Search Results (1,362)

Treat-to-target management in inflammatory bowel disease (IBD) combines symptoms, fecal and serum biomarkers, endoscopy, histology, and cross-sectional imaging, but these measures frequently diverge. Discordance may reflect analytical variation, timing, disease location, phenotype, comorbidity, or partially non-overlapping biological processes. We performed a critical narrative review using a structured PubMed/MEDLINE search, supplemented by citation chaining and publisher searches. Guidelines, systematic reviews, diagnostic studies, cohorts, randomized trials, and selected mechanistic studies were prioritized. Fecal calprotectin (FC) and lactoferrin primarily reflect intestinal neutrophilic inflammation, whereas C-reactive protein (CRP) and related serum indices reflect a nonlocalizing systemic response. The fecal immunochemical test (FIT) detects gastrointestinal bleeding, and leucine-rich alpha-2 glycoprotein (LRG) remains promising but insufficiently standardized. We distinguish five biological biomarker domains—namely, fecal–neutrophil; serum–systemic; epithelial/barrier; restitution/resolution; and fibrosis/extracellular matrix (ECM) remodeling—from symptoms and clinical indices, pharmacologic measurements, and phenotype-directed reference assessments. Circulating barrier, repair, and matrix-turnover markers remain investigational. Reactive therapeutic drug monitoring (TDM) for anti-tumor necrosis factor (anti-TNF) agents has the most mature evidence. Vedolizumab and ustekinumab show exposure–response associations, but actionable thresholds are unvalidated, and clinical TDM is not established for newer biologics or oral small molecules. After objective confirmation of disease activity, the framework may support phenotype-directed therapeutic decisions but is not a validated algorithm. Clinically important disagreement should prompt assessment of sampling, assay, timing, infection, medication-related confounding, and pretest probability before phenotype-directed endoscopy, histology, imaging, or reactive TDM is selected. A single discordant result should neither trigger treatment escalation nor exclude active or structural disease. Full article

Background and Objectives: This study evaluated the interplay between cyberchondria, psychological distress, and symptom severity in female patients with irritable bowel syndrome (IBS). Materials and Methods: The study included 176 female participants: 86 patients with IBS and 90 controls. Participants completed a sociodemographic form, the IBS Symptom Severity Score (IBS-SSS), Cyberchondria Severity Scale–Short Form (CSS-12), Psychological Well-Being Scale (PWBS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). Results: Compared with healthy controls, women with IBS had significantly higher scores on the BAI (p < 0.001), BDI (p < 0.001), and CSS-12 Distress (p = 0.003), Reassurance (p < 0.001), and Compulsion (p < 0.001) subscales, whereas CSS-12 Excessiveness did not differ significantly between the groups (p = 0.211). Unexpectedly, PWBS scores were also significantly higher in women with IBS than in healthy controls (p < 0.001). IBS-SSS scores were significantly higher in the IBS group (p < 0.001). Within the IBS group, IBS-SSS was positively correlated with BAI (r = 0.255, p = 0.018) but not with BDI (r = 0.099, p = 0.365), while BDI was negatively correlated with PWBS (r = −0.320, p = 0.003). PWBS showed a weak positive correlation with CSS-12 Excessiveness (r = 0.215, p = 0.046), but not with the other CSS-12 dimensions. In ROC analysis, BAI (cut-off > 3) showed 88.4% sensitivity and 82.2% specificity; BDI (cut-off > 4), 82.6% and 86.7%; PWBS (cut-off > 33), 70.9% and 98.9%; and IBS-SSS (cut-off > 50), 96.5% and 88.9%, respectively. Conclusions: It was found that women with IBS had higher anxiety and depressive symptom scores compared with healthy female, and that there were differences in various dimensions of cyberchondria. The unexpectedly higher psychological well-being scores observed in the IBS group should be interpreted with caution. These findings point to the potential importance of psychological evaluation as part of a comprehensive assessment of IBS. Effect sizes for the between-group differences were large for the BAI and BDI (Cliff’s delta = 0.74 for both), the CSS-12 Reassurance subscale (delta = 0.53), the PWBS (Cohen’s d = 1.79) and the IBS-SSS (d = 2.84), and small for the Distress (delta = 0.28) and Compulsion (delta = 0.27) subscales. Full article

