Search Results (4,110)

The single-cell spatial transcriptomics (ST) data with cell type and spatial location, i.e., $(C,x,y)$ with C as cell type and $(x,y)$ as its spatial location, produced by recent biotechnologies, such as CosMx and Xenium, contain a huge amount of information about cancer tissue samples, thus have great potential for cancer research via detection of ST-Community which is defined as a collection of cells with distinct cell-type composition and similar neighboring patterns based on nearby cell-percentages. But for huge CosMx single-cell ST data, the existing clustering methods do not work well for st-community detection, and the commonly used kNN compositional data method shows lack of informative neighboring cell patterns. In this article, we propose a novel and more informative disk compositional data (DCD) method for single-cell ST data, which identifies neighboring patterns of each cell via taking into account of ST data features from recent new technologies. After initial processing single-cell ST data into the DCD matrix, an innovative DCD-TMHC computation method for st-community detection is proposed here. Extensive simulation studies and the analysis of CosMx breast cancer data, which is an example of single-cell ST dataset, clearly show that our proposed DCD-TMHC computation method is superior to other existing methods. Based on the st-communities detected for CosMx breast cancer data, the logistic regression analysis results demonstrate that the proposed DCD-TMHC computation method produces better interpretable and superior outcomes, especially in terms of assessment for different cancer categories. These suggest that our proposed novel and informative DCD-TMHC computation method here will be helpful and have an impact on future cancer research based on single-cell ST data, which can improve cancer diagnosis and monitor cancer treatment progress. Full article

Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than “one-size-fits-all” targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer. Full article

Wound-related issues such as delayed healing and patient discomfort remain common challenges in oncoplastic breast surgery and may negatively affect early postoperative recovery. This single-centre, retrospective, within-patient study explored the feasibility and safety of a breast-shaped polyurethane and polyester dressing impregnated with an oxygen-enriched oleic matrix, designed to provide a controlled, low-level release of reactive oxygen species involved in physiological tissue repair. Sixty patients undergoing unilateral lumpectomy with contralateral breast remodelling were included. The advanced dressing was applied to the oncologic breast, while standard premedicated patches were used on the contralateral side, allowing each patient to serve as her own control. Early postoperative outcomes, including wound dehiscence, infection, delayed healing, and qualitative user experience, were assessed descriptively over the first postoperative month. The oxygen-enriched oleic matrix dressing was well tolerated and associated with good skin hydration, comfort, and ease of use. No infections, hematomas, or reoperations were observed, and no relevant differences in early complication patterns emerged between the treated and control sides. Both patients and healthcare personnel reported favourable handling characteristics and comfort, with no device-related adverse events. These preliminary, hypothesis-generating findings suggest that oxygen-enriched oleic matrix breast-shaped dressings are a feasible and safe option for early postoperative wound management in oncoplastic breast surgery. Prospective, adequately powered multicentre studies are warranted to further investigate their potential role within standardized postoperative care pathways. Full article

The HIV-1 envelope glycoprotein gp120 is prominently exposed on the surface of both HIV-1 virions and infected host cells, serving as a key marker of infection. gp120 plays a pivotal role in viral entry by interacting with the primary receptor, CD4, on host cells. Therapeutic strategies targeting the HIV-1 reservoir, such as anti-gp120 antibodies that trigger antibody-dependent cellular cytotoxicity (ADCC) and chimeric antigen receptor T (CAR-T) cells, rely on the presence of gp120 on the surface of infected cells to exert their effects. Consequently, accurate monitoring of gp120 expression on infected cells is essential for evaluating the pharmacological efficacy of these interventions. In this study, a sensitive, specific, and inexpensive enzyme-linked immunosorbent assay (ELISA) for quantifying HIV-1 gp120 glycoprotein was developed using a selected pair of anti-gp120 antibodies. The assay achieved a lower limit of quantitation (LLOQ) of 0.16 pM, demonstrating sensitivity comparable to that of the digital single molecule array (Simoa) platform, which exhibited a LLOQ of 0.23 pM and requires specialized instrumentation. The binding specificity of the antibodies used in the novel assay was confirmed using liquid chromatography–mass spectrometry (LC-MS), and the assay was pharmacologically validated with lysates obtained from 2D10 and MOLT IIIB cell lines. Furthermore, treatment of HIV-infected human primary CD4⁺ T cells with a targeted activator of cell kill (TACK) compound significantly reduced gp120 concentration in CD4⁺ T cell lysate compared to controls. The gp120 marker from infected cell lysates correlated with the number of gp120-positive cells detected by immunocytochemistry, as well as with HIV-1 p24 levels and cell-associated viral RNA measurements. In summary, a novel, simple, and sensitive HIV-1 gp120 ELISA has been developed and validated. This assay holds potential for investigating HIV-1 persistence and evaluating the efficacy of therapeutic agents targeting infected cells. Full article

