Search Results (2,625)

Background: Programmed cell death protein-1 (PD-1) and its ligands, PD-L1 and PD-L2, constitute a central immune checkpoint pathway that regulates T-cell activity and tumor immune escape, while their relationship with STAT signaling remains incompletely understood in ccRCC. Methods: We analyzed 27 paired ccRCC and adjacent non-tumorous human kidney tissue samples. mRNA levels of PD-1, PD-L1, PD-L2, STAT1, and STAT3 were quantified by RT-qPCR. In addition, representative human ccRCC cell lines (CAKI-2 and A-498) were treated with IFN-γ to assess the time-dependent modulation of immune checkpoint molecules and STAT pathway activation. Results: PD-L1 and PD-L2 were significantly upregulated in tumor tissues compared with adjacent normal kidney tissue. Exploratory observation suggests grade dependent increase. Whereas PD-1 was predominantly downregulated, IFN-γ treatment induced a rapid transcriptional upregulation of PD-L1 and PD-L2 in RCC cell lines, with maximal protein accumulation observed at 72 h. STAT1, but not STAT3, exhibited dynamic induction following IFN-γ stimulation, showing temporal association with PD-L1 and PD-L2 upregulation, indicating cell-line-specific regulatory effects. Correlation analyses confirmed a strong correlation between PD-1 and its ligands, whereas STAT1 and STAT3 expression showed no direct association with PD-L1 or PD-L2 levels in cancer samples. Conclusions: Our findings demonstrate that PD-L1 and PD-L2 are frequently upregulated in ccRCC and dynamically regulated by IFN-γ/STAT1-dependent signaling. Our results provide additional insight into the mechanisms of immune escape and underscore the potential of integrated profiling of PD-1 ligands and STAT signaling to guide personalized immunotherapeutic strategies in ccRCC. Full article

The global push for low-carbon electricity generation has made hydrogen-enriched natural gas an attractive near-term decarbonization option. This paper combines experimental and thermodynamic analyses of H₂–CH₄ combustion in gas turbine combustion chambers. Experiments were conducted on a patented two-stage swirl burner across 240 operating conditions. The effects of hydrogen fraction (γ = 0–40%), swirler vane angle (30°, 45°, 60°), equivalence ratio (φ = 0.17–1.00), and fuel injection strategy were measured against NOx and CO emissions and lean blowout stability. Each 10% increase in hydrogen content raised NOx by 23–24% via the Zel’dovich thermal mechanism, while CO fell by up to 28.5% at φ = 0.3 and 60° due to enhanced OH-radical activity. The minimum recorded NOx was 12.08 ppm (Type 2 injection, 30°, γ = 0%, φ = 0.3). Hydrogen addition improved lean blowout stability by 32–46% per 10% H₂. A parallel thermodynamic analysis showed that integrating an organic Rankine cycle (ORC) and supplementary H₂–CH₄ firing in the heat recovery steam generator cuts specific CO₂ emissions by 7.5–10% and raises net efficiency by 0.79–4.0 percentage points. Critical comparison with 28 published studies identified an optimal operating window: γ = 20–30%, φ = 0.5–0.7, 45° vane angle (SW = 0.8). Full article

Autophagy is a central cellular process that recycles intracellular components and supplies precursors for biosynthesis. As a key regulator of autophagosome formation, autophagy-related protein 8 (ATG8) plays an essential role in macromolecular degradation and in the availability of lipid precursors. However, whether enhanced autophagic flux promotes lipid accumulation in oleaginous fungi remains unclear. In this study, atg8-1 and atg8-2 were homologously overexpressed in the oleaginous fungus Mucor circinelloides to evaluate their roles in lipid biosynthesis. The engineered strains McATG8-1T2 and McATG8-2T2 showed significantly increased total fatty acid (TFA) contents (32.9% and 32.5%), representing improvements of 15.0% and 13.7% compared with the control. γ-Linolenic acid levels were also elevated to 16.9% and 16.5%, relative increases of 25.2% and 22.0%, respectively. RT-qPCR analysis revealed coordinated upregulation of genes involved in autophagy, central carbon metabolism, lipid biosynthesis, and the pentose phosphate pathway. Ethanolamine supplementation further enhanced lipid accumulation, increasing TFA contents by 12.2–14.6%. In addition, inhibition of target of rapamycin complex 1 using rapamycin produced a strong synergistic effect with atg8 overexpression, leading to substantial lipid increases under nitrogen-limited and nitrogen-rich conditions. Collectively, these findings demonstrated that ATG8-mediated autophagy enhanced lipid accumulation and acted as a key determinant of lipid synthesis flux. Full article

