Search Results (15,705)

The COVID-19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until 23 July 2023. Since the three-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted co-operatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention. Full article

Obesity is a critical public health issue, necessitating effective weight loss interventions. While various dietary regimens have been explored, individual responses to interventions often vary. This study involved a 3-month dietary intervention aiming at assessing the role of macronutrient composition and the potential role of genetic predisposition in weight loss among Greek adults. This randomized clinical trial followed the CONSORT principles, recruiting 202 participants overall; 94 received a hypocaloric, high-protein diet and 108 received a high-carbohydrate, hypocaloric diet. Genetic predispositions were assessed through 10 target variants known for their BMI associations. Participants’ weight and BMI values were recorded at baseline and post-intervention (n = 202 at baseline, n = 84 post-intervention) and an imputation method was applied to account for the observed missing values. Participants experienced a statistically significant weight loss across all dietary regimens (p < 0.001). Genetic analyses did not display statistically significant effects on weight loss. No significant differences in weight loss were observed between macronutrient groups, aligning with the POUNDS Lost and DIETFITS studies. This study underscores the importance of dietary interventions for weight loss and the potential contributions of genetic makeup. These findings contribute to obesity management within the Greek population and support the need for further research in personalized interventions. Full article

There is a special relationship between major depressive disorder and excessive daytime sleepiness. However, given the negative impact of excessive daytime sleepiness on life quality and cardiovascular outcome in hypertensive patients, the objective of this study was to investigate the potential role played by major depressive disorder in the occurrence of this complaint for this particular subpopulation. Data from 1404 hypertensive patients recruited from the Sleep Unit’s polysomnographic recordings database were analyzed. A score >10 on the Epworth Sleepiness Scale was used to define excessive daytime sleepiness in this study. Logistic regression analyses were performed to investigate the risk of excessive daytime sleepiness associated with major depressive disorder in hypertensive patients. Excessive daytime sleepiness was frequent (40.0%) in our sample of hypertensive patients. After adjustments for major confounding factors, multivariate logistic regression analyses demonstrated that unlike remitted major depressive disorder, only current major depressive disorder was associated with a higher risk of excessive daytime sleepiness in hypertensive patients. Given this potential implication of current major depressive disorder in the occurrence of excessive daytime sleepiness for hypertensive patients, it is therefore essential to achieve the complete remission of this psychiatric disorder to avoid negative consequences associated with this complaint in this particular subpopulation. Full article

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. Methods: In a single-centre study, we recruited 83 children and analysed blood samples to quantify the circulating markers of increased intestinal permeability following SARS-CoV-2 infection. Publicly available proteomics MIS-C datasets were also accessed to assess the evidence for increased intestinal permeability. We further quantified SARS-CoV-2 antigenemia and the humoral response to SARS-CoV-2 spike protein. Results: Following SARS-CoV-2 infection, healthy children demonstrated no dysregulation of the intestinal epithelial barrier. In MIS-C, considerable increases in markers of epithelial dysfunction were observed, with similar increases noted in febrile controls. Furthermore, we found little evidence of persistent SARS-CoV-2 antigenemia in MIS-C. Conclusions: Our results suggest that although increased intestinal epithelial permeability is a feature of MIS-C, it is not unique to the condition, and persistent SARS-CoV-2 antigenemia does not occur. Full article

Cytokine-induced neutrophil chemoattractant 1 (CINC-1), a cluster of differentiation 95 (CD95), fractalkine, and T-cell immunoglobulin and mucin domain 1 (TIM-1) are circulating proteins known to be involved in inflammation. While their roles have been studied in neurological conditions and cardiovascular diseases, their potential as peripheral artery disease (PAD) biomarkers remain unexplored. We conducted a cross-sectional diagnostic study using data from 476 recruited patients (164 without PAD and 312 with PAD). Plasma levels of CINC-1, CD95, fractalkine, and TIM-1 were measured at baseline. A PAD diagnosis was established at recruitment based on clinical exams and investigations, defined as an ankle-brachial index < 0.9 or toe-brachial index < 0.67 with absent/diminished pedal pulses. Using 10-fold cross-validation, we trained a random forest algorithm, incorporating clinical characteristics and biomarkers that showed differential expression in PAD versus non-PAD patients to predict a PAD diagnosis. Among the proteins tested, CINC-1, CD95, and fractalkine were elevated in PAD vs. non-PAD patients, forming a 3-biomarker panel. Our predictive model achieved an AUROC of 0.85 for a PAD diagnosis using clinical features and this 3-biomarker panel. By combining the clinical characteristics with these biomarkers, we developed an accurate predictive model for a PAD diagnosis. This algorithm can assist in PAD screening, risk stratification, and guiding clinical decisions regarding further vascular assessment, referrals, and medical/surgical management to potentially improve patient outcomes. Full article