Thoracoabdominal aortic aneurysm (TAAA) is a complex vascular disorder involving both thoracic and abdominal segments of the aorta and remains associated with substantial morbidity and mortality. One of the most serious complications after thoracoabdominal aortic aneurysm (TAAA) repair is spinal cord ischemia (SCI), which may progress to spinal cord infarction and result in irreversible neurologic deficits including paraplegia, neurogenic bladder dysfunction, and bowel dysfunction. The incidence of SCI after TAAA repair varies with the extent of aneurysmal involvement, operative duration, and patient comorbidities. The primary pathophysiologic mechanism involves interruption of radiculomedullary arterial flow, compounded by systemic hypotension and limited collateral circulation. Because SCI profoundly affects functional recovery and long-term quality of life, prevention and early recognition are central to perioperative management. Established neuroprotective strategies emphasize maintenance of spinal cord perfusion through meticulous hemodynamic optimization, cerebrospinal fluid (CSF) drainage, and temperature modulation. Intraoperative neuromonitoring using motor and somatosensory-evoked potential facilitates early detection, while newer modalities such as near-infrared spectroscopy and CSF lactate monitoring may offer additional insight. When SCI occurs despite prophylaxis, rapid initiation of rescue measures including CSF drainage, hemodynamic augmentation, and other discussed treatments may improve neurologic outcomes. Long-term care focuses on rehabilitation, symptom management, and psychological support. Therefore, this review aims to consolidate medical evidence to improve the prevention, detection, and treatment of spinal cord infarction associated with thoracoabdominal aortic aneurysm repair. Full article

Diarrhea-predominant irritable bowel syndrome (IBS-D) frequently occurs alongside depression, greatly impairing patients’ life quality, with limited targeted treatments. Low-molecular-weight peptides (LMWPs) from Musca domestica larvae exert gut-protective bioactivities, but their efficacy and molecular mechanisms for comorbid IBS-D and depression remain unelucidated. A chronic–acute combined stress (CACS)-induced rat model of IBS-D complicated with depression was established and treated with LMWPs. The study evaluated intestinal and depressive behavioral phenotypes, and integrated 16S rRNA sequencing, untargeted serum metabolomics and quantitative detection of fecal SCFAs for multi-omics correlation analysis. 1. CACS triggered typical comorbid symptoms, which LMWPs alleviated with effects similar to trimebutine maleate. 2. LMWP treatment was associated with reshaped gut microbiota, restored metabolic pathways, altered levels of 27 disease-associated serum metabolites, and increased fecal SCFA levels. 3. Multi-omics correlation analyses suggested that the therapeutic benefits may involve crosstalk among gut microbiota, SCFAs, and tryptophan metabolites. Larva-derived LMWP relieves IBS-D combined with depression by modulating gut microecology, SCFA generation and serum metabolic balance through the gut–brain axis, which can serve as a novel promising therapeutic candidate. Full article

Background/Objectives: Illness uncertainty is inherent in irritable bowel syndrome (IBS); however, the factors that contribute to it and outcomes impacted by it have yet to be assessed in pediatric IBS. As such, the current longitudinal pilot study assessed the relationship between disease characteristics, illness appraisals, mood, and health-related outcomes. Methods: 50 youth (ages 10–18) diagnosed with IBS completed self-report measures across three timepoints. Path analysis models specifying illness uncertainty as the mediator were constructed and assessed with Mplus using Bayesian Estimation. Results: Time-2 illness uncertainty significantly predicted time-3 depressive and anxiety symptoms, higher functional disability, and lower levels of problem- and emotion-focused coping. Exploratory indirect effects demonstrating clinical signals were also identified. Conclusions: Future observational studies with larger samples are needed to further investigate illness appraisals’ relationships with adjustment and health-related outcomes in pediatric IBS. This is a fruitful avenue to identify modifiable areas of targeted intervention. Full article

