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Unlike the original freeware version which runs at 50 frames per second (FPS), Cave Story+ runs at 60 FPS, which causes some minor differences in the game's physics. In a 2010 interview with Destructoid, the game's creator Pixel had this to say about the game's frame rate differences:

"No matter what environment (PC), if it runs well on 60fps, then I will always choose 60fps, without a doubt.

However, at that time, there were lots of PC setups that weren’t 60 fps. There were environments that could set the refresh rate through the program, but there were other environments where you couldn’t. Most PC’s were at a refresh rate slightly higher than 60fps. When that happens, with a one to two second cycle, the periodical scroll of the screen shook erratically and this affected the game experience–which I didn’t like.

In the end, I made it 50 fps because there were no environments at 50 fps. Regardless what environment it’s run on there would be no adverse issues. It’s very important that the movement or motion is consistent no matter what the environment.

At first I had contemplated that it was a refresh rate problem. The environment is restricted, but when I saw how smoothly the game scrolled on 60 fps I thought there couldn’t be any other choice than 60 fps. There were several other people on the Internet who’ve had similar thoughts, but then I saw points like it’s more important to make a fun game than to fixate on the refresh rate. I remember at that time feeling like I finally reached a solution."
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By feeding Quote Ma Pignon in Curly Story, it will trigger his only line in the game: "Curly! It's me, Quote!"
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In the Steam, Wii, and DSi versions, Quote switches outfits based on difficulty settings and during holidays such as Christmas.
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When using the Blade at Lv. 3, a ghostly image of King appears, holding his sword while slashing multiple times; it is most likely his brave spirit remained in the sword, fighting to no end to eventually kill the Doctor. This is proven in the description of the weapon in the Nicalis translation.
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If the Doctor is defeated and Quote manages to get back to the Plantation's passage, the four statues of the Demon Crown's owners will be replaced with four statues for the Island's heroes; Quote, Curly, King, and Toroko.
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After the battle with The Doctor and the Muscle Doctor, if the player speaks to Chako several times, she will mention how Quote is heroic like Arthur, which causes Hearts to appear above the other Mimigas' heads. This is the only way to replenish health before the Undead Core battle.
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It's possible to be hurt and even killed by Toroko while she's blindly attacking Quote in the Shack. In Cave Story+, if the player is killed by Toroko in this manner, they'll earn the Toroko Wins! achievement.
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On the official Cave Story 3D website and in the Cave Story DSiware guide, Quote is called "Mr. Traveler." This is a placeholder name to prevent his name being spoiled, derived from Chako calling him so, after defeating the Doctor in his human and demon form.
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An item called "Chaco's Rouge" ("Chako's Lipstick" in the Aeon Genesis translation) can be found when entering Chako's house. After examining her fireplace and then immediately sleeping in her bed, the item is added to the player's inventory. Chako will also be seen asleep on the bed and will awake if Quote reenters her house. The item has no use.
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In one room, called the Statue Chamber, are statues of all of the previous wearers of the Demon Crown, including the current wearer and antagonist of the game, The Doctor. However, if the player completes a series of complex tasks, they will eventually come back to this room after going through the Sacred Grounds and defeating the Heavy Brace boss. The statues are now destructible, and when destroyed, will appear as Quote (the player character), Toroko, King, and Curly Brace, the main characters of the game.
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Attachment In the original Cave Story, Cave Story +, and Cave Story 3D, there is an item called the Beast Fang that is impossible to obtain through normal means. It is obtainable through hacking, or abusing a glitch in Cave Story 3D.
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Jenka's theme was based on the Finnish folk song 'Letkajenkka'.
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In Grasstown, Santa will tell you that the only way forward is through Chacko's house. Chacko will not only help you by telling how to get through, but you'll also be able to sleep in her bed. This will give you her lipstick and a view of her sleeping in bed. The lipstick has no use.
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Attachment In the original PC version of Cave Story, Balrog used to make his appearance breaking through a wall and saying "Huzzah!". However, in the WiiWare and 3DS ports, that sentence was changed to "Oh Yeah!" to reference the Kool-Aid Man.
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During development, nearly all of the enemies were based on bars of soap. The design of these enemies were the basis for Balrog's design.
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The game took the one-man development team, Daisuke Amaya, five years to make.
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Right after the fight with Curly Brace, you can go into her room. In there, you can find a secret tunnel. At the end, you will find an item called "Curly's Underwear." This item is a joke item, as it has no use and cannot be removed from your inventory.

In the Plus versions of the game, finding this hidden item unlocks "Curly Story".
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Attachment There is a portrait image of Sue as a human within the game. This is never used, but it suggests that sometime during development, Sue, in her human form, had dialog.
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In late 2011, a .zip file was uploaded to the Doukutsu Uploader that contained all 19 versions of orgview made throughout Cave Story's development timeline. Dozens of different beta versions of songs that play in-game, including some unused ones in the final version, were part of the package.

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