Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia.

Background: COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.

Methods: We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.

Immune cell landscape in symptomatic and asymptomatic SARS-CoV-2 infected adults and children in urban Dhaka, Bangladesh.

Objectives: The study of cellular immunity to SARS-CoV-2 is crucial for evaluating the course of the COVID-19 disease and for improving vaccine development. We aimed to assess the phenotypic landscape of circulating lymphocytes and mononuclear cells in adults and children who were seropositive to SARS-CoV-2 in the past 6 months.

Methods: Blood samples (n = 350) were collected in a cross-sectional study in Dhaka, Bangladesh (Oct 2020-Feb 2021).

Obesity control by SHIP inhibition requires pan-paralog inhibition and an intact eosinophil compartment.

Here we extend the understanding of how chemical inhibition of SHIP paralogs controls obesity. We compare different classes of SHIP inhibitors and find that selective inhibitors of SHIP1 or SHIP2 are unable to prevent weight gain and body fat accumulation during increased caloric intake. Surprisingly, only pan-SHIP1/2 inhibitors (pan-SHIPi) prevent diet-induced obesity.

Role of myeloid cells in system-level immunometabolic dysregulation during prolonged successful HIV-1 treatment.

Objective: Why people with HIV-1 on ART (PWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PWH ART and HIV-1 negative individuals (HC).

Design: Cross-sectional study.

Safety and immunogenicity following co-administration of Yellow fever vaccine with Tick-borne encephalitis or Japanese encephalitis vaccines: Results from an open label, non-randomized clinical trial.

Background: Flavivirus infections pose a significant global health burden underscoring the need for the development of safe and effective vaccination strategies. Available flavivirus vaccines are from time to time concomitantly delivered to individuals. Co-administration of different vaccines saves time and visits to health care units and vaccine clinics.

Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.

Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection.

Implication of Oxysterols in Infectious and Non-Communicable Inflammatory Diseases.

Oxysterols, derived from cholesterol oxidation, are formed either by autoxidation, via enzymes, or by both processes [...

A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.

The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a comprehensive topographic atlas of early human lung development. Here we report 83 cell states and several spatially resolved developmental trajectories and predict cell interactions within defined tissue niches.

Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field.

Tuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune responses may be considerably different compared to the systemic circulation. New and improved technologies for quantification and multimodal imaging of mRNA transcripts and protein expression at the single-cell level have enabled significantly improved insights into the local TB granuloma microenvironment.

Staphylococcus aureus populations from the gut and the blood are not distinguished by virulence traits-a critical role of host barrier integrity.

Background: The opportunistic pathogen Staphylococcus aureus is an asymptomatically carried member of the microbiome of about one third of the human population at any given point in time. Body sites known to harbor S. aureus are the skin, nasopharynx, and gut.

Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology.

Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention.

Do task and item difficulty affect overestimation of one's hand hygiene compliance? A cross-sectional survey of physicians and nurses in surgical clinics of six hospitals in Germany.

Background: One barrier to hand hygiene compliance is overestimation of one's own performance. Overconfidence research shows that overestimation tends to be higher for difficult tasks, which suggests that the magnitude of overestimation also depends on how it is assessed. Thus, we tested the hypothesis that overestimation was stronger for hand hygiene indications with low compliance (i.

Associations between subcutaneous adipocyte hypertrophy and nonalcoholic fatty liver disease.

Adipocyte hypertrophy and expression of adipokines in subcutaneous adipose tissue (SAT) have been linked to steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis in morbidly obese (BMI ≥ 40 kg/m) subjects. It is unknown if this is also true for subjects with NAFLD with lesser degrees of obesity (BMI < 35 kg/m). Thirty-two subjects with biopsy-proven NAFLD and 15 non-diabetic controls matched for BMI underwent fine-needle biopsies of SAT.

Small Interfering RNA Delivery Into Primary Human Natural Killer Cells for Functional Gene Analyses.

Studying gene functions in human natural killer (NK) cells is key for advancing the understanding of NK cell biology and holds promise to pave the way for improving NK cell therapies against cancer. However, NK cells are challenging to manipulate, and investigation of gene functions in NK cells is hampered by variable delivery efficiencies and impaired viability upon electroporation, lipofection, or viral transduction. Here, we report a simple workflow for delivery of commercially available small interfering RNA molecules into primary human NK cells to enable functional gene analyses.

Distinct T cell subsets in adipose tissue are associated with obesity.

Adipose tissue inflammation is a driving factor for the development of obesity-associated metabolic disturbances, and a role of adipose tissue T cells in initiating the pro-inflammatory signaling is emerging. However, data on human adipose tissue T cells in obesity are limited, reflected by the lack of phenotypic markers to define tissue-resident T cell subsets. In this study, we performed a deep characterization of T cells in blood and adipose tissue depots using multicolor flow cytometry and RNA sequencing.

Clinical Characteristics and Histopathology in Suspected Necrotizing Soft Tissue Infections.

Background: Necrotizing soft tissue infections (NSTIs) are severe diseases with high morbidity and mortality. The diagnosis is challenging. Several guidelines recommend tissue biopsies as an adjunct diagnostic in routine management, but neither biopsy sampling nor classification is standardized or validated.

Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated in clinical trials, the clinical impact of NK cells on the PD1 cascade is less well understood compared to T cells. Furthermore, while NK cells have effector activity within the TME, under continuous ligand exposure, NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1.

single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection.

MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution HIV-1-infected individuals and rescues their functionality . Single-nucleotide polymorphisms (SNPs) of the gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7.

Adaptive single-KIRNKG2C NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia.

Background: Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)NKG2C adaptive NK cells to maximize missing-self reactivity.

Methods: We developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline.