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NCF1-339 polymorphism is associated with altered formation of neutrophil extracellular traps, high serum interferon activity and antiphospholipid syndrome in systemic lupus erythematosus

Objectives: A single nucleotide polymorphism in the NCF1 gene (NCF1-339, rs201802880), encoding NADPH oxidase type II subunit NCF1/p47phox, reducing production of reactive oxygen species (ROS) is strongly associated with the development of systemic lupus erythematosus (SLE). This study aimed at characterising NCF1-339 effects on neutrophil extracellular trap (NET) formation, type I interferon acti

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporter

Dual modulation of neuron-specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons

Direct neuronal reprogramming can be achieved using different approaches: by expressing neuronal transcription factors or microRNAs; and by knocking down neuronal repressive elements. However, there still exists a high variability in terms of the quality and maturity of the induced neurons obtained, depending on the reprogramming strategy employed. Here, we evaluate different long-term culture con

Plasma Lipidome and Prediction of Type 2 Diabetes in the Population-Based Malmö Diet and Cancer Cohort

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle. RESEARCH DESIGN AND METHODS: At baseline, 178 lipids were measured by mass spectrometry in 3,668 participants wit

Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T c

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

Heart rate and premature atrial contractions at 24hECG independently predict atrial fibrillation in a population-based study

BACKGROUND: Low resting heart rate and premature atrial contractions (PACs) predict incident atrial fibrillation (AF) and could be interdependent, since PACs occur in the gaps between normal beats.OBJECTIVE: To study the association between low heart rate at 24hECG, PACs and incident AF in a prospective population-based cohort.METHODS: In the Malmö Diet and Cancer study, 24hECGs were performed in

Orchid colonization: multiple parallel dispersal events and mosaic genetic structure in Dactylorhiza majalis ssp. lapponica on the Baltic island of Gotland.

Background and Aims The island of Gotland in the Baltic Sea had no contact with surrounding continental areas since the withdrawal of the Weichselian ice sheet at ca 17 ka BP. Plants present on Gotland must have arrived by long distance dispersal, so populations are expected to exhibit reduced levels of genetic diversity compared with surrounding mainlands. However, orchids have very small seeds, Background and AimsThe island of Gotland in the Baltic Sea has had no contact with surrounding continental areas since the withdrawal of the Weichselian ice sheet at approx. 17 ka BP. Plants present on Gotland must have arrived by long-distance dispersal, so populations are expected to exhibit reduced levels of genetic diversity compared with populations on surrounding mainlands. However, orchids

Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE-/- Mice

BACKGROUND: Hypercholesterolemic mice lacking factors required for activation of CD4+ T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major histocompatibility complex class II (M

Vitamin D receptor expression in invasive breast tumors and breast cancer survival

Background: Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts

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

Psychoactive drugs and the management of time

The main objective for this article is to explore how users of psychoactive drugs experience time and the role psychoactive drugs play in the management and construction of time. The data in this study consists of different kinds of written documents such as anecdotal accounts and scientific articles and reports which was collected using a purposeful sampling technique. One important result is tha

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

Diagnostic pathway efficacy for urinary tract cancer : population-based outcome of standardized evaluation for macroscopic haematuria

Objective: This study assessed a national healthcare intervention launched in Sweden in 2015 to reduce the time between macroscopic haematuria, diagnosis and treatment of urinary tract cancer. Methods: The outcome of the first 11 months was evaluated in 1697 individuals referred to a standardized care pathway for urinary tract cancer compared with 174 patients with conventionally diagnosed urothel

Tool Wear Mechanisms of pcBN tooling during High-Speed Machining of Gray Cast Iron

The presence of graphite particles in gray cast iron commonly implies a good machinability, especially if compared to common steels. However, increasing industrial demands have resulted in a new interest for high-speed machining of these materials with higher performing tool materials than the traditionally used. Thus, the research presented in this paper focuses on evaluating the active tool wear

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

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

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