Telmisartan (TEL) is a non-peptide, orally administered antihypertensive agent primarily known as angiotensin II type 1 (AT1) blocker. In this review, we provide a detailed overview of how TEL modulates voltage-gated Na⁺ current (I_Na) and affects action potential (AP) firing behavior. TEL exerts differential stimulatory effects on the peak and late components of I_Na when subjected to brief depolarizing pulses across a range of cell types, such as mHippoE-14 hippocampal neuron, cultured dorsal root ganglion neurons, and HL-1 atrial cardiomyocytes. TEL can augment the non-inactivating (persistent) I_Na elicited by ascending long ramp pulse in mHippoE-14 cells. By using a parvalbumin-expressing interneuron-based modeled cell combined with bifurcation analysis, it is possible to predict how applied current influences subthreshold oscillations and the generation of somatic spiking in the presence of TEL. According to the Hodgkin-Huxley model, mimicking the action of TEL—characterized by an increased peak amplitude of I_Na and a slowed inactivation time course—leads to the emergence of periodic oscillations in membrane potential. Using a Markovian process, a separate model can also be mathematically constructed, showing that changes in certain rate constants can simulate the effect of TEL on I_Na in cardiac cells. The molecular docking prediction between TEL and the Na_V1.7 channel was made by expected formation of hydrophobic interactions as well as hydrogen bonding. In addition to its antagonistic action at the AT1 receptor and its agonistic activation of peroxisome proliferator-activator-γ, TEL may also directly enhance I_Na, thereby modulating AP firing in a variety of excitable cells. Current evidence supports TEL’s modulatory impact on Na_V channel activity and cellular excitability, while also acknowledging that the mechanism—whether direct or indirect—remains under investigation. Full article

In rock tunnel engineering, the discontinuity roughness plays a crucial role in rock mass stability. Nevertheless, no suitable parameter is currently available to describe the multi-scale morphological complexity associated with varying shear directions. Improved 1D and 3D fractal dimensions are proposed and systematically evaluated for their ability to characterize the anisotropy and morphology complexity. The results show that the trends of improved 1D and 3D fractal dimensions are consistent with the Grasselli parameter GP(θ) along the orthogonal direction of the major and minor axes, which effectively characterizes the anisotropy. Meanwhile, they effectively characterize the profile and discontinuity morphology complexity, respectively. On the basis of the evaluation results, a comprehensive parameter is proposed to quantify directional multi-scale morphological complexity, which characterizes the discontinuity anisotropy, local roughness, and global morphological complexity simultaneously. Furthermore, the proposed parameter is compared with GP(θ) based on the Huashansong tunnel, using the concordance correlation coefficient and macro-trend similarity as evaluation criteria. The results show a moderate correlation between the two parameters, with a concordance correlation coefficient of 0.716. The overall similarity score of 85.8 and the macroscopic trend similarity of 71.0 indicate strong consistency in morphological features. In addition, the RMSE and MAE of γ(θ) are 0.25 and 0.19, which is lower than that of the existing GP(θ) and PSD-based methods in the study of characterizing the dominant morphology complexity direction. Full article

