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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
Bmi1 was originally identified as a gene that contributes to the development of mouse lymphoma by inhibiting MYC-induced apoptosis through repression of Ink4a and Arf. It codes for the Polycomb group protein BMI-1 and acts primarily as a transcriptional repressor via chromatin modifications. Although it binds to a large number of genomic regions, the direct BMI-1 target genes described so far do n
Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardi
Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors
Objective: Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.Methods: We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified inci
It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal i
Purpose: Enterolactone (ENL) is formed in the human gut after consumption of lignans, has estrogenic properties, and has been associated with risk of prostate cancer. We examined the association between plasma ENL levels and prostate cancer in a nested case–control study within the population-based Malmö Diet and Cancer cohort. We also examined the association between plasma ENL and dietary and li
Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development.Methods and
Background: Copeptin is a reliable surrogate marker for the neurohypophyseal hormone vasopressin. Elevated plasma level of copeptin has been associated with cardiovascular and metabolic disease risk. Objective: To investigate the association between copeptin and risk of dementia. Methods: In all, 18,240 individuals from Malmö, Sweden, were examined between 2002 and 2006 (mean age 69.3 years, 69.8
Two Burmese eclipse calculations, one lunar and one solar, are analysed using examples from a Burmese manuscript. The fundamental parameters are with some important exceptions the same as in the Suryasiddhanta, but the handling of, for instance, parallax in the solar eclipse is different and much simplified. Specific to Burma are also the shadow calculations.
Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subject
Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide po
Background The relationship between meniscal tears and other joint pathologies with patient-reported symptoms is not clear. We investigated associations between structural knee pathologies identified at surgery with preoperative knee pain and function in patients undergoing arthroscopic meniscal surgery. Methods This study included 443 patients from the Knee Arthroscopy Cohort Southern Denmark (KA
Nanowires (NWs) have unique electrical and optical properties of value for many applications including lighting, sensing, and energy harnessing. Consumer products containing NWs increase the risk of NWs being released in the environment, especially into aquatic ecosystems through sewage systems. Daphnia magna is a common, cosmopolitan freshwater organism sensitive to toxicity tests and represents
The Netherlands is a small country with a relatively large population which experienced a rapid rate of land use changes from 2000 to 2008 years due to the industrialization and population increase. Land use change is especially related to the urban expansion and open agriculture reduction due to the enhanced economic growth. This research reports an investigation into the application of remote se
This study explores the application of spatial modelling techniques to generate susceptibility maps for a neglected zoonotic disease, visceral leishmaniasis (VL), in an endemic area in southern Caucasus that includes Iran, Armenia and Azerbaijan. The social and physical environment of southern Caucasus has been mainly characterized by the presence of several factors that are strongly associated wi
Background-Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. Methods and Results-We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmö Diet and Cancer study.
Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new
OBJECTIVES: Post-stroke cognitive impairment (PSCI) has considerable impact on patients and society. However, long-term studies on PSCI are scarce and may be influenced by assessment methods and selection bias. We aimed to (i) assess the prevalence of long-term PSCI; (ii) compare two common cognitive assessment instruments; and (iii) compare cognitive function of long-term stroke survivors with no
The role of blood pressure (BP) changes in dementia is debatable. We aimed to analyse how resting and postural BP changes relate to incident dementia over a long-term follow-up. In the prospective population-based Malmö Preventive Project, 18,240 study participants (mean age: 45 ± 7 years, 63% male) were examined between 1974 and 1992 with resting and standing BP measurement, and re-examined betwe
