Search Results (8,137)

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disease with both clinical and genetic heterogeneity. Several loss-of-function variants in the chromodomain helicase DNA-binding protein 8 (CHD8) gene have been identified in individuals with ASD and/or developmental delay/intellectual disability. These are associated with specific clinical manifestations, including overgrowth, macrocephaly, sleep disturbance, and gastrointestinal problems. Methods: We performed clinical exome sequencing in a female patient with ASD and macrocephaly. RNA analysis from peripheral blood was carried out to investigate the functional effect of the identified variants. Results: We identified a novel maternally inherited CHD8 variant (c.5390+2T>C). Transcript analysis demonstrated that this variant disrupts the canonical splice donor in intron 30, causing splicing anomalies in the CHD7-binding domain of the CHD8 protein, resulting in a truncated inactive protein. Conclusions: In conclusion, this study identified a novel splice-site variant in the CHD8 gene with experimentally confirmed pathogenic effects on RNA splicing, expanding the mutational spectrum of CHD8-related neurodevelopmental disorders. The considerable intrafamilial phenotypic variability associated with CHD8 haploinsufficiency supports the presence of reduced penetrance and highlights the influence of modifying factors on the clinical expression of CHD8-related disorders. Full article

Research on trauma in autistic individuals has proliferated in recent years. This scoping review aims to (1) provide a comprehensive overview of the literature on trauma and autism, (2) identify and synthesize key themes, and (3) highlight gaps to inform future research. Following Arksey and O’Malley’s (2005) methodological framework and the PRISMA-ScR guideline and checklist (Tricco et al. 2018), we included articles published after 2000 in French or English that explicitly addressed trauma in autistic individuals. Four databases were searched: PsycINFO, Medline, ERIC, and Web of Science. A two-phase selection process yielded 199 eligible studies. Descriptive analyses and collaborative theme development were conducted to map the field. Findings show that most studies were published between 2018 and 2024, with the United States contributing the largest proportion. Four major themes were identified: (1) the relationship between autism and trauma, including prevalence, vulnerability, and consequences; (2) trauma-related symptoms and clinical manifestations; (3) assessment practices; and (4) intervention strategies. This review offers a critical synthesis of current knowledge, emphasizing the need for approaches that use broader definitions of trauma and reflect the diversity and lived experiences of autistic individuals. It also identifies significant methodological and conceptual gaps, calling for future research that addresses subgroup diversity and promotes equitable, trauma-informed practices for autistic individuals. Full article

Background: Increasing evidence suggests that COVID-19 can induce or exacerbate autoimmune disorders, including immune-mediated thyroid dysfunction. The most common autoimmune thyroid diseases are Graves’ disease and Hashimoto’s thyroiditis; the mechanisms by which viral infections like SARS-CoV-2 trigger these diseases are not fully understood. Objectives: This study aims to systematically review published clinical evidence on the presentation, laboratory characteristics, and outcomes of autoimmune thyroid diseases after COVID-19 infection. Methods: The review followed the PRISMA 2020 framework. Scopus, Web of Science, and PubMed were searched for English-language studies between January 2020 and December 2025 using the terms COVID-19, SARS-CoV-2, autoimmune thyroiditis, Graves’ disease, Hashimoto’s thyroiditis, and autoimmune thyroid disease. Results: In total, 46 studies (five cohort studies and 41 case reports/series) involving 3856 patients were analyzed. The findings indicate that a significant increase in TPOAb prevalence occurs post-COVID-19 infection (15.7% vs. 7.7% in controls). New-onset Graves’ disease (GD) post-COVID-19 presented with higher fT3/fT4 ratios and more aggressive thyrotoxicosis compared to non-viral cases. Rare but severe manifestations included thyrotoxic periodic paralysis, Hashimoto’s encephalopathy, and dilated cardiomyopathy. Conclusions: SARS-CoV-2 may act as a trigger for autoimmune thyroid diseases, particularly in moderate-to-severe infections; however, the strength of this association warrants further investigation with controlled prospective data. Standard therapy remains effective, but thyroid function monitoring is advisable during post-COVID-19 recovery. An interdisciplinary approach is essential for early diagnosis and management of systemic complications. Full article

Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to mild and transient neurological symptoms without detectable structural abnormalities on routine imaging. At the mild end of the spectrum, symptoms after a single exposure may resolve quickly, yet repeated exposures—even at very low levels, termed “subconcussive”—can develop into post-concussive syndrome (PCS) or persistent post-concussive symptoms (PPCS) in a subset of individuals. Despite extensive studies, the molecular pathobiology linking primary blast exposure to delayed and sometimes chronic neurobehavioral deficits remains incompletely understood. A mechanistic framework connecting blast-wave physics to biomechanics to biological vulnerability may therefore help define exposure hazards, interpret clinical symptomatology, and guide diagnostic and therapeutic development. This review summarizes the physics of primary blast waves, the resulting biomechanical responses, and candidate biological substrates, emphasizing structures and interfaces with distinct acoustic impedances across anatomical, tissue, cellular, and molecular scales. We synthesize evidence supporting the hypothesis that the cerebral vasculature and endothelial cells represent critically vulnerable substrates of primary blast-wave injury, in part because the vascular tree constitutes the brain’s largest and most widely distributed interface between compartments with different acoustic impedances. Across experimental and human studies, endothelial stress, vascular injury, and downstream neuroinflammation emerge as convergent molecular responses to primary blast exposure. Temporal dynamics are central to understanding pbTBI because many blast-induced processes unfold in sequential phases. These observations support conceptualizing pbTBI as a condition characterized by prominent cerebrovascular injury of varying severity with secondary consequences for neuronal signaling, network function, and behavior. Within this framework, cerebrovascular and neurovascular unit (NVU) dysfunction provides a parsimonious bridge between primary blast-wave exposure and chronic symptom trajectories, where vascular pathology may offer more accessible therapeutic targets than neuronal injury. Key knowledge gaps include identifying which physical component(s) of the blast are most injurious, establishing biologically meaningful dose–response relationships at molecular and physiological levels, and defining windows of vulnerability during recovery that are relevant to repeated exposures. Addressing these gaps is essential for refining safety protocols, improving diagnostic specificity through mechanism-informed biomarkers, and developing evidence-based molecular and vascular therapeutic targets for pbTBI-associated conditions. Progress will require integrating waveform-aware dosimetry with longitudinal physiological and molecular monitoring across both preclinical and human cohorts. Such integration offers a practical path toward translating blast physics into actionable medical guidance for prevention, triage, and recovery management. Full article

Paraneoplastic endocrine syndromes (PESs) are hormonal disturbances associated with malignancies that result from tumor-related production of hormone-like substances, immune-mediated mechanisms, or dysregulated signaling pathways. While they are well recognized in lung and neuroendocrine cancers, their relevance in gastrointestinal tumors remains less clearly defined. This narrative review synthesizes current knowledge on paraneoplastic endocrine manifestations in gastrointestinal malignancies, based on a structured search of the literature in major databases, including PubMed, Scopus, and Web of Science. The analysis focuses on clinically relevant syndromes such as hypercalcemia, Cushing-like manifestations, disorders of water balance, hypoglycemia, and acromegaly, with emphasis on underlying mechanisms, associated tumor types, diagnostic approaches, and therapeutic considerations. Available evidence indicates that gastrointestinal tumors can produce a range of biologically active substances, leading to diverse endocrine manifestations that may precede tumor detection and influence disease course. Among these, hypercalcemia and Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) are among the most frequently reported, while other syndromes, such as ectopic Cushing syndrome or tumor-related hypoglycemia, are less common but often associated with more severe clinical outcomes. Recognition of these manifestations has direct clinical implications, as they may support earlier diagnosis, contribute to prognostic assessment, and guide therapeutic management. Improved awareness and a multidisciplinary approach remain essential for optimizing outcomes in patients with gastrointestinal malignancies. Full article

