Uric acid transporters mediate renal and extrarenal urate handling and may contribute to blood pressure (BP) regulation. This study examined the associations of common single-nucleotide polymorphisms (SNPs) in key urate transporter genes (SLC2A9, ABCG2, SLC17A3, SLC22A7, SLC22A6, SLC22A11, SLC22A12, and ABCC4) with salt sensitivity, longitudinal BP changes, and incident hypertension. Data were derived from the Baoji Salt-Sensitivity Study, a family-based cohort in which 514 Chinese adults completed a controlled dietary sodium intervention and were followed prospectively for 14 years. After multivariable adjustment and multiple-testing correction, ABCG2 rs2054576 and rs4491984 were associated with DBP response to low-salt diet; SLC22A6 rs4149170 with SBP and DBP responses; ABCG2 rs12505410 and SLC22A12 rs7932775 with DBP and MAP responses; and ABCC4 rs1189466 and rs17189390 with SBP, DBP, and MAP responses. During high-salt intake, SLC2A9 rs3733591 was associated with SBP and MAP responses; and SLC22A11 rs3759053, ABCC4 rs17189390 and rs9590211 were associated with SBP, DBP, and MAP responses. Over 14 years of follow-up, SLC2A9 rs3733591 and SLC17A3 rs1165165 were associated with longitudinal systolic BP (SBP) change; ABCG2 rs2054576, SLC22A7 rs2270860, SLC22A12 rs79226484, and ABCC4 rs1189466 were associated with diastolic BP (DBP) and MAP change; and SLC22A6 rs4149170 and ABCC4 rs9590220 and rs7322318 were associated with change in SBP, DBP and MAP. Additionally, ABCC4 rs7982809 and rs869951 were associated with incident hypertension over the 14-year follow-up. These findings suggest that genetic variation in urate transporters may contribute to salt sensitivity, long-term BP progression, and hypertension risk, supporting a possible role for urate-transport pathways in BP regulation.

Personalized segmentation has been shown to improve performance over generalized models in follow-up imaging; however, its robustness across large temporal gaps remains unclear. We propose a fully automated, context-informed personalization framework that integrates radiology report-derived clinical context with imaging features to improve longitudinal liver tumor segmentation.

This retrospective study included 171 patients for generalized model training and 41 longitudinal patients with follow-up CT scans acquired 3-15 months after baseline for personalization and evaluation. We developed a U-Net-based vision-language segmentation framework that automatically summarizes free-text radiology reports, encodes them into language embeddings, and integrates them into intermediate image features to provide clinical context. A generalized model was trained using paired CT-report data. For each longitudinal patient, personalization was performed at the 3-month follow-up using either image-only input (vision-only personalization) or paired image-report input (context-informed personalization). Models were then evaluated on subsequent 6-15-month follow-up scans without further adaptation. Patients were stratified into Stable and Dynamic cohorts based on relative GTV volume variability. Performance was assessed using the Dice similarity coefficient (DSC) and LogPenalty Score (LPS), with additional ablation studies examining language models and report components.

In the Dynamic cohort, vision-only personalization exhibited diminishing gains at later follow-up, whereas context-informed personalization maintained statistically significant improvements in ΔLPS at 9-15 months (p < 0.05). In the Stable cohort, both personalization strategies showed sustained performance with comparable segmentation accuracy, indicating that incorporating report-derived clinical context did not degrade performance in cases with limited anatomical variability. Ablation studies demonstrated that domain-specific encoder-based language models (BioClinicalBERT) outperformed larger generative models and that effective context integration did not require complex architectural modifications.

Incorporating report-derived clinical context improves the longitudinal robustness of personalized liver tumor segmentation, particularly in patients with dynamic tumor evolution. These findings suggest that clinically grounded language representations can stabilize personalization across extended follow-up while enabling fully automated and scalable deployment.

Non-midline, pediatric high-grade gliomas (HGG) represent one of the leading causes of cancer-related deaths in children with underlying molecular genetics and driver mutations that are distinct from adult HGGs. Image-based biomarkers that assist pediatric HGG risk-stratification could potentiate treatment strategies. Towards this, we investigated radiomics approaches for non-midline pediatric HGG prognosis.

We identified 77 children (mean age: 140 months; 43 males) with non-midline-origin, hemispheric pediatric HGG tumors across five pediatric institutions. We extracted 1800 image-biomarker standardization initiative (IBSI)-based radiomics tumor features from treatment-naïve, axial gadolinium-enhanced axial T1- and axial T2-weighted brain MRI (Gad T1-MRI, T2-MRI). We performed k-fold cross validation and Cox regression to identify optimal predictive features of overall survival. We calculated the risk scores for each patient using a linear combination of the selected features weighted by their coefficients determined by the Cox regression model. Patients were stratified based on the median risk score into high- and low-risk groups. Python (version 3.10.0) was used for all model development.