Locally advanced rectal cancer is commonly treated using total neoadjuvant therapy (TNT), which integrates radiotherapy with systemic chemotherapy to improve tumor downstaging, local control, and long-term oncologic outcomes. Despite its central role in treatment, responses to radiotherapy remain highly heterogeneous. While some tumors undergo complete regression, others exhibit intrinsic or acquired treatment resistance, resulting in incomplete tumor control while experiencing treatment-related toxicity. Understanding the biological determinants that govern radiation sensitivity in rectal cancer, therefore, represents a major clinical challenge. Ionizing radiation induces tumor cell death primarily through the generation of reactive oxygen species (ROS) and DNA damage, particularly DNA double-strand breaks. In addition to nuclear DNA injury, radiation-induced oxidative stress can initiate lipid peroxidation within cellular membranes. When lipid peroxide accumulation exceeds the capacity of cellular antioxidant systems, this process can trigger ferroptosis, an iron-dependent form of regulated cell death driven by phospholipid oxidation. Ferroptotic susceptibility is regulated by interconnected metabolic pathways, including cystine transport through system Xc⁻ (SLC7A11/SLC3A2), glutathione synthesis, glutathione peroxidase-4 (GPX4) activity, iron metabolism, and membrane lipid remodeling. Recent evidence further indicates that ferroptosis intersects with antitumor immunity. Ferroptotic tumor cells release oxidized lipid mediators and damage-associated molecular signals that can influence immune activation, while interferon-γ produced by activated CD8⁺ T cells during immune checkpoint blockade suppresses SLC7A11 expression, limiting cystine uptake and promoting ferroptotic tumor cell death. These findings suggest that ferroptosis represents a mechanistic interface between tumor metabolic vulnerability and immune-mediated cytotoxicity. This interaction is particularly relevant in colorectal cancer biology, where immune checkpoint inhibitors demonstrate clinical benefit primarily in tumors with deficient mismatch repair or microsatellite instability-high (MSI-H) status. The vast majority of rectal cancers are microsatellite stable (MSS) and exhibit limited responsiveness to immunotherapy due to reduced immunogenicity and immune exclusion within the tumor microenvironment. Strategies capable of increasing tumor immunogenicity in this setting are therefore of considerable interest. In this review, we examine the molecular mechanisms linking radiation-induced oxidative stress to ferroptosis and tumor immunity in colorectal cancer, while focusing on the clinical context of radiotherapy in rectal cancer. We discuss how lipid metabolism, iron homeostasis, cysteine-dependent antioxidant systems, and immune signaling pathways converge to regulate ferroptotic vulnerability and radiation response. We further explore the therapeutic potential of integrating radiotherapy, ferroptosis-targeting strategies, and immunotherapy to overcome radioresistance and improve treatment outcomes in colorectal cancer. Full article

Chamaecrista nomame (Siebold) H. Ohashi (C. nomame), a leguminous plant traditionally consumed in East Asia, contains diverse bioactive phytochemicals, but whether its activities act convergently under obesity-related pathological conditions remains unclear. This study investigated the anti-inflammatory, anti-obesity, and insulin-sensitizing effects of a 40% ethanol extract of C. nomame (ECNE) and its marker compound luteolin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, differentiating and mature 3T3-L1 adipocytes, and tumor necrosis factor-α (TNF-α)-induced insulin-resistant adipocytes. In LPS-stimulated macrophages, ECNE and luteolin reduced nitric oxide and pro-inflammatory cytokine (TNF-α, interleukin (IL)-6, IL-1β) production, accompanied by suppression of nuclear factor-κB and mitogen-activated protein kinase signaling. In differentiating adipocytes, both reduced lipid accumulation and downregulated peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and adipocyte protein 2. In mature adipocytes, they enhanced insulin-stimulated glucose uptake and Akt phosphorylation. In TNF-α-challenged adipocytes, pretreatment partially restored glucose uptake and Akt phosphorylation while attenuating IL-6 and monocyte chemoattractant protein-1 production. ECNE exerted effects equal to or greater than those of luteolin at equivalent luteolin-based concentrations, indicating contributions from additional phenolic constituents. These findings support ECNE as a multifunctional natural resource against obesity-associated inflammation and insulin resistance. Full article

This study evaluated olive leaf extract (OLE) as a multifunctional dermocosmetic candidate for sebum-related and inflammatory responses relevant to oily and acne-prone skin using an axis-aligned in vitro panel: (i) sebocyte lipogenesis, (ii) inflammatory mediator production in keratinocytes, and (iii) fibroblast-mediated collagen gel contraction. In addition, supportive mechanistic evidence for the sebum-related effects of OLE was obtained by examining signaling proteins associated with sebocyte lipogenesis, including PPAR-γ and SREBP-1. As a result, OLE significantly inhibited linoleic acid-induced lipid accumulation in SEB-1 sebocytes without cytotoxicity. In HaCaT keratinocytes, OLE significantly reduced the production of pro-inflammatory cytokines, including IL-8, TNF-α, and PGE₂, induced by Cutibacterium acnes or UVB. In dermal fibroblast-containing collagen gels, OLE enhanced fibroblast-mediated gel contraction. Additionally, analysis of the main mechanisms of lipid inhibition using SEB-1 sebocytes revealed that OLE exerts a dual regulatory role in lipid synthesis and inflammation by downregulating AKT and ERK phosphorylation and inhibiting PPAR-γ and SREBP-1 expression. Furthermore, among the tested extracts, the 70% ethanol extract (OLE70) exhibited the strongest antioxidant activity, the greatest gel contraction response, and the highest content of oleuropein, a major bioactive phenolic compound derived from olive. Like OLE, oleuropein also showed sebum-regulatory activity by reducing lipid accumulation in SEB-1 sebocytes, an inhibitory effect on IL-8 expression in HaCaT keratinocytes, and an inhibitory effect on the expression of PPAR-γ and SREBP-1, which are involved in sebum secretion. Taken together, these findings suggest that OLE and its major phenolic constituent, oleuropein, may modulate sebum-related, inflammatory, oxidative, and dermal remodeling-associated responses in skin cell models. These results should be interpreted as exploratory and provide a basis for further mechanistic and translational investigation. Full article

