Search Results (3,515)

Adaptive and adverse brain states are often assumed to lie on a shared molecular continuum, but this assumption has rarely been evaluated against explicit transcriptomic alternatives. This study aimed to compare two representations of cross-context brain transcriptomic organization: a transcriptome-wide global-axis model and a low-dimensional reciprocal model. We benchmarked these models across a curated cross-study brain cohort spanning exercise, alcohol-related adversity-like contexts, stress, aging, and neurodegeneration, using prespecified intervention-like and adversity-like directional contrast labels rather than assuming homogeneous biological states. We assessed the competing representations using signed-effect correlations, permutation analyses, non-linear fitting, and held-out reconstruction, and we then examined the resulting structure through region-specific human bulk evaluation and exploratory cellular, single-nucleus, spatial, and chromatin projection analyses. These downstream analyses were used to examine localization and biological interpretability and were not treated as independent evaluation of the module 1/module 2 (M1/M2) partition. The combined signed-effect statistics were interpreted as representation-level directional summaries rather than estimates of a homogeneous cross-study biological effect. The global-axis model received limited support: intervention-like and adversity-like signed-effect summaries were only weakly correlated, were not stronger than permutation null expectations, and were not improved by non-linear fitting. Within the selected reciprocal-gene space, a rank-1 latent profile reconstructed held-out genes more accurately than the hard M1/M2 partition, whereas the M1/M2 discretization provided a more interpretable but selection-conditioned directional summary. Human analyses yielded an asymmetric pattern: a significant M1 association was observed only in the hippocampal dataset, whereas M2, the reciprocal index, and the other examined brain regions showed no consistent corresponding effects; leave-one-stratum-out analyses indicated poor cross-stratum reproducibility of the exact gene-level partition. These findings motivate a low-dimensional reciprocal representation as an exploratory framework while emphasizing context dependence, cohort dependence, and heterogeneity. Full article

Objectives: Human milk composition changes across lactation, but paired within-subject proteomic analyses comparing longitudinal trajectories in term and preterm milk remain limited. We aimed to characterize stage-associated proteomic changes within each cohort and determine whether longitudinal remodeling is shared or divergent between term and preterm lactation. Methods: In this single-center prospective study conducted at the Neonatal Intensive Care Unit, Jagiellonian University Medical College, Kraków, Poland (October 2020–November 2021), 40 lactating mothers (20 preterm, <32 weeks’ gestation, mean age 29.4 ± 6.1 years; 20 term, 37–42 weeks, mean age 30.2 ± 5.5 years) provided paired milk samples at ≤10 days postpartum and week 5. Milk serum proteomes were analyzed by quantitative data-independent acquisition mass spectrometry; differential abundance was assessed using two-sample t-tests with Storey false discovery rate correction (q < 0.05) and fold-change >1.5, followed by ClueGO pathway enrichment. Results: Stage-associated differential abundance was identified for 108 proteins in term milk (58 increased, 50 decreased) and 103 in preterm milk (64 increased, 39 decreased). Of these, 87 were shared between cohorts (80.6% of term, 84.5% of preterm set) with concordant directionality. Shared upregulated pathways included oxidative stress response and glycolysis (e.g., PRDX5, fold change 2.49, q = 0.044); shared downregulated pathways related to mucosal immunity (e.g., tenascin, fold change 9.61–11.41, q < 0.0001). Cohort-specific pathway signals were limited relative to shared remodeling. Conclusions: The human milk serum proteome undergoes substantial longitudinal remodeling in both term and preterm lactation, with most changes following a common temporal pattern; prematurity-related differences appear selective rather than global. These findings support lactation stage as a key determinant of milk proteomic composition and underscore the value of longitudinal, stage-aware study designs, although formal time-by-group interaction testing was not performed. Full article

