Cardiac calcified amorphous tumours (CATs) are rare non-neoplastic intracardiac masses characterized by calcified nodules within an amorphous fibrinous matrix and may clinically mimic thrombi or cardiac neoplasms. We report two uncommon cases of right atrial CAT occurring in young women and provide a narrative review of the literature.

Two patients with right atrial CAT underwent multimodality imaging evaluation, including echocardiography, computed tomography, and cardiac magnetic resonance, followed by surgical excision and histopathological examination. A narrative review of published cases identified through PubMed and Embase between 1972 and 2025 was also performed.

The first patient presented with a calcified right atrial mass extending into the superior vena cava, associated with superior vena cava syndrome and autoimmune disease. The second patient, affected by end-stage renal disease on hemodialysis and thrombophilia, presented with a large calcified right atrial mass associated with a retained dialysis catheter fragment. Histopathological examination confirmed CAT in both cases. The literature review identified 112 published reports comprising 143 patients, including the two cases presented herein, highlighting frequent associations with end-stage renal disease, mitral annular calcification, and embolic complications.

Cardiac CAT remains a rare and likely underrecognized entity with heterogeneous clinical presentation and significant embolic potential. Multimodality imaging is essential for diagnosis and surgical planning, while early surgical excision should be considered in symptomatic or high-risk patients.

Background/Objectives: Sinonasal osteomas are benign, slow-growing tumors that are typically asymptomatic and incidentally detected. However, in rare cases, they may present with atypical and potentially serious complications involving other sinonasal, orbital, or intracranial structures. This review aims to synthesize these unusual manifestations and to highlight the underlying mechanisms, diagnostic challenges, and management implications. Methods: A narrative review of the literature was conducted, focusing on reported cases of sinonasal osteomas with rare or complicated presentations. Studies were analyzed with emphasis on clinical features, imaging findings, pathophysiological mechanisms, and treatment strategies. Results: Unusual presentations of sinonasal osteomas are primarily driven by sinus obstruction, progressive expansion, and skull-base erosion. These processes may result in complications such as pneumocephalus, intracranial mucoceles, cerebrospinal fluid leaks, orbital compression, and secondary infections. Clinical manifestations are often nonspecific, including headache, seizures, visual disturbances, or focal neurological deficits, which may delay diagnosis. High-resolution computed tomography is essential for identifying the osseous lesion and associated bone changes, while magnetic resonance imaging is critical for assessing soft-tissue involvement and intracranial extension. Management is individualized, with surgical resection indicated in most symptomatic or complicated cases, using endoscopic, open, or combined approaches. Conclusions: Although rare, atypical manifestations of sinonasal osteomas can result in significant morbidity. A mechanism-based understanding, supported by appropriate imaging, is essential for accurate diagnosis and timely management. Increased clinical awareness is crucial to improving outcomes in these uncommon but clinically significant cases.

Recovery after major head-and-neck reconstruction extends beyond flap survival and wound closure, involving swallowing, psychological adaptation, body image, and overall quality of life. Integrated multidimensional assessments remain limited in routine reconstructive outcomes research.

The aim of this study was to characterize and compare six-month multidimensional recovery-clinical, functional, nutritional, psychological, and body-image outcomes-between microvascular free-flap and regional pedicled-flap reconstruction and to identify factors that stratify risk for persistent functional and psychosocial impairment.

We conducted a single-center prospective cohort study at the "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania, enrolling 87 adults undergoing major reconstructive surgery after ablative treatment of head-and-neck defects (52 microvascular free flaps; 35 regional pedicled flaps). Patients were assessed at baseline and 6 months using the SF-36, WHOQOL-BREF, Body Image Scale (BIS), HADS, PHQ-9, GAD-7, Functional Oral Intake Scale (FOIS), speech intelligibility, and PEG/tracheostomy dependence.

