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High-dose methotrexate (HDMTX) is a central component in the treatment of acute lymphoblastic leukemia, osteosarcoma, and some lymphomas and brain tumors. MTX is given at lethal doses and then is followed by rescue treatment with folinic acid (FA). Despite FA rescue, many patients suffer severe toxicity. The pharmacokinetics of FA rescue have not been sufficiently studied. However, optimization of
Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic struc
Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of availa
There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluid
We present the idea and illustrate potential benefits of having a tool chain of closely related regular, unscreened and screened hybrid exchange–correlation (XC) functionals, all within the consistent formulation of the van der Waals density functional (vdW-DF) method (Hyldgaard et al (2020 J. Phys.: Condens. Matter 32 393001)). Use of this chain of nonempirical XC functionals allows us to map wheWe present the idea and illustrate potential benefits of having a tool chain of closely related regular, unscreened and screened hybrid exchange–correlation (XC) functionals, all within the consistent formulation of the van der Waals density functional (vdW-DF) method (Hyldgaard et al (2020 J. Phys.: Condens. Matter 32 393001)). Use of this chain of nonempirical XC functionals allows us to map whe
Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynam
ObjectiveTo report trends and characteristics of post-biopsy infections, with regard to etiology and resistance patterns, in a large unique cohort from a single-centre using the same antibiotic prophylactic regimens during a 15-year period.MethodsThis is an observational cross sectional cohort study, including all patients who underwent transrectal prostate biopsy (TR PBx) guided by ultrasound for
Individuals with rapidly progressing atherosclerotic plaques are at higher risk of experiencing acute complications. Currently, we lack knowledge regarding factors in human plaque that cause rapid progression. Using the 14C bomb-pulse dating method, we assessed the physical age of atherosclerotic plaques and which biological processes were associated with rapidly progressing plaques. Interestingly
Swetra is primarily a research project, but its computer programs and reports may result in commercial products. The research group at Lund consists of a few persons only, which has advantages eind disadvantages. The main languages studied are Russian, English and Swedish. The grammatical model is Referent Grammar (RG) and the project is a spin-off of the development of that grammar. Referent Gram
Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging n
Background: High red cell distribution width (RDW) has been increasingly recognized as a risk factor for cardiovascular diseases (CVDs), but the underlying mechanisms remain unknown. Our aim was to explore the associations between RDW and plasma proteins implicated in the pathogenesis of CVD using a targeted proteomics panel. Methods: RDW and 88 plasma proteins were measured in a population-based
Asthma exacerbations are commonly triggered by rhinovirus infections. Viruses can activate the NFκB pathway resulting in airway inflammation and increased Th2 cytokine expression. NFκB signaling is also involved in early activation of IFNβ, which is a central mediator of antiviral responses to rhinovirus infection. Using a mouse model, this study tests our hypothesis that NFκB signaling is involve
Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food
Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the PI3K/AKT, RAS/MAPK and STAT5 signaling pathways. In this study, we examine the pathogenetic impact of somatic hemizygous 13q12.2 microdeletions in B-cell precursor acute lymphoblastic leukemia (B
Objective To investigate the association of infections with the subsequent development of giant cell arteritis (GCA) in a large population-based cohort from a defined geographic area in Sweden.Methods Patients diagnosed with biopsy-confirmed GCA between 2000 and 2016 were identified through the database of the Department of Pathology in Skåne, the southernmost region of Sweden. For each GCA case,
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified
Laser Shock Peening (LSP) and conventional Shot Peening (SP) are processes that aim to improve the surface properties of a workpiece by inducing compressive residual stresses. The peening processes also cause martensitic phase transformation in austenitic steels. Interestingly, experimental studies report significant differences in martensite content depending on the used peening process. This stuLaser Shock Peening (LSP) and conventional Shot Peening (SP) are processes that aim to improve the surface properties of a workpiece by inducing compressive residual stresses. The peening processes also cause martensitic phase transformation in austenitic steels. Interestingly, experimental studies report significant differences in martensite content depending on the used peening process. This stu
Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator Lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenot
Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imagi
Dysregulation of cytokines in the bone marrow microenvironment promotes acute myeloid leukemia cell growth. Due to the complexity and low throughput of in vivo stem-cell based assays, studying the role of cytokines in the bone marrow niche in a screening setting is challenging. Herein, we developed an ex vivo cytokine screen using 11 arrayed molecular barcodes, allowing for a competitive in vivo r