Glutaminyl cyclase (QC) and its isoenzyme (isoQC) catalyze the formation of N-terminal pyroglutamate (pGlu) from glutamine on a number of neuropeptides, peptide hormones and chemokines. Chemokines of the C-C ligand (CCL) motif family are known to contribute to inflammation in neurodegenerative conditions. Here, we used a model of transient focal cerebral ischemia to explore functional, cellular and molecular responses to ischemia in mice lacking genes for QC, isoQC and their substrate CCL2. Mice of the different genotypes were evaluated for functional consequences of stroke, infarct volume, activation of glia cells, and for QC, isoQC and CCL2 expression. The number of QC-immunoreactive, but not of isoQC-immunoreactive, neurons increased robustly in the infarct area at 24 and 72 h after ischemia. In parallel, immunohistochemical signals for the QC substrate CCL2 increased from 24 to 72 h after ischemia induction without differences between genotypes analyzed. The increase in CCL2 was accompanied by morphological activation of Iba1-immunoreactive microglia and recruitment of MHC-II-positive cells at 72 h after ischemia. Among other chemokines quantified in the brain tissue, CCL17 showed higher concentrations at 72 h compared to 24 h after ischemia. Collectively, these data suggest a critical role for QC in inflammatory processes in the stroke-affected brain. Full article

Background: Thoracolumbar transcutaneous spinal cord stimulation (tSCS) non-invasively evokes posterior root-muscle reflexes (PRMR) with the aim of neuromodulating sensorimotor function following spinal cord injury. Research is still in its infancy regarding the effect of body position on the nature of these spinally evoked responses. Therefore, the aim of this study was to investigate the influence of body position on the nature of PRMR responses during tSCS. Methods: A total of 11 (6M, 5F) participants completed a full PRMR recruitment curve from 10 ma up to 120 ma (10 ma increments) at the T11/12 intervertebral space using a singular 3.2 cm diameter cathode. At each intensity, three paired pulses (50 ms inter-pulse interval), followed by three singular pulses with a six-second delay were applied in each body position (supine, supine 90-90, sitting and standing) in a randomised order. The PRMR responses in lower limb muscles were recorded using wireless electromyographic sensors placed on the Soleus, Tibialis Anterior, Rectus Femoris and Bicep Femoris long head. A two-way (body position ´ muscle) repeated measures analysis of variance was used to investigate the effect of body position on PRMR-evoked responses. Results: There was a significant main effect of body position on PRMR resting motor threshold (RMT) (p < 0.001), first response peak-to-peak amplitude (p = 0.003) and percentage post-activation depression (%PAD) (p = 0.012). Sitting had significantly higher RMT and significantly lower first response peak-to-peak amplitudes compared to all other positions, but significant differences in %PAD were only detectible between supine and standing. Conclusions: Body position influences the nature of PRMR-evoked responses during tSCS. Full article

Cyber–physical systems have become critical across industries. They have driven investments in education services to develop well-trained engineers. Education services for cyber–physical systems require the hiring of expert tutors with multidisciplinary knowledge, as well as acquiring expensive facilities/equipment. In response to the challenges posed by the need for the equipment and facilities, a metaverse-based education service that incorporates digital twins has been explored as a solution. However, the issue of recruiting expert tutors who can enhance students’ achievements remains unresolved, making it difficult to effectively cultivate talent. This paper proposes a reference architecture for a learner-centric educational metaverse with an intelligent tutoring framework as its core feature to address these issues. We develop a novel explainable artificial intelligence scheme for multi-class object detection models to assess learners’ achievements within the intelligent tutoring framework. Additionally, a genetic algorithm-based improvement search method is applied to the framework to derive personalized feedback. The proposed metaverse architecture and framework are evaluated through a case study on drone education. The experimental results show that the explainable AI scheme demonstrates an approximately 30% improvement in the explanation accuracy compared to existing methods. The survey results indicate that over 70% of learners significantly improved their skills based on the provided feedback. Full article

