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Deputies responded to a fatal head-on crash east of Syracuse on Highway 2, near the Highway 50 interchange, just before 3:30 a.m. Sunday morning.
One of the deadly crashes happened Friday afternoon near Unadilla, while the second occurred very early Sunday morning near Syracuse.
Two people died in separate crashes that occurred within 48 hours in southeast Nebraska's Otoe County.
Two people were killed in separate Otoe County crashes on Friday and Sunday, according to the Otoe County Sheriff's Office.