Search Results (383)

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, pathologically defined by the accumulation of amyloid-β plaques and tau-related neurofibrillary tangles in the brain. It represents a principal driver of cognitive deterioration in middle-aged and elderly populations. Early diagnosis and pharmacological management of the disease markedly improve both the quality and duration of life. Methods: Electroencephalography (EEG) is critical in detecting and analyzing Alzheimer’s disease. The widespread use of mobile EEG devices in recent years has necessitated real-time and effective data processing. However, extracting disease-specific features from EEG data still poses a significant challenge, especially in cases that must be completed quickly. This study aims to determine the frequency bands associated with Alzheimer’s disease in EEG data obtained from multiple channels and to accelerate the detection methods. An accurate classification that requires little computation is the primary goal. Results: EEG recordings of 48 individuals (24 AD and 24 healthy controls (HC)) obtained from Florida State University were divided into Alpha, Beta, Delta, Gamma, and Theta frequency bands; scalograms and spectrograms were generated for each frequency band. The effectiveness of these bands was evaluated using the MobileNetV2 architecture. The results showed that Delta and Beta frequency bands were the most significant for Alzheimer’s detection. By analyzing the features obtained from the Delta and Beta bands using the MobileNetV2 model integrated with the Dual-Attention Mechanism, it was determined that the attention mechanisms improved model performance by 2%. In addition, the use of an SVM classifier with hyperparameters optimized via Optuna resulted in approximately 3% performance improvement, suggesting that hyperparameter tuning may contribute positively to classification accuracy. Furthermore, combining features obtained from these frequency bands increased the detection performance when evaluated with larger datasets. Conclusions: The study demonstrates the potential of frequency band-based analyses and feature fusion methods to increase the accuracy and efficiency of Alzheimer’s diagnosis using EEG data. The results are promising; however, they should be interpreted with caution regarding their generalizability. Full article

Background and objectives: Desquamative gingivitis (DG) is a clinical term used to describe gingival conditions marked by erythema (unrelated to dental plaque), epithelial desquamation, and various intraoral lesions, with occasional extraoral involvement. It is typically linked to a range of underlying diseases. Materials and methods: A narrative literature review was conducted using PubMed, Scopus, Google Scholar, and the Cochrane Library, searching with keywords like “oral dysplasia”, “oral mucosa lesions”, or “desquamative gingivitis”. In addition to the literature review, a case report of a patient with DG is included to illustrate the diagnostic challenges and treatment considerations in a clinical setting, and to design and test simplified diagnosis and treatment-planning algorithms. Results: Diagnosis can be supported by a standard punch biopsy to obtain tissue samples for histopathological evaluation. The complex clinical case presented illustrates the clinical features of DG and highlights the challenges associated with its diagnosis and management. The mainstay of treatment, as resulted from 96 studies included in our review, involves topical and systemic corticosteroids, with topical calcineurin inhibitors serving as adjunctive therapy. Conclusions: A universally accepted treatment protocol is still lacking for DG, so this report outlines an effective, experience-based therapeutic approach. Additionally, it offers a simplified framework for diagnosis, treatment planning, and therapeutic management, contributing to the growing knowledge base needed for a decision-support algorithm development. Full article

We present the case of a 26-year-old, otherwise healthy female patient who attended dermatology outpatient clinic due to a reddish, asymptomatic plaque located on the midline of the tongue. Dermoscopic examination revealed an area of small, atrophic filiform papillae. Based on clinical and dermoscopic features, median rhomboid glossitis (MRG) was suspected. Histopathological analysis confirmed the diagnosis. Full article

Deep neural networks have led to a substantial increase in multifaceted classification tasks by making use of large-scale and diverse annotated datasets. However, diverse optical coherence tomography (OCT) datasets in cardiovascular imaging remain an uphill task. This research focuses on improving the diversity and generalization ability of augmentation architectures while maintaining the baseline classification accuracy for coronary atrial plaques using a novel dual-generator and dynamically fused discriminator conditional generative adversarial network (DGDFGAN). Our method is demonstrated on an augmented OCT dataset with 6900 images. With dual generators, our network provides the diverse outputs for the same input condition, as each generator acts as a regulator for the other. In our model, this mutual regularization enhances the ability of both generators to generalize better across different features. The fusion discriminators use one discriminator for classification purposes, hence avoiding the need for a separate deep architecture. A loss function, including the SSIM loss and FID scores, confirms that perfect synthetic OCT image aliases are created. We optimize our model via the gray wolf optimizer during model training. Furthermore, an inter-comparison and recorded SSID loss of 0.9542 ± 0.008 and a FID score of 7 are suggestive of better diversity and generation characteristics that outperform the performance of leading GAN architectures. We trust that our approach is practically viable and thus assists professionals in informed decision making in clinical settings. Full article