Background: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. Aim: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. Methods: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN₂W). Results: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). Conclusions: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation. Full article

The prevalence of stroke in Nigeria has continued to be a major public health challenge. Recovery from a stroke episode can be a long-impacting process with reduced quality of life outcomes. Past studies have explored the quality of life (QoL) of stroke survivors. However, none have explored the QoL of stroke survivors in Southeastern Nigeria. This study therefore describes the QoL of Nigerian stroke survivors in Southeastern Nigeria. One hundred and one participants (44 male and 58 female) were recruited into the study. QoL domains were assessed using the stroke-specific Health-Related Quality of Life in Stroke Patients (HRQOLISP). The physical domain was significantly lower than other domains measured (mean = 2.52, SD = 0.76), contributing to poor quality of life. On the other hand, the spiritual domain had the greatest positive influence on QoL (mean = 3.70, SD = 0.50). We found the physical domain was the poorest part of stroke survivors’ stroke experience. The spiritual domain had a positive impact on improving QoL. There is a need for research on interventions relating to the physical rehabilitation of stroke survivors and a review of how the spiritual domain can be enhanced to improve QoL. Full article

Circular RNA (circRNA) is a type of single-stranded RNA that forms a covalently closed continuous loop, unlike linear RNA. The expression of circRNAs in mammals is often conserved across species and shows tissue and cell specificity. Some circRNA serve as gene regulators. However, the biological function of most circRNAs is unclear. CircRNA does not have 5′ or 3′ ends. The unique structure of circRNAs provides them with a much longer half-life and more resistance to RNase R than linear RNAs. Inflammatory lung responses occur in the pathogenesis and recovery of many lung diseases. Macrophages form the first line of host defense/innate immune responses and initiate/mediate lung inflammation. For example, in bacterial pneumonia, upon pro-inflammatory activation, they release early response cytokines/chemokines that recruit neutrophils, macrophages, and lymphocytes to sites of infection and clear pathogens. The functional effects and mechanisms by which circRNAs exert physiological or pathological roles in macrophage activation and lung inflammation remain poorly understood. In this article, we will review the current understanding and progress of circRNA biogenesis, regulation, secretion, and degradation. Furthermore, we will review the current reports on the role of circRNAs in macrophage activation and polarization, as well as in the process of inflammatory lung responses. Full article

Arteriogenesis is an inflammatory driven mechanism, describing the growth of a natural bypass from pre-existing collateral arteries to compensate for an occluded artery. The complement system component C3 is a potent natural inflammatory activator. Here, we investigated its impact on the process of collateral artery growth using C3-deficient (C3 −/−) and wildtype control mice in a murine hindlimb model of arteriogenesis. Induction of arteriogenesis by unilateral femoral artery ligation resulted in decreased perfusion recovery in C3 −/− mice on day 7 as shown by Laser Doppler imaging. Immunofluorescence staining revealed a reduced vascular cell proliferation in C3 −/− mice. Gene expression analysis displayed a significant reduction in monocyte chemoattractant protein-1 (MCP-1) expression in C3 −/− mice. Interestingly, 3 days after induction of arteriogenesis, the number of macrophages (CD68⁺) recruited to growing collaterals was not affected by C3 deficiency. However, a significant reduction in inflammatory M1-like polarized macrophages (CD68⁺/MRC1⁻) was noted. Forced mast cell activation by Compound 48/80 as well as exogenous MCP-1 application rescued the number of M1-like polarized macrophages along with perfusion recovery in C3 −/− mice. In summary, this study demonstrates that complement C3 influences arteriogenesis by mediating MCP-1 expression, which is essential for the induction and enhancement of sterile inflammation. Full article