The Cox regression model that included both clinical (age and sex) and MRI-derived radiomics features demonstrated a concordance of 0.78 (95% CI: 0.70-0.83) compared to concordance of 0.75 (95% CI: 0.69-0.82) that used radiomics features alone and concordance of 0.61 (95% CI: 0.54-0.67) that used clinical features (age and sex) alone. Using the risk scores derived from our radiomics model, we present a Kaplan-Meier curve on our HGG cohort. Median overall survival was 21.7 months in the high-risk group and 44.6 months in the low-risk group (log-rank P = 0.007; hazard ratio 2.42, 95% CI 1.26-4.66).

In this multi-center, pilot study, we identified optimal radiomics features in the creation of a prognostic pediatric HGG model. Computational MRI techniques may offer new approaches for quantitatively evaluating tumor phenotype and serve a potential future role in therapy planning and clinical trials eligibility.

Insulin resistance is common in Saudi women with PCOS and linked to hormonal imbalances. While bone health differences were not significant, trends suggest obesity and vitamin D may influence future risk. Early detection and management of insulin resistance could help reduce long-term health complications in affected women.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hormonal, metabolic, and reproductive dysfunction. Insulin resistance (IR), a hallmark feature of PCOS, is associated with long-term health complications, including adverse effects on bone metabolism.

This study aimed to explore the prevalence of IR in Saudi women with PCOS and investigate its associations with hormonal, metabolic, and bone health parameters.

A cross-sectional study was conducted at the Center of Excellence for Osteoporosis Research, King Abdulaziz University, Jeddah, Saudi Arabia, between December 2018 and June 2019. A total of 144 participants were enrolled, comprising 72 women with PCOS and 72 age- and BMI-matched healthy controls. Anthropometric measurements, biochemical analysis, and bone mineral density (BMD) assessments were performed. IR was evaluated using fasting serum insulin, homeostasis model assessment (HOMA), and glucose-to-insulin ratio (GIR). Statistical analyses included group comparisons and correlation analyses to identify associations.

IR was significantly higher in women with PCOS compared to controls across all diagnostic criteria (P < 0.01). PCOS women had higher luteinizing hormone (LH) levels and LH/FSH ratios (P < 0.001), particularly in insulin-resistant subgroups. No significant differences in BMD or T-scores were observed between groups; however, stratified analyses suggested trends toward higher T-scores in obese PCOS women. Vitamin D deficiency was similarly prevalent in both groups.

This study highlights the substantial metabolic burden of IR in Saudi women with PCOS and its association on hormonal profiles. While no differences in bone health were observed, trends suggest that factors such as BMI and vitamin D status may be associated with skeletal outcomes at later stages. These findings underscore the importance of early IR identification and management to mitigate long-term health complications in PCOS.

Cognitive impairment identified by screening tools is common among patients with oral cancer and may be associated with psychological distress and reduced quality of life. However, evidence regarding these associations in patients with oral cancer, particularly in Chinese populations, remains limited.

To assess the prevalence of screening-positive cognitive impairment and examine its associations with anxiety, depression, and quality of life among Chinese patients with oral cancer.

A cross-sectional study was conducted at a tertiary hospital in Changde, Hunan Province, China, from June 15 to July 15, 2023. Data were collected using an online questionnaire, including demographic and clinical characteristics and standardized instruments: the Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and the University of Washington Quality of Life Questionnaire (UW-QoL). Spearman correlation analysis and multivariable logistic regression were performed to explore factors associated with screening-positive cognitive impairment.

A total of 567 participants were included. The mean MoCA score was 19.25 ± 6.49, and the education-adjusted mean score was 19.55 ± 6.37. Using a MoCA cut-off score of < 24, 67.40% of participants were classified as screening-positive for cognitive impairment. UW-QoL scores were negatively correlated with SAS scores (r =  - 0.2009, p < 0.01) and SDS scores (r =  - 0.2055, p < 0.01), and positively correlated with adjusted MoCA scores (r = 0.2027, p < 0.01). Multivariable logistic regression analysis showed that older age, higher anxiety scores, and higher depression scores were positively associated with screening-positive cognitive impairment, whereas higher UW-QoL scores were negatively associated with cognitive impairment (all p < 0.05).

Screening-positive cognitive impairment was common among patients with oral cancer in China and was associated with psychological distress and quality of life. These findings suggest the potential value of incorporating cognitive and psychological screening into routine clinical care for patients with oral cancer. Longitudinal studies are needed to further clarify the temporal relationships among cognitive impairment, psychological symptoms, and quality of life.

Primary central nervous system lymphoma (PCNSL) involving the hypothalamic-pituitary axis is a rare condition and may present with nonspecific neurologic and endocrine signs, often mimicking more common sellar lesions. We report the case of a 59-year-old woman admitted with subacute behavioral changes, cognitive decline, and polyuria. Magnetic resonance imaging revealed a pituitary-infundibular mass with suprasellar extension and marked bifrontal edema. Endocrine evaluation demonstrated panhypopituitarism and arginine vasopressin deficiency. The clinical course was complicated by severe dysnatremias requiring intensive care management and hormonal replacement. Histopathologic analysis of a transsphenoidal biopsy confirmed diffuse large B-cell lymphoma, with no systemic disease on PET-CT or bone marrow evaluation. The patient was treated with the MATRix chemotherapy regimen followed by autologous stem cell transplantation, achieving sustained complete remission at 3.5 years. Persistent hypogonadotropic hypogonadism remained as a sequelae. This case underscores the diagnostic challenges of sellar involvement by PCNSL and highlights the importance of including lymphoma in the differential diagnosis of hypothalamic-pituitary masses. Acute pituitary failure with severe electrolyte disturbances may precede oncologic diagnosis, and early multidisciplinary management combined with aggressive therapy can result in long-term remission.

