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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

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

Antibiotic use and gut microbiome composition links from individual-level prescription data of 14,979 individuals

Disruptions in gut microbiome are implicated in cardiometabolic disorders and other health outcomes. Antibiotics are known gut microbiome disruptors, but their long-term consequences remain underexplored. Here we combined individual-level data from the Swedish Prescribed Drug Register with fecal metagenomes of 14,979 adults to examine the association between oral antibiotic use over 8 years and gu

CD163+ macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

Mantle cell lymphoma (MCL) is dependent on a supportive tumor immune microenvironment (TIME) in which infiltration of CD163+ macrophages has a negative prognostic impact. This study explores how abundance and spatial localization of CD163+ cells are associated with the biology of MCL, using spatial multiomic investigations of tumor and infiltrating CD163+ and CD3+ cells. A total of 63 proteins wer

The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation : Monthly Notices of the Royal Astronomical Society

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable ‘mini’ integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph cove

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

European project to develop a UV/VUV free-electron laser facility on the ELETTRA storage ring

Sincrotrone Trieste, collaborating with various institutions, has recently begun a 3-year project to develop a UV/VUV free-electron laser on the ELETTRA storage ring. The main features and novel technical aspects of the project are described, including the design of the optical cavity and undulator, the electron beam characteristics and a first assessment of the predicted laser performance. Prelim

Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning : External Validation and Further Model Development

Background: Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using po

Impact of Neoadjuvant Therapy for Pancreatic Cancer : Transatlantic Trend and Postoperative Outcomes Analysis

BACKGROUND: The introduction of modern chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). A recent North American study demonstrated increased use of NAT and improved operative outcomes in patients with PDAC. The aims of this study were to compare the use of NAT and short-term outcomes in patients with PDAC unde

Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive

Vital capacity and COPD : The Swedish CArdioPulmonary bioImage Study (SCAPIS)

Background: Spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is based on the ratio of forced expiratory volume in 1 second (FEV1)/vital capacity (VC), either as a fixed value 1/VC ratio in a general population setting. The second aim was to evaluate the characteristics of subjects with COPD who obtained a higher SVC than FVC. Methods: Subjects (n=1,050) aged 50-64 years were i

Migration strategies of raptors – spatio-temporal adaptations and constraints in travelling and foraging

Popular Abstract in Swedish Min avhandling handlar om flyttning, det vill säga hur levande organismer rör sig mellan olika områden för att utnyttja resurser, undvika födobrist och som en anpassning till klimat- och miljöfaktorer. Vi begränsar det hela till fåglar's flyttning och bland dem ska vi koncentrera os's på rovfåglar. Rovfåglar är beroende av sina bytesdjur, som till exempel kan vara andraMy dissertation is about bird migration and addresses questions about how raptors adapt to the fluctuating environments during the transition seasons between breeding and wintering. The migration is highly affected by local prey abundance, foraging strategies, weather conditions and landscape patterns along the migration routes as well as navigation and orientation mechanisms and cues. Interesting

An Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated

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

The deepest X-ray view of high-redshift galaxies : Constraints on low-rate black hole accretion

We exploit the 7 Ms Chandra observations in the Chandra Deep Field-South (CDF-S), the deepest X-ray survey to date, coupled with CANDELS/GOODS-S data, to measure the total X-ray emission arising from 2076 galaxies at 3.5 ≤ z < 6.5. This aim is achieved by stacking the Chandra data at the positions of optically selected galaxies, reaching effective exposure times of ≥109s.We detect significant (>3.

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systema

Understanding the evolution of immune genes in jawed vertebrates

Driven by co-evolution with pathogens, host immunity continuously adapts to optimize defence against pathogens within a given environment. Recent advances in genetics, genomics and transcriptomics have enabled a more detailed investigation into how immunogenetic variation shapes the diversity of immune responses seen across domestic and wild animal species. However, a deeper understanding of the d