Although research on palliative care in hematological malignancies has increased, research examining quality of death (QOD) and quality of care (QOC) in this population remains limited. This study compared QOD and QOC between patients with hematological malignancies and those with solid tumors.

The authors conducted a secondary analysis of a nationwide mortality follow-up survey of bereaved family members in Japan (2017-2018). The study included 3575 decedents with hematological malignancies and 50,592 with solid tumors. Propensity score matching was performed to adjust for demographic and clinical characteristics. QOD and QOC were assessed using the Good Death Inventory (GDI) and the Care Evaluation Scale 2.0 (CES). Bivariate analyses compared the matched groups.

Overall, QOD and QOC were comparable between groups. However, among the GDI subdomains, patients with hematological malignancies had slightly lower scores for "good relationships with family" (mean difference, 0.2; 95% confidence interval [CI], 0.03-0.3) and "preparation for death" (mean difference, 0.2; 95% CI, 0.04-0.3). In addition, patients with hematological malignancies were less likely to die in palliative care units than those with solid tumors (mean difference, 3.9%; 95% CI, 0.4%-7.4%).

Although overall quality measures were similar, specific QOD domains related to family relationships and preparation for death were slightly lower among patients with hematological malignancies. These findings may reflect limited opportunities for end-of-life discussions due to the unpredictable and rapidly progressive course of hematological malignancies. Enhancing communication about prognosis and goals of care and early integration of palliative care may improve end-of-life experiences.

Robot-assisted partial nephrectomy (RAPN) using the da Vinci Surgical System (DVSS) is broadly performed globally. In Japan, the Hinotori Surgical Robot System (HSRS) has recently been developed. However, few studies have compared perioperative outcomes between HSRS-RAPN and DVSS-RAPN. This study aimed to compare perioperative outcomes between these two robotic platforms.

Clinical data from 86 patients who underwent RAPN from April 2023 to November 2025 were prospectively collected and retrospectively analysed. Propensity score matching (1:1) based on preoperative variables yielded 31 matched pairs. Perioperative outcomes, including trifecta achievement, were compared.

Following matching, baseline characteristics were well balanced. Operative parameters, perioperative complications, positive surgical margins, postoperative renal function, and trifecta rates did not significantly differ between the groups.

HSRS-RAPN can be safely and effectively performed, achieving perioperative outcomes comparable to those of DVSS-RAPN. These findings suggest that HSRS is a feasible alternative robotic platform for RAPN.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis and limited predictive biomarkers for therapy response. Characterizing malignant cell heterogeneity may improve prognostic and therapeutic stratification. We integrated single-cell RNA sequencing (scRNA-seq) data from 58 HNSCC patients (181,003 cells) to define malignant cell subpopulations, their differentiation states, developmental trajectories, cell-cell interactions, and spatial localization. Coexpression gene modules and meta-programs were identified using hdWGCNA and NMF. These programs were projected onto bulk RNA-seq datasets to classify HNSCC subtypes and examine associations with clinical outcomes, tumor microenvironment (TME), genomic instability, and predicted response to immune checkpoint inhibitors (ICIs). Twelve malignant clusters were identified with distinct clinical and molecular features. MC-5 exhibited a stem-like phenotype associated with poor prognosis, while MC-7 and MC-11 showed high TME communication and immune engagement. Coexpression analysis revealed 16 modules and eight meta-programs encompassing proliferation, differentiation, stress response, and immune activity. Translation to bulk RNA-seq defined three HNSCC subtypes (MS-1, MS-2, MS-3) with divergent survival, immune infiltration, stromal composition, and genomic features. MS-2, an immune-enriched subtype, demonstrated superior survival, high HPV positivity, and predicted ICI responsiveness. A 25-gene malignant cell score (MCScore) robustly predicted both prognosis and immunotherapy response. This study provides a comprehensive map of malignant cell heterogeneity in HNSCC, identifies key functional expression programs, and defines molecular subtypes with clinical and therapeutic relevance. Malignant cell-specific signatures, such as MCScore, offer promising tools for patient stratification and precision immunotherapy.

Coffee extracts contain numerous bioactive compounds. Given the dietary link between coffee consumption and colorectal cancer, this study compared the effects of roasted and green (unroasted) coffee extracts on human colorectal cancer cells (HCT116) and non-cancerous fibroblasts (BJ-5ta) to evaluate how processing influences proliferation and molecular signaling. Real-time cell analysis (RTCA), qRT-PCR, and label-free quantitative proteomic analysis were performed to assess cellular responses. MTS and RTCA showed that in BJ-5Ta fibroblasts, coffee extracts increased proliferation in the order CNR < CAR < CAU < CNU, whereas the trend was reversed in HCT116 cancer cells. Proteomic analysis revealed that in BJ-5Ta cells, unroasted coffee extract caused downregulation of the ribosome pathway, and natural coffee extract caused downregulation of the gap junction pathway, indicating reduced protein synthesis and cell-cell communication as a potential stress-adaptive response. In contrast, in HCT116 cells, unroasted coffee extract upregulated the ribosome pathway. Also, natural coffee extract upregulated the pentose phosphate pathway in HCT116 cells, which may enhance NADPH production and reduce oxidative stress. Current evidence suggests coffee's bioactive compounds may have different effects varying by coffee extract type and their preparation.

