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Rare, Damaging DNA Variants in CORIN and Risk of Coronary Artery Disease : Insights From Functional Genomics and Large-Scale Sequencing Analyses

BACKGROUND: Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD). METHODS: We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested

Complementary Feeding Habits in Children Under the Age of 2 Years Living in the City of Adama in the Oromia Region in Central Ethiopia : Traditional Ethiopian Food Study

Updated information on child feeding practices, nutritional status, and trends related to parental sociodemographic variables is required in developing countries. The objective of this study was to describe infant feeding practices and associated sociodemographic factors among Ethiopian children with an emphasis on complementary feeding (CF). Information on infant feeding and anthropometric measur

Socioeconomic and clinical predictors of mortality in patients with acute dyspnea

Background: Factors predicting long-term prognosis in patients with acute dyspnea may guide both acute management and follow-up. The aim of this study was to identify socioeconomic and clinical risk factors for all-cause mortality among acute dyspnea patients admitted to an Emergency Department. Methods: We included 798 patients with acute dyspnea admitted to the ED of Skåne University Hospital, M

Plasma calprotectin in the emergency department : a potential clinical biomarker for patients with infectious diseases

Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other c

Mechanism of Secondary Nucleation at the Single Fibril Level from Direct Observations of Aβ42 Aggregation

The formation of amyloid fibrils and oligomers is a hallmark of several neurodegenerative disorders, including Alzheimer's disease (AD), and contributes to the disease pathway. To progress our understanding of these diseases at a molecular level, it is crucial to determine the mechanisms and rates of amyloid formation and replication. In the context of AD, the self-replication of aggregates of the

Experimental study and modeling of the heat flux acting on the tool flank when machining

Adequate setting of the boundary conditions for the heat equation when modeling the temperature distribution in the cutting tool is one of the key points. The boundary conditions on the tool surfaces can be divided into two groups: conditions that describe heat losses (heat exchange with the environment) and conditions that characterize the heat source that heats up the tool (heat flux from the cu

Effect of energy renovation and occupants' activities on airborne particle concentrations in Swedish rental apartments

Exposure to airborne particles causes detrimental health effects, hence their assessment in indoor environments, where people spend most of the time, is important. The influence of energy renovation and occupants' activities on airborne particle concentrations was assessed in seven occupied Swedish residences. Ultrafine particle (UFP, <100 nm) number concentrations, PM2.5 (<2.5 μm) and black carbo

Proteome of fluid from human ovarian small antral follicles reveals insights in folliculogenesis and oocyte maturation

STUDY QUESTION: Is it possible to identify by mass spectrometry a wider range of proteins and key proteins involved in folliculogenesis and oocyte growth and development by studying follicular fluid (FF) from human small antral follicles (hSAF)?SUMMARY ANSWER: The largest number of proteins currently reported in human FF was identified in this study analysing hSAF where several proteins showed a s

A new pipeline for the normalization and pooling of metabolomics data

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, t

Novel diagnostics and treatment of acute lung injury and transplantation - Preclinical and clinical implementation

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS) limit the utilization of donor lungs for transplantation but is also a common cause of death in the intensive care unit. There is a general lack of diagnostic tools by which to assess lung function in ARDS but, in addition, the treatments offered are limited. In the present thesis, the aim was to explored

Collaboration in grant proposals and assessments in ageing research – justification or a quest for a collaborology?

Orientation towards application, transdisciplinarity and social distribution are prominent ideas when policy prescribes how to conduct research on complex, real-world issues. Issues dealt with in ageing research are both epistemologically complex and politically contentious. By using the metaphor of ‘travelling ideas,' we have followed these ideas on their journey into 17 approved grant proposals

Serum zinc and dietary intake of zinc in relation to risk of different breast cancer subgroups and serum levels as a marker of intake: a prospective nested case-control study

PurposeZinc has been suggested to be protective against breast cancer, but the evidence remains inconclusive. One reason for inconsistent findings in previous studies may be that zinc only influences the risk of developing certain subtypes of breast cancer. Our study is the first study assessing zinc levels in relation to the risk of different breast cancer subgroups, defined by their tumor charac

Cooperativity of α-Synuclein Binding to Lipid Membranes

Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. It provides tight regulation over a narrow concentration interval of a ligand, thus enabling switching to be triggered by small concentration variations. The data presented in this work reveal strong positive cooperativity of α-synuclein binding to phospholipid membranes. Fluorescence cross-correlation

Variability in end-of-life healthcare use in patients with osteoarthritis : a population-based matched cohort study

PURPOSE: To investigate the patterns of healthcare use (HCU) at the last year of life in persons with osteoarthritis (OA).METHODS: Using linked registers, we identified persons aged≥ 65 years who died during 2003-2014 and were resided in the Skåne region during 5-year prior to death. Among these, we randomly matched decedents with a principal OA diagnosis prior to the last year of life (OA cohort,

Targeting NSG Mice Engrafting Cells with a Clinically Applicable Lentiviral Vector Corrects Osteoclasts in Infantile Malignant Osteopetrosis

Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in IMO. Two mammalian

Altered white matter microstructure in lupus patients : A diffusion tensor imaging study

Background: The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms. Methods: Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range

Trans-ethnic association study of blood pressure determinants in over 750,000 individuals

In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program

Lung function and CT lung densitometry in 37-to 39-year-old individuals with alpha-1-antitrypsin deficiency

Background: Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening program in 1972–1974 and has been followed-up since birth. Our aim was to study whether the cohort has signs of emphysema in pulmonary function tests (PFTs)

Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Vari

Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody

Overall survival of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved with platinum-based salt treatments and recently with targeted therapies and immunotherapies. However, treatment failure occurs due to acquired or emerging tumor resistance. We developed a monoclonal antibody against the proform of neurotensin (LF-NTS mAb) that alters the homeostasis of tumor