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Sexual dimorphism in skin immunity is mediated by an androgen-ILC2-dendritic cell axis

Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncovered a dominant role for type 2 innate lymphoid cells (ILC2s) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2s by androgens leads to a reductio

The selection function of the RAVE survey

We characterize the selection function of RAdial Velocity Experiment (RAVE) using 2 Micron All Sky Survey (2MASS) as our underlying population, which we assume represents all stars that could have potentially been observed.We evaluate the completeness fraction as a function of position, magnitude and colour in two ways: first, on a field-by-field basis, and second, in equal-size areas on the sky.

Design and Usability of an E-Health Mobile Application

Health applications have increasingly been used to improve physical, mental and social well-being. Chronic pain (CP) is defined as pain that lasts for a period of three months and causes sporadic or constant discomfort. In Portugal, the treatments for this type of pain are almost exclusively pharmacological and with known limited effects. Endowing patients with self-management skills, will help th

The C-terminal peptide of CCL21 drastically augments CCL21 activity through the dendritic cell lymph node homing receptor CCR7 by interaction with the receptor N-terminus

The endogenous chemokines CCL19 and CCL21 signal via their common receptor CCR7. CCL21 is the main lymph node homing chemokine, but a weak chemo-attractant compared to CCL19. Here we show that the 41-amino acid positively charged peptide, released through C-terminal cleavage of CCL21, C21TP, boosts the immune cell recruiting activity of CCL21 by up to 25-fold and the signaling activity via CCR7 by

Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling

Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six—IL-1

EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo : Current challenges and future solutions

Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prur

Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonym

Combined GLUT1 and OXPHOS inhibition eliminates acute myeloid leukemia cells by restraining their metabolic plasticity

Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells responsible for therapy resistance. Hence, there is an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed an in vivo CRISPR knockout screen to identify potential therapeutic targets by interrogating cell surface dependencies of L

The DNA methylation landscape of primary triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcrip

Signal-Averaged ECG in the Diagnostic Workup for Arrhythmogenic Cardiomyopathy : Insights From the Nordic ARVC Registry

BACKGROUND: The diagnostic role of signal-averaged ECG (SAECG) in arrhythmogenic right ventricular cardiomyopathy (ARVC) has lately been questioned. We assessed the value of SAECG-derived late ventricular potentials (LP) in ARVC diagnosis and its association with disease manifestations.METHODS AND RESULTS: Patients with definite ARVC diagnosis or genotype-positive family members who underwent SAEC

An explorable model of an adverse outcome pathway of cytokine release syndrome related to the administration of immunomodulatory biotherapeutics and cellular therapies

Introduction: Cytokine release syndrome (CRS) is a potentially severe systemic inflammatory condition triggered by various immunomodulatory therapies, making understanding its pathogenesis critical for improving patient outcomes. Results/Methods: By combining immunotoxicology and systems biology approaches, we offer a novel and integrative conceptual model of CRS as an adverse outcome (AO), induce

Human oral, gut, and plaque microbiota in patients with atherosclerosis

Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlate

Osannolika händelser och den svenska realistiska romanen : Ett estetiskt och existentiellt bekymmer

Avhandlingens ämne är osannolika händelser i den realistiska romanen. Den övergripande idén är att realismen utmärks av att osannolika händelser hanteras utifrån ett dubbelt perspektiv: både som ett existentiellt och ett estetiskt bekymmer. Som ett existentiellt bekymmer representerar den narrativa fiktionsberättelsens osannolika händelser den ständigt närvarande möjligheten att en oförutsägbar ocThis thesis deals with improbable events in the realistic novel. The overarchingidea is that realism is distinguished by dealing with improbable events on thebasis of a double perspective: both as an existential and as an aesthetic problem.As an existential problem the improbable events of narrative fiction representthe constantly present possibility of an unexpected and unforeseen event suddenly

Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance

Background: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris. Objectives: The purpose of this study was to determine the association between the usage of FFR and all-cause m

Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity

The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in GALT-free intestinal lamina propria (LP). SM-ILF and

The chemical compositions of accreted and in situ galactic globular clusters according to SDSS/APOGEE

Studies of the kinematics and chemical compositions of Galactic globular clusters (GCs) enable the reconstruction of the history of star formation, chemical evolution, and mass assembly of the Galaxy. Using the latest data release (DR16) of the SDSS/APOGEE survey, we identify 3090 stars associated with 46 GCs. Using a previously defined kinematic association, we break the sample down into eight se

The Open Cluster Chemical Abundances and Mapping Survey. IV. Abundances for 128 Open Clusters Using SDSS/APOGEE DR16

The Open Cluster Chemical Abundances and Mapping (OCCAM) survey aims to constrain key Galactic dynamical and chemical evolution parameters by the construction of a large, comprehensive, uniform, infrared-based spectroscopic data set of hundreds of open clusters. This fourth contribution from the OCCAM survey presents analysis using Sloan Digital Sky Survey/APOGEE DR16 of a sample of 128 open clust

The GALAH survey : Unresolved triple Sun-like stars discovered by the Gaia mission

The latest Gaia data release enables us to accurately identify stars that are more luminous than would be expected on the basis of their spectral type and distance. During an investigation of the 329 best solar twin candidates uncovered among the spectra acquired by the GALAH survey, we identified 64 such overluminous stars. In order to investigate their exact composition, we developed a data-driv

Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally-induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed