The answer is more like 22 from 45. In such a case do you always make it a negative number?

Adding a negative number is the same as subtracting a positive number:

22 + (-45) = 22 - 45 = -23

Another way to think of it is to factor out a -1:

22 - 45 = -1*(45 - 22) = -1(23) = -23

A third way to think of it:

45 = 22 + 23, so

22 - 45 = 22 - (22+23) = (22-22)-23 = 0-23 = -23

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