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When an issue resolves in Safe Mode but persists after booting normally, the most likely cause is startup items. Safe Mode operates with a minimal set of drivers and services, which means that it disables all third-party startup items and extensions. This isolation allows users to identify if the problem is due to one of the applications or processes that load at startup when the system is running normally. Therefore, if the issue reoccurs after booting normally, it's probable that a startup item is conflicting or causing the issue since it is loaded only in the regular boot process.

The other options suggest different causes of issues. Hardware failure would not typically resolve in Safe Mode, as hardware problems tend to be consistent regardless of how the operating system boots. A corrupt operating system might manifest in both Safe Mode and normal boot but would not distinguish behavior between them. Finally, network settings would not usually be a factor related to Safe Mode; those settings can be adjusted regardless of the boot mode, and issues typically do not resolve based on how the system is started. Thus, startup items represent a selective cause that is uniquely related to the differences between Safe Mode and normal operation.