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Multicenter prospective evaluation of diagnostic potential of flow cytometric aberrancies in myelodysplastic syndromes by the ELN iMDS flow working group

Background: Myelodysplastic syndromes (MDS) represent a diagnostic challenge. This prospective multicenter study was conducted to evaluate pre-defined flow cytometric markers in the diagnostic work-up of MDS and chronic myelomonocytic leukemia (CMML). Methods: Thousand six hundred and eighty-two patients with suspected MDS/CMML were analyzed by both cytomorphology according to WHO 2016 criteria an

Polymorphisms within base and nucleotide excision repair pathways and risk of differentiated thyroid carcinoma

The thyrocytes are exposed to high levels of oxidative stress which could induce DNA damages. Base excision repair (BER) is one of the principal mechanisms of defense against oxidative DNA damage, however recent evidences suggest that also nucleotide excision repair (NER) could be involved. The aim of present work was to identify novel differentiated thyroid cancer (DTC) risk variants in BER and N

Hybrid speciation driven by multilocus introgression of ecological traits

Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific trait

Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state

Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via ma

Tau-neurodegeneration mismatch reveals vulnerability and resilience to comorbidities in Alzheimer's continuum

INTRODUCTION: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. METHODS: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were c

Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling

Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cell

High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with Vitamin K antagonists

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recur

Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors

The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-

KRW composition theorems via lifting

One of the major open problems in complexity theory is proving super-logarithmic lower bounds on the depth of circuits (i.e., mathrm{P} nsubseteq text{NC}{1}). Karchmer, Raz, and Wigderson [13] suggested to approach this problem by proving that depth complexity behaves'as expected' with respect to the composition of functions f diamond g. They showed that the validity of this conjecture would impl

Mapping Resonance Structures in Transient Core-Ionized Atoms

The nature of transient electronic states created by photoabsorption critically determines the dynamics of the subsequently evolving system. Here, we investigate K-shell photoionized atomic neon by absorbing a second photon within the Auger-decay lifetime of 2.4 fs using the European XFEL, a unique high-repetition-rate, wavelength-tunable x-ray free-electron laser. By high-resolution electron spec

A systemic overreaction to years versus decades of warming in a subarctic grassland ecosystem

Temperature governs most biotic processes, yet we know little about how warming affects whole ecosystems. Here we examined the responses of 128 components of a subarctic grassland to either 5–8 or >50 years of soil warming. Warming of >50 years drove the ecosystem to a new steady state possessing a distinct biotic composition and reduced species richness, biomass and soil organic matter. However,

The GALAH survey : Chemical homogeneity of the Orion complex

Due to its proximity, the Orion star forming region is often used as a proxy to study processes related to star formation and to observe young stars in the environment they were born in. With the release of Gaia DR2, the distance measurements to the Orion complex are now good enough that the 3D structure of the complex can be explored. Here we test the hypothesis that, due to non-trivial structure

Development and inter-laboratory validation of the VISAGE enhanced tool for age estimation from semen using quantitative DNA methylation analysis

The analysis of DNA methylation has become an established method for chronological age estimation. This has triggered interest in the forensic community to develop new methods for age estimation from biological crime scene material. Various assays are available for age estimation from somatic tissues, the majority from blood. Age prediction from semen requires different DNA methylation markers and

Chemical ozone loss in the Arctic winter 1994/95 as determined by the match technique

The chemically induced ozone loss inside the Arctic vortex during the winter 1994/95 has been quantified by coordinated launches of over 1000 ozonesondes from 35 stations within the Match 94/95 campaign. Trajectory calculations, which allow diabatic heating or cooling, were used to trigger the balloon launches so that the ozone concentrations in a large number of air parcels are each measured twic

Age and diagnostic performance of Alzheimer disease CSF biomarkers

Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain

Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010) : A phase 3b study in refractory multiple myeloma

Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day

Luminosity measurement at ATLAS - Development, construction and test of scintillating fibre prototype detectors

We are reporting about a scintillating fibre tracking detector which is proposed for the precise determination of the absolute luminosity of the CERN LHC at interaction point 1 where the ATLAS experiment is located. The detector needs to track protons elastically scattered under mu rad angles in direct vicinity to the LHC beam. It is based on square shaped scintillating plastic fibres read out by

A pedagogical mentorship model for doctoral students

In Sweden, the pedagogical training of doctoral students varies significantly across universities. While most institutions include at least one mandatory course in higher education teaching and learning, some programs lack this requirement entirely. Whether doctoral students are encouraged or even allowed to take multiple pedagogical courses also varies greatly. This paper explores the benefits ofIn Sweden, the pedagogical training of doctoral students varies significantly across universities. While most institutions include at least one mandatory course in higher education teaching and learning, some programs lack this requirement entirely. Whether doctoral students are encouraged or even allowed to take multiple pedagogical courses also varies greatly. This paper explores the benefits of

A health economic evaluation of the multinational, randomized controlled CONVINCE trial : cost-utility of high-dose online hemodiafiltration compared to high-flux hemodialysis

High-flux hemodialysis (HD) and high-dose hemodiafiltration (HDF) are established treatments for patients with kidney failure. Since HDF has been associated with improved survival rates compared to HD, we evaluated the cost-effectiveness of HDF compared to HD. Cost–utility analyses were performed from a societal perspective alongside the multinational randomized controlled CONVINCE trial. A Markov

Determinants and relationships of climate change, climate change hazards, mental health, and well-being : a systematic review

Introduction: Impacts of climate change on human health receive increasing attention. However, the connections of climate change with well-being and mental health are still poorly understood.Objective: As part of the Horizon Europe project TRIGGER, we aim to deepen the understanding of the relationships between climate change and human mental health and well-being in Europe by focusing on environm