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Owners commonly notice one or more of the following: Limping or lameness: favoring a limb, "toe-touching," or intermittent limping that comes and goes Stiffness after rest: difficulty rising after sleeping, or a slow, stiff first few minutes that loosens with movement Reluctance to jump, climb, or use stairs: hesitating at the car, couch, or staircase they used to handle easily Reduced activity or stamina: shorter walks, less play, or lagging behind on familiar routes Audible joint changes: clicking or popping from a joint, particularly the stifle (knee) Muscle loss: visible thinning of the muscle on one hind limb compared with the other, a sign of chronic underuse Behavioral changes: licking a joint, irritability when a limb is handled, or a drop in overall mood tied to discomfort A sudden non-weight-bearing lameness the dog will not put any weight on a leg warrants prompt veterinary attention rather than watchful waiting, as it can indicate an acute cruciate rupture or fracture

Am J Transl Res 9(6):31383147 Gillies RJ, Robey I, Gatenby RA (2008) Causes and consequences of increased glucose metabolism of cancers

In IMR-5/75 cells, MYCN downregulation still maintains amplification-level expression, which may explain the modest effect on treatment sensitivity

10.1038/s41598-018-19213-4 128 SeibtT