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease characterized by an initial memory impairment that progresses to a widespread cerebrocortical failure, culminating in death. Understanding the molecular mechanisms that protect brain function during aging may help reveal novel targets for the development of effective treatments for the memory and cognitive deficits associated with AD. In this study, we analyzed a gene expression dataset generated from the prefrontal cortices of individuals showing no neurological or cognitive abnormalities. The gene expression profiles were used to identify candidate protective genes. We then compared the expression patterns of these genes in aging with their expression patterns in AD, thereby enabling us to pinpoint the genes that potentially contribute to brain resilience that delays or prevents aging-related dementia. We selected seven genes that are potentially protective for aging and AD, and have known homologues in Caenorhabditis elegans (C. elegans). Among these genes, SRPK2, AAK1, EFR3A and MAPK10 were previously implicated in attenuating AD-related cognitive decline. Our experiments demonstrated that all seven genes prioritized by our resilience model significantly extended the lifespan of C. elegans. Given the important relationship between neuronal functional integrity and lifespan (i.e., lifespan vs. brain health span), this work suggests the predicted AD resilience genes could serve as important candidate targets for therapeutic intervention. Full article

Background/Objectives: Corneal confocal microscopy (CCM) quantifies subbasal corneal nerve fibers noninvasively and may inform peripheral neuroaging. PhenoAge is a validated clinical measure of biological aging linked to morbidity and mortality risk and therefore provides a geriatric-relevant index of systemic aging. We aimed to assess corneal nerve morphology in clinically healthy adults and determine whether CCM-derived parameters are associated with biological age (PhenoAge) beyond chronological age. Methods: Eighty-four healthy volunteers (22–89 years) underwent CCM. PhenoAge was calculated using the Levine algorithm. Associations with chronological age and PhenoAge were tested using Spearman correlations (eye-specific and participant-level mean of both eyes). Paired inter-eye differences were assessed, and linear mixed-effects models (random intercept for participant; fixed effects for age/PhenoAge and eye) were fitted. Results: Mean chronological age was 50.8 ± 15.5 years, and mean PhenoAge was 47.1 ± 16.3 years. No systematic inter-eye differences were detected (all p > 0.05). Across analyses, older age and higher PhenoAge were associated with lower main corneal nerve fiber measures, most consistently for main-fiber density. Participant-level sensitivity analysis (mean of both eyes) confirmed inverse associations of both chronological age and PhenoAge with main-fiber length and density (all p ≤ 0.035). In mixed-effects models, main-fiber density was associated with chronological age (β = −0.020/year, p = 0.032) and PhenoAge (β = −0.019/year, p = 0.037). Conclusions: CCM-derived corneal nerve morphology demonstrates aging-related patterns in clinically healthy adults. The association between PhenoAge and main-fiber density may suggest a systemic biological aging component and warrants longitudinal validation. Full article

(1) Background: Adolescence is a critical period for the development of health-related behaviors, including dietary habits and physical activity. This cross-sectional study examined the associations between participation in organized sports, nutrient intake, and body composition in a sample of Greek adolescents. (2) Methods: A total of 224 adolescents aged 12–18 years from schools in the Attica region, Greece, participated in the study. Physical activity and organized sports participation were assessed using a validated questionnaire. Body composition was estimated using bioelectrical impedance analysis, and dietary intake was evaluated using three-day self-reported food records analyzed with Cronometer^® nutrition analysis software. (3) Results: Boys had higher fat-free mass and basal metabolic rate and lower fat-mass percentage than girls. Organized sports participation was common and differed by sex, with boys reporting higher participation and greater adherence to physical activity recommendations than girls. Organized sports participation was associated with differences in selected nutrient intakes, particularly among late adolescents; however, several differences were attenuated when nutrient intake was standardized per 1000 kcal, suggesting that part of the observed pattern may reflect differences in total energy intake. (4) Conclusions: These cross-sectional findings suggest that age-defined adolescent stage and organized sports participation are associated with differences in sports involvement, body composition, and nutrient intake among Greek adolescents; however, causal relationships cannot be established, and the findings should be interpreted as associations. Full article

Generative artificial intelligence (GenAI) is increasingly shaping assessment practices in higher education. However, its emergence has raised important questions about instructors’ readiness, ethical awareness, and professional support needs. This study examined EFL instructors’ assessment literacy for GenAI in Saudi higher education, with a focus on their assessment literacy level, perceptions of ethical, practical, and pedagogical implications, and training needs. A cross-sectional survey design was employed, and data were collected from 216 EFL instructors across Saudi universities. The instrument was validated through factor analyses, resulting in six constructs that include familiarity and use, assessment literacy, assessment application, ethical fairness, self-efficacy, and professional development. The findings indicate that instructors reported a high level of GenAI-related assessment literacy, especially in areas related to conceptual understanding and evaluative judgment. Ethical concerns were strongly expressed, including issues concerning academic integrity, privacy, and the need for human oversight. Although participants reported confidence in aligning GenAI with pedagogical goals, their practical use was less consistent in tasks requiring contextual judgment. Significant differences were observed across gender, rank, and teaching experience, while age showed a selective pattern. Overall, the study documents the importance of aligning individual competence with institutional support for responsible GenAI use in language assessment. Full article

