Integrating epidemiologic modeling and explainable machine learning to predict and identify factors associated with self-reported depression among adults in Tennessee, United States.

Skeletal muscle is fundamental for performing a wide range of activities, ranging from those associated with sport (i.e., running, jumping) to those required for daily living (i.e., breathing, postural stability). Exercise is a potent stimulus for improving skeletal muscle health, and therefore overall health. Indeed, skeletal muscle is regarded for possessing a remarkable capacity to adapt to exercise stimuli. However, strenuous exercise can result in ultrastructural damage to skeletal muscle (Hyldahl and Hubal ; Mackey and Kjaer , ). This phenomenon is often referred to as exercise-induced muscle damage (EIMD) and is characterized by a variety of symptoms including impaired contractile function (Goodall and Howatson ; Brown et al. ; Mackey et al. ; Neltner et al. ), soreness (Cheung et al. ; Byrne et al. ; Neltner et al. ), and inflammation (Howatson and van Someren ; Peake et al. ). These symptoms can negatively affect exercise performance and in some cases impede activities of daily living (Dannecker and Koltyn ). While a majority of research into the mechanisms of EIMD have largely focused on damage to the muscle fibers (Mackey and Kjaer ; Mackey et al. ), an often overlooked component of skeletal muscle is the extracellular matrix (ECM) in which muscle fibers are embedded (Csapo et al. ). The ECM is comprised of a network of collagens, glycoproteins and polysaccharide molecules creating a complex meshwork that encase the muscle fibers (Thorsteinsdóttir et al. ; Takala and Virtanen ). This scaffolding is crucial in providing structural integrity to muscle and transmitting forces throughout the muscle to facilitate whole-muscle contraction and movement (Mackey et al. ; Hyldahl and Hubal ; Gillies and Lieber ). In addition to its role as a structural scaffold, the ECM also orchestrates complex interactions between the many cell types that reside within skeletal muscle (i.e., satellite cells, immune cells, endothelial cells) and govern muscle adaptation to exercise (Thorsteinsdóttir et al. ; Daley et al. ; Rozario and DeSimone ). Furthermore, remodeling of the skeletal muscle ECM has also been demonstrated as a vital process underlying muscle hypertrophy (Fry et al. ; Hyldahl et al. ), supporting the role of the ECM in muscle health. Previous research has demonstrated damage to the skeletal muscle ECM in response to strenuous exercise, particularly eccentric exercise (Mackey et al. ; Miller et al. ; Hody et al. ; Brown et al. ; Neltner et al. ), highlighting its susceptibility to EIMD. Given the many important functions of the skeletal muscle ECM, disruption to this structure is believed to play an important role in mediating the symptoms associated with EIMD (Mackey et al. ). Following strenuous exercise, symptoms associated with EIMD can persist from days to weeks, as skeletal muscle undergoes repair and regeneration (Dupuy et al. ; Brown et al. ). It is understood that repair of the ECM following EIMD is largely regulated by collagen synthesis (Moore et al. ). The remodeling of skeletal muscle ECM is often observed through increased circulating levels of collagen-specific amino acids, such as hydroxyproline (HYP), which may indicate collagen breakdown (Brown et al. ; Tofas et al. ; Neltner et al. ), and procollagen 1 N-terminal peptide (P1NP), which reflects the synthesis of type-1 collagen (Kehlet et al. ; Shaw et al. ; Lee et al. ). Impairments to the repair and remodeling of the ECM may lead to structural changes that compromise not only contractile function but may potentially contribute to musculoskeletal injuries (Damas et al. ; Krentz and Farthing ; Mackey et al. ). Thus, avenues to enhance the remodeling of the ECM following damaging exercise may expedite muscle recovery and augment subsequent adaptation to exercise.