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Circulating cotinine concentrations and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnos

Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concent

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comp

Statin use and breast cancer survival - A Swedish nationwide study

Background: A sizeable body of evidence suggests that statins can cease breast cancer progression and prevent breast cancer recurrence. The latest studies have, however, not been supportive of such clinically beneficial effects. These discrepancies may be explained by insufficient power. This considerably sized study investigates the association between both pre- and post-diagnostic statin use and

Identification of novel diagnostic biomarkers for deep venous thrombosis

The combination of a negative D-dimer and a Wells score can rule out, but not confirm, a diagnosis of deep venous thrombosis (DVT). We aimed to identify new diagnostic biomarkers for DVT and to investigate their relationship with hypercoagulability markers [D-dimer and activated protein C-protein C inhibitor (APC-PCI) complex]. We screened 92 cardiovascular-specific proteins in plasma samples from

Molecular regulation of differentiation in early B-lymphocyte development

B-lymphocyte differentiation is one of the best understood developmental pathways in the hematopoietic system. Our understanding of the developmental trajectories linking the multipotent hematopoietic stem cell to the mature functional B-lymphocyte is extensive as a result of efforts to identify and prospectively isolate progenitors at defined maturation stages. The identification of defined proge

Exploring spatial patterns of cardiovascular disease in Sweden between 2000 and 2010

AIMS: Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity worldwide, including in Sweden. The main aim of this study was to explore the temporal trends and spatial patterns of CVD in Sweden using spatial autocorrelation analyses.METHODS: The CVD admission rates between 2000 and 2010 throughout Sweden were entered as the input disease data for the analytic processes

Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study

Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers

Hospitalizations due to systemic connective tissue diseases: : Secular trends and regional disparities in Sweden, 1998-2016

AIM: To investigate secular trends and regional disparities in hospitalizations due to systemic connective tissue diseases (SCTD) in Sweden from 1998 to 2016.METHOD: We identified all hospital admissions with a principal diagnosis of SCTD (ICD-10 codes: M30-M36) from the Swedish National Patient Register. Joinpoint regression was used to assess secular trends in age-standardized hospitalization ra

Cohesin in haematopoiesis and leukaemia

Purpose of review Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin h

Vitamin D in Graves Disease : Levels, Correlation with Laboratory and Clinical Parameters, and Genetics

Objective: The aim was to compare the vitamin D levels in patients with Graves disease (GD) with the general population and to correlate the vitamin D levels with laboratory and clinical parameters in GD. Moreover, we examined the genetic variation in genes involved in the vitamin D metabolism and their association with GD.Methods: The levels of vitamin D were compared in 292 patients with newly d

Sick leave before and after arthroscopic partial meniscectomy due to traumatic meniscal tear

Summary Objective There is limited knowledge on sick leave associated with arthroscopic partial meniscectomy (APM) due to traumatic meniscal tear and its potential gender differences. Thus, our aim was to determine gender-specific sick leave before and after APM. Method In Skåne region, Sweden, we identified patients, aged 18–59 years diagnosed with traumatic meniscal tear without ligament injury,

Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease

Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (hunting

Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat

BACKGROUND: In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown. AIM: To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individual

Transposable Elements : A Common Feature of Neurodevelopmental and Neurodegenerative Disorders

The etiology of most neurological disorders is poorly understood and current treatments are largely ineffective. New ideas and concepts are therefore vitally important for future research in this area. This review explores the concept that dysregulation of transposable elements (TEs) contributes to the appearance and pathology of neurodevelopmental and neurodegenerative disorders. Despite TEs maki

Kronisk myeloisk leukemi : Förebild för målstyrd terapi

Vid kronisk myeloisk leukemi har målstyrd, kontinuerlig behandling med tyro­sinkinashämmare lett till dramatiskt förbättrad överlevnad.Chronic myeloid leukemia (CML) pioneered as the first human malignancy linked to a specific cytogenetic aberration (the Philadelphia chromosome), which led the way to specific targeted therapies with imatinib (Glivec) and later tyrosine kinase inhibitors (TKI). Continuous TKI administration, blocking the oncogenic fusion protein Bcr-Abl, has revolutionized the outcome of CML, transforming an almos

Exome-wide association study of plasma lipids in >300,000 individuals

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in m

EZH2 regulates the developmental timing of effectors of the pre-Antigen receptor checkpoints

The histone methyltransferase EZH2 is required for B and T cell development; however, the molecular mechanisms underlying this requirement remain elusive. In a murine model of lymphoid-specific EZH2 deficiency we found that EZH2 was required for proper development of adaptive, but not innate, lymphoid cells. In adaptive lymphoid cells EZH2 prevented the premature expression of Cdkn2a and the conse