Search Results (2,300)

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, profound heterogeneity, and resistance to conventional therapies. This review provides an integrated overview of GBM’s pathophysiology, highlighting key mechanisms such as neuroinflammation, genetic alterations (e.g., EGFR, PDGFRA), the tumor microenvironment, microbiome interactions, and molecular dysregulations involving gangliosides and sphingolipids. Current diagnostic strategies, including imaging, histopathology, immunohistochemistry, and emerging liquid biopsy techniques, are explored for their role in improving early detection and monitoring. Treatment remains challenging, with standard therapies—surgery, radiotherapy, and temozolomide—offering limited survival benefits. Innovative therapies are increasingly being explored and implemented, including immune checkpoint inhibitors, CAR-T cell therapy, dendritic and peptide vaccines, and oncolytic virotherapy. Advances in nanotechnology and personalized medicine, such as individualized multimodal immunotherapy and NanoTherm therapy, are also discussed as strategies to overcome the blood–brain barrier and tumor heterogeneity. Additionally, stem cell-based approaches show promise in targeted drug delivery and immune modulation. Non-conventional strategies such as ketogenic diets and palliative care are also evaluated for their adjunctive potential. While novel therapies hold promise, GBM’s complexity demands continued interdisciplinary research to improve prognosis, treatment response, and patient quality of life. This review underscores the urgent need for personalized, multimodal strategies in combating this devastating malignancy. Full article

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article

Amidst the escalating demand for high-precision structural health monitoring in large-scale engineering applications, carbon fiber-reinforced polymer fiber Bragg grating (CFRP-FBG) sensors have emerged as a pivotal technology for fatigue life evaluation, owing to their exceptional sensitivity and intrinsic immunity to electromagnetic interference. A time-series predictive architecture based on long short-term memory (LSTM) networks is developed in this work to facilitate intelligent fatigue life assessment of structures subjected to complex cyclic loading by capturing and modeling critical spectral characteristics of CFRP-FBG sensors, specifically the side-mode suppression ratio and main-lobe peak-to-valley ratio. To enhance model robustness and generalization, Principal Component Analysis (PCA) was employed to isolate the most salient spectral features, followed by data preprocessing via normalization and model optimization through the integration of the Adam optimizer and Dropout regularization strategy. Relative to conventional Backpropagation (BP) neural networks, the LSTM model demonstrated a substantial improvement in predicting the side-mode suppression ratio, achieving a 61.62% reduction in mean squared error (MSE) and a 34.99% decrease in root mean squared error (RMSE), thereby markedly enhancing robustness to outliers and ensuring greater overall prediction stability. In predicting the peak-to-valley ratio, the model attained a notable 24.9% decrease in mean absolute error (MAE) and a 21.2% reduction in root mean squared error (RMSE), thereby substantially curtailing localized inaccuracies. The forecasted confidence intervals were correspondingly narrower and exhibited diminished fluctuation, highlighting the LSTM architecture’s enhanced proficiency in capturing nonlinear dynamics and modeling temporal dependencies. The proposed method manifests considerable practical engineering relevance and delivers resilient intelligent assistance for the seamless implementation of CFRP-FBG sensor technology in structural health monitoring and fatigue life prognostics. Full article

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Background/Objectives: Pumpkin seed pulp from processing plants offers high nutritional value due to its rich β-carotene content, making it a potential functional feed ingredient. This study investigated the effects of pumpkin seed pulp, which has already been administered as livestock feed, on key physiological parameters in cattle, including the concentration of β-carotene in the blood measured during routine health monitoring. Methods: Here, pumpkin waste cultivated in various fields was processed into cattle feed (pumpkin seed pulp flakes, PSPFs) by grinding and drying, and residual pesticide (heptachlor) and β-carotene contents were measured. A pilot feeding trial was conducted with 13 cattle (7 in the treatment group and 6 in the control group) and blood component analysis was performed, and findings were contextualized with a literature review. Results: Heptachlor concentrations varied depending on the cultivation site of raw pumpkins. Among the six lots produced using raw materials sourced from fields not contracted by the Air Water Group—a collective of companies in which Air Water Inc. holds more than 51% ownership—three exceeded the regulatory limits for animal feed established in Japan. PSPFs contained high levels of β-carotene, as expected. Blood tests before and after the feeding trial indicated absorption of β-carotene in the cattle. Maintaining high plasma β-carotene concentrations in cattle has been associated with improved immune function and reproductive performance. Conclusions: Our study demonstrates that PSPFs are a promising, environmentally friendly, and natural β-carotene-rich feed ingredient. Tracing the cultivation fields of raw pumpkins can help ensure feed safety. Full article