Alpha-gal syndrome (AGS) is a tick-induced, IgE-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose (α-gal), which is expressed on glycoproteins and glycolipids of non-primate mammals but absent in humans. Gastrointestinal (GI) symptoms dominate the clinical presentation in a substantial proportion of patients yet remain systematically under-recognized, frequently being attributed to irritable bowel syndrome (IBS), non-celiac gluten sensitivity (NCGS), or lactose intolerance. This narrative review synthesizes the current evidence on the epidemiology, GI and systemic phenotype, immunological mechanisms, diagnostic strategies, management approaches, quality-of-life burden, and multi-level public health interventions for AGS, and it identifies critical knowledge gaps as of 2026. We searched PubMed/MEDLINE, Embase, and Web of Science from database inception through 31 March 2026, and synthesized the evidence narratively in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA). GI symptoms occur in 47–69% of patients with AGS, with abdominal pain (58%), diarrhea (42%), nausea (39%), and vomiting (31%) as the cardinal manifestations. A characteristic 2–6 h delay between the ingestion of mammalian-derived food and symptom onset—explained by the glycolipid–chylomicron delivery mechanism—drives diagnostic confusion with functional GI disorders. Among 295,400 tested individuals in the United States, 30.5% were α-gal IgE positive, and an estimated 96,000–450,000 Americans were affected between 2010 and 2022. Despite this burden, 42% of U.S. healthcare providers had never heard of AGS. Strict avoidance of mammalian meat improves symptoms in 53–86% of adherent patients, although the condition carries a meaningful risk of anaphylaxis even among GI-predominant presenters. AGS is a prevalent, frequently misdiagnosed, and clinically morbid condition whose GI phenotype lies squarely within the gastroenterologist’s domain. A coordinated response that integrates clinician education, institutional diagnostic algorithms, and national surveillance infrastructure is urgently needed. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with elusive etiology and limited therapeutic options, accompanied by potential side effects. In this study, to investigate the therapeutic potential of Antarctic krill oil (AKO) in a dextran sulfate sodium (DSS)-induced mouse colitis model, animal experiments, molecular assays, transcriptomics, metabolomics, and 16S rRNA gene sequencing were conducted. Our results revealed that supplementation of AKO significantly alleviated colitis symptoms, such as weight loss, and inflammatory responses. Moreover, multi-omics analyses demonstrated that AKO inhibited the PI3K/Akt signaling pathway, remodeled beneficial gut microbiota, and reshaped metabolite profiles associated with glycerolphospholipid metabolism. Remarkably, AKO alleviated DSS-induced colitis, accompanied by coordinated changes in the gut microbiota, metabolites, and transcriptome, which were associated with suppression of key inflammatory pathways. These findings present experimental evidence for the potential of AKO as a marine-based nutritional intervention for UC, and offer novel perspectives on microbiota-targeted therapies for inflammatory diseases. Full article

