This study investigated the effects of anthracyclines on mitochondrial ferritin (MtFt) expression in primary murine cardiomyocytes and in cancer patients. MtFt expression was first evaluated in murine cardiomyocytes before and after doxorubicin exposure. Subsequently, MtFt levels were assessed in peripheral blood cells of 26 cancer patients at baseline, at the end of treatment, and 12 months after the first cycle, together with high-sensitivity troponin T (hsTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and left ventricular ejection fraction (LVEF). Doxorubicin-treated murine cardiomyocytes exhibited increased MtFt expression compared with untreated cells. No patient developed clinically relevant cardiotoxicity. A weak but significant inverse association was observed between MtFt levels and LVEF at the end of treatment. Multivariable linear regression showed no significant predictive effect of hsTnT, NT-proBNP, or time on MtFt changes, although MtFt levels tended to decrease and hsTnT levels to increase over time.

Malignant transformation (MT) is the principal driver of mortality in lower-grade glioma (LGG), yet its preoperative determinants and timing remain poorly defined. We quantified imaging elements of MT and its timing, correcting for bias in dating transformation.

We evaluated contrast enhancement (CE), tumour volume and 99 radiomic features in 155 patients with WHO grade 2-3 LGG, radiologically low-grade at diagnosis with at most minimal enhancement (77 transformations; median surveillance among non-transformers 4.8 years). Because MT is ascertainable only between scans, timing was modelled as interval-censored across four complementary models, with extent of resection (EOR) time-varying.

CE at diagnosis was the strongest predictor of MT, exceeding tumour volume and a co-modelled 99-feature radiomic panel (Bayesian HR 22.1, 95% CrI 10.5-53.2); conditioned on transformation-free survival to six months, HR 5.65 (95% CI 2.23-14.31). No radiomic feature survived shrinkage or native interval-censoring. Initial enhancement predicted post-surgical transformation independently of grade, IDH status and EOR, even after gross-total resection (GTR), itself associated with a two-thirds lower hazard (HR 0.32, 95% CI 0.13-0.77). Interval censoring proved material: conventional dating overstated the hazard four-fold.

CE at diagnosis predicted transformation risk and timing. It remained predictive after GTR removed the enhancing tissue, a postoperative role not previously recognised. The signal was present in each integrated tumour type and survived adjustment for grade, IDH status and EOR, may reflect intrinsic tumour biology and could refine postoperative risk estimation. GTR was the only modifiable determinant. These are the first interval-censored estimates of MT timing.

The benefits of neoadjuvant therapy (NAT) for pancreatic cancer (PC) with portal venous involvement remain debated. This study aimed to compare the short- and long-term outcomes of surgery with or without NAT in patients with PC with suspected venous involvement.

A multicentre retrospective cohort study compared patients who underwent upfront surgery (US) or surgery following NAT for PC with suspicion of venous involvement between 2007 and 2017. The primary endpoints were short-term morbidity and mortality, overall survival and disease-free survival.

We included 361 patients who received NAT and 690 patients who underwent US at nine centres. NAT patients had greater suspicion of venous involvement (96.9% vs. 83.6%, p<0.001), but underwent fewer venous resections (53.7% vs. 79.3%, p<0.001), and had less venous infiltration (52.3% vs 65.9%, p<0.001), perineural invasion (75.2% vs. 90.1%, p<0.001), angioinvasion (59.9% vs. 76.7%, p<0.001), lymph node involvement (60.6% vs. 83.6%, p<0.001) and R1 resections (44.7% vs. 67.2%, p<0.001) than patients who underwent US. Among patients undergoing venous resection, major postoperative complications were similar between the groups. However, without venous resection, NAT patients had significantly fewer (Clavien-Dindo ≥IIIb) postoperative complications (10.8% vs. 24.4%, p=0.02), fewer reoperations (3.0% vs. 11.2%, p=0.006), and lower 90-day mortality (2.4% vs. 7.7%, p=0.03). NAT patients showed improved survival (27.3 vs. 21.2 months, p=0.003).

NAT maybe beneficial for patients with PC with venous involvement, as it might allow better patient selection for surgery and is associated with fewer major postoperative complications and better overall survival.

