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Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and i

Copper is an essential micronutrient and yet is highly toxic to cells at elevated concentrations. P1B-ATPase proteins are critical for this regulation, providing active extrusion across cellular membranes. One unique molecular adaptation of P1B-ATPases compared to other P-type ATPases is the presence of metal-binding domains (MBDs) at the cytosolic termini, which however are poorly characterized w

We present a 200 kHz XUV source driven by an optical parametric chirped pulse amplification system. The advantage for photoemission electron microscopy of this high-repetition rate will be discussed.

The terrestrial planets and the asteroids dominant in the inner asteroid belt are water poor. However, in the protoplanetary disk the temperature should have decreased below water-condensation level well before the disk was photo-evaporated. Thus, the global water depletion of the inner Solar System is puzzling. We show that, even if the inner disk becomes cold, there cannot be direct condensation

Background: A majority of patients with end-stage renal disease suffer from secondary hyperparathyroidism, which is associated with osteoporosis and cardiovascular disease. Parathyroidectomy (PTX) is often necessary despite medical treatment. However, the effect of PTX on cardio- and cerebrovascular events (CVE) remains unclear. Data on the effect of PTX from population-based studies are scarce. S

The integration of geoinformation with BIM (GeoBIM) is critical to underpin solutions to many city-related challenges. However, to achieve an effective integration it is necessary to consider not only data and technical options but also current practice and users’ needs. This paper describes work carried out within the EuroSDR-GeoBIM project to address this challenge. After investigating potential

Biogenic volatile organic compound (BVOC) flux dynamics during the subarctic autumn are largely unexplored and have been considered insignificant due to the relatively low biological activity expected during autumn. Here, we exposed subarctic heath ecosystems to predicted future autumn climate scenarios (ambient, warming, and colder, dark conditions), changes in light availability, and flooding, t

The upcycling trend has received renewed attention in the past few years due to growing concerns for the environment related to increased resource consumption and waste volumes. Indeed, cities across the world are supporting resource upcycling initiatives by establishing do-it-yourself (DIY) repair cafes and makerspaces as a means to transform societies towards sustainable develop-ment. However, t

Enucleation is a crucial event during the erythropoiesis, implicating drastic morphologic and transcriptomic/proteomic changes. While many genes deletion lead to failed or impaired enucleation have been identified, directly triggering the erythroid maturation, particularly enucleation, is still challenging. Inducing enucleation at the desired timing is necessary to develop efficient methods to gen

InP quantum dots (QDs) are the most competitive in terms of environmentally friendly QDs. However, the synthesis of InP QDs requires breakthroughs in low-cost and safe phosphorus precursors such as tri(dimethylamino)phosphine [(DMA)3P]. It is found that even if the oxygen is completely avoided, there are still oxidation state defects at the core/shell interface of InP QDs. Herein, the record-break

Right ventricular (RV) volumes are commonly obtained through time-consuming manual delineations of cardiac magnetic resonance (CMR) images. Deep learning-based methods can generate RV delineations, but few studies have assessed their ability to accelerate clinical practice. Therefore, we aimed to develop a clinical pipeline for deep learning-based RV delineations and validate its ability to reduce

Diabetes mellitus (DM) incidence have been assessed in connection with air pollution exposure in several studies; however, few have investigated associations with source-specific local emissions. This study aims to estimate the risk of DM incidence associated with source-specific air pollution in a Swedish cohort with relatively low exposure. Individuals in the Västerbotten intervention programme

Depending on management practices, agricultural lands can either pose substantial barriers to species movement or can support landscape connectivity by linking areas of high-quality habitat. Balancing connectivity and sustainable food production on agricultural lands is critical to conservation in the conterminous United States (CONUS) where agriculture makes up close to half of total land area. H

OBJECTIVES: The efficacy of long-term opioid therapy (LTOT) in treating patients with chronic non-cancer pain (CnCP) is questionable, and the potential risks of adverse effects are well established. The aims were as follows: (1) compare characteristics in patients exposed to LTOT vs non-exposed. (2) Regarding opioid-exposed patients, describe characteristics of patients with risk factors for opioi

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challeng

BACKGROUND: It has been suggested that endoscopic grading of the gastroesophageal flap valve is a good predictor of the reflux status.METHODS: To test this hypothesis, 268 symptomatic patients underwent endoscopic grading of the gastroesophageal valve using Hill's classification, with grades I through IV. Esophageal acid exposure, lower esophageal sphincter characteristics, and the degree of esoph

INTRODUCTION: Patients with depression have significantly increased mortality from somatic disease. The purpose of this article was to review studies that investigate if there is a prognostic association with depression as co-morbidity in patients with chronic obstructive pulmonary disease (COPD). We chose the following outcomes: mortality, suicide behaviour, risk of COPD exacerbation, use of prim

PURPOSE: The effects of radiotherapy (RT) on the basis of the presence of stromal tumor infiltrating lymphocytes (TILs) have not been studied. The purpose of this study was to analyze the association of TILs with the effect of postoperative RT on ipsilateral breast tumor recurrence (IBTR) in a large randomized trial. METHODS: In the SweBCT91RT (Swedish Breast Cancer Group 91 Radiotherapy) trial, 1

Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We so