Treatment for high-risk localized prostate cancer can be particularly challenging because of an elevated risk of disease recurrence. One of the proposed ways to improve the success of definitive localized treatment (such as radical prostatectomy or radiation therapy) for these patients is the addition of neoadjuvant therapy. Thus, therapeutic strategies that have demonstrated benefit in metastatic prostate cancer settings have been translated to and evaluated in the neoadjuvant setting. The therapies studied include androgen deprivation therapy, ranging from androgen receptor-specific blockade to more comprehensive androgen signaling pathway blockade; chemotherapy, especially taxane-based therapy; immunotherapy; and most recently, prostate-specific membrane antigen radioligand therapy. In this review, we provide an overview of various trials that have explored the pathologic and oncologic results of these therapies in various prostate cancer settings and discuss the emerging role of theranostics in this space.

A major natural killer (NK) cell and CD8⁺ T cell checkpoint is mediated by the inhibitory receptor NKG2A/CD94 and its ligand, human leukocyte antigen E (HLA-E) complexed with nine-amino acid HLA-Ia leader sequence-derived peptides termed VL9 (HLA-E-VL9). Here, we used structure-based design and high-throughput library screening to generate high-affinity antibodies that block NKG2A/CD94 interactions. These antibodies enabled direct NK and CD8⁺ T cell cytotoxicity and mediated NK cell antibody-dependent cellular cytotoxicity (ADCC). Anti-HLA-E-VL9 antibodies enhanced human NK cell line NK-92 killing of HLA-E-VL9⁺ human tumors in mice, demonstrating checkpoint inhibition activity in vivo. Moreover, HLA-E-VL9 was found to be expressed on primary human CD4⁺ T cells infected with HIV in vitro, and its engagement by HLA-E-VL9 antibodies drove elimination of infected cells by NK cell-mediated ADCC. HLA-E-VL9 antibodies also enhanced the killing of HIV-infected cells by NKG2A/CD94⁺ CD8⁺ T cells targeting an HIV Rev-derived epitope that complexes with HLA-E. Therefore, anti-HLA-E-VL9 antibodies represent a candidate therapeutic approach to eliminating pathogenic target cells by enhancing both NK cell and CD8⁺ T cell function and by promoting ADCC.

Achieving tumor-specific delivery and sustained activation of both cytotoxic and immune-modulating agents remains a critical challenge in chemoimmunotherapy. Here, a bacterial platform was engineered to combine enzyme/prodrug chemotherapy with immunotherapy, in which tumor-homing Escherichia coli Nissle 1917 expressed cytosine deaminase to convert the prodrug 5-fluorocytosine into the cytotoxic drug 5-fluorouracil and concurrently produced an IL-15 superagonist and a PD-L1 blocking nanobody in tumors. This platform demonstrated potent antitumor effects in murine MC38 and B16-F10 solid tumor models. Mechanistic analyses showed that bacterial enzyme/prodrug therapy alone elicited both immune activation and compensatory immunosuppressive responses, whereas inclusion of IL-15 superagonist and PD-L1 blockade enhanced activation of antigen-presenting cells, T cells, and natural killer cells and attenuated immunosuppressive pathways. Abscopal and rechallenge experiments indicated that this bacterial chemoimmunotherapy strategy induces systemic antitumor immunity and durable immune memory. In summary, our approach integrates enzyme/prodrug therapy and immunotherapy into a single bacterial delivery system, overcoming key limitations of conventional therapies by providing a rationally designed framework for spatially controlled chemoimmunotherapy.

Endocrine resistance in ER⁺ breast cancer remains a major clinical challenge. Here, we identify RHAMM as a key driver of resistance by orchestrating polyploid cancer cell (PCC) formation. Single-cell transcriptomics uncovered a G2/M-enriched, RHAMM⁺ subpopulation in endocrine-resistant tumors. Mechanistically, RHAMM binds Septin9/10 to promote aberrant cytoskeleton polymerization, activating YAP independent of Hippo signaling, which induces cytokinesis failure and facilitates PCC generation. Concurrently, RHAMM destabilizes p21 mRNA, enabling cell cycle progression despite genomic instability. The RHAMM-p21 axis serves as a bypass mechanism supporting polyploidization. Upon endocrine treatment, RHAMM is transcriptionally up-regulated by Slug. Clinically, RHAMM^high signatures are enriched in metastatic and recurrent ER⁺ tumors and correlate with poor prognosis, highlighting its therapeutic relevance. Importantly, targeting RHAMM or YAP abrogates PCC formation and restores fulvestrant sensitivity. These findings reveal RHAMM-mediated polyploidization as an adaptive mechanism underlying endocrine resistance, suggesting the therapeutic potential of targeting the RHAMM-YAP axis.