EJNMMI Radiopharm Chem
November 2024
Background: Pretargeted radioimmunotherapy of cancer has the potential to increase tumor specific uptake of activity when compared with conventional radioimmunotherapy. This is especially true in radioimmunotherapy with nuclides that exhibit a relatively short half-life. When administering antibody-based pretargeting molecules systemically, the antibodies often show a relatively slow clearance from the blood.
View Article and Find Full Text PDFThe design of the microelectromechanical system (MEMS) disc resonator gyroscope (DRG) structural topology is crucial for its physical properties and performance. However, creating novel high-performance MEMS DRGs has long been viewed as a formidable challenge owing to their enormous design space, the complexity of microscale physical effects, and time-consuming finite element analysis (FEA). Here, we introduce a new machine learning-driven approach to discover high-performance DRG topologies.
View Article and Find Full Text PDFSelenoxide elimination is a widely used method for the synthesis of alkenes because it proceeds under exceptionally mild conditions, typically with excellent regio- and stereoselectivity. Surprisingly, hetero-selenoxide eliminations, where one or both olefinic carbon atoms are replaced with heteroatoms, have been little investigated, and their selenonyl counterparts even less so. A variety of such reactions, where the heteroatoms included combinations of O, N and S, as well as C, were investigated computationally.
View Article and Find Full Text PDFEbselen is a drug in clinical trials for several diseases and degenerative conditions where oxidative stress is implicated. A series of novel ebselen analogues was synthesized, including hydroxy-, alkoxy- and aminomethylene derivatives, as well as hybrid species where the ebselen selenium atom is shared with other potent antioxidant structures, such as cyclic selenenyl sulfide, cyclic seleninate ester and spirodioxyselenurane moieties. Conjugates of ebselen with cholesterol, prednisolone and the radical inhibitor BHT were also prepared.
View Article and Find Full Text PDFBackground: Neuroborreliosis is a tick-borne condition that affects the central and/or peripheral nervous system. Cerebral infarction associated with neuroborreliosis-related vasculitis has been reported in only a handful of cases. Therefore, specific patterns of vascular pathology and prognostic outcome factors are still incompletely understood.
View Article and Find Full Text PDFThe α-emitter At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the At-labeled anti-CD45 monoclonal antibody (mAb) At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Seventeen healthy dogs were injected with either a 0.
View Article and Find Full Text PDFGastrointestinal (GI) cancers are highly heterogeneous at multiple levels. Tumor heterogeneity can be captured by molecular profiling, such as genetic, epigenetic, proteomic, and transcriptomic classification. Transcriptomic subtyping has the advantage of combining genetic and epigenetic information, cancer cell-intrinsic properties, and the tumor microenvironment (TME).
View Article and Find Full Text PDFBackground: Among the anthropometric measurements, calf circumference has been widely used as a simple and practical method to diagnose low muscle mass and sarcopenia. However, the association between this measurement and clinical outcomes in people receiving home enteral nutrition is still unknown. Therefore, this study aimed to investigate the association of calf circumference with mortality, discharge from home enteral nutrition, continuity in home enteral nutrition, and new hospitalizations in adult and older adult people.
View Article and Find Full Text PDFThis work presents a novel consensus molecular subtype (CMS) classifier for colorectal cancer (CRC), optimized for RNA-sequencing data stemming from degraded RNA of clinical formalin-fixed paraffin-embedded (FFPE) tissue samples (the CMSFFPE classifier).
View Article and Find Full Text PDFConsensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA.
View Article and Find Full Text PDFBackground: A significant challenge in cancer therapy lies in eradicating hidden disseminated tumor cells. Within Nuclear Medicine, Targeted Alpha Therapy is a promising approach for cancer treatment tackling disseminated cancer. As tumor size decreases, alpha-particles gain prominence due to their high Linear Energy Transfer (LET) and short path length.
View Article and Find Full Text PDFSimulation models are used to design extruders in the polymer processing industry. This eliminates the need for prototypes and reduces development time for extruders and, in particular, extrusion screws. These programs simulate, among other process parameters, the temperature and pressure curves in the extruder.
View Article and Find Full Text PDFThis study introduces and evaluates the PHAST+ model, part of a computational framework designed to simulate the behavior of auditory nerve fibers in response to the electrical stimulation from a cochlear implant. PHAST+ incorporates a highly efficient method for calculating accommodation and adaptation, making it particularly suited for simulations over extended stimulus durations. The proposed method uses a leaky integrator inspired by classic biophysical nerve models.