Background and objectives: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with endothelial glycocalyx injury and perioperative endothelial dysfunction. Syndecan-1 is commonly used as a biomarker of glycocalyx shedding, but data on its perioperative changes and their relationship with operative and patient-related factors remain limited. The aim of this study was to evaluate perioperative Syndecan-1 dynamics during coronary artery bypass grafting (CABG) with CPB and to assess associations with ischemia–reperfusion exposure and patient characteristics. Materials and methods: This prospective observational study included 147 patients undergoing elective CABG with CPB. Syndecan-1 concentrations were measured at five time points: before induction of anaesthesia, immediately after aortic cross-clamp application, immediately after aortic declamping, on arrival at the ICU and 24 h after surgery. Perioperative changes were analysed using non-parametric tests, Spearman’s rank correlation analysis and mixed-effects modelling. The study was registered at ClinicalTrials.gov (NCT03491163; registered on 29 March 2018). Results: Syndecan-1 concentrations changed significantly over time (p < 0.001), increasing from a baseline median of 49.74 ng/mL to a peak of 147.78 ng/mL at ICU admission, followed by a partial decline to 65.26 ng/mL at 24 h. Aortic cross-clamp duration was weakly but significantly associated with Syndecan-1 concentration at ICU admission (r_s = 0.243, p = 0.003) and with perioperative increases from baseline to ICU admission (ΔS4-1: r_s = 0.196, p = 0.017) and from aortic clamping to ICU admission (ΔS4-2: r_s = 0.207, p = 0.012). No significant associations were observed between CPB duration and Syndecan-1 concentrations in univariable analyses. In the mixed-effects model, a significant non-linear temporal pattern of Syndecan-1 concentrations was observed (both linear and quadratic time terms, p < 0.001). Male sex (β = 0.247, p = 0.009) and aortic cross-clamp duration (β = 0.016, p = 0.005) were independently associated with higher Syndecan-1 concentrations, whereas smoking status, age, BMI, diabetes status, EuroSCORE II, and CPB duration were not independently associated. Conclusions: Syndecan-1 concentrations increase significantly during cardiac surgery with cardiopulmonary bypass, peaking at ICU admission and partially declining within 24 h. Aortic cross-clamping duration, but not total CPB duration, showed weak associations with glycocalyx shedding. Male sex was independently associated with higher Syndecan-1 concentrations. These findings support ischemia–reperfusion injury as an important contributor to endothelial glycocalyx shedding during cardiac surgery. Full article

Background: Human brucellosis is a widespread zoonotic febrile illness in livestock-rearing endemic regions, including Türkiye (pooled human seroprevalence approximately 4.5%). Age-stratified item-level knowledge profiles paired with information-source patterns are rarely reported in adult populations. We aimed to describe age-stratified brucellosis knowledge and information-source ecosystems in a hospital-attending adult sample from an endemic Turkish province. Methods: A hospital-based cross-sectional survey enrolled 397 adults in Balıkesir, Türkiye. A 17-question instrument assessed demographics, prior awareness, a 26-item composite knowledge score among aware respondents, and information sources. Item-level recognition was compared across four age strata, with multivariable logistic regression identifying independent predictors. Results: Of 397 adults (mean age 36.1 years; 62.7% male), 233 (58.7%) reported prior awareness, increasing with age (51.8% in 18–29 vs. 74.5% in ≥60 years; p < 0.001). Among aware respondents, composite knowledge declined with age (mean 8.52 vs. 5.94; p < 0.001). Raw dairy transmission and treatment availability were uniformly recognized (>80% across all strata). Recognition of clinical symptoms (fever 68.9% vs. 34.3%; p = 0.005) and veterinary signs (decreased milk yield 36.9% vs. 8.6%; p = 0.001) was substantially lower in older respondents. Internet citation declined with age (41.7% to 17.1%), while older respondents relied more on interpersonal networks. Conclusions: Brucellosis knowledge was not uniformly distributed across the adult age spectrum. Dominant transmission and treatment messages were near-universally recognized, while clinical-symptom and veterinary-sign recognition showed substantial age-related deficits, accompanied by generational divergence in information-source ecosystems. These findings suggest that age-tailored, channel-specific reinforcement of less-recognized clinical and veterinary knowledge, delivered through trusted healthcare-worker channels, may strengthen brucellosis education in endemic Turkish settings. Community-based replication is required before broader policy translation. Full article