At 6 months, most SF-36 and WHOQOL-BREF domains improved with moderate effect sizes (d = 0.3-0.7; all p ≤ 0.009), and body image distress decreased significantly (ΔBIS -2.9 ± 4.6; p < 0.001), whereas social functioning showed no robust gain (p = 0.098; not surviving false-discovery-rate correction). Pedicled reconstruction was associated with higher PEG dependence (37.1% vs. 9.6%; p = 0.005) and worse FOIS (4.7 ± 1.4 vs. 5.6 ± 1.2; p = 0.003). Major complications were linked to blunted or worsening psychological trajectories and a threefold higher rate of clinically significant depression (HADS-D ≥ 11: 66.7% vs. 18.7%; p = 0.001). In a reduced four-predictor multivariable model, pedicled flap (aOR 4.6), adjuvant radiotherapy (aOR 2.8), major complication (aOR 3.3), and lower baseline FOIS (aOR 0.5 per point) were independently associated with PEG dependence (optimism-corrected AUC 0.79). Clustering identified three recovery phenotypes-functional/emotional responders, psychological/body-image responders, and global slow recovery-with significantly different PEG rates (5.9%, 21.4%, 40.0%; p = 0.006). Exploratory mediation analysis suggested that the association between reconstruction technique and mental quality-of-life recovery was partly statistically accounted for by swallowing and body-image improvement.

Recovery after major head-and-neck reconstruction is multidimensional and heterogeneous. Baseline swallowing function, reconstruction technique, radiotherapy, and major complications jointly stratify risk for persistent functional and psychosocial impairment, supporting risk-adapted multidisciplinary rehabilitation and early psycho-oncologic screening.

Nano-carbon biointerfaces offer versatile platforms for cancer biomarker detection, but their progression from analytical proof-of-concept to clinically usable diagnostic evidence remains uneven. This scoping review maps 191 primary studies published from 2024 to 2026, covering nano-carbon families, surface chemistries, transduction architectures, biological matrices, and translational endpoints in cancer biosensing. The evidence space spans four nano-carbon dimensional classes: zero-dimensional carbon dots and quantum dots, one-dimensional carbon nanotubes, two-dimensional graphene-derived materials, and three-dimensional hybrid composites. Across these platforms, analytical sensitivity did not scale monotonically with nano-carbon dimensionality; instead, performance was shaped by the interaction between material architecture, biointerface chemistry, recognition strategy, transduction modality, and matrix context. A Translational Readiness Matrix showed that approximately 67% of studies remained at Low Evidence Level, whereas only approximately 10% reached Strong Evidence Level. Five recurring bottlenecks constrained translation: incomplete reproducibility reporting, limited Real-matrix Validation, scarce comparator-based clinical evidence, insufficient manufacturing-scale data, and weak regulatory or deployment planning. To address these gaps, this review proposes a nine-item minimum reporting checklist and a four-stage validation roadmap to support more reproducible, comparable, and clinically oriented nano-carbon biosensor development.

Lymph node metastasis (LNM) is a key prognostic factor in esophageal squamous cell carcinoma (ESCC), and accurate preoperative prediction remains challenging. Blood biomarkers provide a conventional, preoperative diagnostic technique that is cost-effective and free from radiation risks. So far, previous studies have been published on the precise diagnosis of lymph node metastases using conventional ultrasound or CT techniques. While there is a lack of research studies that address the diagnosis of LNM from blood biomarkers. In this work, we acquired a cohort of blood biomarkers of 1933 patients and designed a weighted neural network (WNN) model for the accurate prediction of LNM from blood biomarkers. The WNN model is designed with a neural network classifier trained on blood biomarkers labeled with pathological nodal (pN) stages of LNM. The experimental findings demonstrate that the WNN model achieved 83.1% accuracy and an AUC of 0.88 on the original, non-augmented test set for diagnosing LNM, while CT only achieved 50.4% accuracy (AUC 0.60) and ultrasound achieved 60.5% accuracy (AUC 0.67). Additionally, SHAP analysis reveals that three blood biomarkers-white blood cells (WBC#), monocytes (Mono#), and neutrophils (Neut#)-significantly impact the WNN model's output. This WNN model shows promise as a research tool to diagnose LNM.

