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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

Population-Level Analysis to Determine Parameters That Drive Variation in the Plasma Metabolite Profiles

The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of fli

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of over

Death after awakening from post-anoxic coma : The "best CPC" project

Background: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. Methods: Observational multicenter cohort study on patients resuscitated from CA in eight European

The Physical Housing Environment and Subjective Well-Being Among Older People Using Long-Term Care Services in Japan

For older people using long-term care services, the conditions of their life-space may be critical. The relationships between the physical housing environment and aspects of health were examined among older people in Japan (aged 65+ years, N = 1,928) by multivariable logistic regression analysis, adjusting for sociodemographic characteristics. Lack of safety, low access to emergency assistance, lo

Low incidence of hemorrhagic cystitis following ex vivo T-cell depleted haploidentical hematopoietic cell transplantation in children

Hemorrhagic cystitis (HC) is a debilitating complication following allogenic hematopoietic cell transplantation (HCT). HLA disparity and T-cell depletion have been implicated as risk factors for HC. However, reports on the incidence and risk factors for HC in ex vivo T-cell depleted haploidentical HCT (haploHCT) in children are lacking. We studied 96 haploHCT procedures performed in 83 children be

Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies

Monoclonal antibodies targeting CD20 are central in the treatment of B-cell lymphomas. In diffuse large B-cell lymphoma (DLBCL), inactivating mutations of the histone acetyltransferases CREB-binding protein (CBP) and EP300 are common. Moreover, knockdown of CBP in DLBCL has been shown to result in aberrant transcriptional silencing. Expression of CD20 is sensitive to epigenetic manipulation, and h

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

Homelessness and risk of end-stage renal disease

To identify homeless people with chronic kidney disease (CKD) who were at highest risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674 domiciled people with CKD receiving public health care. We developed four risk prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888 domiciled people progressed to ESRD during follow-up (median: 6.6 years). Homeless

Metabolically healthy obesity (MHO) in the Malmö diet cancer study - Epidemiology and prospective risks

BACKGROUND/AIMS: Metabolically healthy obesity (MHO) remains controversial, since the underlying mechanisms behind this phenotype remain unclear. We aimed to investigate the characteristics of MHO, as well as prospective risks.METHOD: A cross-sectional analysis was carried out in a subsample of 3812 obese subjects selected from the Malmo diet cancer study (n=28,403). Subjects with MHO (n=1182) wer

Impact of a national guideline on use of knee arthroscopy : An interrupted time-series analysis

OBJECTIVE: To assess the impact of the Swedish health authority recommendation against the use of knee arthroscopy in patients aged ≥40 years with knee osteoarthritis (OA).DESIGN: Interrupted time series analysis.SETTING: Public health care in Skåne region.PARTICIPANTS: Patients aged ≥40 years who underwent knee arthroscopy from January 2010 to December 2015.INTERVENTION(S): National guideline's r

COSCA (Core Outcome Set for Cardiac Arrest) in Adults : An Advisory Statement From the International Liaison Committee on Resuscitation

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on R

COSCA (Core Outcome Set for Cardiac Arrest) in Adults : An Advisory Statement From the International Liaison Committee on Resuscitation

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on R

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

Associations among housing accessibility, housing-related control beliefs and independence in activities of daily living : a cross-sectional study among younger old in Sweden

There is some evidence that housing accessibility, external housing-related control beliefs (HCB) and activities of daily living (ADL) are associated in complex ways; however, these pathways have not been explored in younger old. The aim was to assess the role of external HCB in the relationship between housing accessibility and ADL by applying moderation and mediation models. This was a cross-sec

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