The postnatal period involves significant emotional and relational shifts that can challenge early mother–infant interactions, particularly under conditions of psychosocial vulnerability (e.g., maternal anxiety/depression) or infant-related risk (e.g., preterm birth). Maternal mentalization, operationalized as Parental Reflective Functioning (PRF), is a key protective factor for sensitive caregiving and dyadic regulation. Objectives: This protocol describes a multicenter, open-label, single-arm feasibility study evaluating a brief, fully online, mentalization-based video-feedback intervention (VFI-RF). The study is designed to assess the feasibility and acceptability of the intervention, rather than its efficacy. We aim to recruit 48 mothers, 24 in each of two risk groups, through socio-health services and neonatal intensive care units. Risk Group 1 will include mothers with clinically significant depressive and/or anxiety symptoms, defined as EPDS > 9 and/or GAD-7 ≥ 10, whereas Risk Group 2 will include mothers of preterm infants, defined as infants born before 37 weeks of gestation. Methods: The intervention consists of 8 + 2 synchronous online sessions over approximately 5 months. Mothers record brief everyday caregiving interactions (~5 min) to review with a trained clinician, focusing on the infant’s internal states and reflective meaning-making. Assessments occur at baseline (T0, infant age ~3 months), post-intervention (T1, ~8 months), and follow-up (T2, ~12 months). Primary feasibility outcomes include recruitment/referral metrics, uptake, retention, assessment completion, missing data, and participant-reported acceptability. Secondary exploratory clinical outcomes include maternal PRF, symptoms, parenting stress, social support, and mother–infant attachment, evaluated via validated self-report questionnaires. Results: The study is designed to evaluate referral and recruitment patterns, intervention uptake, and participant retention, as well as the acceptability and suitability of study procedures and outcome measures for a future controlled trial. Preliminary trajectories of change in maternal reflective functioning and early relational indicators will be examined descriptively and exploratorily. Conclusions: Findings will inform the feasibility and refinement of a brief online mentalization-based video-feedback intervention to support at-risk mother–infant dyads during the first postnatal year. Trial registration: Registered on Open Science Framework, osf.io/6g9ja, date of registration 4th March 2026. Full article

Background: Substance Use Disorder (SUD) is frequently associated with psychiatric comorbidity, including psychotic symptoms, impulsivity and neurodevelopmental traits. The influence of age and duration of substance use on these clinical characteristics and on treatment retention remains insufficiently understood. Objectives: To examine the influence between age, duration of substance use, clinical presentation, patterns of violence, and treatment retention in individuals with SUD. Methods: A prospective 6-month cohort study was conducted at the Alcoholism Treatment Unit of the CAUSA Hospital Complex in Salamanca, Spain. A total of 264 patients with SUD were classified into two groups: prolonged substance use (≥55 years of age or ≥25 years of substance use; n = 127) and shorter substance use trajectories (<55 years and <25 years of substance use; n = 137). Participants completed structured clinical interviews and validated measures of quality of life, impulsivity, autistic traits, addiction severity, psychotic symptoms and violence. Non-parametric analyses were applied (α = 0.05; 95% CI). Results: Younger participants showed a significantly higher prevalence of auditory and visual hallucinations and persecutory delusions at baseline. During follow-up, both groups exhibited a reduction in physical aggression while driving and an increase in insults and verbal threats. No significant differences were observed in recent uncontrolled violence. Positive screening results for ADHD, autistic traits and impulsivity were not associated with treatment retention. Lower baseline physical functioning was associated with reduced completion of the 6-month follow-up assessment. Conclusions: Age and duration of substance use were associated with differences in the clinical presentation of SUD. Younger individuals exhibited a greater burden of psychotic symptoms and violence-related behaviours, whereas poorer physical functioning was associated with lower follow-up retention among individuals with prolonged substance use histories. These findings support the importance of age-sensitive assessment and management strategies in patients with SUD. Full article

