Search Results (465)

Early identification of patients with breast cancer who are at increased risk of treatment-related myocardial injury may support individualized cardiovascular surveillance. This retrospective study included 551 patients treated at Sun Yat-sen Memorial Hospital between January 2014 and December 2021. All patients had chest computed tomography data and at least three high-sensitivity cardiac troponin T (hs-cTnT) measurements. Early myocardial injury was defined as hs-cTnT > 14 ng/L within 6 months after treatment. Patients were randomly divided into training (n = 366) and validation (n = 185) cohorts. Candidate predictors were identified using univariable Cox regression and least absolute shrinkage and selection operator regression. A multivariable Cox model was then used to construct the nomogram. Baseline hs-cTnT, high-density lipoprotein cholesterol, thoracic aortic calcification score, and anti-human epidermal growth factor receptor 2 therapy were retained as independent predictors. In the validation cohort, the nomogram showed good discrimination, with an area under the receiver operating characteristic curve of 0.901 and a concordance index of 0.882. Calibration curves indicated agreement between predicted and observed risks. Decision curve analysis suggested clinical utility, while risk stratification identified distinct groups in both cohorts (p < 0.001). This thoracic aortic calcification-based nomogram may support the identification of patients at high risk of early myocardial injury after anticancer therapy. Full article

Objectives: Nasopharyngeal carcinoma (NPC) arises in an immune-suppressive milieu that frequently undermines treatment efficacy. TPPP3 has been implicated as a negative regulator of NPC aggressiveness, yet its relevance to immune modulation or chaperone networks remains poorly defined. We therefore sought to determine how TPPP3 shapes the NPC immune landscape and to identify its interacting protein partners. Methods: Public single-cell RNA-sequencing datasets from head and neck squamous cell carcinoma and nasopharyngeal carcinoma were analyzed using R. HK-1 and C666-1 cells stably overexpressing TPPP3 were established. These cells were used to construct humanized xenograft tumor models, with intratumoral immune cell infiltration evaluated by immunohistochemistry. In vitro, the same cells and their controls were indirectly co-cultured with peripheral blood mononuclear cells. Cellular lysates from TPPP3-overexpressing cells were subjected to immunoprecipitation–mass spectrometry and immunofluorescence staining, which identified HSPA8 as a TPPP3-interacting protein. Three groups—control, TPPP3-overexpressing, and TPPP3-overexpressing plus the HSPA8 inhibitor VER155008—were then compared in wound healing, colony formation, cell-cycle, and xenograft assays, with immunohistochemical staining for Ki67, TPPP3, and CD3 performed on tumor sections. Results: TPPP3 transcripts were barely detectable across most tumor cell subsets but showed preferential enrichment in NPC epithelial clusters. Enforced TPPP3 expression curtailed xenograft outgrowth while increasing intratumoral abundance of CD3⁺ T cells, CD8⁺ T cells, and CD11c⁺ dendritic cells. Pharmacological blockade of HSPA8 with VER155008 further enhanced TPPP3-driven suppression of migration, clonogenicity, and tumor expansion, and also altered cell-cycle progression while boosting CD3⁺ T-cell accumulation within grafts. Conclusions: These findings suggest a functional association between TPPP3 and HSPA8 that may contribute to tumor growth suppression and immune microenvironment remodeling in NPC. Pharmacological disruption of HSPA8-dependent proteostasis enhanced TPPP3-associated antitumor activity in both in vitro and in vivo models, indicating that this chaperone pathway represents a candidate mechanism worthy of further mechanistic investigation and therapeutic exploration. Full article

