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Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patien

Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans

AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular e

Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression : A prospective, open-label, multicenter, randomized, phase 3 study

Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T

MNK2 governs the macrophage antiinflammatory phenotype

Tumor-associated macrophages (TAMs) continuously fine tune their immune modulatory properties, but how gene expression programs coordinate this immune cell plasticity is largely unknown. Selective mRNA translation, controlled by MNK1/MNK2 and mTOR pathways impinging on eIF4E, facilitates reshaping of proteomes without changes in abundance of corresponding mRNAs. Using polysome profiling developed

The Gaia-ESO Survey : Mg-Al anti-correlation in iDR4 globular clusters

We use Gaia-ESO (GES) Survey iDR4 data to explore the Mg-Al anti-correlation in globular clusters that were observed as calibrators, as a demonstration of the quality of Gaia-ESO Survey data and analysis. The results compare well with the available literature, within 0.1 dex or less, after a small (compared to the internal spreads) offset between the UVES and GIRAFFE data of 0.10-0.15 dex was take

Plasma metabolite profiles, cellular cholesterol efflux, and non-traditional cardiovascular risk in patients with CKD

BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that c

Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome

OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial.STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy popul

Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index

Background: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality. Methods: Prospective, observational, cohort study in patients ≥

Peritoneal metastases from small bowel cancer : Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in The Netherlands

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is currently considered the standard of care for pseudomyxoma peritonei, mesothelioma and peritoneal metastases (PM) from colorectal cancer. CRS + HIPEC has also been suggested as a potential treatment option in PM of the much rarer small bowel cancer. Therefore, the current study was undertaken to inve

Strong regional influence of climatic forcing datasets on global crop model ensembles

We present results from the Agricultural Model Intercomparison and Improvement Project (AgMIP) Global Gridded Crop Model Intercomparison (GGCMI) Phase I, which aligned 14 global gridded crop models (GGCMs) and 11 climatic forcing datasets (CFDs) in order to understand how the selection of climate data affects simulated historical crop productivity of maize, wheat, rice and soybean. Results show th

Trade-offs between reducing complex terminology and producing accurate interpretations from environmental DNA : Comment on “Environmental DNA: What's behind the term?” by Pawlowski et al., (2020)

In a recent paper, “Environmental DNA: What's behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring,” Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their propos

Bowel function and associated risk factors at preschool and early childhood age in children with anorectal malformation type rectovestibular fistula : An ARM-Net consortium study

Background: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel fu

Current and historical factors drive variation of reproductive traits in unisexual mosses in Europe : A case study

Unisexual bryophytes provide excellent models to study the mechanisms that regulate the frequency of sexual versus asexual reproduction in plants, and their ecological and evolutionary implications. Here, we determined sex expression, phenotypic sex ratio, and individual shoot traits in 242 populations of the cosmopolitan moss Pseudoscleropodium purum spanning its whole distributional range. We te

Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

Acute respiratory distress syndrome (ARDS), an inflammatory condition with high mortality rates, is common in severe COVID-19, whose risk is reduced by metformin rather than other anti-diabetic medications. Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. We show that m

Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2 : the BRCA1 and BRCA2 Cohort Consortium

INTRODUCTION: Height, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes.PATIENTS AND METHODS: An international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for prem

Cell-specific effects in different immune subsets associated with SOCS1 genotypes in multiple sclerosis

BACKGROUND: Single nucleotide polymorphisms (SNPs) near SOCS1 are associated with multiple sclerosis (MS), but the most important SNPs in the area and mechanisms by which they influence the disease are unknown.METHODS: A haplotype-tagging association study was performed covering 60.5kbp around SOCS1, and the index SNP was validated in a total of 2292 individuals. mRNA expression of SOCS1 and nearb

Neurologic Injury in Patients Treated With Extracorporeal Membrane Oxygenation for Postcardiotomy Cardiogenic Shock

Objective: To investigate the frequency, predictors, and outcomes of neurologic injury in adults treated with postcardiotomy extracorporeal membrane oxygenation (PC-ECMO). Design: A retrospective multicenter registry study. Setting: Twenty-one European institutions where cardiac surgery is performed. Participants: A total of 781 adult patients who required PC-ECMO during 2010 to 2018 were divided