View Article and Find Full Text PDFCancer Biother Radiopharm
February 2024
Real-time quantification of radioligand binding to cells under -like conditions improves evaluation of clinical potential. SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis.
View Article and Find Full Text PDFIn recent years, variational quantum algorithms such as the Quantum Approximation Optimization Algorithm (QAOA) have gained popularity as they provide the hope of using NISQ devices to tackle hard combinatorial optimization problems. It is, however, known that at low depth, certain locality constraints of QAOA limit its performance. To go beyond these limitations, a non-local variant of QAOA, namely recursive QAOA (RQAOA), was proposed to improve the quality of approximate solutions.
View Article and Find Full Text PDFBackground: Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome.
View Article and Find Full Text PDFThe discovery and synthetic applications of novel organoselenium compounds and their reactions proceeded rapidly during the past fifty years and such processes are now carried out routinely in many laboratories. At the same time, the growing demand for new enantioselective processes provided new challenges. The convergence of selenium chemistry and asymmetric synthesis led to key developments in the 1970s, although the majority of early work was based on stoichiometric processes.
View Article and Find Full Text PDFThe present work is on a comprehensive surface atomic structure investigation of β-GaO (100). The β-GaO single crystal was studied by a structural model system in the simulations and characterization X-ray photoelectron spectroscopy (XPS), low-energy electron diffraction (LEED) and X-ray photoelectron diffraction (XPD) allowed for probing the outermost layers' properties. XPD characterization allows for the collection of valuable element-specific short-range information from the β-GaO surface, and the results were compared to a systematic and precise multiple scattering simulation approach.
View Article and Find Full Text PDFA new approach to the marine alkaloid cylindricine C afforded its previously unreported (±)-2,13-di- stereoisomer as the major product along with a minor amount of the racemic parent alkaloid. Key steps included a stereoselective dianion alkylation of a monoester of 1,2-cyclohexanedicarboxylic acid and an annulation based on the tandem conjugate addition of a primary amine to an acetylenic sulfone, followed by intramolecular acylation of the resulting sulfone-stabilized carbanion. The -azadecalin moiety thus formed, comprising the cyclohexane A-ring and enaminone B-ring of the products, was further elaborated by the selenenyl chloride-induced cyclofunctionalization of a pendant butenyl substituent with the enaminone moiety, followed by a seleno-Pummerer reaction.
View Article and Find Full Text PDFWe present IOHexperimenter, the experimentation module of the IOHprofiler project. IOHexperimenter aims at providing an easy-to-use and customizable toolbox for benchmarking iterative optimization heuristics such as local search, evolutionary and genetic algorithms, and Bayesian optimization techniques. IOHexperimenter can be used as a stand-alone tool or as part of a benchmarking pipeline that uses other modules of the IOHprofiler environment.
View Article and Find Full Text PDFThirty years, 1993-2023, is a huge time frame in science. We address some major developments in the field of evolutionary algorithms, with applications in parameter optimization, over these 30 years. These include the covariance matrix adaptation evolution strategy and some fast-growing fields such as multimodal optimization, surrogate-assisted optimization, multiobjective optimization, and automated algorithm design.
View Article and Find Full Text PDFThe antioxidant drug ebselen has been widely studied in both laboratories and in clinical trials. The catalytic mechanism by which it destroys hydrogen peroxide via reduction with glutathione or other thiols is complex and has been the subject of considerable debate. During reinvestigations of several key steps, we found that the seleninamide that comprises the first oxidation product of ebselen underwent facile reversible methanolysis to an unstable seleninate ester and two dimeric products.
View Article and Find Full Text PDFInositol 1,4,5-trisphosphate receptor type 1 (ITPR1) is an intracellular Ca release channel important for a number of fundamental cellular functions. Consistent with its critical physiological significance, mutations in ITPR1 are associated with disease. Surprisingly, nearly all the disease-associated ITPR1 mutations characterized to date are loss of function.
View Article and Find Full Text PDFTo enhance targeting efficacy in the radioimmunotherapy of disseminated cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with a modified monoclonal antibody that has an affinity for both tumor antigens and radiolabeled carriers. In this work, we aimed to synthesize and evaluate poly-L-lysine-based effector molecules for pretargeting applications based on the tetrazine and trans-cyclooctene reaction using At for targeted alpha therapy and I as a surrogate for the imaging radionuclides I.
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