Background/Objectives: Fibromyalgia (FM) is increasingly recognized as a multisystem disorder characterized by central sensitization and visceral symptom involvement. Irritable bowel syndrome (IBS) and overactive bladder (OAB), which share overlapping pathophysiological mechanisms related to altered visceral processing, are both commonly reported in FM. However, whether gastrointestinal and urinary symptoms cluster within the same patients and whether such clustering is associated with greater FM severity remain insufficiently explored. This study aimed to evaluate the overlap between IBS and OAB in women with FM and to determine whether their coexistence is associated with differences in FM severity. Methods: This cross-sectional observational study included 74 women with FM evaluated at the Physical Medicine and Rehabilitation outpatient clinic of Memorial Ataşehir Hospital between August and December 2025. FM severity was assessed using the Widespread Pain Index (WPI), Symptom Severity Scale (SSS), and FM Severity Score (GSS). OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS), and IBS status was determined based on prior clinical diagnosis. For subgroup severity analyses, patients were categorized as IBS + OAB, OAB only, or neither condition; the two patients with IBS alone were excluded from these comparisons because of the small cell size (n = 72). Results: IBS was present in 13 patients (17.6%) and OAB in 46 patients (62.2%). A substantial overlap between bowel and bladder symptoms was observed: 84.6% of IBS-positive patients had OAB, and IBS prevalence was higher in OAB-positive than OAB-negative patients (23.9% vs. 7.1%; OR = 4.56, 95% CI 0.93–22.24), although this association did not reach statistical significance (p = 0.063). Significant overall group differences were observed for SSS (p < 0.001) and GSS (p = 0.001), whereas WPI did not differ significantly across groups (p = 0.228). Patients with concomitant IBS and OAB had significantly higher GSS scores than both the OAB-only (adjusted p = 0.003) and neither-condition groups (adjusted p = 0.001). In multivariable analysis adjusted for age, concomitant IBS and OAB remained significantly associated with higher GSS (B = 3.77, 95% CI 1.59–5.95; p = 0.001). The regression model explained 18.2% of the variance in GSS (R² = 0.182; p = 0.003). Conclusions: Concomitant IBS and OAB in women with FM were associated with greater overall FM symptom burden, particularly higher SSS and GSS scores, whereas widespread pain severity did not differ significantly across groups. The presence of either IBS or OAB may warrant evaluation for the other condition, as bowel–bladder symptom clustering may characterize a subgroup with greater overall symptom burden and support consideration of a more integrated clinical assessment. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) frequently experience food-related symptoms and express a strong need for dietary guidance, yet evidence-based recommendations remain limited. This often leads to self-imposed dietary restrictions, potentially compromising nutritional intake and food-related quality of life (Fr-QoL). The primary aim of this study was to evaluate changes in Fr-QoL, following personalized feedback on an IBD-specific food frequency questionnaire and access to an online nutritional knowledge portal over a 6-month period. Secondary exploratory outcomes included changes in dietary intake and diet quality. Methods: In this nationwide pre–post study, 108 patients with IBD completed baseline and 6-month assessments. Dietary intake was measured using the validated GINQ-FFQ and Fr-QoL using a 29-item questionnaire. Nutrient intake was compared with EFSA reference values. Participants received automated personalized feedback and had access to educational tools and dietitian resources. Changes over time were analyzed using paired statistical tests. Results: A significant improvement in Fr-QoL was observed (mean difference 8.1 points, 95% CI 5.5–10.7; p < 0.001; Cohen’s d = 0.39). Baseline intake was characterized by high fat and low fiber consumption. After 6 months, total energy intake decreased (p < 0.001), along with reductions in protein, fat, carbohydrates, fiber, and several micronutrients, including iron, folate, vitamin B6, vitamin C, potassium, magnesium, and zinc. Diet quality did not improve, and adherence to EFSA guidelines remained suboptimal. The digital tools were positively evaluated. Conclusions: In this single-arm pre–post study, Fr-QoL scores were higher at follow-up than at baseline among participants who completed both assessments, whereas dietary intake and overall diet quality did not improve. The findings support the feasibility and acceptability of the developed digital tools for dietary assessment and nutrition education, although their effectiveness requires further evaluation in controlled studies. Additional strategies, including structured dietitian-led support combined with digital resources, may be required to optimize nutritional outcomes in patients with IBD. Full article