Disparities in neurosurgical care are increasingly recognized, yet how they affect the diagnosis and management of vestibular schwannoma (VS) remains unclear. Differences in tumor size at diagnosis, treatment selection, and outcomes may be influenced by race, insurance status, income, and geography. To date, no comprehensive synthesis has addressed these inequities in patients with sporadic VS. To systematically evaluate the literature for evidence of social determinants of health (SDoH) in the diagnosis, treatment, and outcomes of patients with sporadic vestibular schwannoma. We conducted a PRISMA-guided systematic review of PubMed, Embase, and Web of Science (2000-2024). Included studies examined adult patients with sporadic VS and reported at least one socioeconomic variable. Non-English studies and those involving pediatric patients were excluded. Studies focusing on neurofibromatosis type 2 were excluded. Screening and data extraction were conducted independently by multiple reviewers using Covidence. Outcomes of interest included tumor size, treatment modality (surgery, radiosurgery, observation), hearing preservation, complications, and recurrence. Study quality was assessed using the GRADE framework and evaluated across the domains of risk of bias, inconsistency, indirectness, imprecision, and publication bias. Of 487 records identified, 40 met inclusion criteria. Most were US-based, retrospective studies that utilized national databases for patient recruitment. Race and insurance status were the most frequently reported variables; income and geographic indicators were less commonly assessed. Outcomes described the likelihood of treatment received, including surgery or SRS, complications including morbidity and mortality, length of stay, and discharge disposition including rehab and readmission. Few studies assessed functional status (n=2), hearing outcomes (n=2), or quality of life (n=1). In total, 358,843 patients were included across the 40 studies analyzed. This review suggests that disparities in vestibular schwannoma care are multi-factorial, with race and insurance status showing the most consistent associations between management, outcomes, and disparities. As treatment continues to evolve and become more centralized, future work should prioritize multi-institutional studies to incorporate patient-level socioeconomic data and evaluate outcomes beyond management selection.

The da Vinci 5 (DV5) system has purported advantages over existing platforms, including forced feedback. We compare perioperative safety, operative efficiency and early oncologic quality between DV5 and Xi robotic platforms for anatomic lung resection. A total of 419 robotic lung resections were performed between January 2025 and August 2026. Propensity-score overlap weighting balanced and matched 294 patients (47 DV5, 247 Xi) for age, sex, ASA class, BMI, forced expiratory volume in 1 s, tumor size, clinical T and N category, resection type and laterality. Effects were reported with robust and bootstrap 95% confidence intervals. Sensitivity analyses included 1:1 and 1:3 propensity matching comparisons and E-value assessment. From January 2025 to August 2026, 294 patients (47 DV5, 247 Xi) had balanced baseline characteristics (SMD < 0.01). Operative time was shorter with DV5 (96.4 vs. 118.7 min; 95% CI, - 36.2 to - 8.5). Lymph node yield was comparable (DV5 29.9 vs. Xi 31.6; [- 7.2 to + 3.7]). Blood loss (p < 0.01), length of stay (1.05 vs. 1.28 days; [- 0.53, + 0.06]) and stapler loads (8.5 vs. 9.6; [- 2.81 to + 0.55]) were numerically lower with DV5. Major complications were numerically lower with DV5 (1/47 [2.0%] vs. 20/247 [8.2%]; -16.0 to + 3.6). Both had 100% R0 resections and no conversion. There was no 30- or 90-day mortality. In this first clinical comparison of da Vinci 5 and Xi for robotic anatomic lung resection, DV5 preserved the safety and oncologic quality of Xi while being associated with shorter operative times. Prospective multi-institutional studies are required to confirm these findings.