Prostate cancer remains a major cause of cancer-related mortality, and new therapeutic strategies are needed for advanced disease. Niclosamide and related salicylanilide compounds have emerged as multitarget anticancer agents, but the molecular contexts associated with their activity remain incompletely understood. Here, we applied a phenotype-oriented integrative framework to characterize the molecular context and phenotypic activity of NSC828786, a niclosamide-like salicylanilide derivative. Cross-cohort transcriptomic analyses identified AMACR (alpha-methylacyl-CoA racemase) and HPN (hepsin) as consistently upregulated genes in independent prostate adenocarcinoma cohorts. NCI-60 profiling demonstrated broad-spectrum low-micromolar antiproliferative activity, including AR-negative prostate cancer and breast cancer cell lines spanning multiple receptor subtypes; however, quantitative ranking did not support preferential receptor subtype selectivity. CellMiner COMPARE analysis showed no significant correlation between baseline AMACR or HPN expression and NSC828786 sensitivity. Structure-based analyses supported computational compatibility of NSC828786 with predicted HPN- and AMACR-associated binding regions, while zebrafish assays showed no overt developmental abnormalities at concentrations ≤ 5 μM. These findings identify NSC828786 as a phenotypically active salicylanilide derivative and position HPN and AMACR as exploratory candidate molecular associations warranting further mechanistic and target engagement studies.

Most cancers are fatal and remain challenging to cure due to changes in tumorigenesis and therapeutic resistance. Despite significant advancements in cancer therapy, a substantial proportion of malignancies exhibit resistance to conventional therapies, driven primarily by cancer plasticity and the emergence of multidrug resistance. Recent cancer treatments include cytotoxic chemotherapy, molecular targeted therapy, and immune checkpoint inhibitors. A major hallmark of cancer cells is their ability to develop sophisticated evasion mechanisms that bypass programmed cell death when exposed to anti-cancer drugs. In addition, malignant cells evade the efficacy of anti-cancer drugs by altering cell proliferation, survival, and metastasis. To suppress oncogenic characteristics, necroptosis-based therapies have attracted substantial attention, as they can inhibit tumorigenesis and improve treatment outcomes across many cancer types. Furthermore, an increasing body of research focuses on suppressing tumorigenesis by targeting receptors that are overexpressed in cancer cells. In this review, we elucidate how tumorigenesis is inhibited by regulating the epidermal growth factor receptor (EGFR)-tumor necrosis factor receptor (TNFR) signaling pathway in necroptosis. By delineating the underlying mechanisms of these receptors, we propose that the induction of necroptosis via EGFR and TNFR represents an innovative paradigm for targeted therapy, offering a strategy to enhance clinical outcomes in treatment-resistant cancers.

Soft tissue sarcomas (STSs) are rare and heterogeneous mesenchymal malignancies characterized by diverse molecular profiles and immune landscapes. Although immunotherapy has revolutionized the treatment of specific solid tumors, its efficacy in STSs remains limited and variable across histotypes. This review explores the panorama of biomarkers of immunotherapy sensitiveness in STSs, with particular emphasis on tumor-intrinsic features and on tumor microenvironment (TME) signatures. Current evidence highlights low tumor mutational burden, rare microsatellite instability, heterogeneous antigen expression, and epigenetic suppression of antigen presentation as hallmarks of the immune resistance that is characteristic of many STSs. However, growing evidence underlines TME composition as a major determinant of response to different types of immunotherapy. Indeed, the presence of B-cell-rich tertiary lymphoid structures and certain traits of adaptive immune responses are provenly associated with enhanced sensitivity to immunotherapy and enhanced outcomes. We further discuss emerging strategies aimed at enhancing STS immunogenicity, either by increasing intrinsic tumor immunogenicity or remodeling TME composition and functional profile. Collectively, the available data support a paradigm shift from a sarcoma cell-centered approach toward a multi-compartment TME-including strategy, providing a framework for the development of more effective and personalized immunotherapeutic strategies in STS.

