Recent scientific data recognize the B7-H3 checkpoint molecule as a potential target for immunotherapy of pediatric solid tumors (PSTs). B7-H3 is highly expressed in extracranial PSTs such as neuroblastoma, rhabdomyosarcoma, nephroblastoma, osteosarcoma, and Ewing sarcoma, whereas its expression is absent or very low in normal tissues and organs. The influence of B7-H3 on the biological behavior of malignant solid neoplasms of childhood is expressed through different molecular mechanisms, including stimulation of immune evasion and tumor invasion, and cell-cycle disruption. It has been shown that B7-H3 knockdown decreased tumor cell proliferation and migration, suppressed tumor growth, and enhanced anti-tumor immune response in some pediatric solid cancers. Antibody-drug conjugates targeting B7-H3 exhibited profound anti-tumor effects against preclinical models of pediatric solid malignancies. Moreover, B7-H3-targeting chimeric antigen receptor (CAR)-T cells demonstrated significant in vivo activity against different xenograft models of neuroblastoma, Ewing sarcoma, and osteosarcoma. Finally, clinical studies demonstrated the potent anti-tumor activity of B7-H3-targeting antibody-radioimmunoconjugates in metastatic neuroblastoma. This review summarizes the established data from various PST-related studies, including in vitro, in vivo, and clinical research, and explains all the benefits and potential obstacles of targeting B7-H3 by novel immunotherapeutic agents designed to treat malignant extracranial solid tumors of childhood.

The protein kinase known as the mammalian/mechanistic target of rapamycin (mTOR) is present in numerous cells and plays a vital role in regulating cellular growth, metabolism, and survival through two complexes, mTORC1 and mTORC2. Even though the role of mTORC1 in development and metabolism has been extensively studied, the regulatory signals of mTORC2 and diversity of its function in the cell still need to be fully understood. The body of research shows that mTORC2 plays an important role in regulating cellular metabolism, and its dysregulation is associated to many diseases such as cancer, diabetes, and neurodegenerative disorders. Studies have reported altered mTORC2 signaling in several neurodegenerative and neurodevelopmental disorders. Furthermore, genetic studies have revealed the crucial role of mTORC2 in maintaining physiological structure and function in neurons, as well as oligodendrocytes myelination. This protein complex is responsible for various processes related to the structural organization and movement of neurons, interneuronal communication, and their adaptive ability. These processes include organizing the actin cytoskeleton, control of ion channels' function and neurotransmitter receptors, and regulating signal transduction. This review aims to provide an overview of the current understanding of mTORC2, including its components and known functions, in regulating various cellular processes, with special accent on its role in the nervous system.

Background: Doctoral programmes are an important pillar of medical education, and although many universities award the best theses, the criteria for selection of awardees and the topics of their doctoral theses are seldom analysed. Objectives: To analyse the landscape of doctoral research through assessing the temporal trends in the criteria related to recognising the best theses. Methods: A total of 55 award-winning doctoral theses, from those submitted to the Faculty of Medicine, University of Belgrade, over 7 years (2016–2022), were examined, focusing on the number of awardees, publications based on the theses, research subfields, and keywords. Results: The awardees comprised 36 women (65%) and 19 men (35%). The number of award-winning theses per year in clinical medicine and public health increased over the years (P < .05 for both the fields). The awardees had published a total of 134 articles based on their theses before the thesis defence, and half of these were published in open-access journals. The journals that each published at least 4 of these articles were PLOS One, Experimental and Molecular Pathology, and Oxidative Medicine and Cellular Longevity. The cumulative impact factor of these publications showed no significant increase (P > .05). The subfields that accounted for at least 5 of the publi-cations were molecular medicine (13 publications) among the basic or translational fields, cardiology (5) among clinical medicine, and epidemiology (7) among public health. Mapping the co-occurrence of keywords from all the dissertations identified some research hotspots, which included cancer, oxidative stress, Parkinsonism, risk factors, genetic polymorphisms, and biomarkers. Conclusion: The increasing number of award-winning theses reflects the rising quality of doctoral research and the growing motivation of candidates to choose indexed journals as outlets for papers based on the theses. This approach can serve as a basis for strategic evaluation of the practices for evaluating PhD theses and for identifying strong and weak spots in the research landscape of medical schools to guide future doctoral research and the competitiveness of doctoral programmes.

With the increase in life expectancy, the prevalence of neurodegenerative disorders is expected to rise in many countries of the world. The need for reliable biomarkers in neurodegenerative diseases is crucial to improving timely and accurate clinical diagnostics, facilitating the development of disease-modifying therapies, and monitoring patient progress. In many cases, complex pathology of neurodegenerative diseases can be reflected in the extracellular fluid, allowing for the development of soluble biomarkers that can mirror neuropathology in the cerebrospinal fluid or blood. This review is an overview of the current findings, the latest developments in the field, as well as applications of fluid-based biomarkers in neurodegenerative diseases.