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"with significant differences" is correct and usable in written English.
You can use it when you want to emphasize that two or more things have major differences. For example, you could say, "The two approaches to problem-solving have a lot in common, but they also differ in several ways, with significant differences."
Exact(60)
Both aimed at the center of the political spectrum, but with significant differences.
It's a state-operated program with significant differences from state to state".
The House and Senate did manage to pass bills authorizing the aid, but with significant differences.
The war also became increasingly "feminized" in the popular literature of both regions, albeit with significant differences.
On Monday, the two houses issued separate packages of five bills each to address the voting changes, with significant differences.
Since then, critics argue, chaos has resulted, with significant differences across the country in the ways that the statute is interpreted.
Like "The Eye of the Elephant," this book is about their experience in Zambia, and covers much of the same time period, but with significant differences.
The similarities coexist with significant differences, however.
Asterisks indicate comparisons with significant differences.
The families with significant differences among fertilization regimes are presented in Fig. 1.
Most strikingly, percolation phenomena occur for multi-component mixtures with significant differences in mobility.
More suggestions(15)
with noticeable differences
with appreciable differences
with remarkable differences
with noteworthy differences
with substantial differences
with considerable differences
with tremendous differences
with large differences
with significance differences
with important differences
with significant assets
with insignificant differences
with significant savings
with significant efforts
with minor differences
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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