Search Results (21,702)

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these. Patients and Methods: Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS). Results: Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31–55) and 43% (30.1–55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms. Conclusions: Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies. Full article

Background: Recombinant growth hormone (rhGH) has been used since 1985 to treat growth hormone (GH)-induced short stature, typically associated with transient adverse events. However, lipoatrophy, characterized by irreversible damage to subcutaneous fat, was first reported in 1999 and linked to antibody formation. In 2021, localized lipoatrophy was observed in 14.5% of patients receiving daily rhGH, with repeated injections at the same sites being a common contributing factor. Long-acting rhGH (LAGH) preparation offers the advantage of weekly injections, enhancing patient comfort and adherence to treatment. Methods: This case report discusses a 5.5-year-old girl born at 40 weeks of gestation with a birth weight of 2300 g, diagnosed with idiopathic short stature and borderline GH secretion, along with a history of mild intrauterine growth retardation. Results: After initiating treatment with the non-pegylated fusion protein formulation of LAGH at the standard dose of 0.66 mg/kg body weight weekly, administered by her family, she developed localized lipoatrophy at the injection site within eleven weeks. The injections were performed consistently in the same area of the right upper arm, where lipoatrophy emerged. Following the onset of this adverse effect, her treatment was adjusted to daily rhGH, with strict instructions to rotate injection sites. Despite these clear instructions, follow-up revealed that the parents continued to administer injections with the non-pegylated LAGH fusion protein formulation, this time in the left upper arm, leading to a recurrence of lipoatrophy within eight weeks. Conclusions: The recurrence underscores the importance of proper injection techniques, particularly site rotation, in preventing localized adverse effects. Given the limitations of this case, where the recommended adjustments were not followed by the parents, it is crucial to emphasize that the administration of the preparation should be discontinued immediately upon the appearance of side effects such as lipoatrophy. Individual reactions to drugs are always possible, and this highlights the need for clinician vigilance in monitoring and addressing adverse effects promptly during treatments with LAGH. Full article

In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, as an RNA vaccine, offers significant advantages in preventing infectious diseases by serving as a vector for protein expression through non-canonical translation. Notably, circRNA vaccines have demonstrated enduring antigenic expression and generate a larger percentage of neutralizing antibodies compared to mRNA vaccines administered at the same dosage. Furthermore, circRNA vaccines can elicit robust cellular and humoral immunity, indicating their potential for tumor vaccine development. However, certain challenges must be addressed to facilitate the widespread use of circRNA vaccines in both infectious disease prevention and tumor treatment. These challenges include the low efficiency of linear RNA circularization, the suboptimal targeting of delivery systems, and the assessment of potential side effects. This work aims to describe the characteristics and functions of circRNAs, elucidate the mechanism behind circRNA vaccines, and discuss their applications in the prevention of infectious diseases and the treatment of tumors, along with their potential future applications. Full article

Background: Myocardial disease is an important component of the wide field of cardiovascular disease. However, the phenomenon of multiple myocardial diseases in a single patient remains understudied. Aim: To investigate the prevalence and impact of myocarditis in patients with genetic cardiomyopathies and to evaluate the outcomes of myocarditis treatment in the context of cardiomyopathies. Methods: A total of 342 patients with primary cardiomyopathies were enrolled. The study cohort included 125 patients with left ventricular non-compaction (LVNC), 100 with primary myocardial hypertrophy syndrome, 70 with arrhythmogenic right ventricular cardiomyopathy (ARVC), 60 with dilated cardiomyopathy (DCM), and 30 with restrictive cardiomyopathy (RCM). The diagnosis of myocarditis was based on data from myocardial morphological examination or a non-invasive diagnostic algorithm consisting of an analysis of clinical presentation, anti-cardiac antibody (Ab) titres, and cardiac MRI. Results: The prevalence of myocarditis was 74.3% in ARVC, 56.7% in DCM, 54.4% in LVNC, 37.5% in RCM, and 30.9% in HCM. Myocarditis had a primary viral or secondary autoimmune nature and manifested with the onset or worsening of chronic heart failure (CHF) and arrhythmias. Treatment of myocarditis in cardiomyopathies has been shown to stabilise or improve patient condition and reduce the risk of adverse outcomes. Conclusions: In cardiomyopathies, the genetic basis and inflammation are components of a single continuum, which forms a complex phenotype. In genetic cardiomyopathies, myocarditis should be actively diagnosed and treated as it is an important therapeutic target. Full article