This study aimed to investigate the prevalence of human pegivirus type 1 (HPgV-1) among healthy individuals, type 2 diabetes patients, and cancer patients in Taizhou, Jiangsu, China. A total of 2872 participants, including 2052 healthy individuals, 373 type 2 diabetes patients, and 447 cancer patients, were enrolled at Taizhou Fourth People’s Hospital between 2022 and 2024. Serum samples were collected from each participant, and HPgV-1 RNA was detected using a reverse transcription-polymerase chain reaction (RT-PCR) assay. The positive rates were compared across the three groups. The age range of healthy individuals was 5–91 years, while that of type 2 diabetes and cancer patients was 25–85 years and 34–91 years, respectively. The prevalence of HPgV-1 among healthy individuals was 15.3% (313/2052), which was significantly higher than that in type 2 diabetes patients (11.0%, 41/373, p < 0.05) and cancer patients (9.2%, 41/447, p < 0.001). In healthy individuals, the prevalence of HPgV-1 increased from childhood to young adulthood, peaking in the 19–40 years age group, followed by a decline after 40 years of age, indicating an age-related pattern. Similarly, HPgV-1 load increased from childhood to adulthood. No significant gender differences in HPgV-1 prevalence were observed across the three cohorts. In conclusion, HPgV-1 infection exhibits an age-dependent prevalence, with the lowest rate in children and adolescents and the highest in young adults (19–40 years). The significantly lower prevalence of HPgV-1 in type 2 diabetes and cancer patients raises the intriguing question of whether HPgV-1 infection may play a protective or contributory role in the pathogenesis of diabetes and cancers. Full article

Population ageing is reshaping the use and evaluation of everyday urban green spaces, especially in old urban districts where nearby public spaces support walking, resting, exercise, and social contact. Conventional age-friendly assessments often emphasise whether formal infrastructure is provided, but facility provision alone does not ensure experiential fit with older adults’ functional capacities, daily routines, and social practices. This exploratory multiple-case study examines user-initiated informal adaptations in three neighbourhood-scale green spaces in Gulou District, Nanjing, China. Facility audits, approximately 30 h of non-participant observation, semi-structured interviews with 36 older users, and 220 valid questionnaires were combined through cross-case coding and qualitative triangulation. Three adaptation types were identified: supplementary, modifying, and appropriative adaptations. These practices were interpreted as context-dependent behavioural signals potentially associated with safety and convenience, ergonomic support and material-thermal comfort, social accessibility and spatial accommodation, and social support. Adaptation patterns varied descriptively across sites and age groups in relation to facility conditions, spatial organisation, activity intensity, and user characteristics. The findings suggest that, when interpreted alongside facility audits, interviews, and site context, older adults’ everyday adaptations may help identify possible mismatches between formal provision and actual use, offering a low-cost interpretative perspective for inclusive, incremental, and socially sustainable green-space renewal. Full article

Hepcidin is a multifunctional peptide involved in innate immunity and iron homeostasis, yet its earliest developmental regulation in sturgeons remains poorly understood. Here, we investigated maternal loading and embryonic expression patterns of hepcidin transcripts (hamp) in Siberian sturgeon (Acipenser baerii). RT-qPCR detected hamp transcripts in all 17 unfertilized egg (UFE) batches examined; however, maternally loaded transcript abundance varied markedly among batches, with up to a 14.8-fold difference, indicating substantial heterogeneity in the molecular starting state of embryos. In contrast, female traits, including age, body weight, and condition factor, as well as fertilization rate and hatching success, were not significantly correlated with UFE hamp transcript abundance (Spearman’s rank correlation with BH-FDR adjustment; q > 0.05). Developmental expression analysis from UFE to first hatch was then performed using five developmental series (DevSeries 1–5) that represented relatively high, intermediate, and low UFE baseline levels within the statistically differentiated UFE dataset (Welch ANOVA/Games–Howell post hoc, p < 0.05). The developmental dataset showed significant DevSeries, stage, and DevSeries × stage effects, indicating that embryonic hamp expression profiles differed among DevSeries (two-way ANOVA, p < 0.05). High-loading DevSeries (DevSeries 2 and 4) showed prolonged early persistence followed by later re-elevation, whereas low-loading DevSeries (DevSeries 3 and 5) maintained lower overall abundance but displayed more evident stage-linked increases during embryogenesis. Collectively, these findings show that maternally loaded hamp transcripts are associated with embryonic expression profiles and support the view that maternal transcript abundance provides an initial baseline that should be considered when interpreting early developmental expression profiles of immune- and iron-regulation-related genes in this chondrostean species. Full article