Arterial wall fragility represents a unifying pathophysiological substrate underlying a broad spectrum of aortic diseases, including aneurysms, dissections, intramural hematoma, penetrating atherosclerotic ulcers, and aortitis. Rather than distinct entities, these conditions increasingly appear as interconnected manifestations of impaired wall integrity and maladaptive vascular remodeling. This narrative review provides a structured overview of the imaging correlates of arterial wall fragility from a CT-centered, multimodality perspective. Computed Tomography Angiography (CTA) remains the first-line imaging modality in acute settings, enabling rapid and comprehensive assessment of vascular anatomy, luminal integrity, and the presence of life-threatening complications. Complementary modalities, including magnetic resonance imaging and ultrasound, contribute additional information on tissue characterization and hemodynamic evaluation in selected stable patients, follow-up settings, or specific clinical scenarios. Across imaging modalities, specific features—such as false lumen patency, intramural hematoma characteristics, ulcer-like projections, aneurysm morphology, and periaortic inflammatory changes—have been reported as markers of wall instability. These imaging-derived findings may provide clinically relevant information beyond traditional diameter-based assessment and support more refined risk stratification. Emerging approaches, including artificial intelligence, radiomics, computational modeling, and advanced MRI techniques, are expanding the role of imaging toward quantitative evaluation. However, their routine clinical implementation still requires standardization and prospective validation. Overall, a CT-centered multimodality imaging strategy may support a more comprehensive assessment of arterial wall fragility and contribute to individualized clinical decision-making in patients with aortic disease. Full article

In this study, we aimed to investigate the clinical characteristics of pulmonary cryptococcosis (PC) patients without acquired immunodeficiency disease (AIDS). In this retrospective study, a total of 101 patients with non-AIDS PC diagnosed at Tangdu Hospital between January 2014 and October 2025 were enrolled. The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, and clinical outcomes were analyzed. Univariate and multivariate logistic regression analyses were used to identify risk factors for cryptococcal meningitis (CM). Among 101 patients (mean age 53.13 ± 12.31 years; 66.3% male), 56.4% were asymptomatic. Underlying diseases were present in 55.4% (mainly hypertension and diabetes), and CM occurred in 17.8% (18/101). Patients with CM had a higher proportion of underlying diseases (83.3% vs. 49.4%) and lower levels of red blood cells, hemoglobin, total protein, albumin, globulin, and potassium. Multivariate analysis revealed underlying diseases (OR = 7.246, 95% CI: 1.426~55.33), hypoglobulinemia (OR = 0.847, 95% CI: 0.734~0.956), and hypokalemia (OR = 0.177, 95% CI: 0.028~0.778) as independent risk factors for CM. The combined model showed good predictive value (AUC = 0.863). Non-AIDS PC often presents asymptomatically. Patients with underlying diseases, hypoglobulinemia, or hypokalemia are at significantly higher risk for concurrent CM and warrant aggressive central nervous system evaluation. Full article

Background/Objectives: Respiratory dysfunction in Parkinson’s disease (PD) is a clinically relevant but frequently underrecognized manifestation associated with functional impairment and increased risk of respiratory complications. This study compared spirometry and impulse oscillometry (IOS) in the assessment of respiratory function in PD, with particular focus on the detection of subtle or peripheral airway abnormalities. Methods: A prospective, single-center, cross-sectional study was conducted, including 108 participants (55 patients with PD and 53 control subjects). Pulmonary function was evaluated using standardized spirometry and IOS protocols. Group comparisons were performed using non-parametric tests, while multivariable regression analyses adjusted for potential confounding factors, including age, body mass index, smoking status, pollutant exposure, and cardiovascular comorbidities. Results: IOS identified a higher frequency of abnormal categorical findings compared with spirometry, including among subjects with normal spirometric values. Although dyspnea was more frequent in patients with PD in unadjusted analyses, multivariable regression demonstrated that PD was not an independent predictor of respiratory dysfunction. Pollutant exposure was significantly associated with abnormal IOS findings (p = 0.011). No significant differences were observed between PD and control groups regarding continuous spirometric or oscillometric parameters. Only a weak association between disease severity and FEV1 (%) was identified, whereas no significant correlations were observed for oscillometric parameters. Conclusions: IOS may provide complementary information regarding subtle or peripheral respiratory abnormalities in patients with PD. The findings suggest that respiratory alterations in this population are likely multifactorial and not independently determined by PD itself. Incorporating oscillometric assessment into respiratory evaluation may contribute to the identification of subtle respiratory mechanical alterations in patients with PD. Full article

