Advances in experimental medicine and biology最新文献

Radiomics, a quantitative approach to extracting features from medical images, represents a new frontier in skull base oncology. Novel image analysis approaches have enabled us to capture patterns from images imperceptible by the human eye. This rich source of data can be combined with a range of clinical features, holding the potential to be a noninvasive source of biomarkers. Applications of radiomics in skull base pathologies have centered around three common tumor classes: meningioma, sellar/parasellar tumors, and vestibular schwannomas. Radiomic investigations can be categorized into five domains: tumor detection/segmentation, classification between tumor types, tumor grading, detection of tumor features, and prognostication. Various computational architectures have been employed across these domains, with deep-learning methods becoming more common versus machine learning. Across radiomic applications, contrast-enhanced T1-weighted MRI images remain the most utilized sequence for model development. Efforts to standardize and connect radiomic features to tumor biology have facilitated more clinically applicable radiomic models. Despite the advancement in model performance, several challenges continue to hinder translatability, including small sample sizes and model training on homogenous single institution data. To recognize the potential of radiomics for skull base oncology, prospective, multi-institutional collaboration will be the cornerstone for a validated radiomic technology.

"Bayesian Neural Networks in Predictive Neurosurgery" explains both conceptually and theoretically the combination of statistical techniques for clinical prediction models, including artificial neural networks, Bayesian regression, and Bayesian neural networks. This clinical prediction system incorporates both prior knowledge and one's own experiences (Bayesian analysis) as well as recognizes complex statistical associations between prognostic and outcome variables (artificial neural networks).

The immune system plays a dual role in human health, functioning both as a protector against pathogens and, at times, as a contributor to disease. This feature emphasizes the importance to uncover the underlying causes of its malfunctions, necessitating an in-depth analysis in both pathological and physiological conditions to better understand the immune system and immune disorders. Recent advances in scientific technology have enabled extensive investigations into gene regulation, a crucial mechanism governing cellular functionality. Studying gene regulatory mechanisms within the immune system is a promising avenue for enhancing our understanding of immune cells and the immune system as a whole. The gene regulatory mechanisms, revealed through various methodologies, and their implications in the field of immunology are discussed in this chapter.

Since its discovery, Aire has been the topic of numerous studies in its role as a transcriptional regulator in the thymus where it promotes the "promiscuous" expression of a large repertoire of tissue-restricted antigens (TRAs) that are normally expressed only in the immune periphery. This process occurs in specialized medullary thymic epithelial cells (mTECs) and mediates the elimination of self-reactive T cells or promotes their conversion to the Foxp3⁺ regulatory T cell lineage, both of which are required for the prevention of autoimmunity. In recent years, there has been increasing interest in the role of extrathymic Aire expression in peripheral organs. The focus has primarily been on the identification of the cellular source(s) and mechanism(s) by which extrathymic AIRE affects tolerance-related or other physiological processes. A cadre of OMICs tools including single cell RNA sequencing and novel transgenic models to trace Aire expression to perform lineage tracing experiments have shed light on a phenomenon that is more complex than previously thought. In this chapter, we provide a deeper analysis of how extrathymic Aire research has developed and progressed, how cellular sources were identified, and how the function of AIRE was determined. Current data suggests that extrathymic AIRE fulfills a function that differs from what has been observed in the thymus and strongly argues that its main purpose is to regulate transcriptional programs in a cell content-dependent manner. Surprisingly, there is data that also suggests a non-transcriptional role of extrathymic AIRE in the cytoplasm. We have arrived at a potential turning point that will take the field from the classical understanding of AIRE as a transcription factor in control of TRA expression to its role in immunological and non-immunological processes in the periphery.

One of the difficulties in studying the pathogenesis of autoimmune diseases is that the disease is multifactorial involving sex, age, MHC, environment, and some genetic factors. Because deficiency of Aire, a transcriptional regulator, is an autoimmune disease caused by a single gene abnormality, Aire is an ideal research target for approaching the enigma of autoimmunity, e.g., the mechanisms underlying Aire deficiency can be studied using genetically modified animals. Nevertheless, the exact mechanisms of the breakdown of self-tolerance due to Aire's dysfunction have not yet been fully clarified. This is due, at least in part, to the lack of information on the exact target genes controlled by Aire. State-of-the-art research infrastructures such as single-cell analysis are now in place to elucidate the essential function of Aire. The knowledge gained through the study of Aire-mediated tolerance should help our understanding of the pathogenesis of autoimmune disease in general.

