Feasibility of simultaneous PET/MR imaging in the head and upper neck area

Objective: The aim of this pilot study was to test and demonstrate the feasibility of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) of the head and upper neck area using a new hybrid PET/MRI system. Methods: Eight patients with malignant head and neck tumours were included in the pilot study. Directly after routine PET/CT imaging with a whole-body system using the glucose derivative 2-[18F]fluoro-2deoxy-D-glucose (FDG) as a radiotracer additional measurements were performed with a prototype PET/MRI system for simultaneous PET and MR imaging. Physiological radiotracer uptake within regular anatomical structures as well as tumour uptake were evaluated visually and semiquantitatively (metabolic ratios) in relation to cerebellar uptake on the PET/MRI and PET/CT systems. Results: The MR datasets showed excellent image quality without any recognisable artefacts caused by the inserted PET system. PET images obtained with the PET/MRI system exhibited better detailed resolution and greater image contrast in comparison to those from the PET/CT system. An excellent agreement between metabolic ratios obtained with both PET systems was found: R = 0.99 for structures with physiological tracer uptake, R = 0.96 for tumours. Conclusion: Simultaneous PET/MRI of the head and upper neck area is feasible with the new hybrid PET/MRI prototyp

Influence of polymorphism within the heme oxygenase-I promoter on overall survival and transplantation-related mortality after allogeneic stem cell transplantation

AbstractAside from major and minor histocompatibility antigens, genetic polymorphisms of various donor and host genes have been found to be risk factors for graft-versus-host disease and transplantation-related mortality (TRM). The heme oxygenase I (HO-I) protein has been implicated in regulating inflammatory response and has been described as a “protective gene” in solid organ transplantation. In humans, the promoter region displays length polymorphism due to a variable number of GT repeats. Individuals exhibiting 29 or fewer GT repeats express higher levels of HO-I on cellular stress compared with individuals with 30 or more GT repeats. We retrospectively analyzed length polymorphisms of 92 donor–host pairs undergoing allogeneic stem cell transplantation. Our findings demonstrate that mainly donor polymorphism leading to high expression of HO-1 (<30 GT repeats) on stress signals is associated with reduced overall survival, and that TRM is significantly increased in this group. This reduction in survival was most prominent when unrelated donors were used. Polymorphisms of the recipient HO-1 genes did not influence posttransplantation outcomes. We conclude that HO-1 polymorphism represents a new genetic risk factor for TRM and overall survival

Modular Mechatronics Infrastructure for Robotic Planetary Exploration Assets in a Field Operation Scenario

In 2021 the Modular Mechatronics Infrastructure (MMI) was introduced as a solution to reduce weight, costs, and development time in robotic lanetary missions. With standardized interfaces and multi-functional elements, this modular approach is planned to be used more often in sustainable exploration activities on the Moon and Mars. The German multi-robot research project “Autonomous Robotic Networks to Help Modern Societies (ARCHES)” has explored this concept with the use of various collaborative robotic assets which have their capabilities extended by the MMI. Different scientific payloads, engineering infrastructure modules, and specific purpose tools can be integrated to and manipulated by a robotic arm and a standardized electromechanical docking-interface. Throughout the MMI’s design and implementation phase the performed preliminary tests confirmed that the different systems of the robotic cooperative team such as the Docking Interface System (DIS), the Power Management System (PMS), and the Data Communication System (DCS) functioned successfully. During the summer of 2022 a Demonstration Mission on Mount Etna (Sicily, Italy) was carried out as part of the ARCHES Project. This field scenario allowed the validation of the robotics systems in an analogue harsh environment and the confirmation of enhanced operations with the application of this modular method. Among the numerous activities performed in this volcanic terrain there are the efficient assembling of the Low Frequency Array (LOFAR) network, the energy-saving and reduced complexity of a detached Laser Induced Breakdown Spectroscopy (LIBS) module, and the uninterrupted powered operation between modules when switching between different power sources. The field data collected during this analogue campaign provided important outcomes for the modular robotics application. Modular and autonomous robots certainly benefit from their versatility, reusability, less complex systems, reduced requirements for space qualification, and lower risks for the mission. These characteristics will ensure that long duration and complex robotic planetary endeavours are not as challenging as they used to be in the past

Design and Implementation of a Modular Mechatronics Infrastructure for Robotic Planetary Exploration Assets