Multiple Sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system characterized by leukocyte infiltration, inflammation, demyelination, and progressive neurodegeneration. Susceptibility to MS is influenced by genetic factors, including variants within the human leukocyte antigen (HLA) region, (notably HLA-DR15), and multiple single nucleotide polymorphisms that modulate T cell function and immune regulation. Clinically, early manifestations such as visual disturbances, sensory deficits, fatigue, and impaired coordination often precede more advanced features, including cognitive decline and bladder or bowel dysfunction. Although experimental and genetic models of neuroinflammation have facilitated the development of therapies that reduce relapse rates and slow disease progression, the underlying pathological mechanisms remain incompletely understood. Emerging evidence points to the importance of cytoskeletal organization and membrane-associated signaling platforms in maintaining neuronal and immune cell function. Disruption of these systems may contribute to demyelination and neuroinflammatory cascades. Within this context, a systems biology perspective is particularly valuable, as it emphasizes the integration of multiple, interdependent pathways rather than isolated mechanisms. Caveolin-1 (Cav-1), an integral membrane protein of caveolae, has gained attention as a potential central regulator due to its role in coordinating signaling processes across diverse cellular compartments. In this review, we examine the potential genetic and functional contributions of Cav-1 to MS pathophysiology, with a focus on its involvement in oxidative stress, inflammation, blood–brain barrier integrity, and autophagy. By framing these processes as components of an interconnected network, we highlight Cav-1 as a context-dependent modulator that may influence both disease progression and severity. However, despite its mechanistic relevance, the translational potential of Cav-1 remains uncertain, and further studies are required to clarify its precise role and evaluate its suitability as a therapeutic target in MS. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare systemic autoimmune disorders marked by inflammation and damage to small- and medium-sized blood vessels. The clinical presentation of AAV is highly variable, ranging from isolated organ involvement to severe, life-threatening multisystem disease, posing significant challenges in diagnosis, treatment, and prognosis. Objective: To demonstrate the clinical heterogeneity and different outcomes in three pediatric cases of ANCA-positive disease and emphasize the importance of integrating clinical findings with laboratory and imaging investigations for accurate diagnosis. Methods: We present three pediatric patients (ages 12–15 years) with ANCA-positive results but distinct clinical presentations, evaluated at the Children’s Emergency Hospital “Louis Turcanu”, Timisoara, between 2020 and 2024. All cases were investigated according to EULAR/PRINTO/PReS criteria for pediatric vasculitis. Results: Case 1 (PR3-ANCA positive) developed severe multi-organ involvement, including granulomatosis with polyangiitis (GPA) with pulmonary hemorrhage, pericarditis, thrombotic events, and renal impairment, requiring intensive immunosuppression with cyclophosphamide, rituximab, and mycophenolate mofetil, ultimately developing chronic kidney disease stage 3a. Case 2 (BPI-ANCA positive) presented with purpuric lesions and painless joint swelling, responding favorably to corticosteroid therapy with subsequent remission. Case 3 (MPO-ANCA) manifested as polyarticular arthritis without other organ involvement and was ultimately diagnosed as seronegative juvenile idiopathic arthritis (JIA), achieving complete remission with adalimumab therapy. Conclusions: This case series highlights the diverse clinical and biological features of ANCA-positive conditions in children, emphasizing that ANCA positivity requires careful clinical correlation as it may indicate true vasculitis requiring aggressive treatment or alternative diagnoses such as JIA with incidental ANCA positivity. Tailored therapeutic strategies based on clinical presentation and continued research are essential to improve patient outcomes. Full article