Studying a patient with Pompe disease (PD) is like opening Pandora’s box. The specialist is faced with numerous clinical features similar to those of several diseases, and very often the symptoms are well hidden and none is associated with this rare disease. In recent years, scientific interest in this disease has been growing more and more, but still no symptom is recognized as key to a correct diagnosis of it, nor is there any specific disease marker to date. New diagnostic/therapeutic proposals on disease allow for the diffusion of knowledge of this pathology for timely diagnosis of the patient. Due to unawareness and difficulty in diagnosis, many adults with PD are diagnosed with great delay. In this article, we report and discuss current knowledge of PD and provide new data from work conducted on a cohort of 2934 Italian subjects recruited in recent years. A genetic analysis of the GAA gene was performed on patients with significant clinical signs and pathological enzyme activity to define the genetic profile of subjects. This identified 39 symptomatic PD subjects with low acid alpha-glucosidase enzyme activity and the presence of two causative mutations in GAA gene regions. Furthermore, 22 subjects with genetic variants of uncertain significance (GVUS) were identified. Full article

ACTN3 R577X and ACE I/D polymorphisms are associated with endurance exercise ability. This case–control study explored the association of ACTN3 and ACE gene polymorphisms with elite pure endurance in Korean athletes, hypothesizing that individuals with both ACTN3 XX and ACE II genotypes would exhibit superior endurance. We recruited 934 elite athletes (713 males, 221 females) and selected 45 pure endurance athletes (36 males, 9 females) requiring “≥90% aerobic energy metabolism during sports events”, in addition to 679 healthy non-athlete Koreans (361 males, 318 females) as controls. Genomic DNA was extracted and genotyped for ACTN3 R577X and ACE I/D polymorphisms. ACE ID (p = 0.090) and ACTN3 RX+XX (p = 0.029) genotype distributions were significantly different between the two groups. Complex ACTN3-ACE genotypes also exhibited significant differences (p = 0.014), with dominant complex genotypes positively affecting endurance (p = 0.039). The presence of RX+II or XX+II was associated with a 1.763-fold higher likelihood of possessing a superior endurance capacity than that seen in healthy controls (90% CI = 1.037–3.089). Our findings propose an association of combined ACTN3 RX+XX and ACE II genotypes with enhanced endurance performance in elite Korean athletes. While causality remains to be confirmed, our study highlights the potential of ACTN3-ACE polymorphisms in predicting elite endurance. Full article

Acute coronary syndrome (ACS) represents an important clinical manifestation of coronary artery disease (CAD) and is characterized by a particularly poor prognosis. Myocardial reperfusion through primary percutaneous coronary intervention (PPCI) is imperative in the event of acute ST elevation myocardial infarction (STEMI). Interleukin-22 (IL-22) regulates immune and inflammatory responses. This interleukin has been described in the scenario of the CAD, but there are no data in patients with STEMI undergoing PPCI. Objectives: The goals of this study were to investigate the differences in circulating IL-22 levels between patients with STEMI undergoing PPCI and healthy controls and to determine whether these differences were associated with the culprit coronary artery, door-to-balloon time (DBT), final angiographic result, CAD classification, and presence of diabetes mellitus (DM). Methods: A total of 280 participants were recruited, comprising 210 STEMI cases and 70 healthy controls. Participants underwent clinical and angiographic evaluations, and serum IL-22 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Data analysis was performed using the Mann–Whitney and Fisher tests, with p < 0.05 indicating significance. Results: Serum IL-22 levels were lower in cases (149.63, 84.99–294.56) than in the controls (482.67, 344.33–641.00); p < 0.001. Lower IL-22 levels were associated with the right coronary artery (RCA) (144.57, 70.84–242.43; 146.00, 63.60–279.67; 191.71, 121.80–388.97); p = 0.033. IL-22 was lower with shorter DBT (≤60 min, 106.00, 49.60–171.71; >60 min, 153.00, 88.86–313.60); p = 0.043. Conclusions: IL-22 levels were significantly lower in patients with STEMI than in healthy controls. Full article