We conducted an online cross-sectional study to assess malnutrition risk, food and nutrition insecurity, and perceived barriers and facilitators to dietary management among adults (18–64 years old) with a self-reported clinical diagnosis of inflammatory bowel disease (IBD) in outpatient and community settings. We assessed malnutrition risk using the Saskatchewan IBD-Nutrition Risk screening tool, food security risk using the two-item Hunger Vital Signs questionnaire, and nutrition security risk using a validated four-item tool. Open-ended questions elucidated barriers and facilitators to dietary management of IBD. Among 57 participants who self-reported a clinical diagnosis of IBD, 52.6% (n = 30/57) had ulcerative colitis, and 47.4% (n = 27/57) had Crohn’s disease. Nutrition insecurity was higher among those at high risk of malnutrition than among those at low-to-medium risk (p = 0.018), and there were no differences in food security status (p = 0.081). Using univariate logistic regression, the odds of being classified as having a high risk of malnutrition were associated with being male, following a special diet or nutrition plan, experiencing IBD-related flare-ups, and nutrition insecurity. Furthermore, healthcare professionals and social support, as well as digital resources/nutrition-related apps, were identified as facilitators to dietary management, while barriers included food access and expense, limited nutrition knowledge and resources, and fear of IBD-related symptom flare-ups. Although self-reported malnutrition risk and food and nutrition insecurity are common, larger prospective studies incorporating validated disease-activity measures and comprehensive nutritional assessment are needed to clarify these relationships and evaluate integrated dietetic and social-support interventions. Full article

Parkinson’s disease (PD) is a multisystem disorder in which gastrointestinal dysfunction often precedes motor symptoms, yet the molecular links between peripheral stress and central neurodegeneration remain unclear. We investigated whether genes commonly dysregulated in PD and a classic model of intestinal inflammation (IBD) might reveal conserved stress-responsive molecules relevant to brain pathology. Shared gene signatures between PD and inflammatory bowel disease (IBD) were identified from peripheral blood transcriptomes using weighted gene co-expression network analysis (WGCNA). Hub genes were prioritized via protein–protein interaction (PPI) analysis and evaluated for expression consistency in independent brain tissue transcriptomic datasets. Single-cell RNA sequencing (scRNA-seq) of the PD substantia nigra was used to define the cellular context of the key hub gene, and CellChat analysis assessed intercellular communication changes. Immunofluorescence validation was performed in an MPTP-induced PD mouse model. We identified 79 shared genes and 6 hub genes, among which only HSP90AA1 showed consistent upregulation across independent PD transcriptomic validation datasets. Functional enrichment highlighted inflammation-related pathways. Because peripheral immune infiltration showed only minor changes, we further investigated the cellular context of HSP90AA1 within the PD brain. ScRNA-seq analysis of the PD substantia nigra demonstrated that HSP90AA1 was expressed across multiple cell populations. Integration with transcriptional regulatory analysis identified TP53 as a potential upstream regulator, and the strongest TP53–HSP90AA1 co-expression and cellular colocalization signals were observed in astrocytes, prompting further astrocyte-focused investigation. CellChat analysis revealed altered intercellular communication patterns in PD substantia nigra, including changes in synapse-associated ligand–receptor interaction signatures, particularly involving NCAM-related pathways. In the MPTP-induced PD mouse model, immunofluorescence identified astrocytic HSP90α upregulation, and increased nuclear p53 signal in astrocytes, accompanied by dopaminergic neuron loss. Conclusion: Astrocytic upregulation of HSP90AA1 is associated with altered synapse-related intercellular communication patterns in the PD substantia nigra, potentially involving a predicted TP53 associated regulatory component. These findings, validated in an MPTP mouse model, identify HSP90AA1 as a candidate stress-responsive hub linking peripheral inflammatory states with astrocyte-associated molecular alterations in PD, providing a framework for further experimental investigation. Full article