Computed tomography (CT) is used to support the diagnosis of equine temporomandibular joint (TMJ) disease; however, its diagnostic accuracy remains unclear. This study aimed to evaluate the relationship between CT findings and histopathological manifestations of osteoarthritis (OA) in equine TMJs. A total of 82 TMJs were CT-imaged, sampled, grouped into age-related and OA-related groups, and analyzed for frequency distributions, correlations, and CT-based TMJ OA diagnosis. CT findings were observed in 79% of joints, including ‘CT anatomical variations’ considering to reflect age-related remodeling. Only 50% of joints showed co-occurrence of CT findings and histopathological manifestations of OA, confirming that not all CT findings are indicative of disease. Including all CT findings in the CT-based diagnosis of TMJ OA yielded a specificity of 0.41 (95% CI: 0.26–0.58), suggesting a high rate of false-positive diagnoses. Excluding all ‘CT anatomical variations’ resulted in a sensitivity of 0.56 (95% CI: 0.40–0.72), indicating a substantial number of false-negative diagnoses. However, inclusion of specific ‘CT anatomical variation’—subchondral bone cysts—into the studied CT-based diagnosis increased sensitivity to 0.79 (95% CI: 0.62 to 0.89) while maintaining high specificity of 0.92 (95% CI: 0.80–0.98). Including this subset of CT findings in the diagnosis of equine TMJ OA may improve the accuracy of disease detection; however, the clinical relevance of the present cadaver investigation needs to be confirmed in in vivo studies. Full article

Background: Primary hyperparathyroidism (PHPT) has undergone notable clinical changes over recent decades, with asymptomatic cases now prevailing in Western countries. In contrast, a broad spectrum of clinical manifestations remains common in Romania, an Eastern European country. This study aims to provide a representative descriptive analysis of clinical presentations and related complications observed in this setting. Methods: We performed a cross-sectional, single-center study of 413 consecutive PHPT cases diagnosed between 2000 and 2020 at a tertiary endocrinology center in Romania. Data included demographics, clinical features, biochemistry, bone turnover markers, 25OHD, BMD by DXA, TBS, fractures, renal involvement, and etiology. Results: Patients were predominantly female (88.6%), with a mean age of 60 ± 11.7 years and a mean BMI of 27.3 ± 5.7 kg/m². Familial forms were identified in 4.4%. Mean serum calcium was 11.28 ± 1.09 mg/dL, mean PTH 248.31 ± 361.94 pg/mL, and mean 25OHD 17.95 ± 9.6 ng/mL. Symptomatic hypercalcemia was present in 23.2% and severe vitamin D deficiency in 21%. Fractures were present in 25.2% and osteitis fibrosa cystica in 1.7%. Mean T-scores (SD): LS –2.23, FN –1.85, 1/3 distal radius –1.96. Osteoporosis prevalence: LS 47%, FN 24.1%, 1/3 distal radius 38%. Mean TBS was 1.258 ± 0.115. Renal involvement included calcifications (56.7%), nephrolithiasis (53%), nephrocalcinosis (3.6%), hypercalciuria (31.7%), and reduced renal function (9.93%). Non-classical manifestations were mainly cardiovascular (58%) and osteoarticular (24.5%). Parathyroidectomy was performed in 217 patients (53%); histopathology showed adenoma (88.8%), carcinoma (5.2%), and hyperplasia (6%), with a mean adenoma weight of 2.86 ± 5.92 g. Conclusions: PHPT in Romania shows a heterogeneous phenotypic spectrum, reflecting variability in clinical presentation and suggesting an evolving epidemiological profile. Full article

Background/Objectives: Childhood interstitial lung disease (chILD) represents a heterogeneous group of rare pulmonary disorders. Practical diagnostic approaches tested for feasibility and impact in comprehensive cohorts are lacking. We aimed to assess a simple etiologically focused classification approach, clarify the role of genetic testing and quantify the impact of non-pulmonary organ manifestations. Methods: We hypothesized that chILD can be classified in a clinically meaningful and versatile way by answering three questions: Which children have an etiological chILD diagnosis due to (1) identified (exposure-related) cause/lung injury, or (2) systemic disease? (3) In how many children without an etiological diagnosis can a genetic cause be identified? We also calculated the predictive value of non-pulmonary organ involvement for underlying systemic conditions. Results: Among 1693 patients, 24.7% were grouped as ILD related to exposure, 22.7% as ILD with systemic condition, 16.6% as ILD with genetic diagnosis of systemic disease, 10.0% as ILD with genetic diagnosis affecting the lungs only, and 25.8% as ILD without genetic diagnosis. The average genetic diagnostic yield was 50.8%, with higher rates in interstitial pneumonia (61.4%) or pulmonary alveolar proteinosis (87.1%). The presence of ≥two non-pulmonary organ manifestations increased the likelihood of an underlying systemic disease by three to five-fold. Conclusions: An etiological diagnostic strategy effectively classifies chILD and guides genetic testing. Exome or genome sequencing should be considered if ≥two non-pulmonary organs are involved or if the initial diagnosis becomes uncertain due to an unusual disease course or signs of a second underlying condition. Full article