The parasitic protozoa, Toxoplasma gondii (T. gondii), is a model organism for one health because of its wide-ranging impacts on humans, wildlife, and domestic animals. Intermediate hosts, including white-tailed deer (Odocoileus virginianus), have been implicated in its maintenance. Prior analysis of Toxoplasma gondii seroprevalence in New York State deer focused on rural areas; however, the high density of domestic cats (Felis catus) in urban areas has been implicated in its spread amongst deer. To address this, the seroprevalence of Toxoplasma gondii was assessed across two suburban and urban areas with known deer overabundance in Onondaga and Suffolk County. Here, domestic cats are the only likely definitive host. Between 2019 and 2023, serum from culled deer was collected, and Toxoplasma gondii seropositivity was determined using the modified agglutination test. Overall seroprevalence was 49.31% (n = 144) but was significantly higher in Onondaga (64%) compared to Suffolk County (36%), despite similarities between these two regions. Deer from Onondaga also had higher antibody titers. These data suggest that although urbanization may be a predictor of Toxoplasma gondii seropositivity in deer, there are additional contributing factors. Overall, this study emphasizes the need for continued surveillance in intermediate hosts and informs public health and wildlife management decisions aimed at limiting the impact of Toxoplasma gondii. Full article

Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential. Methods: Using both primary donor AML cells and cell lines, we developed an in vitro co-culture model of the AML BMME. We used this model to identify the most effective agent(s) to block AML cell adherence and reverse adhesion-mediated treatment resistance. Results: We identified that anti-CD44 treatment significantly increased the efficacy of cytarabine. However, some AML cells remained adhered, and transcriptional analysis identified focal adhesion kinase (FAK) signaling as a contributing factor; the adhered cells showed elevated FAK phosphorylation that was reduced by the FAK inhibitor, defactinib. Importantly, we demonstrated that anti-CD44 and defactinib were highly synergistic at diminishing the adhesion of the most primitive CD34^high AML cells in primary autologous co-cultures. Conclusions: Taken together, we identified anti-CD44 and defactinib as a promising therapeutic combination to release AML cells from the chemoprotective AML BMME. As anti-CD44 is already available as a recombinant humanized monoclonal antibody, the combination of this agent with defactinib could be rapidly tested in AML clinical trials. Full article

Goose parvovirus (GPV) is an etiological agent of Derzsy’s disease, afflicting geese and Muscovy ducks worldwide. Its high mortality rate among goslings and ducklings causes large losses to the waterfowl industry. Toward molecular and structural characterization, virus-like particles (VLPs) of GPV were produced, and the capsid structure was determined by cryogenic electron microscopy (cryo-EM) at a resolution of 2.4 Å. The capsid exhibited structural features conserved among parvoviruses, including surface two-fold depressions, three-fold protrusions, and five-fold channels. A structural comparison of the GPV viral protein (VP) structure with other adeno-associated viruses (AAVs), including human AAV2, AAV5, and quail AAV (QAAV), revealed unique conformations of several surface-accessible variable regions (VRs). Furthermore, the GPV capsid was found to be thermally stable at physiological pH, but less so under lower pH conditions. As a member of the genus Dependoparvovirus, GPV could also be bound by cross-reactive anti-AAV capsid antibodies that bind to the five-fold region of the viruses, as shown by native immuno-dot blot analysis. Finally, the GPV VP structure was compared to those of other bird dependoparvoviruses, which revealed that VR-III may be important for GPV and Muscovy duck parvovirus (MDPV) infection. Full article

