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How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function. Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

Previous studies showed that radiologists can detect the gist of an abnormality in a mammogram based on a half-second image presentation through global processing of screening mammograms. This study investigated the intra- and inter-observer reliability of the radiologists’ initial impressions about the abnormality (or \"gist signal\"). It also examined if a subset of radiologists produced more reliable and accurate gist signals. Thirty-nine radiologists provided their initial impressions on two separate occasions, viewing each mammogram for half a second each time. The intra-class correlation (ICC) values showed poor to moderate intra-reader reliability. Only 13 radiologists had an ICC of 0.6 or above, which is considered the minimum standard for reliability, and only three radiologists had an ICC exceeding 0.7. The median value for the weighted Cohen’s Kappa was 0.478 (interquartile range = 0.419–0.555). The Mann-Whitney U-test showed that the \"Gist Experts\", defined as those who outperformed others, had significantly higher ICC values (p = 0.002) and weighted Cohen’s Kappa scores (p = 0.026). However, even for these experts, the intra-radiologist agreements were not strong, as an ICC of at least 0.75 indicates good reliability and the signal from none of the readers reached this level of reliability as determined by ICC values. The inter-reader reliability of the gist signal was poor, with an ICC score of 0.31 (CI = 0.26–0.37). The Fleiss Kappa score of 0.106 (CI = 0.105–0.106), indicating only slight inter-reader agreement, confirms the findings from the ICC analysis. The intra- and inter-reader reliability analysis showed that the radiologists’ initial impressions are not reliable signals. In particular, the absence of an abnormal gist does not reliably signal a normal case, so radiologists should keep searching. This highlights the importance of \"discovery scanning,\" or coarse screening to detect potential targets before ending the visual search.

i NKT cells in adipose tissue are anti-inflammatory. Brenner and colleagues show that adipose i NKT cells have a unique transcriptional program, produce IL-2 and IL-10 and lack expression of the transcription factor PLZF. Invariant natural killer T cells ( i NKT cells) are lipid-sensing innate T cells that are restricted by the antigen-presenting molecule CD1d and express the transcription factor PLZF. i NKT cells accumulate in adipose tissue, where they are anti-inflammatory, but the factors that contribute to their anti-inflammatory nature, as well as their targets in adipose tissue, are unknown. Here we found that i NKT cells in adipose tissue had a unique transcriptional program and produced interleukin 2 (IL-2) and IL-10. Unlike other i NKT cells, they lacked PLZF but expressed the transcription factor E4BP4, which controlled their IL-10 production. The adipose i NKT cells were a tissue-resident population that induced an anti-inflammatory phenotype in macrophages and, through the production of IL-2, controlled the number, proliferation and suppressor function of regulatory T cells (T reg cells) in adipose tissue. Thus, i NKT cells in adipose tissue are unique regulators of immunological homeostasis in this tissue.

Radiologists can detect abnormality in mammograms at above-chance levels after a momentary glimpse of an image. The study investigated this instantaneous perception of an abnormality, known as a “gist” response, when 23 radiologists viewed prior mammograms of women that were reported as normal, but later diagnosed with breast cancer at subsequent screening. Five categories of cases were included: current cancer-containing mammograms, current mammograms of the normal breast contralateral to the cancer, prior mammograms of normal cases, prior mammograms with visible cancer signs in a breast from women who were initially reported as normal, but later diagnosed with breast cancer at subsequent screening in the same breast, and prior mammograms without any visible cancer signs from women labelled as initially normal but subsequently diagnosed with cancer. Our findings suggest that readers can distinguish patients who were diagnosed with cancer, from individuals without breast cancer (normal category), at above-chance levels based on a half-second glimpse of the mammogram even before any lesion becomes visible on the mammogram. Although 20 of the 23 radiologists demonstrated this ability, radiologists’ abilities for perceiving the gist of the abnormal varied between the readers and appeared to be linked to expertise. These results could have implications for identifying women of higher than average risk of a future malignancy event, thus impacting upon tailored screening strategies.

This book presents, in an easy-to-read format, a summary of the important central aspects of microbial glycobiology; i.e. the study of carbohydrates as related to the biology of microorganisms. Microbial glycobiology represents a multidisciplinary and emerging area with implications for a range of basic and applied research fields, as well as having industrial, medical and biotechnological implications.

Artificial intelligence (AI) is heralded as the most disruptive technology to health services in the 21st century. Many commentary articles published in the general public and health domains recognise that medical imaging is at the forefront of these changes due to our large digital data footprint. Radiomics is transforming medical images into mineable high‐dimensional data to optimise clinical decision‐making; however, some would argue that AI could infiltrate workplaces with very few ethical checks and balances. In this commentary article, we describe how AI is beginning to change medical imaging services and the innovations that are on the horizon. We explore how AI and its various forms, including machine learning, will challenge the way medical imaging is delivered from workflow, image acquisition, image registration to interpretation. Diagnostic radiographers will need to learn to work alongside our ‘virtual colleagues’, and we argue that there are vital changes to entry and advanced curricula together with national professional capabilities to ensure machine‐learning tools are used in the safest and most effective manner for our patients. This article summarises the opportunities for artificial intelligence (AI) translation into medical imaging in the near future. The changing roles for diagnostic radiographers are explored, and a discussion of the challenges for the ethical implementation of AI is included.