Background: Coronary artery calcium (CAC) scores are a widely used surrogate marker for atherosclerotic burden, but they do not fully reflect plaque vulnerability or coronary inflammation. This study aimed to evaluate the relationship between CACs, coronary plaque characteristics, and perivascular inflammatory activity using advanced CCTA and CaRi-Heart^® analysis. Methods: A total of 250 patients with no prior cardiovascular disease were retrospectively evaluated and stratified by CACs into three groups: 0 (n = 28), 1–100 (n = 121), and >100 (n = 101). Coronary plaque morphology, high-risk plaque (HRP) features, CAD-RADS scores, and AI-derived fat attenuation index (FAI) centiles were assessed. Results: Significant differences across CAC categories were observed for several key parameters. The number of diseased coronary segments increased markedly (from 1.39 ± 1.10 vs. 2.97 ± 1.57 vs. 3.94 ± 2.10; p < 0.0001, one-way ANOVA). A similar upward trend was seen for segment involvement scores, HRP prevalence, and the proportions of mixed and calcified plaque components. Regression analysis demonstrated that CACs correlated significantly with segment burden (r² = 0.2520), CAD-RADS (r² = 0.1352), and the FAI score centile (r² = 0.0568). Conclusions: This study highlights the limitations of CACs as a standalone risk stratification tool. Vulnerable and inflamed plaques may already be present in patients with low or zero CACs. Integrating CCTA with perivascular FAI mapping enables earlier detection of biologically active atherosclerosis and supports more precise clinical decision-making. Full article

Background and Objectives: In vivo data on healed coronary plaques (HCPs), the hallmark of previous plaque disruption, remains scarce. The study aimed to use optical coherence tomography (OCT) imaging to assess the prevalence, morphological features, and clinical significance of culprit HCPs in patients with acute coronary syndrome (ACS). Materials and Methods: A total of 87 ACS patients (74.3% non-ST-segment elevation ACS) who underwent pre-procedural OCT imaging of the culprit vessel at a single center were retrospectively analyzed. A pilot subgroup of patients with intracoronary thrombi at the culprit site, in various stages of organization and healing, enabled a detailed morphological characterization of HCP despite the absence of histological validation. Three distinct HCP imaging aspects were identified: type I—overlaying fibrous tissue, type II—overlaying lipid tissue, and type III—overlaying calcific tissue. HCP presence was subsequently assessed in the entire population. Clinical correlations included associations with post-stenting outcomes, particularly edge dissections (ED). Results: Culprit HCPs were identified in 78 patients (89.7%): type I—30.8%, type II—51.3%, and type III—17.9%. Regarding the underlying substrate and complication mechanism, type I HCP was associated with pathological intimal thickening (70.8%) and plaque erosion (75%), type II with lipid-rich plaque (80%) and plaque rupture (PR) (82.5%), and type III correlated with calcific plaque (92.9%, p < 0.0001) and both PR and calcified nodule (p < 0.0001). A unique signal-rich ring was observed at the HCP–tissue interface in both type II (77.5%) and type III (78.6%, p < 0.0001). There was a significant correlation between stent ED and HCP presence at landing zones (LZ) (HR 4.14, 95% CI: 1.79–9.55; p < 0.001). Conclusions: OCT analysis of intracoronary organizing fresh thrombi allowed detailed characterization of culprit HCPs and in vivo classification into three imaging types. This approach likely contributed to the high observed detection rate of HCP by enhancing recognition of subtle OCT features. HCP may create mechanical vulnerability if located at the stent LZ. Our improved HCP detection techniques may help optimize stent-related outcomes of OCT-guided procedures by choosing an HCP-free LZ or longer stents. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Moyamoya disease (MMD) is primarily associated with genetic variants in RNF213. RNF213 p.R4810K (c.14429G>A, p.Arg4810Lys) is a founder variant predominantly found in East Asian populations and is strongly associated with MMD, a rare cerebrovascular condition characterized by progressive stenosis of intracranial arteries and the development of abnormal collateral networks. Recent evidence suggests that RNF213 variants are also enriched in non-moyamoya intracranial arteriopathies, such as large-artery atherosclerotic stroke and intracranial arterial stenosis/occlusion (ICASO), particularly in east Asian individuals with early-onset or cryptogenic stroke. This expanded phenotypic spectrum, termed RNF213-related vasculopathy (RRV), represents a distinct pathogenic entity that may involve unique pathogenic processes separate from traditional atherosclerosis. In this review, we synthesize current genetic, clinical, radiological, and experimental findings that delineate the unique features of RRV. Patients with RRV typically exhibit a lower burden of traditional vascular risk factors, negative vascular remodeling in the absence of atheromatous plaques, and an increased propensity for disease progression. RNF213 variants may compromise vascular resilience by impairing adaptive responses to hemodynamic stress. Furthermore, emerging cellular and animal model data indicate that RNF213 influences angiogenesis, lipid metabolism, and stress responses, offering mechanistic insights into its role in maintaining vascular integrity. Recognizing RRV as a distinct clinical entity has important implications for diagnosis, risk stratification, and the development of genome-informed therapeutic strategies. Full article

