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As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g. , monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk–benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

The American Society for Transplantation and Cellular Therapy (ASTCT) published its first white paper on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) in 2015. It was identified at the time that periodic updates of indications would be required to stay abreast with state of the art and emerging indications and therapy. In recent years the field has not only seen an improvement in transplantation technology, thus widening the therapeutic scope of HCT, but additionally a whole new treatment strategy using modified immune effector cells, including chimeric antigen receptor T cells and engineered T-cell receptors, has emerged. The guidelines review committee of the ASTCT deemed it optimal to update the ASTCT recommendations for indications for HCT to include new data and to incorporate indications for immune effector cell therapy (IECT) where appropriate. The guidelines committee established a multiple stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on indications for HCT and IECT. This article presents the updated recommendations from the ASTCT on indications for HCT and IECT. Indications for HCT/IECT were categorized as (1) Standard of care, where indication is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but have been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where demonstrated effectiveness exists but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early-phase clinical studies show HCT/IECT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT/IECT. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available. [ABSTRACT FROM AUTHOR]

Failure analysis construction of car tyres is a highly demanding process requiring very specific methods of analysis. Industrial metrotomography is one of suitable analytical tool in this area. However, the method used for failure analysis construction of car tyres may have its limits. The paper provides a detailed research for the analysis of 5 typical types of damage occurring in car tyres, analysing the possibilities of such a technology as well as occurrence of undesirable phenomena. Results provided further on refer to occurrence of undesirable phenomenon such as various artifacts due to their construction, but also confirm suitability of application of the method for car tyres research of failure analysis. • The analysis of 5 typical types of damage occurring in car tyres. • Analysing the possibilities of a technology industrial metrotomography. • Investigation of processes of car tyres damaging. [ABSTRACT FROM AUTHOR]

Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD+ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD+ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38+ CD4+ T cells / CD38+ CD8+ T cells in cellular immunity and the effects of the CD38-NAD+ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells. [Display omitted] • As a NAD consuming enzyme, CD38 is closely related to the number and function of T cells. • The expression of CD38 in CD4+ T cells and CD8+ T cell affects the function of CD4+T cell. • The expression level of CD38 on T cell surface is associated with disease prediction and prognosis. [ABSTRACT FROM AUTHOR]

Topic Signficance & Study Purpose/Background/Rationale We initially conducted a quality review of patients treated with CAR-T therapies and noted inconsistencies in cytokine release syndrome (CRS) and neurotoxicity grading due to data located in various areas within our EMR and fragmented documentation between the EMR and paper record. Consistent documentation of CAR T-cell toxicity amongst providers is important for assesment and management of toxicities post-infusion in cellular therapy programs. EMR flowsheets facilitate tracking and communication within the healthcare team and ensuring proper clinical documentation. Method, Interventions, & Analysis Key members from the Informatics and Adult Stem Cell Transplant Program collaborated to develop a flowsheet to capture all elements to grade, identify symptoms and toxicities. To enhace clinical documentation, we created a tool that brings in several flowsheet enteries to the notes and to guide providers for accruate grading of CRS and neurotoxicity related to CAR T-cell infusions for the Epic® EMR. Findings & Interpretation These electronic tools were developed during the planning phase of the CAR T-cell program. Two flowsheets were used by nurses to document CRS (Figure 1) and neurotoxicity (Figure 2) based on practice guidelines established by program leaders. The flowsheet enteries were added to provider's daily documentation through "smart phrases" (Figure 3) that captured grading of toxicities and guided clinical decision making. Discussion and Implications Development of tools to standardize symptomology reporting and effectively capture data is imperative for CAR T-cell therapy programs. EMR tools can facilitate management and streamline data collection for reporting of toxicities. As more patients receive this novel immunotherapy, it will be important to have tools in place to assist with tracking patient outcomes. The future goal is to have grading auto-generated to enhance real time care delivery with alert based warnings for worsening CRS or neurotoxicity, and for these tools to reflect current standards of care, including revised consensus criteria for grading and reporting of CAR-T toxicities currently being developed by the ASBMT. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a decentralized car parking approach for vast car park areas based on cooperation among vehicles through vehicle-to-vehicle communication, called Cooperative Car Parking (CoPark). In CoPark, the task of finding car parking spaces inside a large car parking area is done via smart agents in vehicles opportunistically cooperating with each other to locate parking spaces as near as possible to the final destination with reduced searching time. We comprehensively investigate a range of car parking circumstances and situations in our simulations to evaluate the proposed CoPark approach. We show that by strategic cooperation between agents in the CoPark approach, greater satisfaction can be achieved in terms of individual and social benefits, in the form of reduced search times for car park spaces and reduced walking distances from where cars are parked to a destination building. • A new cooperative car parking approach, CoPark-WS, for cars to find parking spaces and to resolve contention for spaces. • The searching time and walking distance are considered in vehicle decisions in CoPark-WS. • The performance of CoPark-WS is evaluated via extensive simulations. • Results show promise for cooperative parking without centralized coordination. [ABSTRACT FROM AUTHOR]

The current and the new generation of Internet of Things (IoT) devices present several challenges, among them the software update of legacy and new devices using wireless connections. In this paper, we study a problem of scheduling massive Firmware-Over-The-Air updates for millions of connected cars. We model this problem as a new generic problem called Time- and Machine-Dependent Scheduling Problem (TMDSP) that resembles project scheduling problems with variable-intensity activities. In the TMDSP, jobs, machine utilization, and production rates vary over time. In each period, a given job can be executed by a subset of machines with different capacities and production rates. The objective is to deploy a feasible schedule with minimum total completion time. We explore solving the problem using several approaches among than Biased Random-Key Genetic Algorithm (BRKGA), Iterated Local Search (ILS), Simulating Annealing (SA), two variations of Tabu Search (TB), and traditional genetic algorithms (TGA), in addition to a Mixed Integer Programming (MIP) model. We test the proposed approaches on a synthetic benchmark and very large real instances in IoT space. While using a commercial solver and the MIP model, we are able to solve only a few real instances (with, at most, 1,976 cars and 9,116 sectors); on the other hand, BRKGA presents significantly better results when compared to ILS, MIP solver and a simple multi-start heuristic. • We study a problem of scheduling Firmware-Over-The-Air updates for connected cars. • We present a new problem called Time- and Machine-Dependent Scheduling Problem. • We propose several metaheuristics and an integer programming model. • Tests were performed on synthetic and real scenarios with massive number of cars. • Tests suggest that the biased random-key genetic algorithm has better performance. [ABSTRACT FROM AUTHOR]