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The acceleration of DNA sequencing in samples from patients and population studies has resulted in extensive catalogues of human genetic variation, but the interpretation of rare genetic variants remains problematic. A notable example of this challenge is the existence of disruptive variants in dosage-sensitive disease genes, even in apparently healthy individuals. Here, by manual curation of puta
Structural variants (SVs) rearrange large segments of DNA1 and can have profound consequences in evolution and human disease2,3. As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD)4 have become integral in the interpretation of single-nucleotide v
Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors,
Background: Anal cancer is a rare disease, which might be the reason for the "one size fits all" approach still used for radiotherapy target contouring. To refine and individualize future guidelines, detailed and contemporary pattern of recurrence studies are needed. Methods: Consecutive anal cancer patients, all treated with curative intent intensity-modulated radiotherapy (IMRT), were retrospect
OBJECTIVE: To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies. METHODS: A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 partic
Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia c
Tau is a hallmark pathology of Alzheimer's disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer's disease co
AIMS: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with
OBJECTIVES: Atherothrombosis in the carotid arteries is a main cause of ischemic stroke and may depend on plaque propensity to complicate with rupture or erosion, in turn related to vulnerability features amenable to in vivo imaging. This would provide an opportunity for risk stratification and-potentially-local treatment of more vulnerable plaques. We here review current information on this topic
Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer’s disease (AD), by using a single dynamic [18F]flortaucipir positron emission tomography (PET) scan. Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [18F]flortauc
We show in this study the impact of transglutaminase (SB6), glycerol (Gly) and linoleic acid (LA) on the development of gliadin (Glia) solid edible foams. Two concentrations of SB6 were tested, 0.58 U/g and 1.17 U/g, and sufficiently high concentration of SB6 was found essential to crosslink the gliadins. Greater cross-linking in foam prepared with gliadin and 1.17 U/g of SB6 (2-TG-Glia) was follo
Objectives: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. Methods: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest
The nucleation of Alzheimer-associated Aβ peptide monomers can be catalyzed by preexisting Aβ fibrils. This leads to autocatalytic amplification of aggregate mass and underlies self-replication and generation of toxic oligomers associated with several neurodegenerative diseases. However, the nature of the interactions between the monomeric species and the fibrils during this key process, and indee
Background: External housing-related control beliefs (HCB) and general self-efficacy (GSE) influence different health outcomes in the general ageing population, but there is no information of their role in people ageing with Parkinson's disease (PD). This study aimed to longitudinally assess the role of external HCB and GSE on the association between housing accessibility and activities of daily l
Background: Novel technical solutions are called for to promote home-based exercise among community-dwelling stroke survivors supported by their caregivers. Lack of resources and knowledge about how to accomplish it, has been demonstrated. The objective of this study is to describe in detail the development of ActivABLES, a technical intervention to promote home-based exercise and physical activit
Coastal systems can act as filters for anthropogenic nutrient input into marine environments. Here, we assess the processes controlling the removal of phosphorus (P) and nitrogen (N) for four sites in the eutrophic Stockholm archipelago. Bottom water concentrations of oxygen (O2) and P are inversely correlated. This is attributed to the seasonal release of P from iron-oxide-bound (Fe-oxidebound) P
As the galactoside binding family of galectin proteins is involved in many physiological and pathological processes, the inhibitors of these proteins are considered to be of significant interest in the treatment of diseases such as cancer and fibrosis. Herein, fused tricyclic carbohydrate-benzene hybrid core structures are reported to be the selective inhibitors of galectin-1 and the N-terminal do
Objectives: The aim of this feasibility study was to evaluate the added value of contrast-enhanced mammography (CEM) in preoperative staging of malignant breast lesions, beyond standard assessment with digital mammography and ultrasound, as a base for a future prospective randomized trial. Materials and methods: Forty-seven patients, with confirmed or strongly suspected malignant breast lesions af
