Multi-vessel coronary artery disease (MVCD), defined as stenosis affecting ≥2 major coronary arteries, confers poor clinical outcomes in patients with coronary artery disease (CAD). Cytochrome P450 2C19 (CYP2C19) CYP2C19 participates in lipid metabolism and inflammatory regulation, which may be associated with individual variations in the severity of coronary artery lesions. This study aimed to explore the clinical and genetic factors associated with MVCD focusing on CYP2C19 polymorphisms and chronic metabolic diseases.

This single‑center cross‑sectional study enrolled 4124 patients with angiographically confirmed CAD, who were divided into single‑vessel CAD (n=846) and MVCD (n=3278) groups. Baseline clinical data and CYP2C19 genotypes were collected. The chi-square test, Hardy-Weinberg equilibrium test, and logistic regression analyses were performed for statistical evaluation.

Higher prevalences of hypertension, type 2 diabetes mellitus, and dyslipidemia were observed in MVCD patients. CYP2C19*2 (rs4244285, 681G>A) and *3 (rs4986893, 636G>A) allele frequencies were markedly elevated in the MVCD group. Logistic regression analysis confirmed that hypertension (odds ratio (OR)=1.485, 95% confidence interval (CI): 1.267‑1.740, p<0.001), T2DM (OR=2.441, 95% CI: 2.006‑2.970, p<0.001), dyslipidemia (OR=1.313, 95% CI: 1.097‑1.572, p=0.003), and CYP2C19 poor metabolizer (*2/*2, *2/*3 and *3/*3 genotypes) status (OR=1.744, 95% CI: 1.360‑2.237, p<0.001) was independently associated with MVCD. The combined impaired CYP2C19 metabolic phenotype (intermediate (*1/*2 and *1/*3 genotypes) plus poor metabolizers) was also independently correlated with MVCD (adjusted OR=1.285, 95% CI: 1.095-1.508, p=0.002).

Clinical metabolic comorbidities and the combined impaired CYP2C19 metabolic phenotype are associated with MVCD. These findings may provide valuable reference for risk assessment of severe CAD.

Multi-cancer early detection (MCED) tests present a paradigm transform in cancer screening by detecting multiple cancer types from one blood sample. While studies have shown high levels of public interest in MCED screening, little is known about factors shaping individuals' perception of the emerging technology. Guided by the PRECEDE-PROCEED framework, we aimed to identify factors associated with the perception of value of MCED testing among American adults.

We conducted a cross-sectional secondary analysis of the Health Information National Trends Survey cycle 7 (HINTS 7) to identify factors associated with the perceived value of MCED screening. After removing respondents with missing outcome data, our final sample size was 6,728. Using the PRECEDE-PROCEED framework, candidate predictors were grouped into predisposing, reinforcing, and enabling factors. We used descriptive, survey-weighted analyses, spearman correlation analyses, survey-weighted multivariable logistic regression, and supervised machine learning analyses (logistic regression and random forest) to explore the associations.

Overall, 74.9% of the sample perceived MCED testing as very valuable. Trust-related domains showed the strongest associations with the outcome, including trust in physicians (OR = 1.89), trust in science (OR = 1.80), and trust in the healthcare system (OR = 1.64). Cancer information seeking (OR = 1.59), online health information use (OR = 1.63), smartphone access (OR = 1.54), cancer fatalistic beliefs (OR = 1.52), trust in government (OR = 1.50), knowledge of hepatitis B as a cancer risk factor (OR = 1.48), and family history of cancer (OR = 1.45) were also significantly associated with higher perceived value. Machine learning analyses demonstrated consistent predictor rankings, highlighting trust and health information engagement as the most influential determinants.

The value of MCED screening was largely driven by trust, cancer information seeking, and access to healthcare and health information resources. Our study highlights the efficacy of the PRECEDE-PROCEED approach to studying factors associated with complex health outcomes. Future implementation strategies should prioritize equitable communication, strengthen public trust, and improve access to reliable health information to facilitate informed decision-making regarding MCED testing.