This study evaluated the clinical utility of a polygenic risk score (PRS)-based multigene panel test for predicting diabetes mellitus (DM) in a healthy population. A total of 302 individuals underwent genetic testing using the HelloGene™ DM panel, which includes four DM-related single nucleotide polymorphisms (CDKAL1, HHEX, KCNQ1, and TCF7L2). PRS values were calculated using an algorithm developed from the Korean Genome and Epidemiology Study (KoGES; n = 39,605), and participants were classified into four genetic risk groups (low, moderate, high, and very high). Fasting blood glucose, glycated hemoglobin (HbA1c), and body mass index were assessed at baseline and after at least three years of follow-up, and lifestyle factors including smoking, alcohol consumption, and exercise status were recorded. No significant differences in age, sex, or lifestyle habits were observed among PRS groups. The very high-risk group showed significantly higher follow-up fasting blood glucose levels (p = 0.001) and higher baseline and follow-up HbA1c levels (p = 0.0025 and p = 0.001, respectively), as well as a 4.5-fold increased risk of developing DM compared with other groups. Smoking significantly modified genetic risk, with smokers in the very high-risk group showing a 25% higher likelihood of developing DM. CDKAL1 and TCF7L2 variants were most prevalent in the moderate- and high-risk groups, while HHEX variants in the high-risk group showed the greatest susceptibility, particularly among current smokers. Overall, PRS-based genetic testing demonstrated potential clinical utility for stratifying individuals according to relative diabetes risk, highlighting a possible interaction between genetic susceptibility and lifestyle factors such as smoking Full article

Background: Artificial Intelligence (AI) has emerged as a transformative tool in in vitro fertilization (IVF) as it has done in other sectors. In IVF, AI offers advancements in embryo selection, treatment personalization, and outcome prediction. It does so by leveraging deep learning and computer vision, as well as AI-driven platforms such as ERICA, iDAScore, and IVY where the goal is to address the limitations of traditional embryo assessment. Key amongst them are the issues of subjectivity, labor intensity, and limited predictive power. Despite rapid technological progress, the integration of AI into routine IVF practice faces key challenges. These are issues related to clinical validation, ethical dilemmas, and workflow adaptation. Rationale/Objectives: This review synthesizes current evidence to evaluate the role of AI in IVF, focusing on six critical dimensions: (1) the evolution of AI from traditional embryology to algorithmic assessment, (2) clinical validation and regulatory considerations, (3) limitations and ethical challenges, (4) pathways for clinical integration, (5) real-world applications and outcomes, and (6) future directions and policy recommendations. The objective is to provide a comprehensive roadmap for the responsible adoption of AI in reproductive medicine. Outcomes: AI demonstrates significant potential to improve the precision and efficiency of IVF. Studies report that AI models can achieve 10 to 25% higher accuracy in predicting embryo viability and implantation potential compared to traditional morphological assessment by embryologists. This enhanced predictive power supports more consistent embryo ranking, facilitates elective single-embryo transfer (eSET) strategies, and is associated with 30 to 50% reductions in embryologist workload per embryo cohort. Early adopters report promising trends. However, large-scale randomized controlled trials have yet to conclusively demonstrate a statistically significant increase in live birth rates per transfer compared to expert embryologist selection. The most immediate and evidenced value of AI lies in hybrid decision-making models. This is where it augments embryologists by providing data-driven, objective support, thereby standardizing workflows and reducing subjectivity. Wider Implications: The sustainable integration of AI into IVF banks on three key aspects: robust evidence generation, interdisciplinary collaboration, and global standardization. To foster these, policymakers ought to establish regulatory frameworks for transparency and bias mitigation. On their part, clinicians need training to interpret AI outputs critically. Ethically, safeguarding patient trust and equity is non-negotiable. Future innovations, mainly AI-enhanced genomics and real-time monitoring, could further personalize care. However, their success depends on addressing current limitations. By balancing innovation with ethical vigilance, AI holds the potential to revolutionize IVF while upholding the highest standards of patient care. Full article

