Science news from the medical university Karolinska Institutet (KI) in Sweden. Our vision is to advance knowledge about life and strive towards better health for all. https://ki.se/
Link to publication ⬇️ link.springer.com/article/10.1...
Single-cell analysis of the progeria arterial wall reveals progerin-induced progressive, cell type-specific dysfunction and somatic mutation accumulation - Genome MedicineBackground The premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by de novo LMNA mutations producing the aberrant Lamin A isoform progerin. HGPS patients die from cardiova...link.springer.comLink to publication ⬇️ link.springer.com/article/10.1...
Selenite modulates phenotype-dependent epithelial–mesenchymal plasticity in pancreatic ductal adenocarcinoma: integrated in vitro analyses and patient-derived ex vivo tissue-slice cultures - Journal o...Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by profound therapy resistance, desmoplasia, and phenotypic plasticity. While sodium selenite is a redox-active compound with report...link.springer.comLink to publication ⬇️ heart.bmj.com/content/earl...
Feasibility of early double sequential defibrillation in out-of-hospital cardiac arrest: the double-D randomised pilot trialBackground Double sequential defibrillation (DSD) is a promising treatment for patients with out-of-hospital cardiac arrest (OHCA) with refractory ventricular fibrillation. The reproducibility and gen...heart.bmj.comLink to publication: doi.org/10.1186/s130...
Systemic multi-omics analysis reveals interferon response heterogeneity and links lipid metabolism to immune alterations in severe COVID-19 - Genome MedicineBackground Interferons play a central role in antiviral defense, but their dysregulation contributes to inflammation and immune dysfunction in respiratory viral infections, including COVID-19. While interferon-stimulated genes (ISGs) are essential effectors of this response, their expression patterns in patients are heterogeneous and not always predictive of disease severity. The immunometabolic consequences of this heterogeneity remain poorly understood. Methods We analyzed hospitalized COVID-19 patients (n = 37) and uninfected controls (n = 31) using whole-blood transcriptomics, immune cell deconvolution, plasma proteomics, and standardized plasma metabolomics from a previously generated dataset within this cohort. Patients were stratified into low (LIS), moderate (MIS), and high (HIS) ISG score clusters. Plasma innate immune activation markers were measured by ELISA. Interferon-directed antibody reactivity was analyzed by multiplex bead-based assays measuring antigen reactivity. Functional immune responses were assessed via ex vivo stimulation of healthy donor immune cells with patient plasma, and correlations were performed between metabolites and immune activation markers. Results HIS patients exhibited increased inflammatory mediators and innate immune cell expansion compared with LIS and MIS groups. However, within the HIS group, severe cases displayed distinct metabolic and immune dysregulation. Specifically, severe HIS cases showed reductions in phospholipids, sphingolipids, and tricarboxylic acid cycle intermediates, suggestive of disrupted mitochondrial and lipid metabolism. Plasma from severe HIS patients tended to impair neutrophil and monocyte activation, indicating functional attenuation of innate immune activation within a shared high-ISG background. Correlation analysis revealed that branched-chain lipids, tryptophan-derived metabolites, and a branched-chain dicarboxylic acid were positively associated with immune activation markers. Although type-I interferon neutralization was detected in a subset of patients with IFN antigen reactivity, these samples did not fully account for the observed ISG heterogeneity or disease severity. Conclusions High ISG expression in COVID-19 defines a transcriptional endotype associated with systemic inflammation and innate immune activation. However, severe cases within this group exhibit metabolic constraints and reduced innate immune responsiveness, supporting an immune-metabolic axis in which inflammatory mediators and altered lipid/energy metabolism intersect with innate immune function. These findings motivate future studies to determine whether interferon-associated immune-metabolic states during acute infection relate to persistent inflammation or post-acute sequelae in selected patient subsets.doi.orgLink to publication ⬇️ jamanetwork.com/journals/jam...
Diet Quality and Dementia Risk in Older Adults With Alzheimer PathologyThis cohort study examines the association of diet quality with dementia risk across biomarkers for Alzheimer disease pathology and neurodegenerative and glial processes in older adults without dement...jamanetwork.comLink to publication: doi.org/10.1111/dom....
Underdiagnosed and Undertreated: Obesity and Its Cardiometabolic Burden in Swedish Clinical Practice—Insights From the AROS DatabaseAims
To quantify real-world diagnosis and treatment of obesity in Sweden, describe cardiometabolic comorbidity burden across obesity classes, and compare long-term cardiovascular outcomes with the g.....doi.orgLink to publication ⬇️ journals.plos.org/plosmedicine...
The data transparency crisis in research: Lessons from systematic reviews and meta-analysesSystematic reviews and meta-analyses underpin clinical guidelines and health policy, yet their validity may be compromised by limited access to underlying datasets and associated analytical code. This...journals.plos.orgLink to publication ⬇️ jamanetwork.com/journals/jam...