Hypoxia and the evolving concept of pseudohypoxia are critical in driving tumor angiogenesis, contributing to malignancy progression and therapeutic resistance. Angiogenesis, a common feature of many solid tumors, is promoted by hypoxia-induced overexpression of pro-angiogenic factors (e.g., VEGF, FGF) and genetic mutations (e.g., VHL, SDH) that stabilize hypoxia-inducible factors (HIF) even in normal oxygen conditions, a phenomenon known as pseudohypoxia. Recent experimental studies challenge the view that hypoxia universally enhances vessel growth. In certain models, severe oxygen deprivation impairs angiogenesis. Furthermore, tumor-mediated metabolic reprogramming can drive immune evasion via HIF stabilization in immune cells. These paradoxes, together with persistent therapy resistance and the limited effectiveness of current anti-angiogenic treatments, reveal critical gaps in our understanding of how hypoxic signaling modulates vascular and immune dynamics within the tumor microenvironment. These complexities demand more detailed exploration of underlying processes and the development of innovative therapeutic strategies. Here, we review recent mechanistic studies on tumor angiogenesis, summarizing therapeutic and diagnostic advances from both preclinical and clinical studies. We further discuss strategies to exploit hypoxic vulnerabilities, including HIF inhibitors, hypoxia-activated prodrugs, vascular normalization, combination regimens to restore immunity, biomarker-guided patient selection, and advanced hypoxia-targeted imaging to improve outcomes in angiogenesis-driven cancers.

Chronic lymphocytic leukemia (CLL) is characterized by clinical and biological heterogeneity shaped by intrinsic signaling programs and microenvironmental interactions. Established biomarkers, including IGHV mutation status and TP53 alterations, provide important clinical and molecular information, but do not fully capture the diversity of pathways that sustain leukemic cell fitness. Aberrant calcium signaling contributes to leukemic survival; however, the clinical relevance of Ca²⁺/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a calcium-responsive kinase, has not been defined. This study evaluated CaMKK2 as a candidate marker associated with high-risk disease biology and a pathway of interest for further study.

CaMKK2 expression was quantified in purified CD19⁺ CLL cells from a clinically annotated cohort balanced by immunoglobulin heavy chain variable region (IGHV) mutation status. Associations with time to treatment and overall survival were analyzed. Functional relevance was assessed by pharmacologic inhibition of CaMKK2 in primary CLL cells using metabolic (MTS) and apoptosis (Annexin V/PI) assays. Correlations between CaMKK2 expression and inhibitor sensitivity were determined. The impact of CaMKK2 inhibition on nurse-like cell (NLC) differentiation and macrophage-mediated leukemic support was evaluated in ex vivo culture systems.

Elevated CaMKK2 expression was enriched in IGHV-unmutated CLL and associated with shorter time to treatment and inferior overall survival. Pharmacological inhibition of CaMKK2 was associated with reduced primary CLL viability in a dose-dependent manner and increased Annexin V/PI-defined total cell death with sensitivity correlating with CaMKK2 expression levels. Inhibition also attenuated CD163⁺ macrophage polarization and impaired NLC-mediated support of leukemic cells.

CaMKK2 expression is associated with IGHV-unmutated, high-risk CLL biology. Pharmacologic inhibition of CaMKK2 was associated with reduced leukemic cell viability and altered macrophage phenotypes in ex vivo systems. These findings are exploratory, derived from a limited cohort, and support further investigation into the role of CaMKK2 in CLL biology, but do not establish independent prognostic value or direct on-target causality.