Background: The emergence of therapy-related myelodysplastic syndrome (t-MN) after autologous stem cell transplantation (ASCT) is well documented. However, with the growing use of chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies, concerns about secondary myeloid neoplasms, particularly MN, have arisen. The mechanisms and cytogenetic features associated with post-CAR-T MN, especially chromosome 7 abnormalities, remain underexplored. Objectives: To compare the incidence, timing, and cytogenetic characteristics of MN developing after CAR-T-cell therapy versus ASCT, and to evaluate the potential association between CAR-T therapy, persistent cytopenias, and these specific alterations. Study Design: This was a retrospective, single-center study of 275 patients with B-cell malignancies treated between 2015 and 2024 at Hospital Universitario Central de Asturias (Spain). Of these, 259 patients underwent ASCT and 16 received CAR-T-cell therapy (axicabtageneciloleucel n = 13, tisagenlecleucel n = 2, brexucabtageneautoleucel n = 1). Clinical, cytogenetic, and laboratory data were collected and analyzed. Incidence rates were compared using Fisher’s exact test, and time-to-event outcomes was evaluated using the Mann–Whitney U test (given the small number of events). Statistical significance was set at p < 0.05. Results: Myeloid neoplasms were diagnosed in 3 of 259 ASCT patients (1.15%) and in 2 of 16 CAR-T-cell patients (12.5%) (p = 0.03). The median time to myeloid neoplasm diagnosis was numerically shorter in the CAR-T group (15.5 vs. 69 months, p = 0.096). All post-CAR-T cases presented persistent cytopenias and cytokine release syndrome (CRS). Cytogenetic analyses revealed de novo monosomy 7 and 7q deletion in both CAR-T-related cases, whereas no chromosome 7 abnormalities were detected in ASCT-related cases. Pre-treatment samples did not show these abnormalities, although limitations in the sensitivity of the assays preclude the definitive exclusion of minor pre-existing clones. Both affected CAR-T patients had prolonged CAR-T cell persistence and required transfusional support due to hematologic toxicity. One patient was diagnosed with high-risk MN with 5q and 7q deletion and the other with Clonal Cytopenia of Uncertain Significance (CCUS) with monosomy 7. Conclusions: CAR-T-cell therapy was associated with a significantly higher and earlier incidence of myeloid neoplasms compared to ASCT in this cohort. The development of post-CAR-T myeloid neoplasm was characterized by persistent cytopenias, prolonged CAR-T cell persistence, and de novo chromosome 7 alterations. While the small sample size necessitates cautious interpretation, these findings may suggest a distinct pathogenesis potentially linked to inflammation, immune toxicity, or the expansion of pre-existing clones. This highlights the need for long-term hematologic monitoring and evaluation for clonal hematopoiesis prior to CAR-T-cell therapy, especially in heavily pretreated patients. Full article