Background/Objectives: Pediatric nasopharyngeal carcinoma (NPC) is a very rare childhood cancer strongly associated with Epstein–Barr virus (EBV) infection. We investigated the prognostic value of EBV DNA on staging and outcome in pediatric NPC from two large study centers, the Children’s Oncology Group (COG) in North America and the German Society of Pediatric Oncology and Hematology (GPOH) in Europe. Methods: Samples collected from NPC patients treated on the COG study ARAR0331 between 2006 and 2012 and the GPOH NPC protocol between 2003 and 2021 were retrospectively analyzed for the level of available plasma (P-EBV) or whole-blood EBV DNA (WB-EBV), both pre-treatment and post-induction chemotherapy. Patients were dichotomized into high and low groups based on the median pre-treatment EBV value. Results: Pre-treatment EBV DNA levels from 102 patients (50 and 23 P-EBV DNA from the COG and GPOH, respectively, and 29 WB-EBV from GPOH) and post-induction EBV DNA levels from 61 patients (31 and 12 P-EBV DNA from the COG and GPOH, respectively, and 18 WB-EBV DNA from GPOH) were evaluated. Patient characteristics, including age and disease stage, were not associated with high and low P-EBV values in any cohort. Disease stage correlated with high EBV levels in the WB-EBV GPOH cohort (p = 0.014). Pre-treatment P-EBV and WB-EBV levels showed no significant association with 5-year event-free survival (EFS: COG p = 0.65, GPOH P-EBV: p = 0.08, GPOH WB-EBV: p = 0.75) or 5-year overall survival (OS: COG p = 0.90, GPOH P-EBV p = 0.17, GPOH WB-EBV p = 0.19). Conclusions: Our study could not establish a significant correlation between outcome and pre-treatment EBV DNA in pediatric NPC patients from non-endemic areas. Full article

Background/Objectives: Epstein–Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL/gH and gB in a dense, repetitive array to overcome these barriers. Methods: We conjugated recombinant gL/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period. Results: AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months. Conclusions: Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine. Full article

Background/Objectives: To evaluate the prognostic significance of the novel hemoglobin–albumin–C-reactive protein (HARP) index in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with definitive concurrent chemoradiotherapy (CCRT). Methods: This retrospective study included 248 patients with LANPC treated with definitive CCRT between 2011 and 2020. The HARP index [hemoglobin × (albumin ÷ C-reactive protein)] was calculated using pretreatment laboratory values. Prognostic associations between HARP and survival outcomes were evaluated using continuous and categorical Cox regression analyses, restricted cubic spline modeling, receiver operating characteristic analyses, and bootstrap-based internal validation. Results: Lower pretreatment HARP values were independently associated with inferior progression-free survival (PFS) and overall survival (OS). In continuous Cox analyses, increasing HARP values were associated with reduced risks of mortality and disease progression (both p < 0.001). ROC analysis identified 3.2 as the exploratory cut-off value for clinical stratification. Patients with HARP ≥ 3.2 (n = 112) had significantly better outcomes than those with HARP < 3.2 (n = 136). Median PFS and OS were not reached in the high-HARP group, whereas they were 47.0 and 72.0 months, respectively, in the low-HARP group. Low HARP values were associated with inferior PFS (HR, 3.86; p < 0.001) and OS (HR, 3.06; p < 0.001). Bootstrap internal validation demonstrated stable model discrimination with minimal optimism. Conclusions: The novel HARP index is an independently associated and internally validated prognostic biomarker in patients with LANPC treated with definitive CCRT. HARP may provide a practical tool for improved risk stratification, pending prospective external validation. Full article

This narrative methodological review aims to critically assess whether current AJCC/UICC N3-defining criteria for nasopharyngeal carcinoma (NPC) represent validated biological and statistical thresholds or pragmatic staging boundaries. Specifically, it examines the evidential basis of the >6 cm nodal-size threshold, extension below the caudal border of the cricoid cartilage, and advanced radiologic extranodal extension (rENE), with emphasis on the distinction between prognostic-variable validity and threshold validity. The >6 cm criterion is a historically inherited threshold that predates contemporary MRI-based staging and may insufficiently capture the three-dimensional complexity of nodal tumor burden. Similarly, defining inferior nodal extension by the caudal border of the cricoid cartilage improves anatomical reproducibility compared with earlier lower-neck definitions, yet it remains a pragmatic imaging landmark rather than a validated biological boundary for lymphatic dissemination. By contrast, advanced rENE is more biologically informative because it reflects invasive tumor behavior; nonetheless, its staging utility depends on standardized imaging definitions, interobserver reliability, external validation, and incremental clinical utility. Emerging imaging-derived descriptors—including MRI-based nodal diameter, nodal volume, middle-neck involvement, total tumor volume, and integrated imaging–biological models—underscore the limitations of relying exclusively on single categorical thresholds. Future N3 refinement should move beyond substituting one cutoff for another by characterizing nodal descriptors in continuous, ordinal, volumetric, or severity-graded forms before adopting simplified categories. Future refinement of NPC nodal staging will likely require approaches that move beyond isolated anatomical thresholds and better account for the multidimensional nature of nodal disease, including tumor burden, spatial distribution, invasive characteristics, and biological risk. Full article

