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RNAi Screen Identifies MTA1 as an Epigenetic Modifier of Differentiation Commitment in Human HSPCs

The molecular mechanisms regulating key fate decisions of hematopoietic stem cells (HSCs) remain incompletely understood. Here, we targeted global shRNA libraries to primary human hematopoietic stem and progenitor cells (HSPCs) to screen for modifiers of self-renewal and differentiation, and identified metastasis-associated 1 (MTA1) as a negative regulator of human HSPC propagation in vitro. Knock

Prevalence of germline pathogenic variants in 22 cancer susceptibility genes in Swedish pediatric cancer patients

Up to 10% of pediatric cancer patients harbor pathogenic germline variants in one or more cancer susceptibility genes. A recent study from the US reported pathogenic variants in 22 out of 60 analyzed autosomal dominant cancer susceptibility genes, implicating 8.5% of pediatric cancer patients. Here we aimed to assess the prevalence of germline pathogenic variants in these 22 genes in a population-

Waist circumference and a body shape index and prostate cancer risk and mortality

We recently found a negative association between body mass index (BMI) and the risk of localised prostate cancer (PCa), no association with advanced PCa, and a positive association with PCa‐specific mortality. In a 15% subpopulation of that study, we here investigated the measures of abdominal adiposity including waist circumference (WC) and A Body Shape Index (ABSI) in relation to PCa risk and mo

The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells

Small Cajal body-specific RNAs (scaRNAs) guide post-transcriptional modification of spliceosomal RNA and, while commonly altered in cancer, have poorly defined roles in tumorigenesis. Here, we uncover that SCARNA15 directs alternative splicing (AS) and stress adaptation in cancer cells. Specifically, we find that SCARNA15 guides critical pseudouridylation (Ψ) of U2 spliceosomal RNA to fine-tune AS

Vibrotactile sense might improve over time in paediatric subjects with type 1 diabetes - a mid-term follow-up using multifrequency vibrometry

AimImpaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time.MethodsA VibroSense Meter I device was used to determine the vibrotactile perception thresholds (

Defining the Emerging Blood System During Development at Single-Cell Resolution

Developmental hematopoiesis differs from adult and is far less described. In the developing embryo, waves of lineage-restricted blood precede the ultimate emergence of definitive hematopoietic stem cells (dHSCs) capable of maintaining hematopoiesis throughout life. During the last two decades, the advent of single-cell genomics has provided tools to circumvent previously impeding characteristics o

Incidence and predictors of severe infections in ANCA-associated vasculitis: a population-based cohort study.

Objective. To determine the incidence rate, predictors and outcome of severe infections in a population-based cohort of ANCA-associated vasculitis (AAV). Methods. The study included 325 cases of AAV (152 female) diagnosed from 1997 through 2016 from a defined geographic area in Sweden. All severe infection events (requiring hospitalization and treatment with intravenous antimicrobials) were identi

Comparison of RNA- and DNA-based methods for measurable residual disease analysis in NPM1-mutated acute myeloid leukemia

Introduction: Reverse transcriptase quantitative PCR (RT-qPCR) is considered the method of choice for measurable residual disease (MRD) assessment in NPM1-mutated acute myeloid leukemia (AML). MRD can also be determined with DNA-based methods offering certain advantages. We here compared the DNA-based methods quantitative PCR (qPCR), droplet digital PCR (ddPCR), and targeted deep sequencing (deep

Sex-Specific Associations of Circulating Uric Acid with Risk of Diabetes Incidence : A Population-Based Cohort Study from Sweden

Objective: To explore the longitudinal, as well as sex-specific, associations between circulating uric acid (UA) and diabetes incidence.Methods: A cohort study of the Malmö Diet Cancer-cardiovascular Cohort (Malmö, Sweden) consisting of 3140 individuals without diabetes at baseline, was followed up until the end of 2018. Incident diabetes cases were identified by linking to local and national diab

Within-session reproducibility of forced oscillometry

BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations a

Insulin action and secretion independent of traditional risk factors predict new-onset type 2 diabetes in Iraqi and Swedish born citizens - The MEDIM cohort study

AIMS: Our aim was to study the incidence of type 2 diabetes in a population-based cohort of Swedish and Iraqi born individuals, focussing on traditional risk factors, insulin action, insulin secretion and ethnicity.MATERIALS AND METHODS: The cohort consisted of 1164 Iraqi and 693 Swedish-born citizens. We investigated the association between new-onset type 2 diabetes and the predictors including l

Mapping of Perfusion During Full-Thickness Blepharotomy Using Laser Speckle Contrast Imaging

PURPOSE: The aim of this study was to monitor how the blood perfusion in human upper eyelids is affected during full-thickness blepharotomy.METHODS: Seven eyelids in 5 patients with upper eyelid retraction due to Graves' disease underwent full-thickness blepharotomy. Perfusion was measured using laser speckle contrast imaging in the eyelid margin and in the conjunctival pedicle.RESULTS: Immediatel

Pseudouridine-modified tRNA fragments repress aberrant protein synthesis and predict leukaemic progression in myelodysplastic syndrome

Transfer RNA-derived fragments (tRFs) are emerging small noncoding RNAs that, although commonly altered in cancer, have poorly defined roles in tumorigenesis1. Here we show that pseudouridylation (Ψ) of a stem cell-enriched tRF subtype2, mini tRFs containing a 5′ terminal oligoguanine (mTOG), selectively inhibits aberrant protein synthesis programmes, thereby promoting engraftment and differentiat

Photophysical Integrity of the Iron(III) Scorpionate Framework in Iron(III)-NHC Complexes with Long-Lived 2LMCT Excited States

Fe(III) complexes with N-heterocyclic carbene (NHC) ligands belong to the rare examples of Earth-abundant transition metal complexes with long-lived luminescent charge-transfer excited states that enable applications as photosensitizers for charge separation reactions. We report three new hexa-NHC complexes of this class: [Fe(brphtmeimb)2]PF6(brphtmeimb = [(4-bromophenyl)tris(3-methylimidazol-2-yl

Histology-based blood leukocyte profiling reveals parallel Th2 and Th17 signatures in seasonal allergic rhinitis

BACKGROUND: Allergic rhinitis (AR), a common condition in the westernized world, is suggested to be more immunologically complex than the archetypical 'Th2' inflammation. New approaches are needed to decode this complexity.AIMS/OBJECTIVES: In this study, we explored a novel histology-based analysis for circulating blood leukocyte profiling in 16 patients with seasonal AR outside and during the pol

A prospective, controlled study on the utility of rotational thromboelastometry in surgery for acute type A aortic dissection

To evaluate the hemostatic system with ROTEM in patients undergoing surgery for acute type aortic dissection (ATAAD) using elective aortic procedures as controls. This was a prospective, controlled, observational study. The study was performed at a tertiary referral center and university hospital. Twenty-three patients with ATAAD were compared to 20 control patients undergoing elective surgery of

Detection of unilateral arm paresis after stroke by wearable accelerometers and machine learning

Recent advances in stroke treatment have provided effective tools to successfully treat ischemic stroke, but still a majority of patients are not treated due to late arrival to hospital. With modern stroke treatment, earlier arrival would greatly improve the overall treatment results. This prospective study was performed to asses the capability of bilateral accelerometers worn in bracelets 24/7 to

The genomics of heart failure : design and rationale of the HERMES consortium

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and perf

Proteomic data analysis for differential profiling of the autoimmune diseases SLE, RA, SS, and ANCA-associated vasculitis

Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), and