Evidence for Irradiation Triggered Nonuniform Defects Distribution in Multiharmonic Magnetic Susceptibility of Neutron Irradiated YBa2Cu3O7?δ

Multiharmonic ac-magnetic susceptibility χ₁, χ₂, χ₃, of neutron irradiated Li-doped YBa₂Cu₃O_{7− x} has revealed a nonmonotonic dependence of all harmonics on the neutron fluence. The irradiation has a strongly depressive influence on the intergrain connection suggesting an increase of the effective thickness of the intergranular Josephson junction at a neutron fluence of 0.98 × 10¹⁷ cm⁻². Less damaged are the intragrain properties. A spectacular enhancement of the superconducting intragranular properties reflected in the characteristics of all harmonics was observed at highest fluence Φ = 9.98 × 10¹⁷ cm⁻². We assume that this effect results from the development of a space inhomogeneous distribution with alternating defectless and defect-rich regions.     

Intraoperative Tumor Detection Using Pafolacianine

Cancer is a leading cause of death worldwide, with increasing numbers of new cases each year. For the vast majority of cancer patients, surgery is the most effective procedure for the complete removal of the malignant tissue. However, relapse due to the incomplete resection of the tumor occurs very often, as the surgeon must rely primarily on visual and tactile feedback. Intraoperative near-infrared imaging with pafolacianine is a newly developed technology designed for cancer detection during surgery, which has been proven to show excellent results in terms of safety and efficacy. Therefore, pafolacianine was approved by the U.S. Food and Drug Administration (FDA) on 29 November 2021, as an additional approach that can be used to identify malignant lesions and to ensure the total resection of the tumors in ovarian cancer patients. Currently, various studies have demonstrated the positive effects of pafolacianine’s use in a wide variety of other malignancies, with promising results expected in further research. This review focuses on the applications of the FDA-approved pafolacianine for the accurate intraoperative detection of malignant tissues. The cancer-targeting fluorescent ligands can shift the paradigm of surgical oncology by enabling the visualization of cancer lesions that are difficult to detect by inspection or palpation. The enhanced detection and removal of hard-to-detect cancer tissues during surgery will lead to remarkable outcomes for cancer patients and society, specifically by decreasing the cancer relapse rate, increasing the life expectancy and quality of life, and decreasing future rates of hospitalization, interventions, and costs.     

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1^−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2^−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

Adjusting Some Properties of Poly(methacrylic acid) (Nano)Composite Hydrogels by Means of Silicon-Containing Inorganic Fillers

The present work aims to show how the main properties of poly(methacrylic acid) (PMAA) hydrogels can be engineered by means of several silicon-based fillers (Laponite XLS/XLG, montmorillonite (Mt), pyrogenic silica (PS)) employed at 10 wt% concentration based on MAA. Various techniques (FT-IR, XRD, TGA, SEM, TEM, DLS, rheological measurements, UV-VIS) were used to comparatively study the effect of these fillers, in correlation with their characteristics, upon the structure and swelling, viscoelastic, and water decontamination properties of (nano)composite hydrogels. The experiments demonstrated that the nanocomposite hydrogel morphology was dictated by the way the filler particles dispersed in water. The equilibrium swelling degree (SDe) depended on both the pH of the environment and the filler nature. At pH 1.2, a slight crosslinking effect of the fillers was evidenced, increasing in the order Mt < Laponite < PS. At pH > pKa_MAA (pH 5.4; 7.4; 9.5), the Laponite/Mt-containing hydrogels displayed a higher SDe as compared to the neat one, while at pH 7.4/9.5 the PS-filled hydrogels surprisingly displayed the highest SDe. Rheological measurements on as-prepared hydrogels showed that the filler addition improved the mechanical properties. After equilibrium swelling at pH 5.4, G’ and G” depended on the filler, the Laponite-reinforced hydrogels proving to be the strongest. The (nano)composite hydrogels synthesized displayed filler-dependent absorption properties of two cationic dyes used as model water pollutants, Laponite XLS-reinforced hydrogel demonstrating both the highest absorption rate and absorption capacity. Besides wastewater purification, the (nano)composite hydrogels described here may also find applications in the pharmaceutical field as devices for the controlled release of drugs.     

Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.     

Novel self-assembled mesalamine–sucralfate complexes: preparation,characterization, and formulation aspects

Two well-known active agents, mesalamine (MES) and sucralfate (SUC), were investigated for possible utilization as fixed-dose combination product. The anti-inflammatory action of MES in association with bioadhesiveness and mucosal healing properties of SUC were considered promising for the development of a new compound containing both molecules, aimed as an improved treatment of ulcerative colitis. The present study investigates the capacity of the two active agents to interact and generate a new and stable entity via self-assembling. Spray-drying was used to co-process the two active principles from an aqueous mixture where the ratio MES:SUC was in the range 25:75, 50:50, and 75:25. The structural data (X-Ray, FTIR, SEM, DSC, and ¹H NMR) have shown that MES and SUC are interacting leading to complexes with properties differing from those of each separate active agent and from their physical blends. ¹H NMR results indicated that complexation occurred when the aqueous suspensions of drugs were mixed, prior to spray-drying. Drug–drug self-assembling was the driving mechanism in the formation of the new entity. Based on the structural data, a hypothetical structure of the complex was proposed. Co-processing of MES and SUC represents a simple and useful procedure to prepare new self-assembled compounds by valorizing the ionic interactions between the two entities. Preliminary studies with oral solid dosage forms based on MES–SUC complexes tested in vitro have shown a controlled MES release, opening the perspective of a new colon-targeted delivery system and a novel class of compounds with therapeutic application in inflammatory bowel diseases.     

Low-voltage improved accuracy Gaussian function generator with fourth-order approximation

An original realization of a CMOS Gaussian function generator is presented. The proposed method is based on a new approximation function that is able to fourth-order match the Gaussian function. The current-mode operation of the circuit strongly reduces the technological-caused errors and the errors introduced by temperature variations, with the result of an important increasing of the accuracy for the squaring circuit that represents the functional core of the Gaussian generator (0.1%). Additionally, the bandwidth of the generator is increased as a result of its current-mode operation. Because of the utilization of the new fourth-order approximation function, the deviation from the ideal Gaussian function is smaller than 1 dB for an extended range of the input variable. The circuit is designed for implementing in 0.18 μm CMOS technology, its proposed architecture being compatible with a low-voltage operation (V_DD=1 V). The proposed Gaussian function generator based on the new approximation function allows to extend its capability of generating any continuous mathematical functions, this feature being obtained by changing the approximation function coefficients.