Irritable bowel syndrome (IBS) symptoms are often triggered by the consumption of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), which are widely found in cereal-based foods, dairy products, fruits, legumes, and vegetables. Among these, cereal-based products are one of the main dietary sources of fructans. Consequently, low-FODMAP dietary strategies have gained increasing attention as an effective approach for managing IBS symptoms. This study adopted an integrated strategy based on the parallel selection of low-FODMAP flours and the screening of lactic acid bacteria (LAB) and yeasts, with the aim of identifying the best-performing flour and microbial starter to support the of low-FODMAP bread formulation. Sixteen soft and durum wheat flours were characterized for fructan content, chemical, physical, and rheological properties, revealing marked variability among the samples and highlighting the importance of raw material selection. Together, 150 LAB and 7 commercial yeasts were evaluated for their ability to modulate fructans, fructose, glucose and mannitol during 24 h model-dough fermentation. Most strains promoted substantial reduction in FODMAP levels, with variability depending on microorganisms, inoculum concentration, and fermentation time. Overall, the findings of this study provide a foundation for subsequent investigations focused on the development and characterization of low-FODMAP bread using the selected flour-starter combinations. Full article

Background and Objectives: This study aimed to characterize physicians’ knowledge and practice patterns regarding the use of probiotics in the management of irritable bowel syndrome (IBS). By examining clinical experiences and barriers to adoption, this research sought to identify critical gaps in practice and establish a foundation for evidence-based improvements in patient care. Materials and Methods: The survey was conducted in accordance with the CROSS (Consensus-based Checklist for Reporting of Survey Studies) guidelines. Attendees of a medical congress, specifically general practitioners, gastroenterologists, surgeons, and internists with an interest in the clinical significance and therapeutic modulation of the human microbiome, were invited to participate. Participants completed a 38-item, paper-based questionnaire. The instrument assessed respondents’ self-perceived knowledge of probiotics, their understanding of probiotic definitions and specific strains, and their current clinical practice patterns—particularly regarding the management of irritable bowel syndrome (IBS). Additionally, the survey explored information sources, the frequency of self-prescription, and the perceived need for further education, with a specific focus on safety profiles and clinical concerns. Results: Of the 70 invited attendees, 68 completed the survey, yielding a response rate of 97.1%. The respondent cohort included 40 general practitioners (GPs), 20 gastroenterologists (GEs), four surgeons (SSs), and four internists (SIMs). More than half of the respondents were female (n = 37, 54.4%), with a median age of 43 years (range: 28–70). Exactly half of the respondents (n = 34, 50.0%) agreed that probiotics always have a role in the management of irritable bowel syndrome (IBS); however, only 44.1% (n = 30) reported familiarity with the relevant scientific literature on probiotics. Furthermore, respondents more frequently recognized bacterial species associated with single-strain probiotic formulations compared to those in multi-strain mixtures. The primary concern regarding the administration of probiotics for IBS was this lack of familiarity with the scientific literature, cited by 23.5% of respondents. Notably, 100% of the surveyed cohort expressed a need for further education on the topic. Conclusions: The emergence of scientific and clinical evidence results in a clinical practice characterized by high prescribing habits, despite the lack of formal approval. These findings highlight evidence showing the effectiveness of certain probiotic strains in managing IBS symptoms, suggesting the need for standardized guidelines. Given the demonstrated need for further education among the surveyed cohort, integrating probiotic-specific training into both undergraduate medical curricula and continuing professional development programs could significantly enhance the clinical knowledge and awareness of both current and future practitioners. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by immune dysregulation, microbiota imbalance, and intestinal barrier damage. Unconjugated bilirubin (UCB) shows promise in treating UC due to its anti-inflammatory properties but is limited by poor solubility and potential toxicity. This study developed a chitosan-based controlled-release microsphere (CBMS) treatment to overcome these issues. CBMS utilizes the mucoadhesive properties of chitosan to achieve targeted, controlled UCB release in the colon, enhancing its stability and bioavailability. In a DSS-induced UC mouse model, CBMS alleviated clinical symptoms, reduced colon shortening, and improved histological outcomes, including reduced inflammation and enhanced mucosal repair. The mechanism involves CBMS retention in the intestinal lumen, UCB inactivation of digestive proteases, and restoration of microbiota balance, suppressing pro-inflammatory pathways. CBMS offers a promising new therapeutic strategy for UC and insights into polysaccharide-based drug delivery systems. Full article