Adoptive cell therapy (ACT) with T cells modified with a chimeric antigen receptor (CAR T cells) has dramatically improved outcomes in hematologic cancers. However, its efficacy in solid tumors, such as melanoma, is hampered by several factors. These include heterogeneous expression of tumor-associated antigens (TAA) and an immunosuppressive, profibrotic tumor microenvironment (TME), which restricts cytotoxic CAR T cells trafficking into the tumor, as well as their persistence and cytolytic activity. As a result, responses to CAR T cell monotherapy in melanoma and other solid tumors are typically weak, transient or even absent. Emerging evidence suggests that combining traditional chemotherapy with CAR T cell therapy can enhance the antitumor activity of CAR T cells in solid malignancies. Partial tumor cell killing by chemotherapy improves access to TAA and disrupts the TME by affecting the global structure of the tumor tissue. Here, we developed an immunocompetent syngeneic B16 melanoma mouse model to test a combination of classical dacarbazine (DTIC) chemotherapy with ACT with murine CAR T cells. B16-F10 (next as B16) melanoma cells were modified to express a human/murine hybrid epidermal growth factor receptor (EGFR) recognized by a murine CAR bearing a single-chain variable fragment (scFv) derived from cetuximab, an anti-EGFR monoclonal antibody approved for the treatment of colorectal and certain other solid tumors. Prior to CAR T cells administration, cyclophosphamide (CPA) pre-conditioning was used. We demonstrated that DTIC therapy followed by infusion of murine CAR T cells targeting the human/murine hybrid EGFR (EGFR mCAR T cells) provided superior tumor control and prolonged survival compared to monotherapy with either DTIC or EGFR mCAR T cells alone. These findings support the potential feasibility of a combined therapeutic strategy for human melanoma involving DTIC treatment followed by EGFR CAR T cells infusion after CPA pre-conditioning. Full article

Four new porous homochiral metal–organic frameworks (MOFs), [M₂(camph)₂(bpa)]∙Solv (M = Co(II), Ni(II), Cu(II) and Zn(II)), based on (+)-camphoric acid (H₂camph) and 1,2-bis(4-pyridyl)ethane (bpa) were synthesized and characterized. The crystal structures of [Ni₂(camph)₂(bpa)] and [Zn₂(camph)₂(bpa)] were established by single-crystal X-ray diffraction analysis. Powder X-ray data prove the phase purity and isostructural nature of all four compounds. The thermal stability of [M₂(camph)₂(bpa)] was found to depend on the electronic configuration, as well as on the redox properties of the metal cation, and varied from 225 °C (M = Zn²⁺) to 375 °C (M = Ni²⁺). The reversible, solvent-induced sponge-like dynamics of the coordination frameworks was thoroughly investigated. Changes in the positions of reflexes, related to the length of the flexible bpa linker, were observed by powder XRD, pointing to transitions between an open-framework phase and a squeezed, non-porous phase in a crystal-to-crystal manner, while the integrity and connectivity of the coordination network were maintained. Size-selective adsorption from a benzene–cyclohexane 1:1 mixture on [Zn₂(camph)₂(bpa)] was studied by ¹H NMR analysis. The benzene-favorable composition of guest molecules (C₆H₆:C₆H₁₂ = 5:1) occluded within the host crystalline sponge revealed a preferable adsorption affinity towards smaller benzene compared with larger cyclohexane. High framework stability in various solvents, as well as successful molecular separation in the liquid state, validates the potential utilization of chiral porous metal(II) camphorate MOFs in important stereoselective applications. Full article

Over the past two decades, terahertz (THz) spectroscopy has demonstrated remarkable potential for the investigation of liquids, including studies of living organisms and biological components in their natural, aqueous environments. The main advantages of THz radiation lie in its ability to interact with collective and low-energy vibrational modes of macromolecules and microorganisms, while being non-harmful due to the low photon energy involved. These characteristics make THz spectroscopy particularly valuable for research in liquids compared to other well-established techniques such as Raman and infrared spectroscopy. In this study, we offer a concise overview and comparison of two case studies from our earlier publications, highlighting how Ultrabroadband THz spectroscopy and Intense THz Spectroscopy serve as complementary methods for advancing research in liquids. Ultrabroadband THz spectroscopy enables simultaneous probing of both intermolecular and intramolecular interactions in a single experiment. On the other hand, intense THz spectroscopy greatly simplifies the determination of the optical constants of liquid solutions, eliminating the need for additional assumptions or prior knowledge. Moreover, it offers high sensitivity, allowing the detection of dilute solutions and subtle spectral variations. Currently, these two techniques typically rely on different THz sources, as achieving both broadband coverage and high intensity in a single setup remains challenging. In fact, the experimental results reviewed here were obtained at two different times and within two distinct scientific collaborations. In particular, the intense source was accessed through a collaboration with Prof. Novelli at Ruhr University in Bochum. Integrating both capabilities into a single apparatus would be highly desirable. Therefore, we also present a theoretical investigation of a novel experimental approach that could enable combined ultrabroadband and intense THz spectroscopy, merging the strengths of both methods. Full article

