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Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery

Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targe

No particle mass enhancement from induced atmospheric ageing at a rural site in northern Europe

A large portion of atmospheric aerosol particles consists of secondary material produced by oxidation reactions. The relative importance of secondary organic aerosol (SOA) can increase with improved emission regulations. A relatively simple way to study potential particle formation in the atmosphere is by using oxidation flow reactors (OFRs) which simulate atmospheric ageing. Here we report on the

Polygenic Risk Score for Coronary Heart Disease Modifies the Elevated Risk by Cigarette Smoking for Disease Incidence

BACKGROUND: Coronary heart disease (CHD) is a multifactorial disease with both genetic and environmental components. Smoking is the most important modifiable risk factor for CHD. Our aim was to test whether the increased CHD incidence by smoking is modified by genetic predisposition to CHD. METHODS AND RESULTS: Our study included 24 443 individuals from the MDCS (Malmö Diet and Cancer Study). A we

Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics

Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The hum

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes : the EPIC-InterAct case–cohort study

Aims/hypothesis: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. Methods: We used the European EPIC-InterAct case–cohort study including 11,124 incident adult-onse

Associations between physical activity and autonomic function during deep breathing test : the Swedish CArdioPulmonary bioImage Study (SCAPIS)

PURPOSE: The deep breathing test (DBT) is a sensitive test of cardiovagal function. The aim of this study was to explore associations between physical activity and sedentary time, measured by accelerometer, and autonomic function, using DBT.METHODS: In the Swedish Cardio-Pulmonary bioImage Study, men and women aged 50-64 were randomly invited from the general population. A total of 4325 subjects w

Spatiotemporal and microstructural characterization of heterotopic ossification in healing rat Achilles tendons

Achilles tendon rupture is a common debilitating medical condition. The healing process is slow and can be affected by heterotopic ossification (HO), which occurs when pathologic bone-like tissue is deposited instead of the soft collagenous tendon tissue. Little is known about the temporal and spatial progression of HO during Achilles tendon healing. In this study we characterize HO deposition, mi

Stratified Genetic Analysis Reveals Sex Differences In MPO-ANCA-associated Vasculitis

OBJECTIVE: To identify and genetically characterize subgroups of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) based on sex and ANCA subtype.METHODS: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for ass

Identification of phenotypically, functionally, and anatomically distinct stromal niche populations in human bone marrow based on single-cell RNA sequencing

Hematopoiesis is regulated by the bone marrow (BM) stroma. However, cellular identities and functions of the different BM stromal elements in humans remain poorly defined. Based on single-cell RNA sequencing (scRNAseq), we systematically characterized the human non-hematopoietic BM stromal compartment and we investigated stromal cell regulation principles based on the RNA velocity analysis using s

A molecular dynamics study on the influence of vacancies and interstitial helium on mechanical properties of tungsten

Tungsten is a prime candidate material for use in plasma facing components in nuclear fusion reactors. This would entail weathering extreme conditions, such as high thermal loads and particle bombardment. It is of vital importance to understand how tungsten mechanically responds to these conditions, and how it is impacted by the defects that form. The current communication considers how the mechan

Identification and quantification of degradome components in human synovial fluid reveals an increased proteolytic activity in knee osteoarthritis patients vs controls

Synovial fluid (SF) may contain cleavage products of proteolytic activities. Our aim was to characterize the degradome through analysis of proteolytic activity and differential abundance of these components in a peptidomic analysis of SF in knee osteoarthritis (OA) patients versus controls (n = 23). SF samples from end-stage knee osteoarthritis patients undergoing total knee replacement surgery an

Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions

Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever design of their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish

Reprogramming primary melanoma cells to dendritic cell fate enhances tumor immunogenicity

Background Direct cell reprogramming is characterized by the use of defined factors to rewire the transcriptional and epigenetic network of one cell-type into one of a different lineage. We have recently identified the transcription factors PU.1, IRF8, and BAFT3 (PIB) as sufficient to induce a type 1 conventional dendritic cell (cDC1) fate in both somatic and cancer cells.1,2 cDC1 is a rare dendri

Assessing efficacy and immune-stimulatory effects of tumor-derived dendritic cell reprogramming using immuno-competent 3D tumor spheroid model

Immunotherapy has brought hope for cancer treatment, but its clinical success remains limited. Recently, overexpression of the transcription factors PU.1, IRF8 and BATF3 (PIB) was shown to induce direct reprogramming of tumor cells into antigen-presenting type 1 conventional dendritic cells (cDC1s), a rare subset of immune cells with pivotal role in anti-cancer immunity. This strategy might open a

A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes : Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study

Background AU Self-reported: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly adherence to the Mediterranean diet has been: modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured

Airspace Dimension Assessment for early detection of lung function impairment in the peripheral airways of firefighters

Introduction Firefighters have increased risk of chronic respiratory disease. Standard clinical techniques used in medical checkups may not detect the earliest microstructural changes in peripheral airways. A new technique called Airspace Dimension Assessment (AiDA) has been shown to enable early detection of emphysema in COPD. This method may be useful in the occupational setting to detect early

Fluorescence Microscopy of Nanochannel-Confined DNA

Stretching of DNA in nanoscale confinement allows for several important studies. The genetic contents of the DNA can be visualized on the single DNA molecule level, and the polymer physics of confined DNA and also DNA/protein and other DNA/DNA-binding molecule interactions can be explored. This chapter describes the basic steps to fabricate the nanostructures, perform the experiments, and analyze