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Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantat
Acute myeloid leukemia (AML) is a complex hematological malignancy marked by proliferation of immature myeloid cells with a dismal 5-year survival. A major challenge is the persistence of leukemia stem cells (LSCs) after standard treatment, leading to relapse. This thesis employs in vivo CRISPR/Cas9 screening to investigate critical AML and LSC molecular mechanisms, interrogating the dependancies
Enabling techniques for separating target cells, such as subgroups of white blood cells and cancercells from blood and other body fluids, are necessary for lab work facilitation, inline integration withhigh-end bioanalytical instrumentation, and for point-of-care or home testing. The work of this thesisaddresses this need by further studying an equilibrium-based ultrasonic wave-based technology ca
During Achilles tendon healing in rodents, besides the expected tendon tissue, also cartilage-, bone- and fat-like tissue features have been observed during the first twenty weeks of healing. Several studies have hypothesized that mechanical loading may play a key role in the formation of different tissue types during healing. We recently developed a computational mechanobiological framework to pr
Objective: To explore how cancer survivors have experienced their contacts with primary care after being diagnosed with cancer, focusing on the integration between cancer specialist and primary care, and participants’ views on what could make primary care services better at catering to the needs of cancer survivors. Design: A qualitative study in which data was collected through semi-structured di
OBJECTIVE: Orthostatic hypotension and resting heart rate (RHR) are associated with cardiovascular disease (CVD). However, it is unknown how these factors relate to subclinical CVD. We examined the relationship between orthostatic blood pressure (BP) response, RHR and cardiovascular risk factors, including coronary artery calcification score (CACS) and arterial stiffness, in the general population
Amyloid fibrils are associated with a number of different neurodegenerative diseases. Detailed knowledge of the fibril structure will be of importance in the search of therapy and may guide experiments to understand amyloid formation. In this paper we investigate the morphology of α-synuclein amyloid fibrils, associated with Parkinson’s disease, formed under different conditions. In particular, we
One of the core pathological features of Parkinson's disease (PD) is the loss of the dopaminergic nigrostriatal pathway which lies at the heart of many of the motor features of this condition as well as some of the cognitive problems. The importance of this pathological event is evident through the clinical benefits that are seen when patients with PD are treated with dopaminergic agents, at least
Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: This analysis includes 1,886 incident endometrial ca
Purpose We determined the characteristics of Chinese men undergoing initial prostate biopsy and evaluated the relationship between prostate specific antigen levels and prostate cancer/high grade prostate cancer detection in a large Chinese multicenter cohort. Materials and Methods This retrospective study included 13,904 urology outpatients who had undergone biopsy for the indications of prostate
Inducible defences allow prey to increase survival chances when predators are present while avoiding unnecessary costs in their absence. Many studies report considerable inter-individual variation in inducible defence expression, yet what underlies this variation is poorly understood. A classic vertebrate example of a predator-induced morphological defence is the increased body depth in crucian ca
Importance Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.Objective To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Design, Setting, and Participants Cross-s
BACKGROUND: X-ray micro-tomography (μCT) is a powerful non-destructive 3D imaging method applied in many scientific fields. In combination with propagation-based phase-contrast, the method is suitable for samples with low absorption contrast. Phase contrast tomography has become available in the lab with the ongoing development of micro-focused tube sources, but it requires sensitive and high-reso
Background: Brain metastases are associated with considerable negative effects on patients’ outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases. Materials and methods: Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. Afte
The derivation of dopamine neurons from human embryonic stem cells (hESCs) now offers a promising alternative to fetal tissue for cell replacement therapy (CRT) in Parkinson´s disease (PD). Using the appropriate chemical cues in vitro, hESCs can be patterned towards bona-fide ventral midbrain (VM) DA neurons that survive, reinnervate, release DA and provide functional recovery when transplanted in
BackgroundImmunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who
Background: Few MRA-based studies have systematically evaluated the prevalence and laterality of a fetal configuration of the posterior cerebral artery (FTP) in ischemic stroke populations versus other populations. This common variant is important in the setting of acute stroke and secondary prevention decisions. Objective: To determine the prevalence and laterality of FTP configurations in MRI-DW
BACKGROUND: We recently showed that striatal overexpression of brain derived neurotrophic factor (BDNF) by adeno-associated viral (AAV) vector exacerbated L-DOPA-induced dyskinesia (LID) in 6-OHDA-lesioned rats. An extensive sprouting of striatal serotonergic terminals accompanied this effect, accounting for the increased susceptibility to LID.OBJECTIVE: We set to investigate whether the BDNF effe