Background: Colorectal cancer is a common malignancy and 5-fluorouracil (FU) remains a mainstay of chemotherapy despite its toxicity. As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention. Methods: This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP. Results: The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4⁺ T and CD8⁺ T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-γ and decrease IL-6 and TNF-α. Conclusions: In conclusion, a moderate dose (0.67 g/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes. Full article

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. App^NL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD. Full article

Research Purpose: This study investigates the role of digital investor behavior, measured through Google Trends, alongside technical indicators such as RSI and Bollinger Bands, in forecasting volatility in the Dubai Financial Market. The aim is to develop a hybrid analytical framework that integrates behavioral and technical dimensions to enhance predictive accuracy in emerging markets. Study Methodology: Daily data from 2020 to 2025 were collected, covering both crisis and post-crisis periods. Digital attention was quantified using Google Trends search indices, while technical indicators included RSI and Bollinger Bands calculated over a 7-day horizon. Volatility was modeled using ARCH, GARCH, and EGARCH frameworks, with Max Drawdown employed as a complementary risk metric to capture extreme market movements. Findings: Digital investor attention shows a predictive association with volatility, particularly when combined with technical indicators. Models incorporating both behavioral and technical variables demonstrated superior predictive performance. The EGARCH model successfully captured the asymmetric impact of negative shocks (γ < 0, p < 0.05), while Max Drawdown provided additional insights into risk exposure during periods of heightened market stress, achieving an R² of 95.36%. Scientific value: This study positions digital attention as a complementary variable that improves forecasting, moving beyond conventional price-based models in volatility modeling; by integrating Google Trends with technical analysis, the research introduces a hybrid forecasting framework that can be adapted to other emerging markets. Practical Implications: The findings offer practical value for policymakers and investors. Regulators can use digital attention measures as early warning signals to anticipate volatility, while investors can integrate behavioral and technical indicators to improve risk management and trading strategies. From a foresight perspective, the study contributes to building more resilient financial systems by embedding behavioral data into predictive tools. Full article

Natural killer T (NKT) cells bridge innate and adaptive immune responses and play a critical role in anti-tumor immunity. The goal of the study was to assess NKT cell and T cell function in lymphoma patients and to investigate whether specific cytokines correlate with outcomes and/or immune cell function. Patient diagnoses were confirmed by histology. NKT and T cell number and function were assessed by flow cytometry and stimulation with artificial antigen-presenting cells (aAPCs) followed by ELISA and quantitative RT-PCR (qPCR). Cytokine expression levels were compared using online databases, and protein levels in the plasma were assessed by ELISA. NKT cell activation, indicated by at least 1.5-fold IFN-γ induction over baseline following stimulation, was detected in 82% of healthy donors, compared to 44% of lymphoma patients. Lymphoma patients have significantly higher levels of circulating pro- and anti-inflammatory cytokines IL-10, IL-6, and Sema4D as compared to healthy donors. In addition, NKT cell function in the blood correlated with NKT cell function in the bone marrow in lymphoma patients. We found that aAPC-qPCR can be used to quickly assess immune cell function in cancer patients. Circulating NKT cell function positively correlated with bone marrow NKT cell function, suggesting that circulating NKT responses reflect systemic immune competence. Outcome-associated transcriptomic analyses showed that lower expression of TGF-β, IL-6, IL-10, and IFN-γ mRNA correlated with poorer clinical outcomes, whereas higher Sema4D expression was associated with worse prognosis, identifying Sema4D as a potential immunologic biomarker linked to disease progression and immune dysfunction in B cell lymphoma. Full article

