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The phrase "a major difference was" is correct and usable in written English.
It can be used when discussing or comparing two or more subjects, highlighting a significant distinction between them.
Example: "In the study, a major difference was observed in the results between the two groups, indicating varying levels of effectiveness."
Alternatives: "a significant difference was" or "a key difference was".
Exact(26)
She said that she had worked with terminal cancer patients and that a major difference was that AIDS commonly affected younger men at an age when many were not prepared to face disability, decline and death.
A major difference was that beetles, especially T. castaneum, were captured far less frequently in traps away from storage in India than in Australia, a pattern that needs to be confirmed before a biological basis for it is sought.
For both exposed and infected macrophages, a major difference was found between 1 and 4 h along PC1, which highlights genes that were highly induced or repressed at 4 h in these subpopulations (clusters 1 and 4, respectively; Fig. 2b, d).
A major difference was the lack of vowel and syllable duration cues in the beginning learners' production.
A major difference was the presence of one more methyl group [δ H 2.55 (3H, s), δ C 24.2] at C-1 in 1, which was confirmed by the significant HMBC correlations from H-17 (δ H 2.55) to C-1 (δ C 157.8) and C-2 (δ C 122.0) (Fig. 3), as well as the obvious triplet signal of H-1 in 10 was disappeared in 1.
A major difference was the promotion of various game settings beyond that of traditional fantasy.
Similar(34)
The area where Mr. Eddington is expected to make a major difference is with the morale of employees.
A major difference is that reflexology locates these pressure or reflex points only in the hands and feet.
So to say that it's major concern, or that it's going to make a major difference, is not necessarily the view we take at this point".
A major difference is that birds don't really have tails, or if they do, they're fairly naff, feathery things.
A major difference is that the Senate would continue the $70 million taxpayer subsidy of the Tennessee Valley Authority, which the House would end.
More suggestions(2)
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Since I tried Ludwig back in 2017, I have been constantly using it in both editing and translation. Ever since, I suggest it to my translators at ProSciEditing.

Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com