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Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors

DNA methylation contributes to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements. In this study, we use CRISPR-Cas9 technology to delete DNMT1, the DNA methyltransferase key for DNA methylation maintenance, in human neural progenitor cells (hNPCs). We observe that inactivation of DNMT1 in hNPCs results in viable, proliferating cells despi

Mortality patterns in long-term survivors of childhood or adolescent central nervous system tumour in Sweden

PURPOSE: A growing number of young patients with central nervous system (CNS) tumour survived for more than five years. However, these long-term survivors might be at risk of multiple late effects thus leading to a higher risk of late mortality. We aimed to explore the risk of late mortality and the pattern of mortality among long-term survivors of childhood or adolescent CNS tumour.METHODS: We id

Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to syste

Incidence of Nocturia in Men with Lower Urinary Tract Symptoms Associated with Benign Prostatic Enlargement and Outcomes After Medical Treatment : Results from the Evolution European Association of Urology Research Foundation Prospective Multinational Registry

Background Nocturia is one of the most prevalent and bothersome lower urinary tract symptoms (LUTS) in men, leading to increased morbidity and mortality and a considerable economic burden on healthcare systems. Understanding its natural history, effect of pharmacotherapy, and predictors of failure of pharmacotherapy would allow optimised patient management. Objective To evaluate the prevalence an

Loci associated with ischaemic stroke and its subtypes (SiGN): A genome-wide association study

Background: The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additio

Use of terbinafine and risk of death in patients with prostate cancer : A population-based cohort study

Terbinafine is used for the treatment of several superficial fungal infections. In silico analyses and animal models suggest that terbinafine might have an anti-tumor effect. We aimed to explore whether subsequent administration of terbinafine might be associated with a lower mortality rate in patients with prostate cancer. We identified patients diagnosed with prostate cancer between July 2005 an

Amyloids and protein aggregation

A general discovery in protein science in the past few decades has been the finding that a number of unrelated proteins and peptides all have a marked propensity to form amyloid fibrils in vivo and in vitro. These structures have become known as the pathological hallmark of some of the most prevalent neurodegenerative diseases. More recently, the process of amyloid formation has been demystified t

Investigating the prognostic value of mammographic breast density and mammographic tumor appearance in women with invasive breast cancer : The Malmö Diet and cancer study

Background: High breast density is a risk factor for breast cancer. However, whether density is a prognostic factor is debatable. Also, tumor appearances are related to tumor characteristics. Here we investigate the relationship between breast cancer-specific survival and mammographic breast density and mammographic tumor appearances. Methods: Women in the Malmö Diet and Cancer study with invasive

Coronary artery restenosis and target lesion revascularisation in women by pregnancy history

Background Women's pregnancy history is associated with incident risk of coronary artery disease with some evidence also suggesting a relevance for prognosis following treatment. Objectives To study the associations between maternal history of preterm delivery, a history of small for gestational age infant, parity and age at first delivery with clinical restenosis after percutaneous coronary inter

Pain and labor outcomes : A longitudinal study of adults with cerebral palsy in Sweden

BACKGROUND: Pain is a global health concern with substantial societal costs and limits the activity participation of individuals. The prevalence of pain is estimated to be high among individuals with cerebral palsy (CP).OBJECTIVES: To estimate the association between pain and labor outcomes for adults with CP in Sweden.METHODS: A longitudinal cohort study based on data from Swedish population-base

The role of pain and walking difficulties in shaping willingness to undergo joint surgery for osteoarthritis : Data from the Swedish BOA register

OBJECTIVES: To investigate whether the association between pain intensity and willingness to undergo surgery is explained by walking difficulties, in patients with knee or hip osteoarthritis (OA).METHODS: This is an observational study using data from the Better management of patients with Osteoarthritis (BOA) register, which collects data from a publicly financed self-management programme for peo

Amyloid formation as a protein phase transition

The formation of amyloid fibrils is a general class of protein self-assembly behaviour, which is associated with both functional biology and the development of a number of disorders, such as Alzheimer and Parkinson diseases. In this Review, we discuss how general physical concepts from the study of phase transitions can be used to illuminate the fundamental mechanisms of amyloid self-assembly. We

Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery

While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-r

Acoustofluidic Three-Dimensional Motion of Suspended Cells at Near-Zero Acoustic Contrast in Homogeneous Media

Acoustic separation of suspension cells can be achieved by altering the properties of the cell medium. Cells of different types can then migrate in opposing directions in the sound field due to differences in their relative density and compressibility with respect to the surrounding fluid. For near-zero acoustic contrast the acoustic radiation force on cells becomes negligible, and it is the prima

The 5-Hydroxymethylcytosine Landscape of Prostate Cancer

Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first st

Long-Term Outcome Following Coronary Artery Stenting by History of Preterm Delivery

BackgroundWomen are at a greater risk of a major adverse cardiovascular event (MACE) after percutaneous coronary intervention than men. A history of preterm delivery is a female-specific risk factor for coronary artery disease, but its relevance in the treatment of coronary artery disease is unknown.ObjectivesThe purpose of this study was to analyze the association between a history of preterm del