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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced

The effect of smoking on carotid intima-media thickness progression rate and rate of lumen diameter reduction.

The purpose of the study was to investigate the long-term associations between smoking habits, environmental tobacco smoke exposure (ETS), carotid intima-media thickness (IMT) progression rate, and rate of lumen diameter reduction in the carotid artery during a 16-year follow-up. Another objective was to investigate if an effect of smoking on progression rate could be explained by increased low gr

A low-frequency inactivating AKT2 variant enriched in the finnish population is associated with fasting insulin levels and type 2 diabetes risk

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding var

Ultra-high field magnetic resonance imaging parameter mapping in the posterior horn of ex vivo human menisci

Objective: To investigate the relationship between meniscus magnetic resonance (MR) relaxation parameters and meniscus degradation through quantitative imaging of ex vivo posterior horns of menisci from subjects with and without knee osteoarthritis (OA). Design: We sampled medial and lateral menisci from ten medial compartment knee OA patients (mean age 63 years) undergoing total knee replacement

The climate, the fuel and the land use: long-term regional variability of biomass burning in boreal forests

The influence of different drivers on changes in North American and European boreal forests biomass burning (BB) during the Holocene was investigated based on the following hypotheses: land use was important only in the southernmost regions, while elsewhere climate was the main driver modulated by changes in fuel type. BB was reconstructed by means of 88 sedimentary charcoal records divided into s

ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis

Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of

Fasting levels of growth hormone are associated with carotid intima media thickness but are not affected by fluvastatin treatment

Background: Growth hormone (GH) has been linked to cardiovascular disease but the exact mechanism of this association is still unclear. We here test if the fasting levels of GH are cross-sectionally associated with carotid intima media thickness (IMT) and whether treatment with fluvastatin affects the fasting level of GH. Methods: We examined the association between GH and IMT in 4425 individuals

Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study

Objective: Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.Methods: We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified inci

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6 dependent manner

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apopt

CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting

Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+CD38low) and

Missed Evaporation from Atmospherically Relevant Inorganic Mixtures Confounds Experimental Aerosol Studies

Sea salt aerosol particles are highly abundant in the atmosphere and play important roles in the global radiative balance. After influence from continental air, they are typically composed of Na+, Cl-, NH4+, and SO42- and organics. Analogous particle systems are often studied in laboratory settings by atomizing and drying particles from a solution. Here, we present evidence that such laboratory st

Reduced volume of diabetic pancreatic islets in rodents detected by synchrotron X-ray phase-contrast microtomography and deep learning network

The pancreatic islet is a highly structured micro-organ that produces insulin in response to rising blood glucose. Here we develop a label-free and automatic imaging approach to visualize the islets in situ in diabetic rodents by the synchrotron radiation X-ray phase-contrast microtomography (SRμCT) at the ID17 station of the European Synchrotron Radiation Facility. The large-size images (3.2 mm ×

Molecular dynamics simulations of nanometric cutting of single crystal copper sheets using a diamond tool

Nanometric cutting of a single crystal copper workpiece of different crystallographic orientations by a stiff cylindrical cubic diamond tool has been investigated by MD simulations using the freeware LAMMPS. The chip evolves during the cutting process and forms depending on crystal orientation, cutting velocity and tool geometry. It was found that no significant difference in the cutting force mag

Direct role of FLT3 in regulation of early lymphoid progenitors

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid-primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock-out (Flt3fl/fl) mouse model to address the direct role

Recombinant α 1-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a 177Lu-DOTATATE Mouse Radiation Model.

177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although 177Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associate

A Systematic Review of Mesenchymal Epithelial Transition Factor (MET) and Its Impact in the Development and Treatment of Non-Small-Cell Lung Cancer.

Lung cancer represents the leading cause of annual cancer-related deaths worldwide, accounting for 12.9%. The available treatment options for patients who experience disease progression remain limited. Targeted therapeutic approaches are promising but further understanding of the role of genetic alterations in tumorigenesis is imperative. The MET gene has garnered great interest in this regard. Th

Time evolution of surface species during the ALD of high-k oxide on InAs

Understanding the reaction mechanisms involved during the early stage of atomic layer deposition (ALD) of HfO2 on InAs is a key requirement for improving interfaces in III-V semiconductor-based devices. InAs is an excellent candidate to outperform silicon regarding speed and power consumption, and combined with HfO2, it gives promise for a new generation of ultra-fast MOSFETs. However, an improved