Publications by authors named "J Flach"

Background: Blockchain has been proposed as a critical technology to facilitate more patient-centric research and health information sharing. For instance, it can be applied to coordinate and document dynamic informed consent, a procedure that allows individuals to continuously review and renew their consent to the collection, use, or sharing of their private health information. Such has been suggested to facilitate ethical, compliant longitudinal research, and patient engagement.

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Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling.

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The wet bulb globe temperature (WBGT)-based occupational exposure limits (OELs) were developed from steady exposures to heat stress at constant WBGT and metabolic rate (M). The exposure limits were based on compensable heat stress exposures at the upper limit of the prescriptive zone for most healthy people. Professional practice allows for using time-weighted averages (TWAs) of WBGT and M to account for heterogeneous heat stress exposures.

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Patient-derived xenograft (PDX) models have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in myelodysplastic syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, engraftment efficiencies frequently remain low. Humanized three-dimensional scaffold models (ossicle xenotransplantation models) in immunocompromised mice have recently been found to enable improved engraftment rates of healthy and malignant human hematopoiesis.

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Transcription poses a threat to genomic stability through the formation of R-loops that can obstruct progression of replication forks. R-loops are three-stranded nucleic acid structures formed by an RNA-DNA hybrid with a displaced non-template DNA strand. We developed RNA-DNA Proximity Proteomics to map the R-loop proximal proteome of human cells using quantitative mass spectrometry.

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