Ferroptosis can be inhibited by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in cancers. ETS variant transcription factor 4 (ETV4) is aberrantly expressed in various cancers. Elevated transcription of guanosine triphosphate cyclohydrolase 1 (GCH1) contributes to tumor malignancy. This study investigated the involvement of IGF2BP3, ETV4, and GCH1 in ferroptosis in gastric cancer (GC).

GC cells and tissue samples were used to detect IGF2BP3, ETV4, and GCH1 expression. The relationships between IGF2BP3, ETV4, and GCH1 were assessed using RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual-luciferase reporter assay. BALB/c nude mice were utilized to establish GC tumor xenografts. Cell cloning and Transwell were used to detect the proliferation, migration, and invasion of cells.

IGF2BP3 and ETV4 were upregulated in GC. IGF2BP3 regulated ETV4 protein level by mediating its mRNA stability. Knockdown of ETV4 inhibited GC cell proliferation, migration, and invasion, and promoted their ferroptosis. ETV4 also promoted the transcription of GCH1 by directly binding to its promoter region. GCH1 overexpression diminished the facilitating effect of ETV4 knockdown on ferroptosis in GC. Overexpression of GCH1 also eliminated the promoting impact of IGF2BP3 knockdown on GC cell proliferation, migration, and invasion. Lastly, inhibition of GCH1 reversed the promoting effect of IGF2BP3 overexpression on GC tumor growth in vivo.

IGF2BP3 promotes tumor growth and inhibits ferroptosis in GC by regulating ETV4, while ETV4 promotes GCH1 expression by direct interaction with its promoter. GCH1 overexpression counteracts the effects of ETV4 and IGF2BP3 on GC.

Stathmin-3 (STMN3) is a member of the microtubule-destabilizing regulatory protein family and functions to promote microtubule depolymerization. It specifically binds to the α/β heterodimers of microtubules, facilitating their depolymerization and inhibiting polymerization, thereby influencing cell morphology and function. Recent studies have indicated that aberrant expression of STMN3 is closely associated with the development of various diseases. In the field of oncology, STMN3 has been found to be dysregulated in multiple cancer types and is strongly linked to tumor initiation, progression, and metastasis. Owing to these characteristics, STMN3 is involved in diverse physiological and pathological processes as well as critical signaling pathways, demonstrating its potential as a multifunctional regulatory molecule. This article reviews and analyzes the roles and mechanisms of STMN3 in tumorigenesis, with the aim of identifying potential therapeutic targets and contributing to the development of precision medicine strategies for cancer treatment. This study is a narrative review on the role of STMN3 in tumors, which is guided by the Scale for the Assessment of narrative review articles (SANRA). Literature retrieval was conducted in public databases such as PubMed and Web of Science using "STMN3″, "SCLIP", "tumor", and "cancer" as key words, with no restriction on publication time. Relevant studies were screened based on research content and data integrity, including bioinformatic analyses and in vitro/in vivo experimental studies.

Two isoforms of the 90-kDa heat shock protein (Hsp90), stress-inducible Hsp90α and constitutively expressed Hsp90β, function in mammalian cells as molecular chaperones that promote the folding of specific client proteins involved in essential cellular processes and regulatory pathways. A number of Hsp90 client proteins take part in cancer progression, and the inhibition of Hsp90 induces the degradation of oncogenic client proteins and cancer cell death. Hsp90 inhibitors specific for individual Hsp90 isoforms have a significant potential for the development of anticancer therapeutics due to reduced toxicity. Cells with knocked-out genes encoding Hsp90 isoforms represent excellent cellular models to investigate the rearrangement of the cell chaperone machinery in response to the suppression/loss of the Hsp90 isoforms.

Recently, we have shown that the knockout of the HSP90AA1 gene encoding Hsp90α in human fibrosarcoma HT1080 cells does not affect basic cellular processes in normal and stressful conditions, which suggests an adaptation of the cell chaperone machinery to the loss of Hsp90α. Here, we demonstrated that the lack of Hsp90α in HT1080 cells leads to an up-regulation of the constitutively expressed Hsp90β and several important Hsp90 co-chaperones (Aha1, Hop, and others). The expression of the major chaperones of the Hsp70 machinery (Hsp70-1, Hsp70-2, Hsc70) was also significantly induced. The components of the prefoldin-chaperonin folding arm and PFDL, R2TP, and R2SP complexes, as well as the major mitochondrial chaperones, were also largely up-regulated in Hsp90α-KO cells, while the expression of ER-resident chaperones/co-chaperones was either repressed or did not change.

