Yes, you can work with multiple App studio documents at the same time, i.e. while uploading one issue and creating or modify another one. When you click on the upload button in AppStudio Publishing palette, QuarkXPress saves a local file and upload it to the portal. While uploading the document to AppStudio portal, QuarkXPress has nothing to do with the open document, because it has already saved a local file, hence you can work with a project while uploading the same or another to AppStudio portal.