Traditionally, the robotic systems which aim to explore other celestial bodies include all instruments and tools necessary for the mission. This makes them unique developments. Usually, they are heavy, complex, costly and do not provide any interchangeable parts that could be replaced in the event of permanent failure. However, for future missions, agencies, institutes and commercial companies are developing robotics systems based on the concept of modular robotics. This new strategy becomes critical for planetary exploration because it is able to reduce load, costs and development time. In the German multi robot research project, ‘’Autonomous Robotic Networks to Help Modern Societies (ARCHES)”, led by the German Aerospace Center (DLR), this modern design methodology is followed. Cooperation among robots and modularity are the core of its structure. These characteristics are present in the collaboration between the rovers and the uncrewed aerial vehicle (UAV) during navigation tasks, or when the Lightweight Rover Unit (LRU) interacts with changeable manipulator tools and payload boxes through its robotic arm and its standardized electromechanical interface. Examples of these modules include scientific packages, power supply systems, communication and data acquisition architectures, soil sample storage units, and specific purpose end-effectors. The focus of this work is in the design and implementation of a mechatronics infrastructure (MI) which encompasses the docking interface, the payload modules, and the power and data management electronics board inside each box. These three elements are essential for the extension of the capabilities of the rover and the enhancement of the robotics systems according to the tasks to be performed. This will ensure that robots can cooperate with each other either in scientific missions or in the construction and maintenance of large structures. The MI’s hardware and software developed in this project will be tested and validated in the ARCHES demonstration mission on Mount Etna, Sicily, in Italy between 13th June and 9th July 2022. Finally, it is important to highlight that modularity and standardization were considered at all levels of the infrastructure. From the robotics systems to the internal architecture of each payload module, these concepts can provide versatility and reliability to the cooperative robotic network. This will improve the problem-solving capabilities of robots performing complex tasks in future planetary exploration missions

Modular Mechatronics Infrastructure for Robotic Planetary Exploration Assets in a Field Operation Scenario

In 2021 the Modular Mechatronics Infrastructure (MMI) was introduced as a solution to reduce weight, costs, and development time in robotic planetary missions. With standardized interfaces and multi-functional elements, this modular approach is planned to be used more often in sustainable exploration activities on the Moon and Mars. The German multi-robot research project “Autonomous Robotic Networks to Help Modern Societies (ARCHES)” has explored this concept with the use of various collaborative robotic assets which have their capabilities extended by the MMI. Different scientific payloads, engineering infrastructure modules, and specific purpose tools can be integrated to and manipulated by a robotic arm and a standardized electromechanical docking-interface. Throughout the MMI’s design and implementation phase the performed preliminary tests confirmed that the different systems of the robotic cooperative team such as the Docking Interface System (DIS), the Power Management System (PMS), and the Data Communication System (DCS) functioned successfully. During the summer of 2022 a Demonstration Mission on Mount Etna (Sicily, Italy) was carried out as part of the ARCHES Project. This field scenario allowed the validation of the robotics systems in an analogue harsh environment and the confirmation of enhanced operations with the application of this modular method. Among the numerous activities performed in this volcanic terrain there are the efficient assembling of the Low Frequency Array (LOFAR) network, the energy-saving and reduced complexity of a detached Laser Induced Breakdown Spectroscopy (LIBS) module, and the uninterrupted powered operation between modules when switching between different power sources. The field data collected during this analogue campaign provided important outcomes for the modular robotics application. Modular and autonomous robots certainly benefit from their versatility, reusability, less complex systems, reduced requirements for space qualification, and lower risks for the mission. These characteristics will ensure that long duration and complex robotic planetary endeavours are not as challenging as they used to be in the past

Stromal Interferon-γ Signaling and Cross-Presentation Are Required to Eliminate Antigen-Loss Variants of B Cell Lymphomas in Mice

To study mechanisms of T cell-mediated rejection of B cell lymphomas, we developed a murine lymphoma model wherein three potential rejection antigens, human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into wild-type mice 60–70% of systemically growing lymphomas expressing all three antigens were rejected; lymphomas expressing only human c-MYC protein were not rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class I and II upregulation, and lost antigen expression, indicating immune escape. In contrast to wild-type recipients, 80–100% of STAT1-, IFN-γ-, or IFN-γ receptor-deficient recipients died of lymphoma, indicating that host IFN-γ signaling is critical for rejection. Lymphomas arising in IFN-γ- and IFN-γ-receptor-deficient mice had invariably lost antigen expression, suggesting that poor overall survival of these recipients was due to inefficient elimination of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma cells in wild-type animals was dependent on cross-presentation of antigen by cells of the tumor stroma. These findings provide first evidence for an important role of the tumor stroma in T cell-mediated control of hematologic neoplasias and highlight the importance of incorporating stroma-targeting strategies into future immunotherapeutic approaches

Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

BACKGROUND: Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. METHODS: A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. RESULTS: In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. CONCLUSION: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients