Refine
Year of publication
Document Type
- Article (21)
Language
- English (21)
Keywords
Institute
- Fakultät für Angewandte Informatik (9)
- Institut für Informatik (6)
- Medizinische Fakultät (6)
- Universitätsklinikum (6)
- Institut für Physik (4)
- Lehrstuhl für Epidemiologie (4)
- Mathematisch-Naturwissenschaftlich-Technische Fakultät (4)
- Institut für Geographie (3)
- Lehrstuhl für Embedded Intelligence for Health Care and Wellbeing (3)
- Lehrstuhl für Regionales Klima und Hydrologie (3)
The brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain.
Agonistic antibodies against the co-stimulatory receptor OX-40 have shown promising activity in preclinical models, but clinical activity has only been observed in isolated cases. While co-stimulation of T cells is described as the primary pharmacological mechanism of these antibodies, high expression of OX-40 on tumor-infiltrating regulatory T cells has also been observed and discussed as a potentially confounding factor in a clinical setting.
We present HFB10-1E1, a novel OX-40 agonistic antibody with an optimized pharmacological profile. HFB10-1E1 binds specifically to a unique epitope on human OX-40 and cross-reacts with cynomolgus monkey OX-40. Upon cross-linking, HFB10-1E1 induces NFκB signaling in a reporter cell line and leads to co-stimulation of T cells in vitro. The agonistic activity of HFB10-1E1 is further enhanced in the presence of the endogenous ligand OX-40L. In contrast to other anti-OX-40 antibodies, treatment with HFB10-1E1 does not result in reduced expression of OX-40 on T cells, which will ease the prediction of clinical dose-schedule and potentially lead to better activity. HFB10-1E1 demonstrates more potent in vivo anti-tumor activity in human OX-40 knock-in mice bearing MC-38 syngeneic tumors as compared to a previously published anti-OX-40 antibody. HFB10-1E1 has a favorable developability profile, and stable cell lines with high production yield have been obtained.
Further, we present a novel concept for identifying potential responding patients to HFB10-1E1 using HiFiBiO's proprietary Drug Intelligent Science (DIS™) platform. The DIS approach for discovery of predictive response biomarkers combines high-throughput single-cell profiling of a patient's T cell repertoire with functional read-outs to characterize tumor-specific T cell clones responsive to HFB10-1E1. Our results provide the foundation for the implementation of the DIS™ platform to guide the clinical development of HFB10-1E1 for selected patients that are most likely to benefit from the treatment.
HFB10-1E1 is being developed as a potential novel treatment option for cancer coupled with a patient stratification biomarker.
MEDAS: an open-source platform as a service to help break the walls between medicine and informatics
(2022)
Coexistence of magnetic order and two-dimensional superconductivity at LaAlO3/SrTiO3 interfaces
(2011)
Background
Atopic dermatitis (AD), which can significantly impact quality of life, is a complex, heterogeneous skin disease affecting all ages and therefore can lead to very different patient journeys. Understanding the patient journey within the healthcare system is essential for improving care outcomes.
Objectives
To explore the patient journey of individuals with AD in Germany, with a specific focus on the utilization of Internet resources throughout this process.
Methods
A cross-sectional study using a self-administered questionnaire was conducted from June 2021 to February 2022. Participants were recruited from dermatology private practices, a university hospital and online platforms.
Results
The study included 276 participants (62.3% female; mean age: 46.3 ± 18.4 years; mean disease duration: 26.9 ± 17.5 years; mean DLQ Index: 10.0 ± 5.6). Around 191 participants were currently receiving medical treatment, with 9.1% receiving biologic therapy. Most of the people initially contacted a GP (42.4%) and were diagnosed by a dermatologist first (57.6%). Around 47.1% were currently in treatment by a dermatologist, seeking dermatological care on average 4.5 times a year. Almost all individuals (86.2%) have already consulted more than one physician during their patient journey. Overall, participants consulted a median of five physicians, while those with severe AD consulted a median of six physicians. Initial symptoms to diagnosis and between consulting two different physicians both had a median duration of 6 months. Dissatisfaction with treatment outcomes emerged as a common reason for changing physicians. Approximately 76.4% of participants used the Internet for disease-related information, primarily relying on Google. Overall, 63% found the information quality unsatisfactory.
Conclusions
The study underlines the widespread utilization of medical treatment and the proactive healthcare-seeking behaviour during a long patient journey. Dissatisfaction with treatment outcomes, alternative medicine and the quality of the Internet sources emphasize the potential for improving the comprehensive disease management to improve care outcomes.
Afforestation as a climate change mitigation option has been the subject of intense debate and study over the last few decades, particularly in the tropics where agricultural activity is expanding. However, the impact of such landcover changes on the surface energy budget, temperature, and precipitation remains unclear as feedbacks between various components are difficult to resolve and interpret. Contributing to this scientific debate, regional climate models of varying complexity can be used to test how regional climate reacts to afforestation. In this study, the focus is on the gauged Nzoia basin (12,700 km2) located in a heavily farmed region of tropical Africa. A reanalysis product is dynamically downscaled with a coupled atmospheric-hydrological model (WRF-Hydro) to finely resolve the land-atmosphere system in the Nzoia region. To overcome the problem of Nzoia river flooding over its banks we enhance WRF-Hydro with an overbank flow routing option, which improves the representation of daily discharge based on the Nash-Sutcliffe efficiency and Kling-Gupta efficiency (from -2.69 to 0.30, and -0.36 to 0.63, respectively). Changing grassland and cropland areas to savannas, woody savannas, and evergreen broadleaf forest in three synthetic numerical experiments allows the assessment of potential regional climate impacts of three afforestation strategies. In all three cases, the afforestation-induced decrease in soil evaporation is larger than the afforestation-induced increase in plant transpiration, thus increasing sensible heat flux and triggering a localized negative feedback process leading to more precipitation and more runoff. This effect is more pronounced with the woody savannas experiment, with 7% less evapotranspiration, but 13% more precipitation, 8% more surface runoff, and 12% more underground runoff predicted in the Nzoia basin. This study demonstrates a potentially large impact of afforestation on regional water resources, which should be investigated in more detail for policy making purposes.
