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Patients typically present with bilateral and symmetrical enlargement of the legs, with a clear demarcation at the ankles commonly referred to as the cuffing sign while the feet and hands remain unaffected

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Other factors, including host immune response, viral genotype, and environmental influences, likely play crucial roles in determining disease outcomes

The central biological clock is more directly regulated by light and melatonin, and its redox rhythm may be less dependent on oxidase and antioxidant enzymes compared with the peripheral biological clock

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