Background: Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. A hallmark of the disease is the rapid remission of proteinuria following a high dose of steroids. Recurrent disease or steroid dependence are common, leading to a high steroid burden and the introduction of steroid sparing therapy. Anti-CD20 antibodies have been increasingly used with excellent results in complicated INS. Nevertheless, their use can be limited by the occurrence of infusion-related reactions (IRRs). Methods: This report discusses further treatment options for children who are intolerant to RTX and presents the first report of a successful switch to obinutuzumab (OBI) for a child with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS) and RTX intolerance who was unresponsive to a desensitization protocol. Results: A 12-year-old boy with SDNS since the age of 2, was treated with steroids, cyclophosphamide and cyclosporine A (CsA). Because of the prolonged use of calcineurin inhibitors, a course of rituximab (RTX) was planned. Unfortunately, during first infusion, the boy presented with IRR. A desensitization protocol following the first unsuccessful infusion also failed. Facing the risks of long-term cyclosporine therapy, a decision was made to switch to another type of anti-CD20 antibody. Obinutuzumab infusion with a modified premedication scheme was uneventful. Conclusions: Switching therapy to obinutuzumab may be considered an option in nephrotic children who are intolerant to RTX when alternative therapies have been exhausted. The addition of montelukast to premedication and employment of desensitization protocols may decrease the risk of infusion-related reactions to anti-CD20 agents. Full article

Background: Antibodies against Ku have been described in patients with various connective tissue diseases. The objective of this study was to describe the clinical, functional, and imaging characteristics of interstitial lung disease in patients with anti-Ku antibodies. Methods: This single-center, retrospective observational study was conducted at a tertiary referral institution. Patients with positive anti-Ku antibodies and interstitial lung disease identified between 2007 and 2022 were included. Clinical, immunological, functional, and imaging data were systematically reviewed. Results: Nineteen patients (ten females) with a mean age of 59 ± 12.6 years were included. The most frequent associated diagnosis was systemic sclerosis (42%), followed by rheumatoid arthritis (26%), Sjögren syndrome, undifferentiated connective tissue disease, and overlap between systemic sclerosis and idiopathic inflammatory myopathy (scleromyositis). Imaging revealed frequent septal and intralobular reticulations and ground-glass opacities, with nonspecific interstitial pneumonia as the predominant pattern (53%). The mean forced vital capacity was 82% ± 26 of the predicted value, and the mean diffusing capacity for carbon monoxide was 55% ± 21. Over the first year of follow-up, the mean annual forced vital capacity decline was 140 mL/year (range: 0–1610 mL/year). The overall survival rate was 82% at 5 years and 67% at 10 years. Conclusions: Most patients with interstitial lung disease and anti-Ku antibodies presented with dyspnea, a mild-to-moderate restrictive ventilatory pattern, and reduced diffusing capacity for carbon monoxide. The CT pattern was heterogeneous but was consistent with nonspecific interstitial pneumonia in half of the patients. Full article

Impedance-based biosensing has emerged as a critical technology for high-sensitivity biomolecular detection, yet traditional approaches often rely on bulky, costly impedance analyzers, limiting their portability and usability in point-of-care applications. Addressing these limitations, this paper proposes an advanced biosensing system integrating a Silicon Nanowire Field-Effect Transistor (SiNW-FET) biosensor with a high-gain amplification circuit and a 1D Convolutional Neural Network (CNN) implemented on FPGA hardware. This attempt combines SiNW-FET biosensing technology with FPGA-implemented deep learning noise reduction, creating a compact system capable of real-time viral detection with minimal computational latency. The integration of a 1D CNN model on FPGA hardware for adaptive, non-linear noise filtering sets this design apart from conventional filtering approaches by achieving high accuracy and low power consumption in a portable format. This integration of SiNW-FET with FPGA-based CNN noise reduction offers a unique approach, as prior noise reduction techniques for biosensors typically rely on linear filtering or digital smoothing, which lack adaptive capabilities for complex, non-linear noise patterns. By introducing the 1D CNN on FPGA, this architecture enables real-time, high-fidelity noise reduction, preserving critical signal characteristics without compromising processing speed. Notably, the findings presented in this work are based exclusively on comprehensive simulations using COMSOL and MATLAB, as no physical prototypes or biomarker detection experiments were conducted. The SiNW-FET biosensor, functionalized with antibodies specific to viral antigens, detects impedance shifts caused by antibody–antigen interactions, providing a highly sensitive platform for viral detection. A high-gain folded-cascade amplifier enhances the Signal-to-Noise Ratio (SNR) to approximately 70 dB, verified through COMSOL and MATLAB simulations. Additionally, a 1D CNN model is employed for adaptive noise reduction, filtering out non-linear noise patterns and achieving an approximate 75% noise reduction across a broad frequency range. The CNN model, implemented on an Altera DE2 FPGA, enables high-throughput, low-latency signal processing, making the system viable for real-time applications. Performance evaluations confirmed the proposed system’s capability to enhance the SNR significantly while maintaining a compact and energy-efficient design suitable for portable diagnostics. This integrated architecture thus provides a powerful solution for high-precision, real-time viral detection, and continuous health monitoring, advancing the role of biosensors in accessible point-of-care diagnostics. Full article

