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Correlative optical photothermal infrared and X-ray fluorescence for chemical imaging of trace elements and relevant molecular structures directly in neurons

Alzheimer’s disease (AD) is the most common cause of dementia, costing about 1% of the global economy. Failures ofclinical trials targeting amyloid-βprotein (Aβ), a key trigger of AD, have been explained by drug inefficiency regardlessof the mechanisms of amyloid neurotoxicity, which are very difficult to address by available technologies. Here, wecombine two imaging modalities that stand at oppos

Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals

Background: Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods: Participa

Molecular patterns of resistance to immune checkpoint blockade in melanoma

Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanom

A temporal developmental map separates human NK cells from noncytotoxic ILCs through clonal and single-cell analysis

Natural killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. Although the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mice, this process is not well characterized in humans

Exploring the Functional Landscape of the p53 Regulatory Domain : The Stabilizing Role of Post-Translational Modifications

This study focuses on the intrinsically disordered regulatory domain of p53 and the impact of post-translational modifications. Through fully atomistic explicit water molecular dynamics simulations, we show the wealth of information and detailed understanding that can be obtained by varying the number of phosphorylated amino acids and implementing a restriction in the conformational entropy of the

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates

Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature

Knowledge of human fetal blood development and how it differs from adult blood is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space, adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single-cell immunopheno

Biomarkers of blood cadmium and incidence of cardiovascular events in non-smokers : Results from a population-based proteomics study

Background: Cadmium is a toxic metal with multiple adverse health effects, including risk of cardiovascular disease (CVD). The mechanistic link between cadmium and CVD is unclear. Our aim was to examine the associations between blood cadmium (B-Cd) and 88 potential protein biomarkers of CVD. Methods: B-Cd and 88 plasma proteins were measured in a community-based prospective cohort, the Malmö Diet

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

Design of an AI Support for Diagnosis of Dyspneic Adults at Time of Triage in the Emergency Department

We created an AI support for diagnosis in dyspneic adults at time of triage in the emergency department.Complete data from an entire regional health care system was analyzed, to find AI-derived, unknown, important diagnostic predictors. Most important were prior diagnoses of heart failure or COPD, daily smoking, atrial fibrillation/flutter, life difficulties and maternal care.Sensitivity for AHF,

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

MAC-1 marks a quiescent and functionally superior HSC subset during regeneration

Mouse hematopoietic stem cells (HSCs) have been extensively defined both molecularly and functionally at steady state, while regenerative stress induces immunophenotypical changes that limit high purity isolation and analysis. It is therefore important to identify markers that specifically label activated HSCs to gain further knowledge about their molecular and functional properties. Here, we asse

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

Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se

Bimolecular Reaction Mechanism in the Amido Complex-Based Atomic Layer Deposition of HfO2

The surface chemistry of the initial growth during the first or first few precursor cycles in atomic layer deposition is decisive for how the growth proceeds later on and thus for the quality of the thin films grown. Yet, although general schemes of the surface chemistry of atomic layer deposition have been developed for many processes and precursors, in many cases, knowledge of this surface chemi