Breast cancer is the most common neoplasm diagnosed amongst women worldwide and is the leading cause of female cancer death. However, breast cancer in China is not comprehensively understood compared with Westernised countries, although the 5-year prevalence statistics indicate that approximately 11 % of worldwide breast cancer occurs in China and that the incidence has increased rapidly in recent decades. This paper reviews the descriptive epidemiology of Chinese breast cancer in terms of incidence, mortality, survival and prevalence, and explores relevant factors such as age of manifestation and geographic locations. The statistics are compared with data from the Westernised world with particular emphasis on the United States and Australia. Potential causal agents responsible for differences in breast cancer epidemiology between Chinese and other populations are also explored. The need to minimise variability and discrepancies in methods of data acquisition, analysis and presentation is highlighted.

A first‐order process in the growth of continents is the collision and accretion of terranes against continental margins. Collision leads to the formation of a suture zone between the accreted terrane and the former continental margin. New insights on the suturing process are observed from two receiver function transects across the Mesozoic Alaska Range suture zone. Three distinct crustal sections are identified from observations of crustal thickness, intracrustal discontinuities, and Vp/Vs: a northern section with ∼27 km thick crust of felsic to intermediate composition, a central section that is ∼37 km thick that exhibits intracrustal discontinuities and has felsic to intermediate composition, and a southern section that is ∼30 km thick and has a more mafic composition. We interpret these sections to correspond with the former continental margin (Yukon composite terrane), the suture zone proper, and the allochthonous oceanic terrane (Wrangellia composite terrane). The boundary between the Yukon composite terrane and the suture zone appears to be a subhorizontal discontinuity that accommodated underthrusting of crust from the suture zone beneath the former continental margin. The boundary between the suture zone and the Wrangellia composite terrane, in contrast, appears to be a relatively discrete, vertical boundary. The observed variability in the crust across the Alaska Range suture zone is likely controlled by the differing compositions of the terranes involved, which influences how each section responds to precollisional, syncollisional, and postcollisional deformation. Key Points Crustal configuration of a suture zone Juxtaposition of different types of crust in a collisional zone Differences in crustal types in a collisional zone guide deformation

Key Points Invariant natural killer T (iNKT) cells are a specialized T cell population that recognizes lipid antigens that are presented by a cell-surface molecule known as CD1d. They have been shown to have important roles in many diverse immune responses. iNKT cells recognize both foreign lipid antigens and self lipid antigens. The T cell receptor (TCR)–lipid–CD1d interaction is similar for both self and foreign lipid antigens, despite the differences that exist in these lipid structures. Strong lipid antigens have a 'lock and key' type of binding, whereas weaker antigens require an 'induced fit' mechanism. The production of lipid self antigens for iNKT cells can be upregulated by antigen-presenting cells (APCs) in response to danger signals, such as Toll-like receptor (TLR) agonists. This provides a mechanism for iNKT cell activation in the absence of foreign lipid antigens. In addition to being activated through their TCRs in response to CD1d-presented lipids, iNKT cells can be activated by indirect stimuli, such as pro-inflammatory cytokines. During many infections, interleukin-12 (IL-12) may have an equally important role to lipid antigens in activating iNKT cells. iNKT cells couple the rapid activation kinetics of innate immune cells with the diverse effector functions of adaptive T cells. Early activation during infection leads to rapid cytokine production in target tissues by polarized iNKT cell subsets. Interactions between iNKT cells and CD1d-expressing APCs lead to bidirectional activation. Cytokines produced by iNKT cells activate and recruit other cell types early during immune responses, while activated APCs direct the ensuing adaptive immune responses. Thus, iNKT cells and their lipid antigens help to orchestrate innate and adaptive immune responses. Invariant natural killer T (iNKT) cells are innate-like lymphocytes that express T cell receptors that can be activated by lipid antigens presented on CD1d molecules. Here, the authors describe different models of iNKT cell activation and discuss how activated iNKT cells can contribute to both protective and pathological immune responses. Invariant natural killer T (iNKT) cells exist in a 'poised effector' state, which enables them to rapidly produce cytokines following activation. Using a nearly monospecific T cell receptor, they recognize self and foreign lipid antigens presented by CD1d in a conserved manner, but their activation can catalyse a spectrum of polarized immune responses. In this Review, we discuss recent advances in our understanding of the innate-like mechanisms underlying iNKT cell activation and describe how lipid antigens, the inflammatory milieu and interactions with other immune cell subsets regulate the functions of iNKT cells in health and disease.

Antagonists of the type 1 cysteinyl leukotriene receptor (CysLT1R) are widely used to treat asthma and allergic rhinitis, with variable response rates. Alveolar macrophages express UDP-specific P2Y6 receptors that can be blocked by off-target effects of CysLT1R antagonists. Sensitizing intranasal doses of an extract from the house dust mite Dermatophagoides farinae (Df) sharply increased the levels of UDP detected in bronchoalveolar lavage fluid of mice. Conditional deletion of P2Y6 receptors before sensitization exacerbated eosinophilic lung inflammation and type 2 cytokine production in response to subsequent Df challenge. P2Y6 receptor signaling was necessary for dectin-2-dependent production of protective IL-12p40 and Th1 chemokines by alveolar macrophages, leading to activation of NK cells to generate IFN-γ. Administration of CysLT1R antagonists during sensitization blocked UDP-elicited potentiation of IL-12p40 production by macrophages in vitro, suppressed the Df-induced production of IL-12p40 and IFN-γ in vivo, and suppressed type 2 inflammation only in P2Y6-deficient mice. Thus, P2Y6 receptor signaling drives an innate macrophage/IL-12/NK cell/IFN-γ axis that prevents inappropriate allergic type 2 immune responses on respiratory allergen exposure and counteracts the Th2 priming effect of CysLT1R signaling at sensitization. Targeting P2Y6 signaling might prove to be a potential additional treatment strategy for allergy.