Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling.

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor.

Hodgkin/Reed-Sternberg cells induce GPNMB expression and release from macrophages to suppress T-cell responses to the Epstein-Barr virus-encoded LMP2A protein.

Not available.

Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma.

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint blockade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis.

Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform.

Genome-scale clustered regularly interspaced short palindromic repeats screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied RNA sequencing and genome-scale loss-of-function clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations.

Aflatoxin B1 and Epstein-Barr virus-induced CCL22 expression stimulates B cell infection.

Epstein-Barr Virus (EBV) infects more than 90% of the adult population worldwide. EBV infection is associated with Burkitt lymphoma (BL) though alone is not sufficient to induce carcinogenesis implying the involvement of co-factors. BL is endemic in African regions faced with mycotoxins exposure.

Machine learning-enabled maternal risk assessment for women with pre-eclampsia (the PIERS-ML model): a modelling study.

Background: Affecting 2-4% of pregnancies, pre-eclampsia is a leading cause of maternal death and morbidity worldwide. Using routinely available data, we aimed to develop and validate a novel machine learning-based and clinical setting-responsive time-of-disease model to rule out and rule in adverse maternal outcomes in women presenting with pre-eclampsia.

Methods: We used health system, demographic, and clinical data from the day of first assessment with pre-eclampsia to predict a Delphi-derived composite outcome of maternal mortality or severe morbidity within 2 days.

The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma.

Background: A total of 30-40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells.

Space object identification and classification from hyperspectral material analysis.

This paper presents a data processing pipeline designed to extract information from the hyperspectral signature of unknown space objects. The methodology proposed in this paper determines the material composition of space objects from single pixel images. Two techniques are used for material identification and classification: one based on machine learning and the other based on a least square match with a library of known spectra.

Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma.

Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances.

Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL.

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome.

Preferential uptake of SARS-CoV-2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature.

Aims: Thrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection; however, the mechanisms inducing endotheliitis and the disruption of endothelial integrity in the microcirculation are poorly understood. We hypothesized that within the vessel wall, pericytes preferentially take up viral particles and mediate the subsequent loss of vascular integrity.

Methods And Results: Immunofluorescence of post-mortem patient sections was used to assess pathophysiological aspects of COVID-19 infection.

Comparison of characteristics and outcomes of patients admitted to hospital with COVID-19 during wave 1 and wave 2 of the current pandemic.

In this study of patients admitted with COVID-19, we examined differences between the two waves in patient characteristics and outcomes. Data were collected from the first COVID-19 admission to the end of study (01/03/2020-31/03/2021). Data were adjusted for age and sex and presented as odds ratios (OR) with 95% confidence intervals (CI).

The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase.

Calcium-dependent signalling in B-cell lymphomas.

Induced waves of calcium fluxes initiate multiple signalling pathways that play an important role in the differentiation and maturation of B-cells. Finely tuned transient Ca fluxes from the endoplasmic reticulum in response to B-cell receptor (BCR) or chemokine receptor activation are followed by more sustained calcium influxes from the extracellular environment and contribute to the mechanisms responsible for the proliferation of B-cells, their migration within lymphoid organs and their differentiation. Dysregulation of these well-balanced mechanisms in B-cell lymphomas results in uncontrolled cell proliferation and resistance to apoptosis.

MicroRNA and Other Non-Coding RNAs in Epstein-Barr Virus-Associated Cancers.

EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion.

Embedded product authentication codes in additive manufactured parts: Imaging and image processing for improved scan ability.

The layer-by-layer printing process of additive manufacturing methods provides new opportunities to embed identification codes inside parts during manufacture. These embedded codes can be used for product authentication and identification of counterfeits. The availability of reverse engineering tools has increased the risk of counterfeit part production and new authentication technologies such as the one proposed in this paper are required for many applications including aerospace components and medical implants and devices.

Early emergency readmission frequency as an indicator of short-, medium- and long-term mortality post-discharge from hospital.

Frequent emergency readmissions, an indicator of quality of care, has been rising in England but the underlying reasons remain unclear. We examined the association of early readmissions with subsequent mortality in adults, taking into account the underlying presenting diagnoses and hospital length of stay (LOS). Data of alive-discharge episodes were prospectively collected between 01/04/2017 and 31/03/2019 in an National Health Service hospital, comprising 32,270 patients (46.

Advanced Symptom Management System for Patients with Malignant Pleural Mesothelioma (ASyMSmeso): Mixed Methods Study.

Background: Patients with malignant pleural mesothelioma (MPM) have a life-limiting illness and short prognosis and experience many debilitating symptoms from early in the illness. Innovations such as remote symptom monitoring are needed to enable patients to maintain wellbeing and manage symptoms in a proactive and timely manner. The Advanced Symptom Management System (ASyMS) has been successfully used to monitor symptoms associated with cancer.

Compact multispectral pushframe camera for nanosatellites.

In this paper we present an evolution of the single-pixel camera architecture, called "pushframe," which addresses the limitations of pushbroom cameras in space-based applications. In particular, it is well-suited to observing fast-moving scenes while retaining high spatial resolution and sensitivity. We show that the system is capable of producing color images with good fidelity and scalable resolution performance.

Design of 2D Sparse Array Transducers for Anomaly Detection in Medical Phantoms.

Aperiodic sparse 2D ultrasonic array configurations, including random array, log spiral array, and sunflower array, have been considered for their potential as conformable transducers able to image within a focal range of 30-80 mm, at an operating frequency of 2 MHz. Optimisation of the imaging performance of potential array patterns has been undertaken based on their simulated far field directivity functions. Two evaluation criteria, peak sidelobe level (PSL) and integrated sidelobe ratio (ISLR), are used to access the performance of each array configuration.