This study aimed to investigate the association between the superoxide dismutase 2 (SOD2)-rs4880 polymorphism and age-related hearing loss (ARHL) in an Iranian population, assessing its impact on age, hearing loss severity, and SOD activity, alongside bioinformatics and molecular docking analyses with TOM20. This case-control study included 145 ARHL patients and 155healthy controls. Serum SOD activity was measured using a commercial kit and rs4880 genotyping was done via PCR-RFLP. Bioinformatics tools focusing on HADDOCK-2.4 were used to assess the interaction between SOD2 signal peptides and the TOM20 receptor. The TT genotype and T allele were associated with increased ARHL risk (OR =1.98, p = 0.032; OR = 1.48, p = 0.018), with a stronger effect in individuals older than 60 years. Serum SOD activity was significantly lower in patients (12.05 ± 2.04 U/ml) than controls (12.62 ± 2.04 U/ml, p = 0.017). Bioinformatics data revealed that the mutant variant exhibits 34% lower alpha-helix propensity compared to the wild-type. Docking results confirmed a weaker binding affinity for the mutant variant compared to the wild-type, suggesting inefficient recognition and recruitment by the mitochondrial import machinery. The SOD2-rs4880 polymorphism may disrupt mitochondrial import via TOM20 and can be considered a molecular risk factor for ARHL, especially in older age.

Urinary bladder cancer (UBC), the tenth most common globally with a male predominance, has its risk factors like smoking and single nucleotide polymorphisms (SNPs), yet the MYC gene's role, especially the rs9642880 GT/TT polymorphism on chromosome 8q24.21, in cancer susceptibility is underexplored. We searched in Medline, Scopus and Web of Science databases for relevant studies. Odds ratios (OR) with 95% confidence intervals (CIs) were computed using DerSimonian and Laird random-effect models. Heterogeneity was assessed using I2 statistics. Statistical analyses were performed using R, version 4.4.2. Data from 53,957 subjects was analyzed, including 8,002 UBC patients and 45,955 controls, with median age ranging from 44.5 to 68.7 years. We found significant association between the rs9642880 GT/TT polymorphism and increased UBC risk (OR 1.249, 95% CI 1.188-1.297, p < 0.001). This association was consistent across American (OR 1.43 95% CI 1.20-1.70), Asian (OR 1.25 95% CI 1.17-1.34), and Caucasian (OR 1.21 95% CI 1.13-1.29) ethnic groups, with low heterogeneity (I2 = 0%). Subgroup analyses by genotyping method and source of control further supported these results. This meta-analysis provides robust evidence that the T allele of the rs9642880 polymorphism in the MYC gene significantly increases susceptibility to UBC across Asian, American, and Caucasian populations.

Adamantinoma is a rare bone tumor characterized by a propensity for local recurrence and distant metastasis. Management of metastatic disease remains challenging owing to the absence of standardized therapy and the limited efficacy of conventional chemotherapy. This case report describes a young woman with adamantinoma harboring an XRCC2 frameshift mutation. She showed a sustained clinical response to fourth-line treatment with the PARP inhibitor olaparib, which lasted 15 months and led to improved performance status. Subsequent progression led to combination therapy with atezolizumab and bevacizumab, maintaining stable disease for eight months. Molecularly guided treatment resulted in an overall survival of 25 months.

Breast cancer (BC) is the world's most prevalent cancer and can affect almost any post-pubertal woman. Early detection is associated with improved survival, and most high-income countries have adopted population-based screening programs to enhance early detection and survival although significant differences in screening age, methodology, and frequency exist. BC is known to be a heritable disease, with a small percentage of women having pathogenic variants in moderate or high-risk genes. However, Polygenic Risk Scores (PRS) incorporate many low penetrance single nucleotide polymorphisms (SNPs) and are the most powerful tool to help stratify women based on their personalized BC risk. PRS are particularly useful if incorporated into established risk prediction models (RPM). Risk stratification using PRS-containing RPMs can guide eligibility for enhanced screening and prevention programmes. This review discusses the role PRS plays in personalized risk prediction screening and prevention approaches as some of the challenges to their use.

This study aims to validate the relevance of IL-17A rs8193036 polymorphisms in susceptibility to Alzheimer's disease. A total of 210healthy volunteers and 260 Alzheimer's disease patients were recruited. The genotype distribution of IL-17A rs8193036 was detected using the TaqMan-qPCR. The RT-qPCR was used to detect the expression of IL-17A in serum. The subjects of each genotype subgroup were statistically compared in terms of IL-17A expression and MMSE score. Logistic regression was used to analyze the independent risk factors for Alzheimer's disease. The CC genotypes of IL-17A rs8193036 showed a high distribution in Alzheimer's disease patients (χ2 = 8.115, OR = 1.879, 95% CI = 1.213-2.910, p = 0.004). The expression of IL-17A was higher, and the ROC curves showed the favorable diagnostic significance of IL-17A in Alzheimer's disease. The serum level of IL-17A was higher in Alzheimer's disease patients with the CC genotype than the TT and CT genotypes. MMSE score of the CC genotype patients was lower than TT and CT genotypes. Gender, Education, MMSE score, IL-17A expression, and rs8193036 CC genotypes were risk factors for Alzheimer's disease. The expression level of IL-17A is higher in Alzheimer's disease patients. The CC genotype of IL-17A rs8193036 is the causative genotype of Alzheimer's disease.

