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.     

A double flow cytometric tag allows tracking of the dynamics of cell cycle progression of newborn Saccharomyces cerevisiae cells during balanced exponential growth

Studies on the dynamics of growth of single eukaryotic cells and their relationships with cell cycle regulations are generally carried out following cell synchronization procedures or, on a relatively low number of cells, by time-lapse studies. Establishment of both time-lapse studies and synchronous cell populations usually requires elaborate experimental efforts and is prone to perturb the physiological state of the cell. In this paper we use a new flow cytometric approach which allows, in asynchronous growing Saccharomyces cerevisiae populations, tagging of both the cell age and the cell protein content of a cohort of daughter cells at the different cell cycle set points. Since the cell protein content is a good estimation of the cell size, it is possible to follow the kinetics of the cell size increase during cell cycle progression. The experimental findings obtained indicate an exponential increase of the cell size during growth, that the daughter and the parent subpopulations grow with the same specific growth rate, that the average cell size increase rate of each individual cell is almost identical to the specific growth rate of the overall population and provide the opportunity to estimate the cell cycle length for the daughter cell population as well as the identification of the complex structure of asynchronously growing yeast populations.     

Licensure in psychology: Alternative directions.

The licensing of psychologists has become an area of intense professional interest. Attempts to provide historical overviews and current data on the status of licensing regulations have become common. This article critiques existing regulations by examining assumptions implicit in the development of licensing procedures. The implications of such assumptions for professional psychology are discussed, and guidelines for alternative licensure developments are presented. The importance of developing valid measures of entry-level and continued professional competence is emphasized. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prospection of the use of encapsulation in food packaging

Food safety and extended shelf life linked to convenience were the major reasons for the development of the packaging field. However, advances in material science and the widespread encapsulation technologies are allowing the establishment of new concepts for packages, such as intelligent and active packages. Particulate systems have been developed in recent years for the most diverse area with several purposes that can be employed to improve packaging performance mainly focusing on the modification of barrier properties. This review analyzes the recent developments using encapsulation in food packaging and the main concepts about mass transfer evolved in the functionality of these packages, as well as discusses the research challenges faced by the food packaging sector.     

A hierarchical structure for surface approximation

Hierarchical triangulation is a method for point selection and surface representation where the surface is approximated at successively finer levels of detail by triangular patches whose projections in the horizontal plane are nested. A tree data structure for this representation can be constructed in O(n²) worst case and O(n log n) average case time, where n is the number of data points considered. Efficient algorithms for approximation of the elevation of an arbitrary point, contour extraction, and conversion of the hierarchical structure into an ordinary triangulated irregular network, are demonstrated. The convergence and the optimality of the approximation and the relationship of the hierarchical triangulation to a structured graph representation are examined.     

Hybrid integral transforms analysis of the bioheat equation with variable properties

Pennes’ equation is the most frequently employed model to describe heat transfer processes within living tissues, with numerous applications in clinical diagnostics and thermal treatments. A number of analytical solutions were provided in the literature that represent the temperature distribution across tissue structures, but considering simplifying assumptions such as uniform and linear thermophysical properties and blood perfusion rates. The present work thus advances such analysis path by considering a heterogeneous medium formulation that allows for spatially variable parameters across the tissue thickness. Besides, the eventual variation of blood perfusion rates with temperature is also accounted for in the proposed model. The Generalized Integral Transform Technique (GITT) is employed to yield a hybrid numerical–analytical solution of the bioheat model in heterogeneous media, which reduces to the exact solution obtained via the Classical Integral Transform Method for a linear formulation with uniform coefficients. The open source UNIT code (“UNified Integral Transforms”) is utilized to obtain numerical results for a set of typical values of the governing parameters, in order to illustrate the convergence behavior of the proposed eigenfunction expansions and inspect the importance of accounting for spatially variable properties in predicting the thermal response of living tissues to external stimulus.     

Effect of the fuel injection strategy on the combustion process in a PFI boosted spark-ignition engine

In this paper, the effect of different fuel injection strategies on the combustion process was investigated in a boosted port fuel injection spark-ignition engine. The experiments were performed on a partially transparent single-cylinder engine, equipped with a four-valve head and boost device. Single and double fuel injection strategies were tested in the open-valve condition. Moreover, two fuel injection pressures were considered. Optical techniques based on 2D-digital imaging were used to follow the flame propagation in the combustion chamber. In particular, the diffusion-controlled flames near valves and on cylinder walls due to the fuel film burning were studied. Two-colour pyrometry was employed to measure soot concentration. In-cylinder optical investigations were correlated to the engine parameters and to the exhaust emissions.     

Degradable Bottlebrush Polypeptides and the Impact of their Architecture on Cell Uptake,Pharmacokinetics, and Biodistribution In Vivo

Bottlebrush polymers are highly promising as unimolecular nanomedicines due to their unique control over the critical parameters of size, shape and chemical function. However, since they are prepared from biopersistent carbon backbones, most known bottlebrush polymers are non-degradable and thus unsuitable for systemic therapeutic administration. Herein, we report the design and synthesis of novel poly(organo)phosphazene-g-poly(α-glutamate) (PPz-g-PGA) bottlebrush polymers with exceptional control over their structure and molecular dimensions (Dh ≈ 15–50 nm). These single macromolecules show outstanding aqueous solubility, ultra-high multivalency and biodegradability, making them ideal as nanomedicines. While well-established in polymer therapeutics, it has hitherto not been possible to prepare defined single macromolecules of PGA in these nanosized dimensions. A direct correlation was observed between the macromolecular dimensions of the bottlebrush polymers and their intracellular uptake in CT26 colon cancer cells. Furthermore, the bottlebrush macromolecular structure visibly enhanced the pharmacokinetics by reducing renal clearance and extending plasma half-lives. Real-time analysis of the biodistribution dynamics showed architecture-driven organ distribution and enhanced tumor accumulation. This work, therefore, introduces a robust, controlled synthesis route to bottlebrush polypeptides, overcoming limitations of current polymer-based nanomedicines and, in doing so, offers valuable insights into the influence of architecture on the in vivo performance of nanomedicines.     

A Genus-Wide Bioactivity Analysis of Daboia (Viperinae: Viperidae) Viper Venoms Reveals Widespread Variation in Haemotoxic Properties

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell’s vipers D. russelii and D. siamensis, found in Asia. Russell’s vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell’s vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell’s vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.