Inflammation is a complex process that protects our body from various insults such as infection, injury, and stress. Proper inflammation is beneficial to eliminate the insults and maintain organ homeostasis, however, it can become detrimental if uncontrolled. To tightly regulate inflammation, post-transcriptional mechanisms governing RNA metabolism play a crucial role in monitoring the expression of immune-related genes, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6). These mechanisms involve the coordinated action of various RNA-binding proteins (RBPs), including the Regnase family, Roquin, and RNA methyltransferases, which are responsible for mRNA decay and/or translation regulation. The collaborative efforts of these RBPs are essential in preventing aberrant immune response activation and consequently safeguarding against inflammatory and autoimmune diseases. This review provides an overview of recent advancements in our understanding of post-transcriptional regulation within the immune system and explores the specific roles of individual RBPs in RNA metabolism and regulation.

T cells play a crucial role in adaptive immunity by recognizing and eliminating foreign pathogens and abnormal cells such as cancer cells. T cell receptor (TCR), which is expressed on the surface of T cells, recognizes and binds to specific antigens presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). This activation process leads to the proliferation and differentiation of T cells, allowing them to carry out their specific immune response functions. This chapter outlines the TCR signaling pathways that are common to different T cell subsets, as well as the recently elucidated TCR signaling pathway specific to CD8⁺ T cells and its role in controlling anti-Toxoplasma and anti-tumor immunity.

The trematodes are a species-rich group of parasites, with some estimates suggesting that there are more than 24,000 species. However, the complexities associated with their taxonomic status and nomenclature can hinder explorations of the biology of wildlife trematodes, including fundamental aspects such as host use, life cycle variation, pathology, and disease. In this chapter, we review work on selected trematodes of amphibians, birds, mammals, and their snail intermediate hosts, with the goal of providing a tool kit on how to study trematodes of wildlife. We provide a brief introduction to each group of wildlife trematodes, followed by some examples of the challenges each group of trematodes has relative to the goal of their identification and understanding of the biology and interactions these organisms have with their wildlife hosts.

The platyhelminth class Trematoda comprises two subclasses with largely disparate species diversity, with the small Aspidogastrea with c.80 species and the speciose Digenea with c.18,000 species, which has attracted much effort towards our understanding of evolutionary relationships among suprageneric taxa. This chapter focuses on insights into the classification of the Digenea, that have become apparent from our advanced understanding of both morphological and molecular data. The field of molecular systematics of the Digenea has experienced significant advances over the past 15 years. Phylogenetic analyses of sequence data predominantly from the 18S and 28S rRNA genes have incorporated a considerable diversity of taxa, thus increasing the accuracy of phylogenetic inferences at higher taxonomic levels. As a result, the status of long-standing supraspecific taxa has been revised, new higher-level taxa have been defined, and inferences made in association with morphological and life-cycle evidence. A substantial effort has been made towards a classification reflecting a natural system of the Digenea by considering morphological evidence in conjunction with phylogenies inferred from molecular data; this has resulted in considerable congruence. However, limited taxon sampling in the phylogeny of the Digenea still remains relevant, especially in relation to some higher-level taxa, and an outline of these omissions is presented. A framework that has led to robust estimates of phylogeny is outlined, and the application of advanced morphological and molecular approaches in digenean taxonomy and systematics is illustrated using the most comprehensively studied digenean superfamilies.

Paragonimiasis is a zoonotic disease caused by lung flukes of the genus Paragonimus. Humans usually become infected by eating freshwater crabs or crayfish containing encysted metacercariae of these worms. However, an alternative route of infection exists: ingestion of raw meat from a mammalian paratenic host. Adult worms normally occur in pairs in cysts in the lungs from which they void their eggs via air passages. The pulmonary form is typical in cases of human infection due to P. westermani, P. heterotremus, and a few other species. Worms may occupy other sites in the body, notably the brain, but lung flukes have made their presence felt in almost every organ. Ectopic paragonimiasis is particularly common when infection is due to members of the P. skrjabini complex. Human paragonimiasis occurs primarily in the tropics and subtropics of Asia, Africa, and the Americas, with different species being responsible in different areas (Table 6.1).