Measured and Estimated Glomerular Filtration Rates and Risk of Adverse Health OutcomesThis study evaluates associations between major clinical outcomes and measured glomerular filtration rate (GFR), estimated GFR (eGFR) for plasma creatinine, eGFR for cystatin C, and eGFR for a combina...jamanetwork.comLink to publication ⬇️ www.sciencedirect.com/science/arti...
Spatiotemporal analysis reveals distinct inflammatory programs underlying chronic colitisInflammatory bowel disease (IBD) is a complex disorder that is often resistant to immunomodulatory treatments. Here, to understand how immune, epithel…www.sciencedirect.comLink to publication: www.nature.com/articles/s41...
Rare regulatory mutations disrupt mesenchymal molecular programs driving endocardial cushion formation in bicuspid aortic valve - Nature CommunicationsBicuspid aortic valve is a congenital malformation that increases risk for cardiac complications. Here, the authors show that rare non-coding mutations contribute to bicuspid aortic valve by disruptin...www.nature.comLink to publication ⬇️ www.thelancet.com/journals/lan...
Aetiology, outcomes, and in-hospital mortality predictors of suspected paediatric central nervous system infections in southwestern Uganda: a prospective cohort studyDespite advances in infectious disease control, children with suspected CNS infections
in southwestern Uganda continue to experience high mortality and neurological sequelae.
Strengthened prevention, ...www.thelancet.comLink to publication: www.nature.com/articles/s41...
Investigating antibody cross-reactivity and transmission dynamics of alphaviruses and flaviviruses using a multiplex serological assay - Nature CommunicationsArboviruses often co-circulate, but cross-reactivity hampers serological diagnostics. Here, the authors paired multiplex serology with competitive immunoassays and Bayesian modelling to quantify antib...www.nature.comLink to publication ⬇️ link.springer.com/article/10.1...
Linking gut microbiome to HIV-1 reservoir size in people living with HIV - Gut PathogensThe gut microbiome is altered during HIV-1 infection and contributes to immune dysfunction and inflammation in people living with HIV (PLWH), these changes may persist despite effective antiretroviral therapy (ART). We explored the associations between the fecal gut microbiome and blood HIV-1 reservoir size in PLWH (n = 30) on long-term ART. The intact proviral DNA assay (IPDA) and shotgun metagenomic sequencing were performed to identify microbial species and metabolic pathways associated with the size of the HIV-1 reservoir. PLWH with a smaller intact reservoir exhibited lower evenness compared to individuals with a larger intact reservoir. We found that Phocaeicola plebeius and Lachnospira sp000437735 were significantly enriched in individuals with a smaller intact reservoir and lower intact-to-total proviral ratio, respectively. We observed a negative association between Faecalibacterium prausnitzii and a positive association of Prevotella copri, with the intact proviral reservoir size. Additionally, the metabolic pathways of glycolysis and branched-chain amino acid biosynthesis were enriched in individuals with larger reservoir. HIV reservoir size in blood is associated with gut microbiome evenness, specific metabolic pathways and microbial signatures, including Lachnospira, Prevotella, and Faecalibacterium. Our findings underscore the potential role of the gut microbiome in viral persistence, raising the possibility that modulating microbial composition could influence the HIV reservoir.link.springer.comLink to publications: www.nature.com/articles/s41... www.nature.com/articles/s41... www.nature.com/articles/s41...
Investigating the replicability of the social and behavioural sciences - NatureA large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.www.nature.comLink to publication ⬇️ academic.oup.com/eurheartj/ad...
Heart failure with reduced ejection fraction in Sweden: patient adherence and persistence to quadruple pharmacotherapy prescriptionAbstractBackground and Aims. Real-world uptake of heart failure with reduced ejection fraction (HFrEF) treatments relies on physician prescriptions but alsacademic.oup.comLink to publication ⬇️ jamanetwork.com/journals/jam...
Modified Checklist for Autism in Toddlers in a Neonatal High-Risk PopulationThis cohort study assesses the diagnostic accuracy of the Modified Checklist for Autism in Toddlers in a neonatal high-risk population in Sweden and identifies factors associated with subsequent clini...jamanetwork.comLink to publication: ard.eular.org/article/S000...
Inhibition of the type I interferon receptor pathway protects against muscle weakness induced by dermatomyositis serumDermatomyositis (DM) is characterised by systemic inflammation, debilitating muscle
weakness, cutaneous lesions, and increased mortality. An upregulation of type I interferon
(IFN)-stimulated genes is...ard.eular.orgLink to publications: www.cell.com/immunity/ful... doi.org/10.1016/j.im...
Genetically diverse influenza antibodies highlight the role of IG germline gene variation and inform population-comprehensive vaccine strategiesVariation in antibody genetics, as illustrated in the accompanying paper by Corcoran
et al., can present a challenge to the development of population-wide protective vaccines.
Fischer, Corcoran, et al...www.cell.com