Dietary supplementation under high ambient temperatures can be considered crucial for supporting immune responses in livestock. In the present paper, Rosmarinus officinalis essential oil (REO) alone and in combination with dried sugar beet pulp (REO + B) was included in the diet of lambs during the fattening period under heat stress conditions. Environmental conditions and physiological and growth parameters of lambs were monitored throughout the trial. Plasma samples were collected to evaluate cytokine secretion (IL-1β, IL-6, and IL-10). Notably, REO inclusion reduced rectal temperature and respiration rate while increasing pro-inflammatory cytokines (IL-1β and IL-6) at the same time, suggesting an enhanced immune response without compromising growth performance. Full article

Background/Objectives: The aim of this study was to systematically assess Adverse Events Following Immunization (AEFI) among children following administration of the human papillomavirus (HPV) vaccine (Cervarix^®) included in the Dutch National Immunization Program (NIP) and to characterize the pattern and recurrence risk of AEFI after HPV revaccination. Methods: A longitudinal cohort event monitoring study, using patient-reported outcomes was used among recipients of the HPV vaccine at 10 years of age. Data were available for 3063 children following the first HPV vaccination and for 2209 children following the second HPV vaccination. Results: The most commonly reported AEFI following HPV vaccination were injection site reactions—reported by 46.5% of participants after the first dose and 31.9% after the second dose—followed by headache (8.2% and 3.9%, respectively) and joint pain (4.5% and 3.7%, respectively). Participants who received both HPV vaccine doses reported more AEFI after the first dose than after the second. Among girls, 61.2% reported at least one AEFI following the first dose, compared to 44.2% after the second dose. For boys, these percentages were 55.3% and 38.5%, respectively. This difference was statistically significant (p = 0.002). For some AEFI, such as injection site reactions, there appears to be a potential increased risk of recurrence following the second dose. Conclusions: This prospective longitudinal cohort event monitoring study showed that AEFI were more frequent after the first HPV dose and more frequent for girls compared to boys. An increased risk of recurrence was seen for AEFI, such as injection site reactions and headache. Furthermore, this study provides insight into the course of AEFI and the extent to which children were affected by these symptoms based on real-world data. Full article

Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo. Full article

Background and Objectives: Flexible ureteroscopic surgery is a common minimally invasive procedure utilized for the management of various urological conditions. While effective, postoperative complications such as fever can occur, necessitating the identification of reliable biomarkers for early detection and management. In this study, we specifically evaluated the predictive performance of three preoperative hematologic indices: the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Materials and Methods: By systematically comparing these biomarkers through receiver operating characteristic (ROC) curve analysis and logistic regression modeling, we aimed to identify the most accurate predictor of postoperative fever development. Our cohort included patients who developed postoperative fever, many of whom exhibited normal WBC counts, allowing us to evaluate the discriminatory power of alternative inflammatory biomarkers. Results: Among the 150 patients, 32 developed postoperative fever. Conventional WBC counts did not predict fever, with 91% of feverish individuals having normal WBC values. In the ROC curve analysis, NLR outperformed SII (AUC 0.847, cutoff 796) and PLR (AUC 0.743, cutoff 106), with an AUC of 0.996 at 2.96. A combined logistic model achieved 100% sensitivity and 91% specificity (AUC = 0.996). Conclusions: This study addresses a critical gap in perioperative monitoring by validating readily available complete blood count-derived ratios as clinically meaningful predictors of postoperative inflammatory responses. Full article

The development of scalable, non-invasive tools to assess tumor responsiveness to structurally active immunoformulations remains a critical unmet need in solid tumor immunotherapy. Here, we introduce a real-time, ex vivo functional system to classify tumor cell lines exposed to a phospholipoproteomic platform, without relying on cytotoxicity, co-culture systems, or molecular profiling. Tumor cells were monitored using IncuCyte^® S3 (Sartorius) real-time imaging under ex vivo neutral conditions. No dendritic cell components or immune co-cultures were used in this mode. All results are derived from direct tumor cell responses to structurally active formulations. Using eight human tumor lines, we captured proliferative behavior, cell death rates, and secretomic profiles to assign each case into stimulatory, inhibitory, or neutral categories. A structured decision-tree logic supported the classification, and a Functional Stratification Index (FSI) was computed to quantify the response magnitude. Inhibitory lines showed early divergence and high IFN-γ/IL-10 ratios; stimulatory ones exhibited a proliferative gain under balanced immune signaling. The results were reproducible across independent batches. This system enables quantitative phenotypic screening under standardized, marker-free conditions and offers an adaptable platform for functional evaluation in immuno-oncology pipelines where traditional cytotoxic endpoints are insufficient. This approach has been codified into the STIP (Structured Traceability and Immunophenotypic Platform), supporting reproducible documentation across tumor models. This platform contributes to upstream validation logic in immuno-oncology workflows and supports early-stage regulatory documentation. Full article

Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article

Background: BK polyomavirus (BKPyV) reactivation is a common complication after kidney transplantation and may result in nephropathy and graft loss. As there is no effective antiviral therapy, management focuses on early detection and reduction of immunosuppression, which increases the risk of rejection. Identifying patients at higher risk remains challenging. Monitoring BKPyV-specific T-cell responses could aid in predicting reactivation. This study evaluated the usefulness of ELISpot to monitor BKPyV-specific cellular immunity before and after kidney transplantation. Methods: A prospective multicenter study was conducted between October 2020 and March 2022. ELISpot assays were performed prior to transplantation and two months afterward. Results: Seventy-two patients were included, with a median age of 56 years; 61% were men, and 24% had undergone previous transplantation. Nine patients developed presumptive BKPyV-nephropathy. No significant differences were found in donor type, induction therapy, or rejection rates between patients with or without nephropathy (p = 0.38). Based on ELISpot results, patients were classified into three groups according to their risk of BKPyV-nephropathy. The high-risk group included those who changed from positive to negative at 2 months post-transplant, representing 40% of presumptive BKPyV-nephropathy cases. Patients who remained negative at 2 months were classified as moderate risk (14.5%), while those with a positive ELISpot at 2 months comprised the low-risk group (0%). In the logistic regression analysis, both the ELISpot risk category [OR 19 (CI 1.7–2.08)] and the use of mTOR inhibitors from the start of transplantation [OR 0.02 (CI 0.01–0.46)] were significantly associated with BKPyV-nephropathy. Conclusions: Monitoring BKPyV-specific T cells with ELISpot before and after kidney transplantation may help stratify patients by risk of reactivation. Loss of BKPyV immunity at two months is associated with nephropathy, while mTOR-based immunosuppression appears protective. This strategy could guide personalized immunosuppression and surveillance. Full article

Background: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors of immunity (IEI). Understanding the phenotypic profiles of Treg subsets and their associations with immune dysregulation is crucial to identifying potential robust and holistic biomarkers for disease activity. Methods: We examined peripheral blood mononuclear cells from 40 patients diagnosed with various autoimmune/inflammatory diseases, including those with genetically confirmed inborn errors of immunity (IEIs), and compared these samples to those from 38 healthy controls of the same age. Utilizing multiparametric flow cytometry, we measured multiple Treg sub-populations and investigated their correlations with lymphocyte subset profiles and the diversity of autoantibodies. We applied advanced statistical and machine learning techniques, such as t-SNE, k-means clustering, and ROC analysis, to analyze immunophenotypic patterns in the patients. Results: Among all Treg sub-populations, only CD4⁺CD127^lowCD25^highFOXP3⁺ Tregs showed a significant decrease in patients compared to healthy controls (p < 0.05), while other Treg phenotypes did not differ. FOXP3 expression showed reduced intensity in patients and demonstrated diagnostic potential (AUC = 0.754). Notably, this Treg subset negatively correlated with CD19⁺ B cell percentages and positively correlated with the diversity of circulating autoantibodies. Unsupervised clustering revealed three distinct immunophenotypic profiles, highlighting heterogeneity among patients and underlining FOXP3-centered immune dysregulation. Conclusions: Our results presented that patients have an impairment in the CD4⁺CD127^lowCD25^highFOXP3⁺ regulatory T cell subset, which is identified by significantly decreased frequency and decreased expression of FOXP3. Immunological heterogeneity among patients was further uncovered by unsupervised clustering, highlighting the critical role that FOXP3-centered regulatory failure plays in the pathophysiology of illness. The combined evaluation of these three immunological factors, centered around FOXP3, holds promise as an integrative tool for monitoring disease progression across various autoimmune and immunodeficient contexts. Full article

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed. Full article

Sepsis represents a major cause of mortality, especially among patients with liver cirrhosis, who are at increased risk due to immune dysfunction, gut-derived bacterial translocation, and altered hepatic metabolism. Traditional biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) often have reduced diagnostic reliability in this subgroup, due to impaired liver and renal function. Presepsin, a soluble fragment of CD14 released during phagocytic activation, has emerged as a promising biomarker for early sepsis detection. This systematic review explores the diagnostic and prognostic utility of presepsin in cirrhotic and non-cirrhotic patients with suspected infection. Data from multiple clinical studies indicate that presepsin levels correlate with infection severity and clinical scores such as SOFA and APACHE II. In cirrhotic patients, presepsin demonstrates superior sensitivity and specificity compared to conventional biomarkers, maintaining diagnostic value despite hepatic dysfunction. Its utility extends to differentiating bacterial infections from fungal infections and monitoring treatment response. While preliminary evidence is compelling, further prospective, multicenter studies are required to validate its integration into standard care algorithms. Presepsin may become a valuable addition to clinical decision-making tools, particularly in hepatology-focused sepsis management. Full article