Two-layered immune escape in AML is overcome by Fcγ receptor activation and inhibition of PGE2 signaling in NK cells.

Loss of anticancer NK cell function in AML patients is associated with fatal disease progression and remains poorly understood. Here, we demonstrate that AML-blasts isolated from patients rapidly inhibit NK cell function and escape NK cell-mediated killing. Transcriptome analysis of NK cells exposed to AML-blasts revealed increased CREM expression and transcriptional activity, indicating enhanced cAMP signalling, confirmed by uniform production of the cAMP-inducing prostanoid PGE2 by all AML-blast isolates from patients.

RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I.

The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I.

Protein turnover regulation is critical for influenza A virus infection.

The abundance of a protein is defined by its continuous synthesis and degradation, a process known as protein turnover. Here, we systematically profiled the turnover of proteins in influenza A virus (IAV)-infected cells using a pulse-chase stable isotope labeling by amino acids in cell culture (SILAC)-based approach combined with downstream statistical modeling. We identified 1,798 virus-affected proteins with turnover changes (tVAPs) out of 7,739 detected proteins (data available at pulsechase.

A targetable type III immune response with increase of IL-17A expressing CD4 T cells is associated with immunotherapy-induced toxicity in melanoma.

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.

Design of a Multiparametric Biosensing Platform and Its Validation in a Study on Spontaneous Cell Detachment from Temperature Gradients.

This article reports on a bioanalytical sensor device that hosts three different transducer principles: impedance spectroscopy, quartz-crystal microbalance with dissipation monitoring, and the thermal-current-based heat-transfer method. These principles utilize a single chip, allowing one to perform either microbalance and heat transfer measurements in parallel or heat transfer and impedance measurements. When taking specific precautions, the three measurement modalities can even be used truly simultaneously.

Importance of K Distribution in Freeze Drying: Part II: Use in Lyo Simulation Modeling.

This article is the second of a series of two articles. In the first article of the series, a new K distribution model and an experimental methodology to measure the K distribution were introduced. In this second part, the K distribution is integrated into a lyo-simulation tool, to more accurately predict the variability of the product temperature, primary drying time, total sublimation mass flow and Pirani signal.

Training in oncoplastic surgery for mastologists.

Objective: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction.

Methods: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction.

Three-dimensional Simulation on Patient-reported Outcomes Following Oncoplastic and Reconstructive Surgery of the Breast: A Randomized Trial.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery.

Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil.

Ancient Mycobacterium leprae genome reveals medieval English red squirrels as animal leprosy host.

Leprosy, one of the oldest recorded diseases in human history, remains prevalent in Asia, Africa, and South America, with over 200,000 cases every year. Although ancient DNA (aDNA) approaches on the major causative agent, Mycobacterium leprae, have elucidated the disease's evolutionary history, the role of animal hosts and interspecies transmission in the past remains unexplored. Research has uncovered relationships between medieval strains isolated from archaeological human remains and modern animal hosts such as the red squirrel in England.

Novel case of combination antibiotic therapy for treatment of a complicated polymicrobial urinary tract infection with one organism harboring a metallo-β-lactamase (MBL) in a pregnant patient.

Carbapenem resistance due to metallo-beta-lactamases (MBLs) is a global phenomenon and an important challenge for antibiotic therapy (Boyd et al., 2020 [1]). While previous reports have demonstrated both and synergy using the combination of ceftazidime-avibactam and aztreonam against , an MBL-harboring organism, this treatment strategy has not been reported during pregnancy (Mojic et al.

Anaplasma phagocytophilum infection associated with strong inflammatory response in 3 cats.

Anaplasmosis is a vector-borne disease caused by spp. which currently is still rarely diagnosed in cats. This article describes 3 independent cases of anaplasmosis in cats from different regions of Germany presented to veterinarians in 2021.

Association of Severe COVID-19 and Persistent COVID-19 Symptoms With Economic Hardship Among US Families.

Importance: Little is known about the association of severe COVID-19 and post-COVID-19 conditions with household finances.

Objective: To examine associations between COVID-19 outcomes, pandemic-related economic hardship, and prepandemic socioeconomic status among families in the US.

Design, Setting, And Participants: This cohort study used data from the Panel Study of Income Dynamics (PSID), a nationally representative, longitudinal study.

High levels of short-chain fatty acids secreted by Candida albicans hyphae induce neutrophil chemotaxis via free fatty acid receptor 2.

Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections.

Proline catabolism is a key factor facilitating Candida albicans pathogenicity.

Candida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report that put1-/- and put2-/- strains, carrying defective Proline UTilization genes, display remarkable proline sensitivity with put2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate pyrroline-5-carboxylate (P5C), which inhibits mitochondrial respiration. The put1-/- and put2-/- mutations attenuate virulence in Drosophila and murine candidemia models and decrease survival in human neutrophils and whole blood.

Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages.

The immune system is in place to assist in ensuring tissue homeostasis, which can be easily perturbed by invading pathogens or nonpathogenic stressors causing tissue damage. Extracellular nucleotides are well known to contribute to innate immune signaling specificity and strength, but how their signaling is relayed downstream of cell surface receptors and how this translates into antiviral immunity is only partially understood. Here, we systematically investigated the responses of human macrophages to extracellular nucleotides, focusing on the nucleotide-sensing GPRC receptors of the P2Y family.

Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin.

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation.

Hourglass-like constrictions on MRI are common in electromyography-confirmed cases of neuralgic amyotrophy (Parsonage-Turner syndrome): A tertiary referral center experience.

Introduction/aims: Hourglass-like constrictions (HGCs) of involved nerves in neuralgic amyotrophy (NA) (Parsonage-Turner syndrome) have been increasingly recognized with magnetic resonance neurography (MRN). This study sought to determine the sensitivity of HGCs, detected by MRN, among electromyography (EMG)-confirmed NA cases.

Methods: This study retrospectively reviewed records of patients with the clinical diagnosis of NA, and with EMG confirmation, who underwent 3-Tesla MRN within 90 days of EMG at a single tertiary referral center between 2011 and 2021.