Background and Objectives: Toxic hepatitis may result from drugs, herbal products, mushroom exposure, or other suspected toxic agents. This study aimed to compare the clinical, laboratory, severity-related, and outcome characteristics of toxic hepatitis according to suspected etiology. Materials and Methods: This retrospective observational study included 175 patients diagnosed with toxic hepatitis between January 2012 and March 2026 at a tertiary referral center with an active liver transplantation program. Patients were categorized into five groups: drug-induced liver injury (DILI) (n = 97), herb-induced liver injury (HILI) (n = 17), mushroom poisoning (n = 24), suspected causative agent exposure (n = 15), and unavailable etiological data (n = 22). Clinical outcomes, laboratory parameters, injury patterns, severity grades, and MELD-Na scores were analyzed. Results: Etiological groups differed significantly in demographic, hematological, biochemical, coagulation, bilirubin, ammonia, MELD-Na, and R-ratio parameters. Mushroom poisoning showed the most pronounced hepatocellular injury profile, with higher median values for AST, ALT, INR, ammonia, MELD-Na, and R ratio: 4856 U/L, 4996 U/L, 5.0, 585 µg/dL, 30, and 78.3, respectively. Recovery was most frequent in the HILI group (94.1%). In multivariable logistic regression analysis, older age (OR = 1.066, 95% CI: 1.03–1.11), lower INR (OR = 0.205, 95% CI: 0.08–0.51), and higher albumin level (OR = 4.255, 95% CI: 1.55–11.63) were independently associated with recovery. Conclusions: Toxic hepatitis showed distinct clinical and biochemical patterns according to etiology. In this selected tertiary referral-center cohort, mushroom poisoning was associated with pronounced hepatocellular injury and frequent liver transplantation, whereas HILI showed a more favorable short-term course. These findings should be interpreted in light of referral bias and the overrepresentation of severe cases. Full article

The rapid evolution of Padel in Saudi Arabia (SA) has positioned the sport as a popular recreational and social activity, mainly among young adults. However, limited research has examined how different forms of sport motivation are associated with mental health outcomes in this emerging context. Drawing on Self-Determination Theory (SDT), this study investigated the associations between intrinsic and extrinsic motivation and depression, stress, and anxiety among Padel players in SA. A quantitative, cross-sectional online survey was conducted with a sample of 475 players, the majority of whom were aged 17–35 and held at least a bachelor’s degree. Data were analysed using Partial Least Squares Structural Equation Modelling (PLS-SEM) to evaluate the relationships between multidimensional motivation factors and mental health symptoms. The findings revealed a nuanced, at times paradoxical, pattern of relationships. Intrinsic motivation to experience stimulation (engaging in an activity because of the positive sensations, excitement, enjoyment, or stimulation that the activity itself provides, rather than for external rewards or pressures) was consistently associated with lower levels of depression, stress, and anxiety, suggesting that enjoyment-driven involvement is associated with better mental health outcomes. In contrast, intrinsic motivation to accomplish was positively correlated with all three mental health indicators, indicating that achievement-oriented engagement might intensify emotional pressure. Among extrinsic motivations, external regulation was significantly associated with poorer mental health outcomes. In contrast, introjected regulation unexpectedly displayed a negative association with psychological distress, demonstrating a potentially adaptive role in this setting. Identified regulation, however, was not significantly associated with any mental health symptoms. These results underscore the “double-edged” nature of sport motivation, showing that not all internal or external motives yield uniformly positive consequences. The study contributed to the growing literature by providing a context-specific understanding of how motivational dynamics function within a rapidly growing sport in Saudi Arabia. In practice, the findings suggested that enjoyment-based involvement was associated with more favourable mental health outcomes, whereas performance-related pressures might be associated with less favourable outcomes. Full article