Cultural ecosystem services (CESs) play a critical role in urban residents’ well-being, yet conventional evaluations rely heavily on green-space area and overlook how facility quality and basic services influence the delivery of actual cultural benefits. To address this methodological gap, this study develops a three-tier evaluation framework—service potential, actual supply capacity, and actual service utility—to quantify multistage attenuation in CES provision across 95 parks in seven central districts of Shenyang, China. The framework integrates 114 quantitative and qualitative indicators from field surveys, national facility standards, and perception-based assessments, enabling a scientifically robust and replicable assessment of how cultural benefits are transformed from ecological structure to human experience. Results reveal that single-index, area-based assessments substantially overestimate CES supply: district-level supply–demand ratios drop from 66 to 195% to only 11–55% once quality and basic services are incorporated. Comprehensive and special parks retain the highest CES potential, whereas community and linear parks undergo significant losses due to aging facilities, insufficient maintenance, and inadequate infrastructure. Education and cultural services exhibit the most severe shortages, with deficits reaching 59–84%, underscoring structural limitations in learning-oriented spaces. By distinguishing structural (quantity), functional (quality), and experiential (basic service) constraints, the framework provides clear diagnostic guidance for targeted planning and management. Its multistage structure also reflects broader principles of sustainable urban development: improving CES requires not only expanding ecological elements but also enhancing service quality, strengthening infrastructure, and promoting equitable access to cultural benefits. The framework’s generalizability makes it applicable to high-density cities worldwide facing land scarcity and green-space inequality, supporting efforts aligned with SDG 11 to build inclusive, resilient, and culturally vibrant urban environments. Full article

Background: BTB and CNC homology 1 (Bach1) are transcriptional regulators involved in the oxidative response and inflammation. Although its biological functions are well characterized, the clinical impact of Bach1 gene polymorphisms (rs2300301, rs1153285, and rs2070401) on respiratory outcomes in preterm infants remains unclear. Methods: This multicenter study included 212 Japanese preterm infants born at <32 weeks of gestation with birth weights <1250 g. Three Bach1 single-nucleotide polymorphisms (SNPs; rs2300301, rs1153285, and rs2070401) were genotyped using TaqMan polymerase chain reaction (PCR). The requirements for home oxygen therapy (HOT) were compared across genotypes. Logistic regression analyses were performed after adjusting for the gestational age, sex, birth weight, and histological chorioamnionitis status. Results: Infants requiring HOT had a significantly lower gestational age (26 ± 1.7 weeks vs. 27 ± 2.2 weeks, p = 0.015) and lower birth weight (774 ± 235 g vs. 818 ± 233 g, p = 0.043) than those who did not. Histological chorioamnionitis was more prevalent in the HOT group (p = 0.022). rs2300301 was associated with HOT in univariate analysis (OR = 1.78, 95% CI: 1.20–2.04, p = 0.015). However, this association did not remain statistically significant after adjustment for gestational age, sex, birth weight, and histological chorioamnionitis (OR = 2.48, 95% CI: 0.90–6.80, p = 0.079). The rs1153285 and rs2070401 SNPs were not significantly associated with HOT expression. Conclusions: Our findings suggest a potential association between the Bach1 rs2300301 polymorphism and prolonged oxygen requirement in preterm infants. Although the adjusted analysis did not confirm the statistical significance, this SNP may serve as a candidate genetic marker for respiratory morbidity. Further studies are required to validate these findings. Full article

