University Medical Center Hamburg-Eppendorf

Cross-bispectral analysis identifies higher-order neural interactions, but the resulting high-dimensional tensors are difficult to interpret at the source level. Standard dimensionality reduction often lacks a physical link to the underlying neural generators. We introduce a low-rank tensor decomposition framework explicitly grounded in the physics of EEG signal generation. The method represents the cross-bispectrum using a single spatial mixing matrix and a compact source-interaction tensor, yielding a structured and physically interpretable model. This formulation enables a direct source-space interpretation and supports subsequent spatial demixing using MOCA to recover distinct source maps. Through extensive simulations, we show that the method robustly captures the dominant bispectral structure across a range of conditions, including varying signal-to-noise ratio, dipole orientation, amplitude balance, and source complexity. Applied to resting-state EEG, the approach identifies anatomically plausible parietal generators associated with prominent alpha-band bispectral interactions. In contrast to standard tensor decompositions such as Tucker and PARAFAC, which rely on unconstrained cores or rank-one assumptions, the proposed framework enforces a compact and interpretable source-interaction structure. This structure significantly improves interpretability and spatial localization while suppressing spurious high-dimensional variability. The proposed low-rank decomposition offers a principled and computationally efficient approach for reducing and interpreting cross-bispectral EEG data. By bridging tensor decomposition with biophysical source models, it enables insights into complex neural coupling that are inaccessible with standard matrix or tensor techniques.

Phosphorylation of the constitutively expressed Hsp70 chaperone Hsc70 at threonine 495 modulates its cellular functions. While the functional consequences of Hsc70 phosphorylation are increasingly understood, analyzing its structural effects is hampered by the need for large amounts of stably phosphorylated protein. Here, we establish a preparative protocol for producing phosphorylated Hsc70 (pHsc70) and its ATPase-deficient T204A (Hsc70T204A) mutant via the Legionella effector kinase LegK4, yielding 10mg protein per liter of cell culture. Hsc70 is expressed in Escherichia coli, purified by immobilized metal affinity chromatography, and enzymatically phosphorylated at T495 under conditions minimizing reverse reactions, achieving phosphorylation levels of ∼70% for Hsc70 and ∼86% for Hsc70T204A. Rigorous depletion of LegK4 following the phosphorylation reaction is critical, as residual kinase promotes dephosphorylation and compromises phosphorylation stability. Phosphorylation at T495 reduces the oligomerization propensity of Hsc70, as evidenced by SAXS measurements showing decreased radius of gyration, maximum particle dimension, and oligomer abundance in phosphorylated Hsc70T204A compared to the unphosphorylated protein across ATP-, ADP-, and apo-states. Thus, this protocol provides robust access to stably phosphorylated Hsc70 suitable for biochemical and structural investigations, and may offer a general strategy for preparative enzymatic phosphorylation using recombinant kinases.

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a group of rare, hereditary, autosomal recessive, lysosomal storage disorders characterized by neurocognitive decline and early mortality. Pronounced visual impairment is frequent and retinal disease is more common in MPS III than in other MPS subtypes. The aim of this study was to characterize the retinal phenotype in MPS III and to provide insights into the disease course. Retrospective monocenter case series. In this study, 27 patients with genetically confirmed MPS III (n = 16 MPS IIIA; n = 9 MPS IIIB; n = 2 MPS IIIC) were included. The disease phenotype was classified as rapid or slowly progressive. All patients underwent spectral-domain optical coherence tomography (OCT) imaging to analyze central retinal thickness, peripapillary retinal nerve fiber layer thickness (RNFL), and configuration of retinal layers. Depending on neurocognitive status and compliance, best-corrected visual acuity (BCVA), slitlamp microscopy, and fundoscopy were performed. The median age at the ophthalmological examination was 6.5 years (range, 1-16 years). Slitlamp examination findings were usually unremarkable. BCVA was assessable in 6 of 27 patients and was within the normal age-adjusted range. Parafoveal degeneration of the outer retinal layers was observed in 59% of patients, whereas foveal thickening of the external limiting membrane was noted in 67%. One MPS IIIA patient showed severe foveal atrophy, and another presented with foveal intraretinal fluid accumulation. Quantitative retinal thickness analysis of all patients showed median values at the lower end of the reference spectrum in the inner perifoveal ring and below the normal range in the outer perifoveal ring, with no distinct pattern that distinguishes the subtypes or phenotypes. RNFL thickness was unremarkable in all patients. This study reveals a pattern of parafoveal degeneration of outer retinal layers in patients with all 3 MPS III subtypes, of whom MPS IIIA patients, known to have a more rapidly progressive neurocognitive disease, show the most severe retinal involvement. We provide natural history data that may contribute to planning and conducting future clinical trials, and we recommend further systematic ophthalmological examinations of MPS III patients to evaluate ocular involvement.

