What diagnostic tests are available for respiratory infections or pulmonary exacerbations in cystic fibrosis: A scoping literature review.

A scoping review methodological framework formed the basis of this review. A search of two electronic databases captured relevant literature published from 2013. 1184 articles were screened, 200 of which met inclusion criteria.

Yolk sac cell atlas reveals multiorgan functions during human early development.

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation.

Perceived feasibility, facilitators and barriers to incorporating point-of-care testing for SARS-CoV-2 into emergency medical services by ambulance service staff: a survey-based approach.

Objectives: This body of work aimed to elicit ambulance service staff's perceptions on the barriers and facilitators to adoption, and clinical utility of incorporating rapid SARS-CoV-2 testing during ambulance assessments.

Design: A mixed-methods survey-based project using a framework analysis method to organise qualitative data.

Setting: Emergency and non-emergency care ambulatory services in the UK were approached to take part.

Care pathway and prioritization of rapid testing for COVID-19 in UK hospitals: a qualitative evaluation.

Objectives: The second wave of the coronavirus pandemic is now established, occurring at a time of winter pressure on acute care in the NHS. This is likely to be more challenging then the first wave for the diagnosis of COVID-19 because of the similar symptomology with other respiratory conditions highly prevalent in winter. This study sought to understand the care pathways in place in UK NHS hospitals during the first wave (March-July 2020) for identification of patients with COVID-19 and to learn lessons to inform optimal testing strategies within the COVID-19 National Diagnostic Research and Evaluation Platform (CONDOR).

Utility of Routine Laboratory Biomarkers to Detect COVID-19: A Systematic Review and Meta-Analysis.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work.

Developmental cell programs are co-opted in inflammatory skin disease.

The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease.

Moderate Exercise Inhibits Age-Related Inflammation, Liver Steatosis, Senescence, and Tumorigenesis.

Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer ( mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development.

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data.

Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity.

Methods: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases.

Differential IRF8 Transcription Factor Requirement Defines Two Pathways of Dendritic Cell Development in Humans.

The formation of mammalian dendritic cells (DCs) is controlled by multiple hematopoietic transcription factors, including IRF8. Loss of IRF8 exerts a differential effect on DC subsets, including plasmacytoid DCs (pDCs) and the classical DC lineages cDC1 and cDC2. In humans, cDC2-related subsets have been described including AXLSIGLEC6 pre-DC, DC2 and DC3.

Donor monocyte-derived macrophages promote human acute graft-versus-host disease.

Myelopoiesis is invariably present and contributes to pathology in animal models of graft-versus-host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties, and role in pathogenesis of these cells, we isolated single-cell suspensions from acute cutaneous GVHD and subjected them to genotype, transcriptome, and in vitro functional analysis.

How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system.

Spatiotemporal immune zonation of the human kidney.

Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney.

Decoding human fetal liver haematopoiesis.

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development.

Lipopolysaccharide inhalation recruits monocytes and dendritic cell subsets to the alveolar airspace.

Mononuclear phagocytes (MPs) including monocytes, macrophages and dendritic cells (DCs) are critical innate immune effectors and initiators of the adaptive immune response. MPs are present in the alveolar airspace at steady state, however little is known about DC recruitment in acute pulmonary inflammation. Here we use lipopolysaccharide inhalation to induce acute inflammation in healthy volunteers and examine the impact on bronchoalveolar lavage fluid and blood MP repertoire.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Attenuate Dendritic Cell Maturation and Function.

Mesenchymal stromal cells (MSCs) are potent regulators of immune responses largely through paracrine signaling. MSC secreted extracellular vesicles (MSC-EVs) are increasingly recognized as the key paracrine factors responsible for the biological and therapeutic function of MSCs. We report the first comprehensive study demonstrating the immunomodulatory effect of MSC-EVs on dendritic cell (DC) maturation and function.

Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response.

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE.

Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation.

Background: The homozygous K108E mutation of interferon regulatory factor 8 (IRF8) is reported to cause dendritic cell (DC) and monocyte deficiency. However, more widespread immune dysfunction is predicted from the multiple roles ascribed to IRF8 in immune cell development and function.

Objective: We sought to describe the effect on hematopoiesis and immunity of the compound heterozygous R83C/R291Q mutation of IRF8, which is present in a patient with recurrent viral infection, granuloproliferation, and intracerebral calcification.

Expression of Serum microRNAs is Altered During Acute Graft-versus-Host Disease.

Acute graft-versus-host disease (aGvHD) is the most frequent and serious complication following hematopoietic stem cell transplantation (HSCT), with a high mortality rate. A clearer understanding of the molecular pathogenesis may allow for improved therapeutic options or guide personalized prophylactic protocols. Circulating microRNAs are expressed in body fluids and have recently been associated with the etiology of aGvHD, but global expression profiling in a HSCT setting is lacking.

Impact of Alemtuzumab Scheduling on Graft-versus-Host Disease after Unrelated Donor Fludarabine and Melphalan Allografts.

Alemtuzumab conditioning is highly effective at reducing the incidence of acute and chronic graft-versus-host disease (GVHD) in reduced-intensity fludarabine and melphalan transplantation with cyclosporine monotherapy. Less frequent and lower dose scheduling may be used with sibling donors, but an optimal regimen for matched unrelated donors has not been defined. In this retrospective observational study of 313 patients, the incidence and severity of GVHD was compared in patients receiving 3 different dose schedules: the standard 100-mg regimen (20 mg on days -7 to -3), 60 mg (30 mg on days -4 and -2), or 50 mg (10 mg on days -7 to -3).

Human dermal CD14⁺ cells are a transient population of monocyte-derived macrophages.

Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1⁺ CLEC9A⁺ DCs and CD1c⁺ DCs are murine CD103⁺ DCs and CD64⁻ CD11b⁺ DCs. In addition, human tissues also contain CD14⁺ cells, currently designated as DCs, with an as-yet unknown murine counterpart.