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive myeloproliferative neoplasm of early childhood characterized by constitutive activation of the RAS-MAPK signaling pathway. RASopathies are a heterogeneous group of complex genetic disorders arising from germline mutations that dysregulate RAS-MAPK signaling. Noonan syndrome, CBL syndrome, and neurofibromatosis type 1 (NF1) are the three major RASopathies predisposing to JMML. More than 90% of JMML cases harbor germline or somatic mutations in one of five canonical driver genes—PTPN11, NRAS, KRAS, NF1, or CBL—establishing JMML as the prototypical malignant manifestation of RASopathy biology. The fifth edition of the World Health Organization Classification of Tumours reclassified JMML as a myeloproliferative neoplasm while the International Consensus Classification adopted JMML under pediatric and/or germline mutation-associated disorders, introducing a JMML-like category for cases lacking five canonical mutations but harboring emerging drivers such as SH2B3::LNK alterations and ALK::ROS1 fusions. The distinction between germline and somatic mutations profoundly influences prognosis: e.g., germline PTPN11-associated myeloproliferations and many germline CBL cases undergo spontaneous resolution, whereas somatic PTPN11- and NF1-mutated JMML is more aggressive and requires prompt allogeneic hematopoietic stem cell transplantation. DNA methylation profiling has emerged as the most robust prognostic framework, with consensus defining high-, intermediate-, and low-methylation subgroups that independently predict outcome. Both genotype and DNA methylation subclassification have been integrated into clinical decision-making, incorporating pretransplant azacitidine, watch-and-wait approaches for favorable-risk patients, and emerging targeted therapies including MEK inhibitors. This review synthesizes recent advances in understanding JMML as a bona fide RASopathy; provides a diagnostic algorithm, molecular landscapes, and prognostic models; and highlights opportunities for molecularly targeted therapeutic intervention. Full article

Background: Central nervous system (CNS) involvement in multiple myeloma (MM) represents an extramedullary manifestation of the disease, which is often really challenging for clinicians, as the neurological symptoms could easily overlap with those related to hypercalcemia, uremia, high viscosity of the blood, or treatment-related neuropathy. Objectives: this retrospective study was conducted at Fundeni Clinical Institute in Bucharest, aiming to identify and systematically analyze a series of clinical cases diagnosed with extramedullary disease. Methods: We have identified 6 out of 583 patients with CNS involvement in our centre between 2019 and 2025. The diagnosis of meningeal myelomatosis was established through cerebrospinal fluid analysis, whereas CNS plasmacytomas were confirmed by CT-guided biopsy followed by immunohistochemistry evaluation. Results: All cases of CNS involvement occurred at relapse, with intervals from initial MM diagnosis to CNS involvement ranging from 9 months to 10 years. CNS-MM was linked to particular features, such as high-risk cytogenetics (four out of six patients), elevated lactate dehydrogenase, and the presence of extramedullary disease, highlighting its association with aggressive disease behaviour. Discussions: Although CNS-MM is correlated with poor prognosis, prolonged survival in one of our patients resulted from multimodal treatment, which included craniospinal radiotherapy, DPd systemic treatment, and intrathecal therapy (over 39 months). This aggressive approach effectively controlled both systemic disease and high-risk CNS involvement. Immunoglobulin isotype switching is a rare form of clonal evolution in MM, illustrated by the same patient whose disease evolved from IgA kappa at diagnosis to IgA lambda at CNS relapse, showing clonal heterogeneity and providing clinical evidence of clonal evolution. Conclusions: CNS involvement in MM usually occurs in a relapsed/refractory setting in patients with advanced, high-risk disease, and it is usually associated with extramedullary disease. Despite using multimodal therapies, outcomes remain poor, highlighting the need for novel and tailored agents. Full article