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Purpose: Recent demonstrations of normal tissue sparing by high-dose, high-dose-rate FLASH radiation therapy have driven considerable interest in its application to improve clinical outcomes. However, significant uncertainty remains about the underlying mechanisms of FLASH sparing and how deliveries can be optimized to maximize benefit from this effect. Rapid oxygen depletion has been suggested as
The S-adenosyl-L-methionine (SAM)-dependent methyltransferases attach a methyl group to the deprotonated methyl lysine (Kme0) using SAM as a donor. An intriguing, yet unanswered, question is how the deprotonation of the methyl lysine takes place which results in a lone pair of electrons at the Nϵ atom of the methyl lysine for the following methyl transfer. PRDM9, one of the few methyltransferases
INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manife
The main sources of non-exhaust particles around metro systems are the wear from wheel-rail contact, brake contact and the contact between mechanical parts in electric power systems. In order to predict the PM10 levels on underground metro platforms, the relation among time, train frequency and PM10 level should be investigated. Two types of particle emission models have previously been published
We have previously demonstrated that a strong correlation exists between systemic vasculitis with proteinase 3-anti-neutrophil cytoplasm antibodies (PR3-ANCA) and heterozygosity for α1-antitrypsin (α1-AT) deficiency, PiZ. In the present study we characterized the PiZ-positive subgroup by laboratory findings, clinical features and outcome. The series studied consisted of 18 PiZ-positive and 81 PiZ-
Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography
Purpose: This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients. Me
Entrepreneurial Ecosystems (EEs) are expected to support high growth entrepreneurship. Yet, little is known about how they actually promote entrepreneurial activities. Based on Giddens’ structuration theory, this paper takes the entrepreneurs’ perspective to understand how they actually use the resources provided by an EE. Based on semi-structured interviews with entrepreneurs and other relevant a
Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy s
One of the factors that can contribute to the resolution of long, doped inorganic scintillators used for nuclear spectroscopy is the variation of the dopant concentration over the length the detector crystal. In this work an investigation of such potential variations in one of the CsI(Tl) scintillators used in the calorimeter, CALIFA, of the R3B experiment at FAIR, has been performed using particl
BACKGROUND: In clinical practice, nurses use their clinical gaze and make observations in order to assess patients' medical conditions and care needs. However, signs of developing intensive care unit delirium (ICUD) are often difficult to determine, as communication with patients is usually limited because of intubation and the seriousness of their medical condition(s). Usually, ICUD is screened a
Endosymbiotic organelles of eukaryotic cells, the plastids, including chloroplasts and mitochondria, are highly integrated into cellular signalling networks. In both heterotrophic and autotrophic organisms, plastids and/or mitochondria require extensive organelle-to-nucleus communication in order to establish a coordinated expression of their own genomes with the nuclear genome, which encodes the
Many hypotheses attempt to explain parasite–host associations, but rarely are they examined together in a single community. For hosts, key traits are the proportion of infected individuals (prevalence) and the diversity of parasites infecting them. A key parasite trait is host specificity, ranging from specialists infecting one or a few closely related species to generalists infecting many species
The number of underground metro stations around the world is steadily increasing and deep stations are becoming more common. Evacuation elevators can be a way to mitigate many of the evacuation problems of deep stations, e.g., fatigue. However, the elevators need to be used by evacuees to be effective. In order to study the influence of evacuation measures on elevator usage, experiments were perfo
Purpose: Trapped fourth ventricle (TFV) is a well-identified problem in hydrocephalic children. Patients with post-hemorrhagic hydrocephalus (PHH) are mostly affected. We tried to find out predisposing factors and describe clinical findings to early diagnose TFV and manage it. Methods: We reviewed our database from 1991 to 2018 and included all patients with TFV who required surgery. We analyzed p
Pleiotropy (multiple phenotypic effects of single genes) and epistasis (gene interaction) have key roles in the development of complex phenotypes, especially in polymorphic taxa. The development of discrete and heritable phenotypic polymorphisms often emerges from major-effect genes that interact with other loci and have pleiotropic effects on multiple traits. We quantified gene expression changes
Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia c