Lung cancer is one of the most common malignant tumors, but traditional treatments, particularly chemotherapy, often face significant challenges, including drug resistance and high systemic toxicity. In this study, we developed a novel acid responsive nanoparticle, La₂O₃@PDA/PTX, by combining lanthanum oxide (La₂O₃), polydopamine (PDA), and paclitaxel (PTX). This nanoparticle demonstrated excellent aqueous stability, high biocompatibility, and low toxicity. Benefiting from its structural design, the nanoparticle enables targeted delivery of PTX while simultaneously elevating intracellular reactive oxygen species (ROS) levels, which synergistically exacerbates oxidative stress injury within tumor cells. Mechanistically, La₂O₃@PDA/PTX inhibited tumor growth and induced apoptosis by increasing intracellular ROS, inducing G2/M cell-cycle arrest, and regulating proliferation and apoptosis related proteins, including Ki67, Bcl-2, and Bax. At the signaling level, La₂O₃@PDA/PTX increased NF-κB p65 phosphorylation and modulated TNF/NF-κB associated signaling, accompanied by changes in tumor associated cytokines and T-cell associated immunofluorescence signals. Furthermore, it effectively inhibited the progression of both subcutaneous and metastatic tumors with no significant adverse effects on major organs or peripheral blood parameters, showing great promise for future translational research. Collectively, this work presents an acid responsive therapeutic strategy combining ROS enhancement, chemotherapy, and TNF/NF-κB associated signaling modulation for lung cancer treatment.

Melanoma remains a highly aggressive malignancy, and many patients fail to achieve durable benefit despite immune checkpoint inhibitor (ICI) therapy. ICIs improve outcomes but lack tumor specificity and do not directly recruit T-cells to tumor cells resulting in substantial side effects, highlighting the need for targeted immunotherapies selectively toward melanoma. Neuron glial antigen-2 (NG2) represents an attractive antigen for T-cell redirecting strategies due to its largely tumor restricted expression.

Here we report the generation and characterization of T-cell engaging NG2‑targeting bispecific antibodies. (bsAbs). To finetune CD3 affinity, we generated two constructs with differing CD3-affinities. NG2xCD3high contains a UCHT-1-based CD3-binder with high affinity, whereas NG2xCD3low carries a UCHT‑1 variant with approximately 100‑fold reduced CD3 affinity. Both constructs were functionally assessed in NG2-high and NG2-low melanoma cell lines covering several key aspects of T-cell mediated immune response.

In cultures with NG2-expressing melanoma cells, both constructs mediated immune-synapse formation, T-cell activation, proliferation, and strictly NG2-dependent tumor cell killing. Both NG2xCD3high and NG2xCD3low supported differentiation into memory T‑cell subsets, but NG2xCD3low induced less cytokine secretion and diminished functional activity, particularly against NG2 lower expressing targets. NG2xCD3high maintained robust cytokine production and sustained cytotoxicity across both NG2‑high and NG2‑low tumor models.

Our data identify NG2 as a promising target for T-cell-redirecting therapy in melanoma and demonstrate that, within the IgG-scFv format, high CD3 affinity is required to achieve potent effector function across differing NG2-expression levels. NG2xCD3high was thus identified as lead candidate for further development in NG2-expressing malignancies.

Immune checkpoint inhibitors are used to treat head and neck cancer (HNC), but clinical responses vary, and systematic genetic evaluation is needed to prioritize candidate susceptibility genes. We applied summary-data-based Mendelian randomization (SMR) and HEIDI testing to screen 624 immune checkpoint-related genes, integrating GWAS data from the Million Veteran Program with blood-derived multi-omics QTLs, and explored replication in FinnGen. Two-sample MR sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) assessed pleiotropy for prioritized candidates, which were further contextualized using tumor expression and survival outcomes (overall survival [OS], progression-free interval [PFI]) in The Cancer Genome Atlas (TCGA-HNSC) cohort. Several SMR-prioritized genes showed directional concordance between genetically predicted effects and tumor expression, including the protective candidate HGF (OR_SMR = 0.37, P = 0.010) and the risk-associated AKT1 (OR_SMR = 1.19, P = 0.024). Both were further supported by two-sample MR sensitivity analyses (HGF: OR_IVW = 0.72, P = 0.007; AKT1: OR_IVW = 1.17, P = 0.009), with no evidence of horizontal pleiotropy (Egger intercept P > 0.05). Higher tumor HGF expression correlated with better OS (HR_Cox = 0.70, P = 0.008) and PFI (HR_Cox = 0.72, P = 0.020), whereas higher AKT1 expression correlated with poorer OS (HR_Cox = 1.42, P = 0.010). None of the eQTL or pQTL associations replicated in FinnGen. By integrating genetic signals with tumor transcriptomic and clinical data, this study prioritized immune checkpoint-related genes potentially involved in HNC susceptibility. HGF and AKT1 emerged as the most consistently supported candidates, showing convergent tumor transcriptomic and survival support despite lacking genetic replication in FinnGen, providing a foundation for further biological investigation.

