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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

Effect of a lifestyle-focused electronic patient support application for improving risk factor management, self-rated health, and prognosis in post-myocardial infarction patients : study protocol for a multi-center randomized controlled trial

BACKGROUND: Cardiac rehabilitation (CR) programs addressing risk factor management, educational interventions, and exercise contribute to reduce mortality after myocardial infarction (MI). However, the fulfillment of guideline-recommended CR targets is currently unsatisfactory. eHealth, i.e., the use of electronic communication for healthcare, including the use of mobile smartphone applications co

Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus

OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia.METHODS: 85 GDM/T2D loci in

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

Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis

Objective: To develop evidence-based guidelines for the management of giant cell arteritis (GCA) as a complement to guidelines in other areas of rheumatology, issued by the Swedish Society of Rheumatology. Methods: A working group selected key areas for recommendations, reviewed the available evidence, and wrote draft guidelines. These were discussed and revised according to standard procedures wi

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

Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk : An internal replication study of 800,000 individuals

Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50–50% cohorts from six European cohorts comprising 813,927 individuals. In the “discovery cohort”, we u

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

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

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

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

Regulation of fungal decomposition at single-cell level

Filamentous fungi play a key role as decomposers in Earth’s nutrient cycles. In soils, substrates are heterogeneously distributed in microenvironments. Hence, individual hyphae of a mycelium may experience very different environmental conditions simultaneously. In the current work, we investigated how fungi cope with local environmental variations at single-cell level. We developed a method based

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

Strategies for bringing stem cell-derived dopamine neurons to the clinic : A European approach (STEM-PD)

The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically

The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response

Checkpoint blockade therapies have changed the clinical management of metastatic melanoma patients considerably, showing survival benefits. Despite the clinical success, not all patients respond to treatment or they develop resistance. Although there are several treatment predictive biomarkers, understanding therapy resistance and the mechanisms of tumor immune evasion is crucial to increase the f

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