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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

Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis

In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibrobla

Low prevalence of known pathogenic mutations in dominant PD genes : A Swedish multicenter study

Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients. Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from popul

First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes

OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODS: We performed the first genome-wide association

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

Copeptin, B-type natriuretic peptide and cystatin C are associated with incident symptomatic PAD

Purpose: The aim of this study is to evaluate plasma biomarkers as predictors for peripheral arterial disease (PAD). Materials and methods: Prospective longitudinal cohort study of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (MDCS) (n = 5550; 1991–94). Cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional proatrial natriu

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

A prediction model for the 40-year risk of knee osteoarthritis in adolescent men

OBJECTIVES: To simplify the previously published Nottingham 12-year risk prediction model for knee osteoarthritis (OA) and examine whether it can be used to predict the 40-year risk of knee OA in young men.METHODS: We included 40 118 men aged 18 undergoing military conscription in Sweden 1969-70. Diagnostic OA codes were obtained from the Swedish National Patient Register 1987-2010. The original N

Stochastic unfolding of nanoconfined DNA : Experiments, model and Bayesian analysis

Nanochannels provide a means for detailed experiments on the effect of confinement on biomacromolecules, such as DNA. Here we introduce a model for the complete unfolding of DNA from the circular to linear configuration. Two main ingredients are the entropic unfolding force and the friction coefficient for the unfolding process, and we describe the associated dynamics by a non-linear Langevin equa

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

Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis

Background and aims: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue de

Pilot Study of Cardiotocography

A major problem in CTG analysis is that detectionof a suspicious pattern in short intervals so that one can reducethe damage caused by a delay of an automatic monitoringsystem. In this paper, we aim for improving intrapartumsurveillance based on signal processing and machine learningtechniques. We evaluate a classification method on a real dataset.

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men

Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study base

SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies

Germline mutations in the SAMD9 and SAMD9L genes, located in tandem on chromosome 7, are associated with a clinical spectrum of disorders including the MIRAGE syndrome, ataxia–pancytopenia syndrome and myelodysplasia and leukemia syndrome with monosomy 7 syndrome. Germline gain-of-function mutations increase SAMD9 or SAMD9L’s normal antiproliferative effect. This causes pancytopenia and generally

Claudin-4 Expression is Associated with Survival in Ovarian Cancer but Not with Chemotherapy Response

The tight junction protein claudin-4 has been reported to be overexpressed in advanced ovarian cancer. We investigated the prognostic significance of claudin-4 overexpression and whether claudin-4 expression could predict platinum response in primary ovarian carcinoma (OC). Claudin-4 expression was evaluated by immunohistochemistry in a tissue microarray of 140 OCs. Multivariable Cox-regression mo

Smoking and Alcohol Intake but Not Muscle Strength in Young Men Increase Fracture Risk at Middle Age : A Cohort Study Linked to the Swedish National Patient Registry

We aimed to determine the relationship between handgrip strength, smoking, and alcohol consumption in young men and fracture risk at middle age. Thus, we carried out a cohort study including young men undergoing conscription examination in Sweden from September 1969 to May 1970 at a typical age of 18 years. Data on muscle strength, height, weight, and lifestyle factors were linked to the National

On the self-assembly of αB-crystallin

The molecular chaperone αB-crystallin is a small heat shock protein that inhibits the aggregation of, among others, Aβ42 and α-synuclein. These proteins are major hallmarks of Alzheimer's and Parkinson's disease, respectively. In order to understand the mechanism with which αB-crystallin performs its chaperone function it is essential to characterize its self-assembly in terms of aggregate size di

Reduced protein solubility - cause or consequence in amyloid disease?

In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propos

Exploring the effect of menstrual loss and dietary habits on iron deficiency in teenagers : A cross-sectional study

Adolescent girls are particularly susceptible to iron deficiency due to increased iron requirements during the pubertal growth spurt, combined with iron loss following menarche. This study aimed to investigate the prevalence of heavy menstrual bleeding in an adolescent population using the SAMANTA questionnaire and to explore its relationship with dietary habits and iron deficiency. This cross-sec

Evaluating cell-specific gene expression using single-cell and single-nuclei RNA-sequencing data from human pancreatic islets of the same donors

Single-cell and single-nuclei RNA-sequencing (scRNA-seq and snRNA-seq) analyze cell-specific transcriptomes. However, only snRNA-seq applies to frozen biobanked samples. For human pancreatic islets, marker genes and reference-based cell type annotation methods are mainly from scRNA-seq datasets and may not be suitable for snRNA-seq. We compared human islet scRNA-seq and snRNA-seq data from the sam