Real-world oncology data are essential for clinical research and precision cancer care. However, genomic biomarkers are often embedded in scanned, unstructured clinical documents requiring manual abstraction before becoming available in cancer registries, delaying real-world evidence generation. This study evaluated and compared three open-source optical character recognition (OCR) approaches, Tesseract, EasyOCR, and a hybrid implementation, to determine which best enables automated extraction of Oncotype DX recurrence scores and improves the timeliness and quality of real-world oncology data.

We evaluated the feasibility of automated genomic data extraction using 675 Oncotype DX reports from a Midwestern U.S. health system. EasyOCR, Tesseract, and a hybrid OCR approach were used to extract recurrence scores from scanned reports. OCR-derived values were compared with manually abstracted scores and local cancer registry data. Performance was assessed using agreement, precision, recall, F1 score, and processing time. Multivariable logistic regression was performed to identify factors associated with discordance between registry-reported and manually abstracted scores.

The hybrid OCR approach demonstrated the highest performance, achieving 97% agreement with manual abstraction, precision of 0.997, recall of 0.972, and an F1 score of 0.984. Registry abstraction demonstrated comparable performance but required greater manual effort. Automated extraction substantially reduced processing time while maintaining high accuracy. Logistic regression showed registry discordance was largely independent of patient and tumor characteristics, with unknown progesterone receptor (PR) status as the only significant predictor.

Automated extraction of genomic biomarkers represents a scalable approach to reducing delays in cancer data availability. Earlier capture of genomic information may support cancer registry modernization and improve real-world evidence generation in precision oncology.

Immunotherapy-targeted combination therapy has transformed hepatocellular carcinoma (HCC) treatment, yet longitudinal patient-reported outcome (PRO) trajectories remain poorly characterized. We prospectively examined decision regret, hope, fatigue and quality of life during first-line treatment.

This convergent mixed-methods study enrolled 33 patients initiating first-line immunotherapy-targeted therapy at a Taiwan medical center (December 2022-October 2023). PROs were assessed across six cycles using validated instruments, and all participants were interviewed. Strands were integrated through joint display analysis.

Twenty-one patients (63.6%) completed six cycles; 12 (36.4%) discontinued. Completers maintained stable PROs with low regret, whereas discontinuers declined faster in EQ-5D utility (interaction B =  - 0.169 per cycle, p = .007) and showed a larger, non-significant rise in regret (+ 9.58, p = .051, d = 0.50; between-group p = .042). Hope declined in both groups (- 1.48, p = .003), correlating negatively with regret (r =  - .383, p = .028). Interviews centered on treatment-related discomfort (24/33), sustained hope for disease control (31/33) and financial strain (25/33); where regret was voiced (3/33) it concerned earlier points in the illness course rather than the current treatment decision. Integration yielded four expanded meta-inferences and one discordance, between measured and voiced regret.

Treatment completers maintain stable PROs, but more than one-third discontinued and experienced worse fatigue and greater regret, supporting pre-treatment counselling that is honest and informative rather than reassuring. Discontinuation marks a psychologically vulnerable transition, while universal hope decline warrants psychosocial monitoring for all patients. Given the sample size, predictors of regret are hypothesis-generating.

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complications of cytotoxic, targeted, immune, and radiation-based therapies. Cancer therapy-related cardiac dysfunction (CTRCD) is used here more narrowly for treatment-related myocardial dysfunction, typically identified by changes in left ventricular ejection fraction, global longitudinal strain, and/or cardiac biomarkers. The pathophysiology of CTR-CVT is multifactorial, but the implicated pathways should not be interpreted as equally causal. The dominant initiating mechanism is therapy-specific - anthracycline injury is best supported by topoisomerase IIβ (TOP2B)-mediated DNA damage with secondary mitochondrial and redox injury; HER2-directed toxicity by disruption of NRG1-ERBB2/ERBB4 survival signalling; fluoropyrimidine toxicity by coronary vasomotor dysfunction; VEGF-pathway inhibition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathways, although the clinical relevance of several regulated cell-death mechanisms remains incompletely established. Genetic susceptibility may further modify risk, but the strength of evidence differs among reported loci. Replicated pharmacogenetic associations, rare variants in established cardiomyopathy genes, and preliminary candidate-gene findings should therefore be considered separately. Most available studies remain limited by small cohorts, heterogeneous phenotyping, ancestry imbalance, and incomplete external replication. This review critically evaluates the hierarchy and strength of mechanistic and genetic evidence and discusses the extent to which these findings can currently inform risk stratification, surveillance, prevention, and treatment in precision cardio-oncology.