This study aimed to explore the Chinese public's experiences with, perceptions of, attitudes toward, and willingness to use genetic testing (GT) in the precision medicine era. A total of 4,208 individuals from 33 provinces in China were recruited to complete a self-administered questionnaire in December 2018. More than half of the respondents believed that GT does more good than harm, while only 5.8% believed that it does more harm than good. Nearly 60% of the respondents expressed willingness to use GT. Higher awareness of GT was correlated with more positive attitudes toward it and a greater willingness to use it. However, the general public had an uneven exposure and susceptibility to misinformation. More educated respondents demonstrated a better understanding of GT but remained vulnerable to the influence of misinformation. Additionally, younger generations tended to be more critical of GT but were more willing to use it than earlier generations. The study reveals a high level of acceptance of GT among the Chinese public, while also suggesting that educational and regulatory measures are needed to improve public understanding of GT and address their particular concerns regarding genetic testing and precision medicine.

Organoids are three-dimensional, self-organizing cell structures grown from human biospecimens that allow researchers to study development, disease, and drug responses. Organoid technology holds promise for precision medicine, as it can tailor therapies to specific individuals. Including diverse groups within organoid research is essential to collect representative data for the development of treatments for all populations and to reduce health disparities. Commercial parties are increasingly involved in organoid research. The involvement of such parties can negatively affect the ways in which underrepresented groups are included and recruited and can affect their willingness to donate their biospecimen. In this paper, we argue that commercial involvement in organoid research poses three problems that can hinder the equal representation of groups or the equitable access to treatments derived from organoid research. First, commercially driven organoid research presents challenges to the informed consent process. Second, commercial involvement can undermine trust among underrepresented groups and reduce their willingness to donate biospecimens. Third, benefit sharing becomes ethically more complex when profits are generated and underrepresented groups are involved. Therefore, researchers and commercial parties should actively address these challenges by (re)establishing trust, using transparent and inclusive communication, ensuring ongoing reciprocity, and uphold shared responsibility.

Personalized medicine (PM) is advancing disease prevention and treatment, but regulatory and clinical concerns persist, requiring evaluation of healthcare professionals' (HPs) knowledge and attitudes. His study assessed PM awareness among HPs at Tabriz University of Medical Sciences, Iran. Participants from diverse clinical departments completed a survey covering PM definitions, benefits, ethical concerns, genetic testing knowledge, attitudes, and barriers. A literature review guided question development. Among 141 HPs (55.3% male, 44.7% female), only 27.7% reported sufficient PM knowledge, though 82.3% acknowledged genetic health influences. Those with adequate knowledge more often endorsed PM tools (92.3% vs. 68.6%, p = 0.01) but expressed greater concern about healthcare disparities (82.1% vs. 67.6%, p = 0.03). Key barriers included cost (17%) and ethical risks, with 72% fearing PM would widen economic gaps and 23.4% anticipating insurance discrimination. Females and married HPs were more concerned about discrimination (p = 0.039 and p = 0.038, respectively). Despite concerns, 80% of physicians supported genome-guided prescribing. While HPs recognize PM's potential, limited awareness and ethical concerns hinder adoption. Addressing knowledge gaps and equity issues through education is crucial for PM integration in Iran.

Vancomycin dosing in neonates is challenging due to developmental pharmacokinetic variability. The study was to characterize vancomycin pharmacokinetics in a large cohort of preterm and term neonates and develop individualized dosing regimens. A 5-year retrospective study of a cohort of 255 neonates was included. An allometric one-compartment model with first-order elimination best described the vancomycin concentrations. The population pharmacokinetic estimates (between subject variability) of clearance (CL) and volume of distribution (V) were 2.58 L·h-1·70 kg-1 (9.00 %) and 52.09 L·70 kg-1 (29.00%), respectively. CL and V were significantly influenced by body weight and postmenstrual age. Vancomycin CL reached 50% of adult values at 43.6 weeks PMA (a sigmoid Emax model). Renal maturation, estimated by creatinine production rate, was a significant covariate. Bayesian-guided individualized dosage regimens were developed and evaluated. Vancomycin overdosage should be avoided in very young premature babies (PMA = 25 weeks). Optimization of efficacy while minimizing toxicity of vancomycin in preterm and term neonates is needed, especially guided by personalized body weight, postmenstrual age, and renal function.

To investigate patient reactions to and understanding of secondary genomic findings with limited to no medical actionability (LMA-SFs) from diagnostic genome sequencing. We analyzed LMA-SFs returned to 47 adults who elected to receive a broad set of these results from 6 categories. Findings indicated elevated risk (reportable/positive) or not (negative/normal). Most participants (N = 43) also completed surveys to report their distress, decision regret, expected health anxiety, and whether and how they perceived results as reassuring or troubling. Most participants received some reportable LMA-SFs for common risk, pharmacogenetic, and carrier status variants. Fewer received reportable APOE haplotype or monogenetic condition variants. None received results indicating high risk for severe neurological disease. Overall, participants (76.7% female, 97.7% White) had low distress, decision regret, and expected health anxiety. None described negative/normal findings as troubling. However, their interpretations of reportable/positive results varied. Even within the same result type, some participants found them troubling, while others found them reassuring based on their perception of the results' utility. Participants' short-term well-being was not reduced by receiving LMA-SFs. Their interpretations suggested varied personal utilities and the need for post-test resources to aid understanding of these types of results and their health significance.