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The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the ch
Background and aims: The endothelium plays a major role in atherosclerosis, yet the endothelial plaque surface is a largely uncharted territory. Here we hypothesize that atherosclerosis-driven remodeling of the endothelium is a dynamic process, involving both damaging and regenerative mechanisms. Methods: Using scanning electron microscopy (SEM) and immuno-SEM, we studied endothelial junction ultr
Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H. influenzae is dependent on specific antibodies and complement, which mediate serum bactericidal activity (SBA) and opsonization. Due to lack of normal classical and lectin complement pathw
Background: Standard biopsy for prostate cancer diagnosis is an unpleasant and sometimes painful procedure with a detection rate as low as around 50%. Consequently, an accurate blood-based test would be highly desirable to improve the predictive accuracy. However, the clinical value of a new blood test for diagnosing prostate cancer depends on its sensitivity and specificity, in relation to the se
To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arteri
Activation of receptor tyrosine kinases needs tight control by tyrosine phosphatases to keep their normal function. In this study, we investigated the regulation of activation of the type III receptor tyrosine kinase KIT by protein tyrosine phosphatase receptor type E (PTPRE). We found that PTPRE can associate with wild-type KIT and inhibit KIT activation in a dose-dependent manner, although the a
Aggression is a known problem in individuals being cared for in forensic settings, yet the evidence base for its treatment is scarce. Virtual Reality (VR) has been proposed as a promising addition to interventions in forensic settings, as it may increase the motivation among participants, bridge the gap between real life, therapeutic and laboratory experiences, and increase the ecological validity
We present a numerical model for the recently introduced simple and inexpensive micromachined aluminum devices with a polydimethylsiloxane (PDMS) cover for microparticle acoustophoresis. We validate the model experimentally for a basic design, where a microchannel is milled into the surface of an aluminum substrate, sealed with a PDMS cover, and driven at MHz frequencies by a piezoelectric lead-zi
Background: Saturated fat (SFA) has consistently been shown to increase liver fat, but the response appears variable at the individual level. Phenotypic and genotypic characteristics have been demonstrated to modify the hypercholesterolemic effect of SFA but it is unclear which characteristics that predict liver fat accumulation in response to a hypercaloric diet high in SFA. Objective: To identif
The CRISPR/Cas9 system is a versatile tool for functional genomics and forward genetic screens in mammalian cells. However, it has been challenging to deliver the CRISPR components to sensitive cell types, such as primary human hematopoietic stem and progenitor cells (HSPCs), partly due to lentiviral transduction of Cas9 being extremely inefficient in these cells. Here, to overcome these hurdles,
Background: In any study with voluntary participation, self-selection risks leading to invalid conclusions. If the determinants of selection are observed, it is however possible to restore the parameters of interest by reweighting the sample to match the population, but this approach has seldom been applied in epidemiological research. Methods: We reweighted the Malmö Diet and Cancer (MDC) study b
The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COV
Dietary carbohydrates have long been expected to be associated with risk of type 2 diabetes; however, the associations for many carbohydrates and carbohydrate-rich foods remain inconclusive. This study analysed associations between intakes of six types of carbohydrates and thirteen carbohydrate-rich foods with incident type 2 diabetes in 26 622 participants (61% women) in the Malmö Diet and Cancer
Aims: The Diabetes Incidence in Kronoberg (DIK) study of adult-onset diabetes used serological classification. Standard Mortality Rates (SMR) and Years of Life Lost (YLL) 15 years after adult-onset (18–100 years) of diabetes were compared to the population of Kronoberg. Methods: Of 1609/1660 (97%) patients, 112 (7%) had type 1 (T1D) (GADA+ and/or ICA+, and/or C-peptide < 0.25 nmol/l), and 1497 (93
Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associate
ObjectiveTo examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS).MethodsFor the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized we
Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to sc
In this work, arrays of predominantly relaxed InGaN platelets with indium contents of up to 18%, free from dislocations and offering a smooth top c-plane, are presented. The InGaN platelets are grown by metal-organic vapor phase epitaxy on a dome-like InGaN surface formed by chemical mechanical polishing of InGaN pyramids defined by 6 equivalent {101¯ 1} planes. The dome-like surface is f
Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/
