheral neuropathy) Difficulty walking and balance problems Cognitive disturbances including memory difficulty and confusion Mood changes, including depression and irritability Glossitis (swollen, inflamed tongue) Early symptoms such as fatigue and mild tingling are often attributed to stress, aging, or other conditions

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Different from the old analysis, we used a simplified reference tissue model (see the section Methods), which does not rely on arterial input function, an approach that is potentially beneficial for eliminating another source of variability (i.e., measurement errors in arterial input function) in the kinetic modeling of PET data [84]

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