Thymic epithelial tumors (TETs) represent the most common primary neoplasms of the anterior mediastinum, yet thymic carcinoma (TC) stands out as an exceptionally rare and biologically aggressive subtype. Unlike thymomas, TCs exhibit marked cytologic atypia, early invasive potential, and a high predisposition for extrathoracic metastasis. We report the case of a 59-year-old male who presented with a seven-month history of progressive, refractory lumbar pain and functional limitation. Initial clinical and laboratory evaluation revealed normocytic anemia, leukocytosis, elevated inflammatory markers, and increased lactate dehydrogenase and beta-2 microglobulin levels. These findings, combined with systemic bone marrow infiltration observed on spinal magnetic resonance imaging, initially suggested a lymphoproliferative disorder. A subsequent thoracic computed tomography scan identified an anterior mediastinal mass with lymphadenopathy. A bone marrow biopsy evidenced infiltration by a poorly differentiated malignant neoplasm, and an immunohistochemical profile of the mediastinal mass confirmed the diagnosis of stage IVb TC, showing positivity for pan-cytokeratin, tumor protein p63, cluster of differentiation 5 (CD5), epithelial membrane antigen (EMA), and cluster of differentiation 117 (CD117), with a Ki-67 proliferation index of 20%, while remaining negative for hematolymphoid, neuroendocrine, and lung-specific markers. The patient was managed through a multidisciplinary approach with systemic palliative chemotherapy. This case highlights a critical diagnostic challenge where TC mimicked a hematological malignancy. The systemic dissemination of TC, particularly the diffuse bone marrow infiltration, is a rare clinical phenotype that obscures the primary mediastinal origin. Our report emphasizes the necessity of including TC in the differential diagnosis of patients presenting with refractory bone pain and systemic hematological abnormalities, even in the absence of respiratory symptoms. Early diagnostic recognition through strategic immunohistochemical profiling is imperative to avoid clinical bias, prevent the initiation of inappropriate therapies, and facilitate a prompt, evidence-based management strategy for patients with advanced, non-resectable disease.

Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare mesenchymal subcutaneous tumor of low malignant potential that occurs in adult women and has typical histological features, including loss of SMARCB1 (INI1) expression. This report describes the case of a 23-year-old woman with a painful vulvar subcutaneous nodule and a diagnosis of MELTVR and describes the challenges in the approach to definitive diagnosis. A 23-year-old woman presented with a three-month history of right pubic pain. Imaging revealed a 25-mm inguinal lesion without metastasis. Biopsy demonstrated spindle and plasmacytoid tumor cells in myxoid and hypercellular areas, suggesting myoepithelioma. Although necrosis and mitotic activity were not evaluable in the biopsy specimen, malignant potential could not be excluded. Complete surgical excision was subsequently performed. The resected tumor measured 45 × 35 × 15 mm and showed multilocular solid and gelatinous areas. Histologically, lobulated growth, marked atypia, necrosis, and mitotic activity (9/10 HPF) were identified. Immunohistochemically, tumor cells showed positivity for estrogen receptor (ER) and progesterone receptor (PgR), along with loss of SMARCB1 (INI1) expression. Other markers, such as neural and myoepithelial markers, were negative. Fluorescence in situ hybridization (FISH) analysis showed no Ewing sarcoma breakpoint region 1 (EWSR1) rearrangement. MELTVR was diagnosed based on integrated clinicopathological and molecular findings. Biopsy specimens may fail to capture key diagnostic features of MELTVR because of intratumoral heterogeneity. Definitive diagnosis requires comprehensive evaluation of resection specimens with immunohistochemical and molecular analyses. This case may contribute to establishing diagnostic criteria for this rare entity.