To describe the conventional sonographic features of oncocytic thyroid neoplasms (OTNs) and compare them with those of papillary thyroid carcinoma (PTC), nodular goiter (NG), and three follicular-pattern comparator groups: follicular adenoma (FA), follicular thyroid carcinoma (FTC), and follicular variant of papillary thyroid carcinoma (FVPTC).

This retrospective study included 344 pathology-confirmed lesions: 41 OTNs, 110 PTCs, 90 NGs, 45 FAs, 24 FTCs, and 34 FVPTCs. Two radiologists independently re-reviewed stored preoperative ultrasound images while blinded to histopathologic diagnoses. Because the original reports did not consistently document C-TIRADS categories, they were reconstructed post hoc from feature-level descriptors. Feature-specific Firth logistic regression models adjusted for age, sex, and maximum lesion diameter, used size-matched sensitivity analyses; 1:1 matching with a 5-mm caliper.

OTNs were larger than PTC, NG, and FVPTC lesions (median maximum diameters: 25.0, 7.0, 9.0, and 10.0 mm, respectively; P < 0.001) but similar in size to FA and FTC lesions. They were commonly wider than tall (100.0%), had smooth margins (80.5%), were isoechoic (65.9%), and were hypervascular (70.7%). After adjustment, all six prespecified features were associated with OTN versus PTC. Compared with NG, smooth margins (aOR, 3.84; 95% CI, 1.30-13.14; P = 0.014) and is echogenicity (aOR, 3.36; 95% CI, 1.19-9.69; P = 0.022) remained associated with OTN. Compared with the pooled follicular-pattern comparator group (FA, FTC, and FVPTC), smooth margins and absence of focal echogenic foci remained associated with OTN (aORs, 3.71 and 2.55; P = 0.002 and 0.022, respectively), but these associations were attenuated after lesion-size matching.

In this surgically selected cohort, OTNs showed several recurring conventional sonographic features, but their appearance overlapped substantially with follicular neoplasms and NG. Ultrasound may raise preoperative suspicion for an oncocytic phenotype but cannot distinguish oncocytic adenoma from oncocytic carcinoma.

Retinoic acid, the active metabolite of vitamin A, is a pleiotropic signaling molecule that integrates developmental, homeostatic, and pathological processes across multiple organ systems. During embryogenesis, RA gradients regulate tissue patterning and lineage commitment, while in adult tissues, RA contributes to epithelial integrity, stem-cell regulation, immune homeostasis, and metabolic balance. Disruption of retinoic acid synthesis, degradation, receptor signaling, or pathway crosstalk underlies a broad spectrum of diseases, including congenital malformations, autoimmune and inflammatory conditions, neurodegenerative disorders, cardiovascular disease, pulmonary and ophthalmic pathologies, and cancer. In the tumor, RA signaling exhibits remarkable plasticity, acting as either a differentiation inducer or a stemness-maintaining factor, depending on genetic, metabolic, and microenvironmental cues. Therapeutically, retinoid-based interventions have revolutionized the treatment of acute promyelocytic leukemia. Still, their broader application has been constrained by resistance mechanisms, pharmacokinetic limitations, tissue-specific effects, and the dual nature of retinoic acid signaling across different disease states. Advances in organoid systems, single-cell and spatial transcriptomics, and multimodal epigenomics are revealing highly localized and cell-type specific retinoid responses, supporting a systems-level model of RA signaling. This framework defines "retinoid endotypes" as tissue- and stage-specific states shaped by retinoid metabolic niches, chromatin state, and microenvironmental organization, with potential to guide patient stratification and precision retinoid therapy.