Therapeutics

Artificial Intelligence (AI) and Precision Medicine are increasingly influencing pediatric pharmacotherapy, where age-dependent pharmacokinetic variability demands highly individualized therapeutic strategies. This review examines current applications of AI in pediatric precision medicine and evaluates their clinical relevance and translational challenges. Recent evidence shows substantial progress across multiple domains. In pharmacogenomics, predictive models have reached R² = 0.95 for drug exposure. Tools for adverse drug reaction detection report sensitivities of 81.5% and specificities of 79.5%. Clinical decision support systems for pediatric epilepsy have achieved diagnostic accuracies of 93.4%. Real-world implementations have been associated with a 75% reduction in prescription distribution errors and a 65% improvement in adverse drug reaction detection. Despite these advances, clinical translation remains limited: only 0.38% of pediatric AI models progress to testing in real patients, and 77% of published studies carry a high risk of bias. These gaps highlight the need for rigorous validation, improved data quality, and careful consideration of ethical and algorithmic constraints. Overall, AI has the potential to shift pediatric pharmacotherapy from empirically driven decisions toward predictive, precision-based approaches. Achieving this goal will require well-designed pediatric studies and sustained interdisciplinary collaboration to ensure safe and effective integration into clinical practice.

Background: The signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a secretory protein that plays a role in cancer, cardiovascular, and immune disorders. SCUBE1, SCUBE2, and SCUBE3 belong to the SCUBE family. They contain multiple copies of EGF-like repeats at the amino acid terminal, a spacer region, three cysteine-rich motifs, and a CUB domain at the carboxyl terminus. The SCUBE family members are multifunctional proteins that act primarily as extracellular ligands or co-receptors in various cells. Methods: In this study, we examined the expression pattern and role of SCUBE3 in various cancers, as well as other diseases such as cardiovascular disease and immune disorders, and its impact on growth and development. Results: SCUBE3 expression is upregulated and secreted by the cells of lung cancer, hepatocellular carcinoma (HCC), melanoma, osteosarcoma, ovarian cancer, glioma, and breast cancer. Extracellular SCUBE3 protein often binds to TGFβRII or acts as a co-receptor for TGFβ and BMP2/BMP4 in regulating cellular signaling. Through the TGFβRII signaling, SCUBE3 activities promote tumor growth, metastasis, invasion, angiogenesis, and poor clinical outcomes. Conversely, in renal cell carcinoma, SCUBE3 expression suppresses growth. Altered SCUBE3 activity is associated with cardiovascular diseases, immune disorders, and hair growth. Conclusions: The review presents mechanistic evidence that SCUBE3 plays a crucial regulatory role in multiple cancers and other diseases. The evidence suggests the SCUBE3 protein could serve as a potential molecular target for various diseases and highlights its usefulness as a minimally invasive diagnostic marker, as it is a secreted protein.

Background: Hyponatremia (serum sodium levels below 135 mEq/L) is the most prevalent electrolyte imbalance, with the syndrome of inappropriate antidiuresis (SIAD) being the most common cause among inpatients. Fluid restriction is the primary treatment for SIAD, yet its efficacy is inconsistent. A novel therapeutic approach involves the use of oral vaptans, such as tolvaptan (TLV), which are non-peptide antagonists of arginine vasopressin receptors. The recommended daily dose of TLV is 15 mg; however, the risk of overcorrection and osmotic demyelination syndrome must be considered. Methods: Consequently, a more cautious approach involving a 7.5 mg dose of TLV was studied in SIAD patients to determine its safety and efficacy compared with a 15 mg dose. Results: The findings of our investigation show that the results obtained from the two doses are highly similar. However, it is important to note that the risk of overcorrection was lower in the 7.5 mg TLV group than in the 15 mg group. Furthermore, a more gradual increase in serum Na was observed in the 7.5 mg group than in the 15 mg group after the most critical first 24 h. Conclusions: TLV therapy can be initiated with a 7.5 mg dose, with serum sodium levels monitored at 12 and 24 h to confirm or adjust the TLV dose as required.