The increasing global burden of liver disease leads to more frequent encounters of anesthesiologists with these high-risk patients. This review summarizes current evidence on perioperative management of patients with liver disease, acute liver failure, and acute-on-chronic liver failure undergoing surgery. The etiology of liver disease is evolving with metabolic dysfunction on the rise creating new perioperative challenges. Patients with liver disease are particularly at risk of cardiovascular events, impaired glucose regulation, and delayed anesthetic recovery. Conventional coagulation assays inadequately reflect bleeding risk in patients with liver disease, whereas viscoelastic-guided coagulation strategies are associated with reduced transfusion requirements. Overall, 90-day mortality is about five-fold higher in patients with liver cirrhosis compared with the general population. Risk scores and clinical assessments are necessary to balance patient- and procedure-related risks during preoperative evaluation. Patients with liver disease undergoing surgery constitute one of the highest-risk surgical populations. Systematic preoperative assessment, individualized anesthetic drug selection, viscoelastic-guided coagulation management, and early multidisciplinary involvement are essential to improve outcomes. High-quality prospective evidence to guide anesthetic practice in patients with liver disease is urgently needed.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) have gained interest as a pharmacological modelbut their immaturity leads to uncertainty regarding translation. We studied the key player in maintaining ionic homeostasis, the Na+/K+-ATPase (NKA), in hiPSC-CM. Atrial and ventricular engineered heart tissues (EHTs) were produced from hiPSC-CMs. For comparison, adult atrial and ventricular tissues were obtained from patients undergoing open heart surgery. We measured NKA gene expression, NKA pump currents (INKA) and ouabain effects on action potentials and contractility. Computational modelling was used to further investigate the direct and indirect impacts of NKA inhibition. The mRNA abundance of the major NKA isoforms was higher in ventricular than atrial cardiomyocytes (adult and hiPSC-CM). Consistently, INKA was also higher in ventricular than in atrial hiPSC-CM and higher in ventricular than in atrial adult cardiomyocytes. Ouabain potency to block INKA did not differ between hiPSC-derived and adult cardiomyocytes. Ouabain shortened plateau phase in EHT and adult tissue. However, lower ouabain concentrations depolarized diastolic potential and depressed force more in EHTs, demonstrating a higher integrated sensitivity to NKA inhibition. Computational modelling indicated that weaker IK1 increases the susceptibility to depolarisation by NKA block. HiPSC-EHTs express NKA with biophysical characteristics and ouabain-sensitivity that are not different from human tissue. Action potential duration responses in EHT reproduces chamber-specific response pattern as seen in human heart. The higher sensitivity of EHTs to depolarize under ouabain-induced block of NKA needs to be considered when employing hiPSC-CM in drug research.

Physical activity (PA) during pregnancy and the postpartum period improves maternal and child health. However, there are no guidelines for Germany and it is not known to what extent midwives are informed about international PA guidelines. This study aimed to characterise midwives' beliefs, current practices, and knowledge of recommendations on PA during pregnancy and the postpartum period. A cross-sectional online survey was carried out among practising midwives (n=311) from May to August 2023. Data were descriptively analysed to characterize midwives' beliefs, current practices, and knowledge about PA, including awareness of international PA recommendations. Most midwives recognised the importance of PA and believed in the importance of their counselling. However, midwives' current practices and recommendations on PA varied widely. Only 16.1% of the midwives reported being aware of international PA guidelines during pregnancy and 5.8% during the postpartum period. Midwives are in a key position to influence maternal and child health, but their knowledge and guidance on PA recommendations leave room for improvement. This highlights the importance of optimized education and training in this area.

Sarcomas and carcinomas represent approximately 1% and 80% of all cancer diagnoses, respectively. Despite their very different prevalence, both tumor types share a critical dependence on mitochondrial functions for metabolic adaptation, survival and progression. Mitochondria act as cellular powerhouses by generating ATP through oxidative phosphorylation; however, their roles extend far beyond energy production. These organelles are central hubs of biosynthetic and catabolic pathways, including the tricarboxylic acid cycle, glutaminolysis, lipid metabolism, branched-chain amino acid catabolism and gluconeogenesis. Moreover, they play a key role in regulating various forms of programmed cell death, such as apoptosis, necroptosis, ferroptosis and pyroptosis. In this review, we provide a comprehensive overview on the contribution of mitochondria to tumor cell metabolism specifically in sarcomas and carcinomas. We describe how mitochondrial DNA-encoded proteins influence tumorigenesis and how mitochondria support cancer stem cell maintenance. We also discuss the therapeutic potential of targeting mitochondrial pathways, highlighting clinical trials and emerging strategies. The available evidence suggests that sarcoma cells might be more responsive to mitochondrial-targeted therapies due to their higher mitochondrial content and activity compared with carcinomas. Lastly, we bring some evidence of the involvement of mitochondria in the tumor microenvironment and discuss the implication of this finding for cancer immunotherapy. Altogether, these insights emphasize the importance of mitochondria as central regulators of cancer cell fate and promising therapeutic targets.