Human metapneumovirus (HMPV) is one of the leading causes of respiratory diseases in infants and children worldwide. Although this pathogen infects mainly young children, elderly and immunocompromised people can be also seriously affected. To date, there is no commercial vaccine available against it. Upon HMPV infection, the host innate arm of defense produces interferons (IFNs), which are critical for limiting HMPV replication. In this review, we offer an updated landscape of the HMPV mediated-IFN response in different models as well as some of the defense tactics employed by the virus to circumvent IFN response.

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected predictions against several cancer types. To shed light on the decision-making process of CancerOmicsNet and to better understand the role of each kinase in the model, we employed a customized saliency map with adjustable channel weights. The saliency map, functioning as an explainable AI tool, allows for the analysis of input contributions to the output of a trained deep-learning model and facilitates the identification of essential kinases involved in tumor progression. The comprehensive survey of biomedical literature for essential kinases selected by CancerOmicsNet demonstrated that it could help pinpoint potential druggable targets for further investigation in diverse cancer types.

The development of cancer causes disruption of anti-tumor immunity required for surveillance and elimination of tumor cells. Immunotherapeutic strategies aim for the restoration or establishment of these anti-tumor immune responses. Cancer immunotherapies include immune checkpoint inhibitors (ICIs), adoptive cellular therapy (ACT), cancer vaccines, and oncolytic virotherapy (OVT). The clinical success of some of these immunotherapeutic modalities, including herpes simplex virus type-1 derived OVT, resulted in Food and Drug Administration (FDA) approval for use in treatment of human cancers. However, a significant proportion of patients do not respond or benefit equally from these immunotherapies. The creation of an immunosuppressive tumor microenvironment (TME) represents an important barrier preventing success of many immunotherapeutic approaches. Mechanisms of immunosuppression in the TME are a major area of current research. In this review, we discuss how oncolytic HSV affects the tumor microenvironment to promote anti-tumor immune responses. Where possible we focus on oncolytic HSV strains for which clinical data is available, and discuss how these viruses alter the vasculature, extracellular matrix and immune responses in the tumor microenvironment.

The recent success of cancer immunotherapies, such as immune checkpoint inhibitor (ICIs), monoclonal antibodies (mAbs), cancer vaccines, and adoptive cellular therapies (ACTs), has revolutionized traditional cancer treatment. However, these immunotherapeutic modalities have variable efficacies, and many of them exhibit adverse effects. Oncolytic viral Immunotherapy (OViT), whereby viruses are used to directly or indirectly induce anti-cancer immune responses, is emerging as a novel immunotherapy for treating patients with different types of cancer. The herpes simplex virus type-1 (HSV-1) possesses many characteristics that inform its use as an effective OViT agents and remains a leading candidate. Its recent clinical success resulted in the Food and Drug Administration (FDA) approval of Talimogene laherparevec (T-VEC or Imlygic) in 2015 for the treatment of advanced melanoma. In this review, we discuss recent advances in the development of oncolytic HSV-1-based OViTs, their anti-tumor mechanism of action, and efficacy data from recent clinical trials. We envision this knowledge may be used to inform the rational design and application of future oHSV in cancer treatment.

Previous work has highlighted the complicated and distinctive dynamics that set signal evolution during a train of spin echoes, especially with nonuniform echo spacing applied to complex molecules like fats. The work presented here regards those signal patterns as codes that can be used as a contrast mechanism, capable of distinguishing mixtures of molecules with an imaging sequence, sidestepping many challenges of spectroscopy. For particular arrays of echo spacings, non-monotonic and distinctive signal evolution can be enhanced to improve contrast between target species. This work presents simulations that show how contrast between two molecules: (a) depends on the specific sequence of echo spacing, (b) is directly linked to the presence of J-coupling, and (c) can be relatively insensitive to variations in B0, T2 and B1. Imaging studies with oils demonstrate this phenomenon experimentally and also show that spin echo codes can be used for quantification. Finally, preliminary experiments apply the method to human liver in vivo, verifying that the presence of fat can lead to nonmonotonic codes like those seen in vitro. In summary, nonuniformly spaced echo trains introduce a new approach to molecular imaging of J-coupled species, such as lipids, which may have implications diagnosing metabolic diseases.