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Cholesterol in mRNA-Lipid Nanoparticles can be Replaced with the Synthetic Mycobacterial Monomycoloyl Glycerol Analogue MMG-1

Messenger RNA (mRNA) vaccines based on lipid nanoparticles (LNPs) are stabilized with cholesterol, which is thought to be a critical LNP component because it is essential for membrane integrity and endosomal escape. Here, it is shown that cholesterol in LNPs can be replaced with an immunopotentiating lipid, i.e., a synthetic analogue of the C-type lectin receptor agonist monomycoloyl glycerol (MMG

Prediction of sentinel lymph node status in patients with early breast cancer using breast imaging as an alternative to surgical staging-a systematic review and meta-analysis

BACKGROUND: Prediction models for sentinel lymph node (SLN) status could potentially substitute surgical axillary staging in patients with early breast cancer. Several imaging modalities have been used with various feature extraction and selection approaches. This systematic review and meta-analysis aimed to evaluate prediction models for SLN status based on breast imaging in patients with early b

The spatiotemporal distribution of human pathogens in ancient Eurasia

Infectious diseases have had devastating effects on human populations throughout history, but important questions about their origins and past dynamics remain1. To create an archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun-sequencing data from 1,313 ancient humans covering 37,000 years of Eurasian history. We demonstrate the widespread presence of ancient bacterial,

Immunity to the microbiota promotes sensory neuron regeneration

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with

Predicting Occlusion Myocardial Infarctions in the Emergency Department Using Artificial Intelligence

ObjectivesThe objective was to develop an artificial intelligence (AI) model for predicting acute coronary occlusion myocardial infarction (OMI) in patients with chest pain at the emergency department (ED), using information that is widely available early in the ED assessment.MethodsIn a cohort of 24,511 consecutive adult ED patients with chest pain from 5 Swedish hospitals, OMI cases were identif

ClusterVAP : study protocol for multicentre proteomic endotyping of ventilator-associated pneumonia

INTRODUCTION: Ventilator-associated pneumonia (VAP) is the most frequent healthcare-associated infection in intensive care units and is associated with high morbidity and mortality. Current diagnostic criteria lack specificity, leading to misclassification and unnecessary antibiotic use. Identifying patient subgroups with a common pathophysiological basis (pneumoclusters) may distinguish true VAP

Capsule Regulation Shapes Klebsiella pneumoniae Pathogenesis by Balancing Adhesion, Biofilm Formation, and Intracellular Survival

Klebsiella pneumoniae is a major opportunistic pathogen, where the polysaccharide capsule is traditionally recognized as a critical virulence determinant. However, its role in surface interactions and intracellular adaptation remains incompletely understood. Here, we combined phenotypic assays with physicochemical analyses to dissect the contribution of the capsule. A wza knockout mutant display

Sequential infiltration synthesis and pattern transfer using 6 nm half-pitch carbohydrate-based fingerprint block copolymer

This study presents how sequential infiltration synthesis of trimethyl aluminium and water into a carbohydrate-based block copolymer was used to enable pattern transfer of 6 nm half-pitch horizontal cylinders into silicon. Specular neutron reflectometry measurements of poly(styrene)-block-maltoheptaose self-assembled into horizontal cylinders indicate an increasing content of alumina after each se

Health, cattle and ploughs : Bioarchaeological consequences of the Secondary Products Revolution in southern Sweden, 2300-1100 BCE

In this thesis diet and health of people who lived in southern Sweden 2300-1100 BCE is studied. The study is based on bioarchaeological analyses of human remains from 46 localities in the areas of Uppland, Närke, Östergötland, Västergötland, and Scania. The studies are based on skeletal remains from a minimum number of 310 individuals that have been analysed both osteologically and biochemically.

Bovine alpha 1-microglobulin/bikunin. Isolation and characterization of liver cDNA and urinary alpha 1-microglobulin

cDNA coding for alpha 1-microglobulin, an immunoregulatory plasmaprotein, was isolated from bovine liver. The sequence of a total of 1258 nucleotides revealed an open reading frame of 352 amino acids. This included alpha 1-microglobulin, 182 amino acids, and bikunin, the light chain of the plasmaprotein inter-alpha-inhibitor, 147 amino acids. The two proteins were connected by a basic tetrapeptide

Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.

Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-deri

A prospective cohort study identifying radiologic and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy

Introduction: Neoadjuvant chemotherapy (NAC) is an established treatment option for early breast cancer, potentially downstaging the tumor and increasing the eligibility for breast-conserving surgery (BCS). The primary aim of this study was to assess the rate of BCS after NAC, and the secondary aim was to identify predictors of application of BCS after NAC. Materials and methods: This was an obser

Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability

Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promoted Bifidobacter

Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies

Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, suc

Paradoxical increase in neuronal DNA fragmentation after neuroprotective free radical scavenger treatment in experimental traumatic brain injury

The mechanisms and role of nerve cell death after traumatic brain injury (TBI) are not fully understood. The authors investigated the effect of pretreatment with the oxygen free radical spin trap alpha-phenyl-N-tert-butyl-nitrone (PBN) on the number of neurons undergoing apoptosis after TBI in rats. Apoptotic cells were identified by the TUNEL method combined with the nuclear stain, Hoechst 33258,

Housing Temperature-Induced Stress Is Suppressing Murine Graft-versus-Host Disease through β2-Adrenergic Receptor Signaling

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic cell transplantation, a potentially curative therapy for hematologic diseases. It has long been thought that murine bone marrow-derived T cells do not mediate severe GVHD because of their quantity and/or phenotype. During the course of experiments testing the impact of housing temperatures on GVHD, we discovered