Humans spend a substantial proportion of their time indoors, where exposure to environmental pollutants such as radon gas and particulate contaminants in household dust is common. While radon is a well-established risk factor for lung cancer, household dust may serve as a reservoir for a complex mixture of indoor and outdoor pollutants. However, the biological effects of such exposures, particularly under sequential conditions, remain incompletely understood. This study aimed to investigate the cytotoxic and genotoxic effects of sequential exposure to household dust extract followed by indoor radon using human lung adenocarcinoma (A549) cells as an in vitro model. Household dust samples from upper northern Thailand were extracted and applied to cells, followed by controlled radon exposure. Cellular responses were evaluated using cell viability assays, cytokinesis-block micronucleus (MN) formation assays, and Western blot analysis of oxidative stress-related (Nrf2/HO-1), DNA damage-related (γ-H2AX), autophagy-related (LC3), and inflammatory-related (IL-6) protein expression. Exposure to household dust extract was associated with reduced cell viability and increased MN formation, while radon exposure alone produced relatively modest effects under the present conditions. Sequential exposure to household dust extract followed by indoor radon was associated with increased oxidative stress-related responses and elevated DNA damage than either treatment alone under the present experimental conditions. A trend toward autophagy-related responses was also observed, and the overall findings may indicate possible combined biological responses under sequential exposure conditions. These findings suggest that sequential exposure may be associated with changes in oxidative stress-related pathways, DNA damage responses, and autophagy-related processes in this in vitro model. However, the results should be interpreted with caution as they are derived from a single cancer cell line and there are limitations to the in vitro exposure model. Further studies using additional cell models and in vivo systems are warranted to further clarify the potential biological and human health relevance of these findings. Full article

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a biomarker of host immune competence. We assessed the association between baseline TTV DNA levels and immune responses to the Mpox virus (MPXV) and dengue virus (DGV) vaccines in two prospective cohorts. Methods: A total of 248 individuals were enrolled, and TTV DNA was quantified before vaccination. Humoral and cellular responses to MVA-BN (for MPXV) and QDENGA (for DGV) vaccines were measured by using serology, neutralization assays, and interferon-γ ELISpot, and correlations with TTV viremia were investigated. Results: TTV DNA was detected in 81.2% of individuals, with a significantly higher prevalence and viral loads in the Mpox-Vac group than in the DGV-Vac group. Between both groups, the only significant association observed was an inverse correlation between pre-vaccination TTV load and DGV neutralizing antibody titers in the DGV-Vac group and was limited to the subset of TTV-positive individuals; no additional correlations with antibody and T responses were identified. For the Mpox-Vac group, stratified analyses in people living with HIV (PLWH) confirmed this lack of association. Conclusions: TTV viremia does not predict vaccine immunogenicity in immunocompetent or mildly immunosuppressed individuals. These results, which derive from within-cohort analyses and do not rely on direct comparisons between heterogeneous vaccine populations, support the role of TTV as a marker of immune status along a continuum of immunosuppression, with predictive value likely confined to populations with more severe immune impairment. Full article

Background: Postmenopausal women are at high risk of Alzheimer’s disease (AD) incidence and progression. Irisin, an exercise-induced myokine, has neuroprotective and antiaging effects against AD, especially in menopausal women suffering from insulin resistance (IR). For the first time, the novel role of irisin induced by melatonin (MTN) or/and physical exercise (PHE) was investigated in the current ovariectomized (OVX)/AD rat model by modulating brain neuroinflammation and IR-related markers. Methods: Fifty female Wistar rats were divided into five groups, with one representing a sham group. AD was induced in the other four bilateral OVX rat groups by daily intraperitoneal injection of D-galactose/AlCl₃ (60 and 10 mg/kg, respectively) for 42 days. Group III–V: Animals were exposed to MTN (10 mg/kg/day; i.p.), PHE, and a combination of these, respectively, in the final 14 days of the experiment. Results: The OVX/AD rats showed significant deterioration in learning, memory, neurochemical, and histopathological examinations, while the MTN or/and PHE treatments significantly increased serum and brain irisin, improving memory in a Y-maze assessment. Thus, hippocampal histopathological alterations and IR-related markers decreased. In addition, suppressed hippocampal amyloid-beta protein expression and neuroinflammatory content of tumor necrosis factor-alpha (TNF-α), p38 mitogen-activated protein kinase (p38 MAPK), and NOD-like receptor protein-3 (NLRP3) were associated with an increase in peroxisome proliferator-activated receptor-gamma (PPAR-γ) protein expression and insulin-like growth factor-1 content in hippocampal tissues, collectively suppressing glial fibrillary acidic protein (GFAP) content, leading to an increase in brain-derived neurotrophic factor expression. Conclusions: Irisin induction may serve as a novel avenue in AD/menopause treatment and prevention via modulating the TNF-α/p38 MAPK/PPAR-γ/NLRP3/GFAP pathway. Full article