Hexagonal rare-earth manganites, as prototypical improper ferroelectrics in which structural distortions give rise to ferroelectricity, exhibit unique physical phenomena that are absent in conventional proper ferroelectrics. Owing to their Z₂ × Z₃ topologically protected ferroelectric domain structure, characterized by the convergence of six domains at vortex core, hexagonal manganites can host charged domain walls exhibiting multiple distinct conductive states and unconventional physical effects such as the half-wave rectification effect within a single bulk single crystal, opening up promising avenues for the practical applications. Moreover, as an excellent experimental platform for verifying the Kibble–Zurek mechanism, hexagonal manganites not only possess a broad application potential but also embody rich and fundamental physical insights. Given a series of recent advances in this field, it is essential to systematically summarize and discuss the key findings, current progress, and future research perspectives concerning the hexagonal manganite system. In this review, the origin of ferroelectricity in hexagonal manganites are first clarified, followed by a discussion of the formation and transformation mechanisms of unique ferroelectric domain structures, as well as the intrinsic mechanical properties. Subsequently, the manipulation of topological defects are compared, including electric fields, thermal treatment, oxygen vacancies, and stress–strain fields. Building upon these discussions, the distinct physical effects observed in hexagonal manganites are comprehensively summarized, such as domain wall conductance, dielectric and ferroelectric properties, and thermal conductivity. Finally, based on a detailed summary of the major achievements, the unresolved issues that warrant further investigation are highlighted, thereby offering guidance for future research directions and providing valuable insights for the broader study of ferroelectric materials. Full article

Accurate Prognostics and Health Management (PHM) of cutting tools in Computer Numerical Control (CNC) milling machines is essential for minimizing downtime, improving product quality, and reducing maintenance costs. Previous studies have frequently applied deep learning, particularly Long Short-Term Memory (LSTM) neural networks, for tool wear prediction and Remaining Useful Life (RUL) prediction. However, they often rely on simplified datasets or single architectures limiting industrial relevance. This study proposes a novel ensemble-LSTM framework that combines LSTM, BiLSTM, Stacked LSTM, and Stacked BiLSTM architectures using a GRU-based meta-learner to exploit their complementary strengths. The framework is evaluated using the publicly available PHM’2010 milling dataset, a well-established industrial benchmark comprising comprehensive time-series sensor measurements collected under variable loads and realistic machining conditions. Experimental results show that the ensemble-LSTM outperforms individual LSTM models, achieving an RMSE of 2.4018 and an MAE of 1.9969, accurately capturing progressive tool wear trends and adapting to unseen operating conditions. The approach provides a robust, reliable solution for real-time predictive maintenance and demonstrates strong potential for industrial tool condition monitoring. Full article

Step length is a fundamental parameter for gait assessment, reflecting complex neuromuscular and biomechanical behavior. Accurate step-length estimation is clinically relevant for monitoring populations with neurological or musculoskeletal conditions, as well as older adults. This study presents a novel biomechanical model, inspired by the inverted double pendulum, for step-length estimation under asymmetric gait conditions using a single inertial sensor on the lower back. Unlike models that assume symmetry, the proposed model explicitly incorporates pelvic rotation, enabling more accurate step length estimation, particularly in individuals with gait impairment. The model was validated against a gold standard OptiTrack^® (Corvallis, OR, USA) system with 33 adults: 21 participants without and 12 with gait impairment. Results show that the model achieved low Median Absolute Errors (MdAE), below 0.04 m in participants without gait impairment and remaining within 0.06 m in those with impairment. Statistical validation confirmed a strong correlation with the reference system (R = 0.96, R² = 0.93) and a clinically trivial mean bias (0.64 cm) from Bland-Altman analysis. These results validate the model’s effectiveness under various gait conditions, suggesting its technical feasibility and strong potential for clinical and real-world applications, particularly for the longitudinal monitoring of patients with functional impairments. Full article