19 Dec 2022

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche.

9 Dec 2022

A new approach to the determination of tubular membrane capacitance: passive membrane electrical properties under reduced electrical conductivity of the extracellular solution

The transverse-axial tubular system (tubular system) of cardiomyocytes plays a key role in excitation-contraction coupling. To determine the area of the tubular membrane in relation to the area of the surface membrane, indirect measurements through the determination of membrane capacitances are currently used in addition to microscopic methods. Unlike existing electrophysiological methods based on an irreversible procedure (osmotic shock), the proposed new approach uses a reversible short-term intermittent increase in the electrical resistance of the extracellular medium. The resulting increase in the lumen resistance of the tubular system makes it possible to determine separate capacitances of the tubular and surface membranes. Based on the analysis of the time course of the capacitive current, computational relations were derived to quantify the elements of the electrical equivalent circuit of the measured cardiomyocyte including both capacitances. 

9 Dec 2022

Use of free radial forearm and pronator quadratus muscle flap: Anatomical study and clinical application

The authors present an anatomical study and clinical experience with radial forearm flap (RFF) and pronator quadratus muscle (PQM) application in the reconstruction of various body areas. The aim was to describe the anatomical placement and proportions of the PQM, the anatomical location of the major arterial branch of the radial artery supplying the PQM, and the application of this knowledge in clinical practice. The anatomical study was based upon an analysis of 13 fresh adult cadaver upper extremities, of which nine were female and four male; both arms from the same donors were used in four cases. The study of the PQM was performed using a dye-containing intraarterial injection, standard macro- and micro-preparation techniques, and chemical digestion. The data on the PQM size in males and females, thickness of the radial artery branch (the principal artery nourishing the muscle), and its position were analysed. The radial artery branch nourishing the PQM was identified in all cadaveric specimens of the anatomical study.

9 Dec 2022

Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury

Background: Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury.

Methods: 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared.

9 Dec 2022

Model-informed unsupervised deep learning approaches to frequency and phase correction of MRS signals

Purpose: A supervised deep learning (DL) approach for frequency and phase correction (FPC) of MRS data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised deep learning-based FPC.

Methods: Two novel deep learning-based FPC methods (deep learning-based Cr referencing and deep learning-based spectral registration), which use a priori physics domain knowledge, are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared with other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance. 

9 Dec 2022

Perinatal maternal mental health and amygdala morphology in young adulthood

The pre- and perinatal environment is thought to play a critical role in shaping brain development. Specifically, maternal mental health and maternal care have been shown to influence offspring brain development in regions implicated in emotional regulation such as the amygdala. In this study, we used data from a neuroimaging follow-up of a prenatal birth-cohort, the European Longitudinal Study of Pregnancy and Childhood, to investigate the impact of early postnatal maternal anxiety/co-dependence, and prenatal and early-postnatal depression and dysregulated mood on amygdala volume and morphology in young adulthood (n = 103). We observed that in typically developing young adults, greater maternal anxiety/co-dependence after birth was significantly associated with lower volume (right: t = -2.913, p = 0.0045, β = -0.523; left: t = -1.471, p = 0.144, β = -0.248) and non-significantly associated with surface area (right: t = -3.502, q = 0.069, <10%FDR, β = -0.090, left: t = -3.137, q = 0.117, <10%FDR, = -0.088) of the amygdala in young adulthood.

7 Dec 2022

Inter-individual differences in baseline dynamic functional connectivity are linked to cognitive aftereffects of tDCS

Transcranial direct current stimulation (tDCS) has the potential to modulate cognitive training in healthy aging; however, results from various studies have been inconsistent. We hypothesized that inter-individual differences in baseline brain state may contribute to the varied results. We aimed to explore whether baseline resting-state dynamic functional connectivity (rs-dFC) and/or conventional resting-state static functional connectivity (rs-sFC) may be related to the magnitude of cognitive aftereffects of tDCS. To achieve this aim, we used data from our double-blind randomized sham-controlled cross-over tDCS trial in 25 healthy seniors in which bifrontal tDCS combined with cognitive training had induced significant behavioral aftereffects. We performed a backward regression analysis including rs-sFC/rs-dFC measures to explain the variability in the magnitude of tDCS-induced improvements in visual object-matching task (VOMT) accuracy. Rs-dFC analysis revealed four rs-dFC states.

29 Nov 2022

Geometric Control of Cell Behavior by Biomolecule Nanodistribution

Many dynamic interactions within the cell microenvironment modulate cell behavior and cell fate. However, the pathways and mechanisms behind cell-cell or cell-extracellular matrix interactions remain understudied, as they occur at a nanoscale level. Recent progress in nanotechnology allows for mimicking of the microenvironment at nanoscale <i>in vitro</i>; electron-beam lithography (EBL) is currently the most promising technique. Although this nanopatterning technique can generate nanostructures of good quality and resolution, it has resulted, thus far, in the production of only simple shapes (e.g., rectangles) over a relatively small area (100 × 100 μm), leaving its potential in biological applications unfulfilled. Here, we used EBL for cell-interaction studies by coating cell-culture-relevant material with electron-conductive indium tin oxide, which formed nanopatterns of complex nanohexagonal structures over a large area (500 × 500 μm).