Publications by authors named "Herbst S"

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.

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The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of Tbx21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate.

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Parkinson's disease is a progressive neurological disorder, characterized by prominent movement dysfunction. The past two decades have seen a rapid expansion of our understanding of the genetic basis of Parkinson's, initially through the identification of monogenic forms and, more recently, through genome-wide association studies identifying common risk variants. Intriguingly, a number of cellular pathways have emerged from these analysis as playing central roles in the aetiopathogenesis of Parkinson's.

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Objective: Determining the cause of severe insulin resistance and early-onset diabetes in the case of a young woman in which a wide range of differential diagnoses did not apply.

Research Design And Methods: Diagnostic workup including medical history, physical examination, specialist consultations, imaging methods, laboratory assessment, and genetic testing carried out by next-generation panel sequencing.

Results: After ruling out several differential diagnoses, genetic testing revealed a previously unknown homozygous variant within the canonical splice site of intron 4 in the WRN gene classified as pathogenic.

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Aim: Selective root-canal retreatment has been proposed as an alternative to full retreatment in multirooted, root-canal-filled teeth with evidence of apical pathology, where only the affected root(s) is retreated. Whilst this option may save costs initially, failures and retreatments may compensate for these initial savings. We assessed the cost-effectiveness of full versus selective root-canal retreatment using data from a recent clinical pilot study, employing a modelling approach.

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Leucine-rich repeat kinase 2 (LRRK2) is a multidomain scaffolding protein with dual guanosine triphosphatase (GTPase) and kinase enzymatic activities, providing this protein with the capacity to regulate a multitude of signalling pathways and act as a key mediator of diverse cellular processes. Much of the interest in LRRK2 derives from mutations in the LRRK2 gene being the most common genetic cause of Parkinson's disease, and from the association of the LRRK2 locus with a number of other human diseases, including inflammatory bowel disease. Therefore, the LRRK2 research field has focused on the link between LRRK2 and pathology, with the aim of uncovering the underlying mechanisms and, ultimately, finding novel therapies and treatments to combat them.

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(1) Background: We aimed to identify factors associated with the presence of apical lesions (AL) in panoramic radiographs and to evaluate the predictive value of the identified factors. (2) Methodology: Panoramic radiographs from 1071 patients (age: 11-93 a, mean: 50.6 a ± 19.

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Rhythmic activity in the delta frequency range (0.5-3 Hz) is a prominent feature of brain dynamics. Here, we examined whether spontaneous delta oscillations, as found in invasive recordings in awake animals, can be observed in non-invasive recordings performed in humans with magnetoencephalography (MEG).

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Large-scale compound screens are a powerful model system for understanding variability of treatment response and discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of the in vivo microenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture.

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In a recent issue of , Zecha et al. present decryptM, an approach aimed at defining the mechanisms of action of anti-cancer therapeutics through systems-level analysis of protein post-translational modifications (PTMs). By using a broad range of concentrations, decryptM generates drug response curves for each detected PTM, enabling identification of drug effects at different therapeutic doses.

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The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling.

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Objectives: First we aimed to identify significant associations between preoperative risk factors and achieving optimal root filling length (RFL) during orthograde root canal treatments (RCT) and second to predict successful RFL using machine learning.

Methods: Teeth receiving RCT at one university clinic from 2016-2020 with complete documentation were included. Successful RFL was defined to be 0-2mm of the apex, suboptimal RFL >2mm or beyond the apex.

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Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones.

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Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68).

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The COVID-19 pandemic and associated lockdowns triggered worldwide changes in the daily routines of human experience. The Blursday database provides repeated measures of subjective time and related processes from participants in nine countries tested on 14 questionnaires and 15 behavioural tasks during the COVID-19 pandemic. A total of 2,840 participants completed at least one task, and 439 participants completed all tasks in the first session.

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The tumour microenvironment and genetic alterations collectively influence drug efficacy in cancer, but current evidence is limited and systematic analyses are lacking. Using chronic lymphocytic leukaemia (CLL) as a model disease, we investigated the influence of 17 microenvironmental stimuli on 12 drugs in 192 genetically characterised patient samples. Based on microenvironmental response, we identified four subgroups with distinct clinical outcomes beyond known prognostic markers.

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BCL-2 inhibition has been shown to be effective in acute myeloid leukemia (AML) in combination with hypomethylating agents or low-dose cytarabine. However, resistance and relapse represent major clinical challenges. Therefore, there is an unmet need to overcome resistance to current venetoclax-based strategies.

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Parkinson's disease (PD) is conventionally described as an α-synuclein aggregation disorder, defined by Lewy bodies and neurites, and mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common autosomal dominant cause of PD. However, LRRK2 mutations may be associated with diverse pathologies in patients with Parkinson's syndrome including tau pathology resembling progressive supranuclear palsy (PSP). The recent discovery that variation at the LRRK2 locus is associated with the progression of PSP highlights the potential importance of LRRK2 in tauopathies.

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Neural circuits must both execute the behavioral repertoire of individuals and account for behavioral variation across species. Understanding how this variation emerges over evolutionary time requires large-scale phylogenetic comparisons of behavioral repertoires. Here, we describe the evolution of walking in fruit flies by capturing high-resolution, unconstrained movement from 13 species and 15 strains of drosophilids.

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Time implicitly shapes cognition, but time is also explicitly represented, for instance, in the form of durations. Parsimoniously, the brain could use the same mechanisms for implicit and explicit timing. Yet, the evidence has been equivocal, revealing both joint versus separate signatures of timing.

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Healthcare is an expensive endeavour, and it is likely that costs for endodontic treatment will grow over the next decade. The assessment of costs and, in most cases, health outcomes, and the comparison of the cost-health ratio of interventions, is at the heart of health economics. The present review aims to introduce the main concepts of health economic analysis, to systematically review the existing economic endodontic literature, and to deduce further action for the community.

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The human brain efficiently extracts the temporal statistics of sensory environments and automatically generates expectations about future events. An influential Hypothesis holds that these expectations can find their implementation in neural oscillations, notably in the delta band (.5-3 Hz).

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Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light.

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Objectives: We aimed to assess patient-, tooth- and treatment-level covariates on the failure of root canal treatments (RT) and to predict failure using machine learning (ML).

Methods: Teeth receiving RT at one large university hospital from 2016 to 2020 with a minimum follow-up of ≥6 months were included. Failure compromised absent radiographic healing and/or the presence of clinical symptoms.

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