Due to their biocompatibility, nontoxicity, and surface conjugation properties, nanomaterials are effective nanocarriers capable of encapsulating chemotherapeutic drugs and facilitating targeted delivery across the blood–brain barrier (BBB). Although research on nanoparticles for brain cancer treatment is still in its early stages, these systems hold great potential to revolutionize drug delivery. Glioblastoma multiforme (GBM) is one of the most common and lethal brain tumors, and its heterogeneous and aggressive nature complicates current treatments, which primarily rely on surgery. One of the significant obstacles to effective treatment is the poor penetration of drugs across the BBB. Moreover, GBM is often referred to as a “cold” tumor, characterized by an immunosuppressive tumor microenvironment (TME) and minimal immune cell infiltration, which limits the effectiveness of immunotherapies. Therefore, developing novel, more effective treatments is critical to improving the survival rate of GBM patients. Current strategies for enhancing treatment outcomes focus on the controlled, targeted delivery of chemotherapeutic agents to GBM cells across the BBB using nanoparticles. These therapies must be designed to engage specialized transport systems, allowing for efficient BBB penetration, improved therapeutic efficacy, and reduced systemic toxicity and drug degradation. Lipid and inorganic nanoparticles can enhance brain delivery while minimizing side effects. These formulations may include epitopes—small antigen fragments that bind directly to free antibodies, B cell receptors, or T cell receptors—that interact with transport systems and enable BBB crossing, thereby boosting therapeutic efficacy. Lipid-based nanoparticles (LNPs), such as liposomes, niosomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), are among the most promising delivery systems due to their unique properties, including their size, surface modification capabilities, and proven biosafety. Additionally, inorganic nanoparticles such as gold nanoparticles, mesoporous silica, superparamagnetic iron oxide nanoparticles, and dendrimers offer promising alternatives. Inorganic nanoparticles (INPs) can be easily engineered, and their surfaces can be modified with various elements or biological ligands to enhance BBB penetration, targeted delivery, and biocompatibility. Strategies such as surface engineering and functionalization have been employed to ensure biocompatibility and reduce cytotoxicity, making these nanoparticles safer for clinical applications. The use of INPs in GBM treatment has shown promise in improving the efficacy of traditional therapies like chemotherapy, radiotherapy, and gene therapy, as well as advancing newer treatment strategies, including immunotherapy, photothermal and photodynamic therapies, and magnetic hyperthermia. This article reviews the latest research on lipid and inorganic nanoparticles in treating GBM, focusing on active and passive targeting approaches. Full article

mRNA technology can replace the expensive recombinant technology for every type of protein, making biological drugs more affordable. It can also expedite the entry of new biological drugs, and copies of approved mRNA products can be treated as generic or biosimilar products due to their chemical nature. The introduction of hundreds of new protein drugs have been blocked due to the high cost of recombinant development. The low CAPEX and OPEX associated with mRNA technology bring it within the reach of developing countries that are currently deprived of life-saving biological drugs. In this paper, we advise developers to introduce novel proteins and switch recombinant manufacturing to mRNA delivery, and we further advise regulatory authorities to allow for the approval of copies of mRNA products with less testing. We anticipate that mRNA technology will make protein drugs, such as natural and engineered proteins, monoclonal antibodies, and vaccines, accessible to billions of patients worldwide. Full article