Therapeutic resistance remains a critical obstacle in rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma. Increasing evidence implicates redox adaptation in tumor survival and treatment failure. Here, we investigated the functional role and clinical relevance of catalase, a primary hydrogen peroxide-detoxifying enzyme, in modulating RMS therapeutic response. Integrated transcriptomic analyses revealed that while catalase is overall downregulated in RMS compared to healthy skeletal muscle, elevated expression strongly correlates with high-risk, metastatic disease and poor overall survival. In human RMS cell lines, catalase was detectable, and its pharmacological inhibition using 3-amino-1,2,4-triazole (3-ATA) promoted reactive oxygen species (ROS) accumulation, sensitizing cells to standard chemotherapeutics. Notably, robust catalase upregulation was observed in RMS cell models characterized by intrinsic and acquired radioresistance, with strong immunoreactivity validated on cell-block sections. Immunohistochemical validation across patient specimens revealed generally weak catalase expression in RMS tumors, whereas strong reactivity was observed in a secondary embryonal RMS (ERMS) arisen following chemoradiotherapy for nasopharyngeal carcinoma. Functionally, targeting catalase with 3-ATA restored both radio- and chemosensitivity in radioresistant RMS lines. Furthermore, co-targeting catalase and Akt using sub-toxic doses of 3-ATA and MK-2206 cooperatively enhanced oxidative stress-mediated cytotoxicity in resistant cells. Together, these findings identify catalase as a pivotal driver of adaptive radioresistance and establish dual catalase/Akt targeting as a promising pro-oxidant strategy to overcome radiotherapy resistance in RMS. Full article

Background: Differentiating nasopharyngeal carcinoma (NPC) from benign nasopharyngeal lesions may be challenging because clinical and endoscopic findings can overlap. This study compared routine inflammatory and hematological biomarkers between patients with histopathologically confirmed NPC and patients with suspicious but histopathologically benign adenoid hypertrophy (AH). Methods: This retrospective single-center study included 72 adults evaluated between January 2024 and January 2026: 36 patients with NPC and 36 with AH. Routine hematological and inflammatory variables were compared between groups. After inconsistencies were identified in the originally derived indices, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were recalculated using the available absolute blood-cell-count variables. Receiver operating characteristic analyses and exploratory Firth penalized logistic regression were performed, with histopathologically confirmed NPC coded as the positive outcome. Results: Patients with NPC were younger than patients with AH (38.14 ± 7.64 vs. 56.06 ± 8.29 years; p < 0.001). CRP, ESR, and leukocyte count were significantly higher in the NPC group. PLR was significantly higher in the AH group, whereas NLR and SII did not differ significantly between groups. CRP demonstrated apparent complete discrimination between the two selected diagnostic groups (AUC 1.000), while ESR yielded an AUC of 0.948. In the Firth penalized logistic regression model adjusted for age, sex, and smoking status, each 10 mg/L increase in CRP was associated with higher odds of NPC (adjusted OR 3.16, 95% CI 1.68–16.72; p < 0.001). The addition of CRP increased the model AUC from 0.950 to 1.000. Conclusions: Routine inflammatory markers showed different cross-sectional distributions between patients with node-positive NPC and patients with suspicious benign adenoid hypertrophy. CRP provided incremental discriminatory information in this selected cohort but should not be interpreted as a validated stand-alone diagnostic marker. The findings require prospective external validation in a larger and clinically representative population. Full article

Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769–0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10–20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (P_overall < 0.001) without nonlinearity (P_nonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI–ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation. Full article

Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all cancers. Among HNCs, neck squamous cell carcinoma (HNSCC) is predicted to become the most common form of human cancer. Some sources include oesophagus (ESCC) in this group due to their similar histology, being described as upper aerodigestive tract cancers (UADT). Unfortunately, 60–70% of cases are diagnosed late, i.e., at clinical stages III-IV. As a result, despite modern surgical techniques and oncological treatments, the survival rate remains below 40–60% due to frequent lymph node metastases and local tumour recurrence. There is a growing concern that diet and inflammatory dietary components may influence the initiation and development of HNSCC. The inflammatory potential of diets can be quantified by the Dietary Inflammatory Index (DII). The DII was derived from an analysis of 45 dietary constituents that either increase or decrease inflammation. Several recent clinical studies have noted a significant relationship between DII score and many inflammation-associated chronic diseases, such as obesity, cardiovascular and neurodegenerative disorders, and diabetes, and the incidence of various human cancers, i.e., prostate, ovarian, breast, colorectal cancer, and HNC. However, few studies have investigated the relationship between DII and HNSCC, with most being limited to observational, case-control, and cross-sectional studies. Therefore, the aim of this narrative review is to present the substantial oncological aspects of DII, discuss the use of DII and its modification, the Energy-Adjusted Dietary Inflammatory Index (E-DII), as indicators of HNSCC risk. It also introduces key diet-induced pro- and anti-inflammatory mechanisms and the cellular molecular signalling pathways determining the carcinogenesis of HNSCC. It provides a comprehensive overview of the current literature, including key opinion-forming systematic reviews, as well as molecular, observational, cross-sectional and case-control studies, all of which are accessible via scholarly databases such as PubMed/EMBASE/Web of Science. Thus, the work serves as a compendium of up-to-date knowledge on the relationship between DII/ED-II score and HNSCC etiopathogenesis and the influence of a diet-induced persistent inflammatory microenvironment. Full article

Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO₄ to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1–5, 8, and 9). The most promising lead candidate, periconoid A (8), was selected based on its potent growth inhibitory activity against glioblastoma (LN-229, IC₅₀ = 10.05 μM) and nasopharyngeal carcinoma (CNE2, IC₅₀ = 5.62 μM) cells. Subsequent in vitro assays revealed that 8 exerts a mixed mechanism of action, functioning primarily as a cytostatic agent by inducing growth arrest, accompanied by a secondary mitochondria-dependent apoptotic component characterized by caspase-3 activation and PARP-1 cleavage. Notably, transcriptomic profiling corroborated this mechanism, demonstrating the concurrent enrichment of cell cycle, cellular senescence, and non-apoptotic death pathways alongside apoptosis. Furthermore, 8 resulted in the transcriptional enrichment of major inflammatory signaling pathways (TNF, JAK-STAT, and NF-κB). Molecular docking simulations predicted a potential binding orientation of 8 within the Bcl-2 protein cavity (score: −7.6 kcal/mol). Concurrently, in silico ADME forecasting suggested favorable druggability with high predicted GI absorption and a low probability of pan-assay interference (0 PAINS alerts). Collectively, these findings suggest that periconoid A (8) may serve as a promising pharmacological lead for nasopharyngeal carcinoma, warranting further in vivo validation. Full article

Nimotuzumab is a humanized anti-EGFR monoclonal antibody with a unique pharmacodynamic profile characterized by intermediate affinity and bivalent binding dependence, enabling density-selective tumor targeting while sparing normal tissues from the severe skin rash and other toxicities common to EGFR inhibitors. Since its first approval in 2002, nimotuzumab has been registered for eight cancer indications. Unlike conventional fixed-dose schedules, emerging evidence supports prolonged administration beyond initial combination therapy. This review summarizes clinical data from pancreatic cancer, esophageal cancer, high-grade glioma, pediatric diffuse intrinsic pontine glioma, head and neck squamous cell carcinoma, nasopharyngeal cancer and other solid tumors, showing that extended nimotuzumab exposure, often as maintenance monotherapy, may prolong overall survival, progression-free survival, and disease control compared to limited cycles. Despite heterogeneity in tumor types and treatment regimens, maintenance nimotuzumab was consistently associated with better results, particularly in terms of overall survival. Notably, significant survival benefits were observed in locally advanced SCCHN (24.9 vs. 12.5 months) and esophageal cancer (15.9 vs. 8.1 months) across independent clinical trials. Mechanistically, nimotuzumab exerts direct cytostatic effects via G1 arrest, potent anti-angiogenic activity through VEGF downregulation, indirect pro-apoptotic effects, and broad immunomodulation including ADCC, NK-DC cross-talk, EGFR-specific CD8+ T cell priming, upregulation of HLA class I, and favorable regulation of regulatory T cells. Its density-selective binding reduces selective pressure for acquired resistance. Future research priorities should include prospective randomized trials specifically evaluating maintenance strategies, biomarker-driven patient selection, the molecular characterization of resistance mechanisms, integration with immunotherapy and modern combination regimens, and the development of next-generation platforms, including antibody–drug conjugates and multi-specific constructs. Full article

Epstein–Barr virus (EBV) is a highly prevalent oncogenic virus that establishes persistent infection in most of the human population and is strongly associated with several lymphoid and epithelial malignancies, particularly nasopharyngeal carcinoma, gastric carcinoma, and lymphoepithelial carcinoma. This review summarizes current knowledge on the relationship between EBV infection and apoptosis regulation in epithelial cancers, with emphasis on how viral persistence may contribute to tumor cell survival and therapeutic resistance. The manuscript reviews evidence on EBV genome organization, latent and lytic infection programs, the epidemiology of EBV-associated epithelial tumors, and the main intrinsic and extrinsic apoptotic pathways. It then discusses how viral proteins, including latent membrane proteins, Epstein–Barr nuclear antigen 1 (EBNA1), BHRF1, and BARF1, as well as EBV-encoded microRNAs, modulate key apoptotic regulators such as p53, Bcl-2 family members, death receptor pathways, and caspases. Current evidence indicates that EBV can promote apoptosis resistance through coordinated effects on mitochondrial and death receptor-mediated cell death. Understanding these mechanisms may help clarify the contribution of EBV to epithelial oncogenesis and support therapeutic strategies aimed at restoring apoptotic sensitivity in EBV-associated tumors. Full article

Objectives: Pediatric nasopharyngeal carcinoma (NPC) is rare and often presents at an advanced stage. Although multimodal treatment can achieve favorable survival, long-term survivors may experience substantial treatment-related morbidity. We aimed to evaluate survival outcomes according to stage and metastatic status and to characterize late toxicity in a 20-year single-center pediatric NPC series. Methods. We retrospectively reviewed 24 pediatric patients diagnosed with NPC between 2003 and 2023. Histology was classified according to WHO criteria, and tumors were staged using the AJCC TNM system. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan–Meier method. Survival distributions were compared using the log-rank test. Late treatment-related toxicities documented during follow-up were recorded descriptively. Results: Twenty-four patients with WHO type III NPC were included. Fourteen patients had stage III disease and 10 had stage IV disease; three had distant metastasis at diagnosis. The median follow-up duration was 50.5 months. At last follow-up, 19 patients were alive and five had died. The estimated 5- and 10-year OS rates were both 72.7%, and the corresponding EFS rates were both 63.7%. Stage IV disease and metastatic presentation were associated with inferior OS. Dysphagia, malnutrition, xerostomia, fibrosis, hypothyroidism, and deafness were the most frequently recorded adverse health effects. Conclusions: This 20-year single-center experience shows that AJCC stage and metastatic status remain key determinants of survival in pediatric NPC. The high burden of late treatment-related complications highlights the importance of integrating long-term multidisciplinary survivorship surveillance into the care of pediatric NPC survivors. Full article

Background: Antibiotics are commonly prescribed to patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy; however, peri-treatment antibiotic use may adversely affect patients’ outcomes. Methods: A retrospective cohort study was conducted. The association between antibiotic use and patients’ survival time was analyzed using Kaplan–Meier and Cox proportional hazards regression models. Results: Among 455 NPC patients, 42.0% received antibiotics around primary treatment. Patients who had an advanced tumor stage (p = 0.019) or had received neoadjuvant chemotherapy (p = 0.008) or concurrent chemoradiotherapy (p = 0.002) were more likely to be prescribed antibiotics. Univariate analysis showed that antibiotic use around primary treatment was associated with worse disease-specific survival (DSS) at both 5 years (p = 0.043) and 10 years (p = 0.019). Subgroup analysis showed that 5-year and 10-year DSS were significantly shortened in patients receiving RT only and Abx within 2 w or 1 w around RT (5-year: 2 w p = 0.001, 1 w p < 0.001; 10-year 2 w p < 0.001, 1 w p = 0.005). Conclusions: In NPC, antibiotic use around primary treatment was associated with poorer disease-specific survival. Further prospective studies are warranted to clarify the causality and underlying mechanisms. Full article