Aromatase inhibitors anastrozole and letrozole (non-steroidal, reversible), and exemestane (steroidal, irreversible) are approved standard therapies (Food and Drug Administration) for hormone receptor-positive breast cancer. Their use is limited by Aromatase Inhibitor-induced Musculoskeletal Signs and Symptoms (AIMSS). Articles on AIMSS mechanisms and biomarkers published between January 1, 1990, and October 31, 2024, in PubMed, EMBASE, and Cochrane Library were identified. Included study designs were randomized and non-randomized trials, observational cohorts, cross-sectional studies, and preclinical animal models. Risk of bias was assessed using the Critical Appraisal Skills Programme tool for observational studies and Risk of Bias 2 for randomized trials. Fifty studies were included (43 human and seven animal). Estrogen deprivation was the central mechanism, affecting immune function, bone remodeling, and nociceptive sensitivity. Genetic variants in Estrogen Receptor 1, CYP19A1, and T-cell Leukemia/Lymphoma 1A were frequently associated with AIMSS. Vitamin D deficiency, polymorphisms in RANKL and Osteoprotegerin contributed to bone-related symptoms. Imaging studies identified tenosynovial thickening, tendon sheath fluid, and subclinical inflammation. Systemic inflammatory markers C-Reactive Protein and Interleukin 6 were elevated in human and animal studies. Transient Receptor Potential Ankyrin 1 and Transient Receptor Potential Vanilloid 4 ion channels were implicated in peripheral sensitization. Insulin-like Growth Factor 1 during AI therapy was independently associated with symptoms. AIMSS involves intersecting hormonal, genetic, inflammatory, and neural pathways. Identification of mechanistic biomarkers may support AIMSS risk stratification and targeted interventions. Further research should validate multi-omic models and explore new strategies to reduce AIMSS and improve treatment compliance. PROSPERO Registration: CRD42025642540.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with substantial mortality and limited prognostic granularity under current staging systems. Artificial intelligence (AI) has shown promise across oncology, but no synthesis has yet evaluated its application specifically to MCC across the clinical continuum, from detection to survival prediction. Methods: This systematic review followed PRISMA and Cochrane guidelines and was prospectively registered with PROSPERO. Four databases (PubMed, Embase, Scopus, and CENTRAL) were searched from inception through June 18, 2026. Eligible studies evaluated AI, machine learning, or computational models using human MCC data. Given anticipated heterogeneity in predictive targets and metrics, a narrative synthesis was performed. Results: Of 950 records identified, seven studies published between 2021 and 2026 met inclusion criteria. Four addressed prognosis or survival, two addressed diagnosis or early detection, and one addressed treatment‐receipt prediction. The best‐performing survival model achieved an AUROC of 0.89 (internal) and 0.81 (external validation), with a concordance index of 0.93. Other analyses suggested improved model fit or additional prognostic information beyond conventional AJCC staging, although direct comparisons of discrimination were not consistently available. A smartphone‐based diagnostic tool achieved an AUC of 0.80 for general malignant‐lesion triage, although sensitivity fell from 82.5% to 67.6% under a real‐world, STARD‐compliant worst‐case analysis; importantly, the cohort included only one MCC lesion, which both the CNN and teledermatology assessment classified as low risk, precluding meaningful MCC‐specific performance estimation. A blood‐based repertoire‐sequencing model reported near‐perfect discrimination but lacked independent MCC validation. Overall risk of bias was high, with the “analysis” domain most frequently downgraded; no study integrating multimodal data was identified. Conclusions: AI applications in MCC remain early stage but demonstrate meaningful potential to refine prognostic stratification beyond conventional staging, although MCC‐specific diagnostic evidence remains severely limited. Broader external validation and multimodal data integration represent the field’s most pressing needs before clinical translation is warranted.

Male infertility has been viewed as a potential biomarker for systemic health and a predictor of future disease. With the global burden of neurodegenerative diseases (NDDs) on the rise, the current systematic review aims to synthesize the reported associations, risks, and shared molecular mechanisms between male infertility and NDDs. Following PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Scopus, and Cochrane CENTRAL in January 2026. Studies examining the relationship between male infertility and NDDs were included. Screening and data extraction were performed by two independent reviewers with a third to resolve conflicts while quality appraisal (ROBINS-E and OHAT) was performed for all included studies. Studies used heterogeneous definitions of male infertility, including clinical diagnosis, semen parameters, and reproductive outcomes. Of the 1566 identified studies, 13 were included in this review including case-control studies, experimental investigations, in vitro studies, bioinformatic analyses, and pedigree studies. The available literature suggests possible mechanistic overlap between male infertility and neurodegenerative disease pathways, particularly in mitochondrial dysfunction, oxidative stress, and proteostasis. However, the evidence remains heterogeneous and preliminary, and large prospective studies are needed before male infertility assessment can be considered a marker of neurodegenerative risk. Registration: The study protocol was registered on PROSPERO (registration code: CRD420261301509).