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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

The efficacy of cancer immunotherapy relies on the recruitment and activation of cytotoxic T cell responses against solid tumors by type 1 conventional dendritic cells (cDC1s). However, the generation of cDC1s for cancer immunotherapy faces significant limitations, including poor cell yield, functional heterogeneity, and susceptibility to immunosuppression in the tumor microenvironment (TME). We r

Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use

Heat transfer and friction factor in a dimple-pin fin wedge duct with various dimple depth and converging angle

Purpose - The dimple is adopted into a pin fin wedge duct which is widely used in modern gas turbine vane cooling structure trailing edge region. The purpose of this paper is to study the effects of dimple depth and duct converging angle on the endwall heat transfer and friction factor in this pin fin wedge duct. Design/methodology/approach - The study is carried out by using the numerical simulat

Autonomy in PhD-education – Supervising for Independence

According to the Swedish higher ordinance of education the development of autonomy of PhD students is of high importance. Graduates should be able to formulate new ideas and to independently assess and evaluate scientific results. Therefore it is interesting to investigate how the relationship between student and supervisor impacts the development of autonomy. In this work, we have evaluated the i

Potential Pitfalls of the Mx1-Cre System : Implications for Experimental Modeling of Normal and Malignant Hematopoiesis

Conditional knockout mice are commonly used to study the function of specific genes in hematopoiesis. Different promoters that drive Cre expression have been utilized, with the interferon-inducible Mx1-Cre still being the most commonly used “deleter strain” in experimental hematology. However, different pitfalls associated with this system could lead to misinterpretation in functional studies. We

Clonal conversion of B lymphoid leukemia reveals cross-lineage transfer of malignant states

Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we

Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis

Background: Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases.We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated

N-Terminal Prosomatostatin and Risk of Vascular Dementia

BACKGROUND: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults.METHODS: In

Generation of high-purity human ventral midbrain dopaminergic progenitors for in vitro maturation and intracerebral transplantation

Generation of precisely patterned neural cells from human pluripotent stem cells (hPSCs) is instrumental in developing disease models and stem cell therapies. Here, we provide a detailed 16-d protocol for obtaining high-purity ventral midbrain (VM) dopamine (DA) progenitors for intracerebral transplantation into animal models and for in vitro maturation into neurons. We have successfully transplan

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate

Impact of gender on echocardiographic characteristics in heart transplant recipients

Aims: Assessment following heart transplantation (HTx) is routinely performed using transthoracic echocardiography. Differences in long-term mortality following HTx related to donor-recipient matching have been reported, but effects of gender on cardiac size and function are not well studied. The aims of this study were to evaluate differences in echocardiographic characteristics of HTx recipients

HMGA2 promotes long-term engraftment and myeloerythroid differentiation of human hematopoietic stem and progenitor cells

Identification of determinants of fate choices in hematopoietic stem cells (HSCs) is essential to improve the clinical use of HSCs and to enhance our understanding of the biology of normal and malignant hematopoiesis. Here, we show that high-mobility group AT hook 2 (HMGA2), a nonhistone chromosomal-binding protein, is highly and preferentially expressed in HSCs and in the most immature progenitor

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that

Skin autofluorescence as a measure of advanced glycation end product levels is associated with carotid atherosclerotic plaque burden in an elderly population

BACKGROUND: Advanced glycation end product is an established risk marker in diabetic vascular disease, but its possible associations with atherosclerosis in a general population are yet to be investigated. We studied the degree of carotid atherosclerosis and its association with skin autofluorescence in an elderly population.METHODS: Carotid ultrasound and skin autofluorescence measurements were p

FADD (Fas-Associated Protein With Death Domain), Caspase-3, and Caspase-8 and Incidence of Ischemic Stroke

Background and Purpose- Apoptosis has been implicated in atherosclerosis and plaque rupture. This population-based study examined the relationship between 3 markers of apoptosis, that is, FADD (Fas-associated protein with death domain), caspase-3, and caspase-8, and incidence of ischemic stroke. Methods- The study population included 4356 participants from the MDCS (Malmö Diet and Cancer Study) ca

Lp-PLA 2 activity and mass and CRP are associated with incident symptomatic peripheral arterial disease

Long follow up is needed in prospective cohort study evaluation of plasma biomarkers for incident peripheral arterial disease (PAD) Middle-aged PAD-free individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5550; 1991–94) were followed prospectively for a median time of 23.4 years. The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) activity and