Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration

PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.     

Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists

Myelodysplastic syndromes (MDS) arising in the context of inherited bone marrow failure syndromes (IBMFS) differ in terms of prognosis and treatment strategy compared to MDS occurring in the adult population without an inherited genetic predisposition. The main molecular pathways affected in IBMFS involve telomere maintenance, DNA repair, biogenesis of ribosomes, control of proliferation and others. The increased knowledge on the genes involved in MDS pathogenesis and the wider availability of molecular diagnostic assessment have led to an improvement in the detection of IBMFS genetic predisposition in MDS patients. A punctual recognition of these disorders implies a strict surveillance of the patient in order to detect early signs of progression and promptly offer allogeneic hematopoietic stem cell transplantation, which is the only curative treatment. Moreover, identifying an inherited mutation allows the screening and counseling of family members and directs the choice of donors in case of need for transplantation. Here we provide an overview of the most recent data on MDS with genetic predisposition highlighting the main steps of the diagnostic and therapeutic management. In order to highlight the pitfalls of detecting IBMFS in adults, we report the case of a 27-year-old man affected by MDS with an underlying telomeropathy.     

Scouting around 1,2,3,4-Tetrahydrochromeno[3,2-c]pyridin-10-ones for Single- and Multitarget Ligands Directed towards Relevant Alzheimer's Targets

A number of 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-one derivatives have been synthesized and screened against different targets involved in the onset and progression of Alzheimer's disease (AD), such as acetyl- and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of β-amyloid (Aβ) and reactive oxygen species (ROS) production. Derivatives 1 c , 3 b , 4 and 5 a showed multifaceted profiles of promising anti-AD features and returned well-balanced multitargeting inhibitory activities. Moreover, compound 1 f , a potent and selective human MAO B inhibitor (IC₅₀=0.89 μM), proved to be a safe neuroprotectant in a human neuroblastoma cell line (SH-SY5Y) by improving viability impaired by Aβ_1–42 and pro-oxidant insult. Furthermore, structure–activity relationships (SARs) and docking models were derived in order to assist further hit-to-lead optimization stage.     

Human Primary Dermal Fibroblasts Interacting with 3-Dimensional Matrices for Surgical Application Show Specific Growth and Gene Expression Programs

Several types of 3-dimensional (3D) biological matrices are employed for clinical and surgical applications, but few indications are available to guide surgeons in the choice among these materials. Here we compare the in vitro growth of human primary fibroblasts on different biological matrices commonly used for clinical and surgical applications and the activation of specific molecular pathways over 30 days of growth. Morphological analyses by Scanning Electron Microscopy and proliferation curves showed that fibroblasts have different ability to attach and proliferate on the different biological matrices. They activated similar gene expression programs, reducing the expression of collagen genes and myofibroblast differentiation markers compared to fibroblasts grown in 2D. However, differences among 3D matrices were observed in the expression of specific metalloproteinases and interleukin-6. Indeed, cell proliferation and expression of matrix degrading enzymes occur in the initial steps of interaction between fibroblast and the investigated meshes, whereas collagen and interleukin-6 expression appear to start later. The data reported here highlight features of fibroblasts grown on different 3D biological matrices and warrant further studies to understand how these findings may be used to help the clinicians choose the correct material for specific applications.     

3D Printing/Interfacial Polymerization Coupling for the Fabrication of Conductive Hydrogel

In this study, 3D printing is coupled with interfacial polymerization to obtain electroactive hydrogels with complex and defined geometry. Conductive hydrogels are created through a two‐step procedure: first a digital light processing 3D printing system is used to fabricate poly(ethylene glycol)diacrylate 3D structure and then pyrrole is oxidized to polypyrrole (PPY), exploiting an interfacial polymerization mechanism through which PPY can be formed in the poly(ethylene glycol) matrix, thus creating a conductive phase.     

Effect of a New High-Pressure Heat Treatment on Additively Manufactured AlSi10Mg Alloy

Metallurgical and Materials Transactions A - The application of an innovative high-pressure T6 treatment (HPT6) to additively manufactured AlSi10Mg alloy is reported in this paper. The aim of this...     

Towards mining the organizational structure of a dynamic event scenario

The increasing volume and value of data is an important enabler for data science. In this study, we consider the event data, i.e. information on things that happen in organizations, machines, systems and people’s lives. Each event refers to a well-defined activity in a certain business process execution, the resource (i.e. person or device) executing or initiating the activity, the timestamp of the event, as well as to various data elements recorded with the event (e.g. the geo-location of an activity). Process mining aims to analyze event data, in order to mine knowledge that can contribute to improving a business process behavior. In particular, the focus of this study is on organizational mining, that is a sub-field of process mining that aims at understanding the life cycle of a dynamic organizational structure (i.e. a configuration of organization units) and the interactions among co-workers (resources) arising from the analysis of real-world event logs. The innovative contribution of this study is that the organizational mining goal is here achieved by combining concepts from process mining, stream mining and social network analysis. This combination is an original contribution of this study, not still explored in organizational mining field. In an assessment, benchmark event data are explored, in order to understand how the presented solution allows us to identify the life cycle a dynamic organizational structure.     

A Monolithic Approach to Fluid–Composite Structure Interaction

We study a nonlinear fluid–structure interaction (FSI) problem between an incompressible, viscous fluid and a composite elastic structure consisting of two layers: a thin layer (membrane) in direct contact with the fluid, and a thick layer (3D linearly elastic structure) sitting on top of the thin layer. The coupling between the fluid and structure, and the coupling between the two structures is achieved via the kinematic and dynamic coupling conditions modeling no-slip and balance of forces, respectively. The coupling is evaluated at the moving fluid–structure interface with mass, i.e., the thin structure. To solve this nonlinear moving-boundary problem in 3D, a monolithic, fully implicit method was developed, and combined with an arbitrary Lagrangian–Eulerian approach to deal with the motion of the fluid domain. This class of problems and its generalizations are important in e.g., modeling FSI between blood flow and arterial walls, which are known to be composed of several different layers, each with different mechanical characteristics and thickness. By using this model we show how multi-layered structure of arterial walls influences the pressure wave propagation in arterial walls, and how the presence of atheroma and the presence of a vascular device called stent, influence intramural strain distribution throughout different layers of the arterial wall. The detailed intramural strain distribution provided by this model can be used in conjunction with ultrasound B-mode scans as a predictive tool for an early detection of atherosclerosis (Zahnd et al. in IEEE international on ultrasonics symposium (IUS), pp 1770–1773, 2011).