Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD–mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-β), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-β (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx. How secondary hyperparathyroidism (SHPT) affects muscle quality in CKD patients is unclear. This observational, prospective study performed muscle phenotyping by performance evaluation, body composition analysis, and muscle biopsies of 30 patients on dialysis with SHPT, before and after parathyroidectomy (PTx). The main findings include evidence of local tissue inflammation and blunting of muscle turnover in patients compared to healthy individuals. Despite no changes to muscle mass or energy expenditure, PTx improved functionality, bone mass, and influenced the molecular phenotyping of muscle tissue by altering the expression of bone-specific proteins and reducing inflammation. These findings suggest that SHPT plays a role in CKD-induced muscle dysfunction and that PTx has a beneficial effect on uremic myopathy.

Background/Objectives: Radiotherapy, radiobiology, and oncology have evolved rapidly over the past six decades. This progress has generated vast but fragmented bodies of scientific evidence. The present study aimed to systematically map and interpret their conceptual and temporal development using artificial intelligence (AI)-based methods. It highlights the integration between molecular mechanisms, clinical applications, and technological innovation within a precision radiotherapy framework. Methods: A corpus of 3343 unique articles (1964–2025) was retrieved from Scopus, PubMed, and Web of Science. Records were harmonized through deduplication, lemmatization, and metadata normalization. Topic modeling using Latent Dirichlet Allocation (LDA) and co-occurrence network analysis were applied to identify dominant research axes. Semantic and temporal analyses were conducted to reveal patterns, emerging trends, and translational connections across decades. Results: Three historical phases were identified. The first was a period of limited production (1964–1990). The second showed moderate growth (1991–2010). The third, from 2011 to 2024, represented exponential expansion, with publication peaks in 2020 and 2023. LDA revealed two principal axes. The first, a clinical–anatomical axis, focused on cancer sites, treatment modalities, and prognosis. The second, a mechanistic–molecular axis, centered on DNA repair, radiosensitivity, and biomarkers. Case synthesis from 2014–2025 defined five operational classes: DNA repair and molecular response; precision oncology and genomic modeling; individual radiosensitivity; mechanisms of radioresistance; and advanced technologies such as FLASH radiotherapy and optimized brachytherapy. Conclusions: AI-driven semantic and temporal analyses showed that radiotherapy has matured into an interconnected and interdisciplinary domain. The derived Precision Radiotherapy Implementation Plan translates molecular and computational insights into clinically actionable strategies. These approaches can enhance survival, reduce toxicity, and inform equitable health policies for advanced cancer care.