We demonstrated here for the first time an adaptation of the cell chaperone machinery to the loss of the Hsp90α chaperone, which may be important for understanding the molecular mechanisms of action of Hsp90α-specific inhibitors and elaborating new therapy strategies in combating cancer, including the combination of Hsp90α-targeted therapy.

Therapeutic resistance is a major cause of treatment failure in glioblastoma (GBM), highlighting the need for physiologically relevant models to identify actionable resistance mechanisms. While two-dimensional (2D) cultures are widely used for target discovery, they poorly represent the tumor microenvironment. In contrast, three-dimensional (3D) spheroid cultures better recapitulate spatial heterogeneity, hypoxic gradients, and stress-adaptive signaling observed in tumors.

We applied an integrated 2D-3D quantitative proteomic approach to identify microenvironment-dependent regulators of chemoresistance in GBM. Proteomic profiling was performed in U87MG and U251MG cells grown as 2D monolayers or 3D spheroids. Differentially expressed proteins were validated by quantitative RT-PCR, and functional studies were conducted using genetic depletion followed by assessment of temozolomide (TMZ) sensitivity.

Comparative analysis identified 13 proteins consistently differentially expressed between 2D and 3D cultures: NDUFB5, RNGTT, MLK4, SYN1, DDX5, EIF2AK2, ITGA1, ZNF33B, ZNF343, WDR19, JPH3, CCT8L2, and FNDC3A. Among these, Mixed Lineage Kinase 4 (MLK4) showed strong and reproducible upregulation in 3D spheroids in both GBM cell lines. Genetic depletion of MLK4 significantly increased TMZ sensitivity without affecting basal cell viability, suggesting a specific role in therapy response. Notably, MLK4 expression was induced only under 3D conditions.

MLK4 functions as a microenvironment-responsive regulator of chemoresistance in GBM. These findings demonstrate that 3D culture systems reveal clinically relevant resistance pathways not detectable in conventional 2D models and highlight 3D proteomic profiling as a powerful strategy for identifying therapeutically actionable targets.

The clinical trajectory of pulmonary vascular disease (PVD) is governed by the functional and molecular integration of the right ventricle (RV) and pulmonary vasculature-the cardiopulmonary unit. Right ventricular-pulmonary arterial (RV-PA) coupling (Ees/Ea) is the principal determinant of survival. This review synthesizes contemporary pathophysiology and therapeutics through the lens of RV-PA coupling, reflecting the recognition of active heart-lung crosstalk. Advancing beyond traditional reviews, this article (1) formalizes a phenotype-guided treatment algorithm based on coupling derangement, (2) integrates emerging concepts of molecular crosstalk mediated by extracellular vesicles, and (3) positions sotatercept as a "coupling drug" targeting both components of the cardiopulmonary unit. We detail maladaptive pathways-including metabolic reprogramming, inflammation, fibrosis, and sex hormone signaling-that degrade RV contractility (Ees) under chronic pressure overload. The pharmacotherapeutic landscape is critically evaluated: from established vasodilators that indirectly support the RV by reducing afterload (Ea) to transformative disease-modifying agents like sotatercept that reverse vascular remodeling and the emerging frontier of direct RV-targeted therapies. We argue that the future of PVD management lies in a precision-based strategy using deep phenotyping to classify patients by dominant coupling derangements and matching them with mechanism-based therapies. The paradigm must shift beyond symptomatic vasodilation toward regimens explicitly designed to restore the physiological balance of the cardiopulmonary unit, carefully distinguishing between validated standards of care and investigational approaches.

This study aimed to develop a method for extracting acoustic features to assess left anterior descending artery (LAD) stenosis severity.

Heart sound data were collected from 75 participants (10 diastoles per participant) using a high-signal-to-noise ratio micro-electro-mechanical systems stethoscope. The diastolic signals were preprocessed, and empirical wavelet transform was applied to decompose their power spectra into three modes (0-150, 150-500, and > 500 Hz). The spectral energies (e(1), e(2), e(3)) of these modes were analyzed, and support vector machine (SVM) and extreme gradient boosting (XGBoost) machine learning algorithms were used to classify LAD stenosis into mild (< 50%), moderate (50%-75%), and severe (> 75%).

Spectral energies e(2) and e(3) significantly increased with stenosis severity, and XGBoost outperformed SVM, achieving a test accuracy of 0.8133 and areas under the curve of 0.9358, 0.9644, and 0.9580 for mild, moderate, and severe stenosis, respectively.

Empirical wavelet transform-extracted spectral energies of e(2) and e(3), combined with XGBoost, effectively determine LAD stenosis degree, offering a non-invasive screening tool.