Introduction: Here we consider the collision of a genetic factor and an essential instigator in Alzheimer’s neuropathogenesis: (i) the Alzheimer’s gene (APOEε4), which downregulates lysosomal autophagy and induces synthesis of (ii) the instigator, interleukin-1β (IL-1β), which drives synthesis of βAPP for Aβ plaques and of MAPKp38 for phosphorylation of tau for formation of neurofibrillary tangles (NFTs), the two cardinal features of AD. Methods: RT-PCR, immunoblotting and immunohistochemistry techniques were used to assess the levels of IL-1β and its signaling cascade in ADε4,4, ε3,3, and age-matched controls (AMC3,3) in hippocampal regions of the brain. Results: IL-1β and its downstream signaling proteins TLR-2, MyD88, NFκB, COX-1, and COX-2 were greater in tissues from ADε4,4 than ADε3,3 or AMC3,3. Cathepsin B, D, and L levels, which play a pivotal role and are necessary for lysosomal autophagy, were lower in ADε4,4 than in ADε3,3 or AMC ε3,3. IL-1β and its downstream signaling cascade TLR-2, MyD88, NFκB, COX-1, and COX-2 expression levels were high in SH-SY5Y and T98G cells transfected with APOεE4. Conclusions: APOEε4 causes Alzheimer’s by downregulating autophagy, thus inducing IL-1β for Aβ plaque and neurofibrillary tangle formation. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Coronary artery disease (CAD) is the main cause of morbidity and death worldwide, and atherosclerosis represents the leading pathophysiological pathway responsible for CAD. Atherosclerotic process is a complex interplay of mechanisms and mediators resulting in plaque formation, progression and destabilization, the latter being the most frequent cause of acute cardiovascular events. Considering the systemic nature of atherosclerosis, polyvascular disease involvement is possible and has been described since 1960s. Accordingly, epidemiologic studies reported that concomitant CAD and atherosclerosis in other arterial beds like carotid arteries, lower limb arteries, mesenteric and renal circulation, and aorta, is frequent and related to increased chance of future cardiovascular events. Although risk factors, atherosclerotic plaque features and mechanisms of plaque destabilization are largely shared across different sites, many studies have reported some disparities among districts. Moreover, simultaneous polyvascular disease has been associated with increased likelihood of having particular plaque characteristics depending on the affected arterial level. In this comprehensive narrative review, we aim to discuss about epidemiology of concomitant CAD and atherosclerosis in other arterial beds, and to examine differences in risk factors, plaque features and mechanisms of plaque instability between CAD and other atherosclerotic locations. Finally, we review the studies observing differences on plaque features according to involved atherosclerotic sites, focusing on CAD. Full article

The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ_1-42 oligomer level. Thus, injection of Aβ_1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ_1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ_1-42 oligomers on contextual learning through the IA task. Full article

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm². Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD. Full article