Reliable biomarkers reflecting tumor biology and histopathological risk status in pheochromocytomas and paragangliomas (PPGL) remain limited. In this study, the expression of biomarkers associated with hypoxia, angiogenesis, and proliferation was evaluated, and their associations with histopathological differentiation in PPGL were investigated.

A total of 35 tumor foci from 31 patients with PPGL who were surgically treated were retrospectively examined. Expression levels of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor (VEGF), CD105 (endoglin), Ki-67, and succinate dehydrogenase subunit B (SDHB) were assessed using immunohistochemical methods. Associations between these markers and clinicopathological characteristics, Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) scores were analyzed.

HIF-2α expression, CD105 microvessel density (MVD) score, and Ki-67 proliferation index were significantly higher in poorly differentiated tumors compared with moderately/well-differentiated tumors (p<0.05 for all). In contrast, VEGF expression did not differ significantly between the groups. The GAPP score showed positive correlations with HIF-2α (r=0.48; p<0.01), CD105 (r=0.54; p<0.001), and Ki-67 (r=0.77; p<0.001). In univariate analyses, bilateral disease, HIF-2α expression, CD105 MVD score, and loss of SDHB expression were associated with higher GAPP scores. However, in multivariable regression analysis, only CD105 was independently associated with the GAPP score (β=0.04; p=0.026).

Increased expression of CD105, HIF-2α, and Ki-67 was associated with poorer histopathological differentiation in PPGL. Among the biomarkers evaluated, only CD105 showed an independent association with the GAPP score, suggesting that tumor-associated neoangiogenesis may contribute to histopathological differentiation in PPGL. These findings support further investigation of CD105 as a potential biomarker for histopathological risk assessment. However, larger studies with long-term clinical outcome data are needed to establish its clinical prognostic value.

Cancer remains a major global health challenge, particularly as several tumors develop resistance to current therapies. Although doxorubicin is widely used to treat various cancers, its effectiveness is often limited by adverse effects, including cardiotoxicity and nephrotoxicity, which restrict its dosing. In search of safer and more effective options, a series of novel piperidine-embedded isoxazol-triazole conjugates (6a-6o) were designed, synthesized, and biologically evaluated against the MCF-7 cell line in this study. The synthesized compounds 6a-6o were characterized using FTIR, HRMS, and ¹H and ¹³C NMR spectroscopy analysis to confirm their structure and verify successful synthesis. The GI₅₀ (Growth Inhibition 50%) values of synthesized compounds 6a-6o were determined using the SRB assay. Among all synthesized compounds, 6m exhibited the most potent antiproliferative activity against MCF-7 cells, having GI50 <10 µg/mL (SI >5), comparable to adriamycin (doxorubicin, GI₅₀ <10 µg/mL). Overall, 6m is a novel anticancer agent with promising abilities against MCF-7 human breast cancer. The results support the compounds relevance as a biologically active agent with effective proliferation-suppressive properties.

Endometrial cancer (EC) is the most common gynecological malignancy in postmenopausal women. Patients with low estrogen receptor alpha (ERα) expression frequently develop aggressive pathological subtypes and have poor prognosis. The role of estradiol (E2) in ERα-low EC remains poorly understood. This study investigated the tumor-promoting effects of E2 using clinical data, in vitro functional assays, and a mouse xenograft model. We found that serum E2 levels were elevated in ERα-low patients, of whom 67.7% showed high tumor expression of G protein-coupled estrogen receptor (GPER). High GPER expression correlated with increased E2 levels, enhanced sphingosine kinase 1 (SphK1) activity, and higher Ki67 proliferation index. In vitro, E2 promoted proliferation, migration, and invasion of HEC-1A cells (low ERα, high GPER). These effects were suppressed by pharmacological inhibition or siRNA knockdown of GPER or SphK1. Mechanistically, E2 activated the ERK1/2 pathway via the GPER/SphK1 axis, leading to upregulation of Cyclin D1, Cyclin E1, and MMP-9. In vivo, E2 stimulated xenograft tumor growth, an effect mitigated by inhibitors of GPER, SphK1, and ERK. Our findings demonstrate that E2 drives progression of ERα-low endometrial cancer through the GPER/SphK1 signaling pathway, revealing potential therapeutic targets for this high-risk subgroup.