Coxiella burnetii is a highly infectious zoonotic pathogenic bacterium that has a major economic impact in the livestock industry throughout the world and causes unpredictable outbreaks in humans worldwide. Although it is known that birds are potential reservoirs of C. burnetii, their role in the epidemiological cycle of the pathogen has not been fully verified. Due to its non-specific symptoms and clinical signs, it is certainly an underdiagnosed disease. The objective of this study was to obtain more information on C. burnetii prevalence in wild birds in Portugal. Blood, plasma, and other tissue samples were obtained from wild birds admitted at wildlife rehabilitation centres in Portugal in the scope of passive surveillance. Antibodies specific to C. burnetii were screened using a commercial enzyme-linked immunosorbent assay according to the manufacturer’s instructions. Evidence of C. burnetii infection was sought based on the detection of bacterial DNA. No positive results were found, either in terms of antibodies to C. burnetii or molecular biology. These serological findings do not indicate the endemic circulation of C. burnetii in wild birds, which can be considered relevant information. However, a more complete and serialized approach over time is necessary to be able to make real inferences about the endemicity of the pathogen in the country and its dispersion among wild avian populations. qPCR results were also negative, a finding suggesting that this host population may not play a significant role in the transmission dynamics of C. burnetii. Given the importance of wild bird species as natural reservoirs of this zoonotic bacterium, we consider these data useful for multidisciplinary work in the prevention and control of Q fever, following a One Health approach. Full article

Background/Objectives: Anti-neutrophil cytoplasmic antibodies (ANCAs) have been found in interstitial lung disease (ILD) in recent years, although its impact on ILD prognosis is less known. To date, ANCAs are not included in the interstitial pneumonia with autoimmune features (IPAF) definition criteria. Therefore, ANCA-ILD, in the absence of known ANCA-associated vasculitis (AAV), could be underdiagnosed. Our aim was to analyze the clinical profile and prognosis of ANCA-ILD patients. Methods: Patients diagnosed with ILD and positive ANCA were enrolled in a retrospective, monocentric cohort study. Lung function outcomes and mortality were assessed according to clinical, serological, radiological, and treatment characteristics. Survival was analyzed using Kaplan–Meier curves and Cox regression models. Results: A total of 23 patients were included, mostly women, with a median time from ILD diagnosis of 36 (24–68) months and a predominant anti-MPO pattern (56.5%). Nearly half of the patients had AAV, mostly microscopic polyangiitis (MPA). The presence of AAV was significantly associated with anti-MPO antibodies and an NSIP radiographic pattern. Overall, the fibrotic pattern (either UIP or fibrotic NSIP) was the most common (73.9%), mainly UIP (51.2%). However, it appeared less frequently in the AAV-ILD group. During follow-up, lung function impairment or radiological progression was observed in 65.2% of patients. Cumulative mortality incidence was high (43.4%), largely due to ILD itself (80%). A UIP pattern was associated with a higher and earlier mortality (HR 34.4 [1.36–132]), while the use of immunosuppressants showed a trend towards lower ILD-related death. Conclusions: In our cohort, ANCA-ILD patients mostly presented with fibrotic patterns, with AAV in almost half of the cases and a high and early mortality rate, which suggests the need to assess ANCA in all ILD patients. Full article

Due to their lipophilicity and low content, the major sesame oleosin allergens, Ses i 4 and Ses i 5, are challenging to identify using conventional techniques. Then, a novel unlabeled electrochemical immunosensor was developed to detect the potential allergic activity of sesame oleosins. The voltammetric immunosensor was constructed using a composite of gold nanoparticles (AuNPs), polyethyleneimine (PEI), and multi-walled carbon nanotubes (MWCNTs), which was synthesized in a one-pot process and modified onto a glass carbon electrode to enhance the catalytic current of the oxygen reduction reaction. The oleosin antibody was then directed and immobilized onto the surface of the electrode, which had been modified with streptavidin (SPA), through the fragment crystallizable (Fc) region of the antibody. Under optimized conditions, the immunosensor exhibited a linear response within a detection range of 50 to 800 ng/L, with detection limits of 0.616 ng/L for Ses i 4 and 0.307 ng/L for Ses i 5, respectively. The immunosensor demonstrated excellent selectivity and stability, making it suitable for the quantification of sesame oleosins. The comparative analysis of various detection methods for sesame allergens was conducted, revealing that the immunosensor achieved a wide detection range and low limit of detection (LOD). Compared to traditional enzyme-linked immunosorbent assay (ELISA), the immunosensor successfully quantified the allergenicity potential of Ses i 4 and Ses i 5 in roasted sesame seeds at temperatures of 120 °C, 150 °C, and 180 °C. This innovative method offers a new perspective for the rapid quantification of sesame oleosins in foods and real-time monitoring of allergic potential, providing significant advancements in the field of food allergy detection. Full article