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The objective was to analyse if magnetic resonance imaging (MRI) can act as a non-radiation exposure surrogate for (18)F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in children with histologically confirmed Hodgkin lymphoma (HL) before treatment. This was done by analysing a potential correlation between apparent diffusion coefficient (ADC) in MRI and the maximum standardized uptake value (SUVmax) in FDG-PET/CT.

Strain-free GaAs/AlGaAs semiconductor quantum dots (QDs) grown by droplet etching and nanohole infilling (DENI) are highly promising candidates for the on-demand generation of indistinguishable and entangled photon sources. The spectroscopic fingerprint and quantum optical properties of QDs are significantly influenced by their morphology. The effects of nanohole geometry and infilled material on the exciton binding energies and fine structure splitting are well-understood. However, a comprehensive understanding of GaAs/AlGaAs QD morphology remains elusive. To address this, we employ high-resolution scanning transmission electron microscopy (STEM) and reverse engineering through selective chemical etching and atomic force microscopy (AFM). Cross-sectional STEM of uncapped QDs reveals an inverted conical nanohole with Al-rich sidewalls and defect-free interfaces. Subsequent selective chemical etching and AFM measurements further reveal asymmetries in element distribution. This study enhances the understanding of DENI QD morphology and provides a fundamental three-dimensional structural model for simulating and optimizing their optoelectronic properties.

Coarse-grained (CG) molecular dynamics (MD) simulations have grown in applicability over the years. The recently released version of the Martini CG force field (Martini 3) has been successfully applied to simulate many processes, including protein-ligand binding. However, the current ligand parametrization scheme is manual and requires an a priori reference all-atom (AA) simulation for benchmarking. For systems with suboptimal AA parameters, which are often unknown, this translates into a CG model that does not reproduce the true dynamical behavior of the underlying molecule. Here, we present Bartender, a quantum mechanics (QM)/MD-based parametrization tool written in Go. Bartender harnesses the power of QM simulations and produces reasonable bonded terms for Martini 3 CG models of small molecules in an efficient and user-friendly manner. For small, ring-like molecules, Bartender generates models whose properties are indistinguishable from the human-made models. For more complex, drug-like ligands, it is able to fit functional forms beyond simple harmonic dihedrals and thus better captures their dynamical behavior. Bartender has the power to both increase the efficiency and the accuracy of Martini 3-based high-throughput applications by producing numerically stable and physically realistic CG models.

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus in vivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) differ in prognosis and treatment. We aimed to non-invasively differentiate iCCA and HCC by means of radiomics extracted from contrast-enhanced standard-of-care computed tomography (CT)., Materials and Methods: In total, 94 patients (male, n = 68, mean age 63.3 ± 12.4 years) with histologically confirmed iCCA (n = 47) or HCC (n = 47) who underwent contrast-enhanced abdominal CT between August 2014 and November 2021 were retrospectively included. The enhancing tumour border was manually segmented in a clinically feasible way by defining three three-dimensional volumes of interest per tumour. Radiomics features were extracted. Intraclass correlation analysis and Pearson metrics were used to stratify robust and non-redundant features with further feature reduction by LASSO (least absolute shrinkage and selection operator). Independent training and testing datasets were used to build four different machine learning models. Performance metrics and feature importance values were computed to increase the models' interpretability., Results: The patient population was split into 65 patients for training (iCCA, n = 32) and 29 patients for testing (iCCA, n = 15). A final combined feature set of three radiomics features and the clinical features age and sex revealed a top test model performance of receiver operating characteristic (ROC) area under the curve (AUC) = 0.82 (95% confidence interval =0.66-0.98; train ROC AUC = 0.82) using a logistic regression classifier. The model was well calibrated, and the Youden J Index suggested an optimal cut-off of 0.501 to discriminate between iCCA and HCC with a sensitivity of 0.733 and a specificity of 0.857., Conclusions: Radiomics-based imaging biomarkers can potentially help to non-invasively discriminate between iCCA and HCC., (Copyright © 2023. Published by Elsevier Ltd.)

SUN domain proteins are conserved proteins of the nuclear envelope and key components of the LINC complexes (for 'linkers of the nucleoskeleton and the cytoskeleton'). Previous studies have demonstrated that the testis-specific SUN domain protein SUN4 (also known as SPAG4) is a vital player in the directed shaping of the spermatid nucleus. However, its molecular properties relating to this crucial function have remained largely unknown, and controversial data for the organization and orientation of SUN4 within the spermatid nuclear envelope have been presented so far. Here, we have re-evaluated this issue in detail and show robust evidence that SUN4 is integral to the inner nuclear membrane, sharing a classical SUN domain protein topology. The C-terminal SUN domain of SUN4 localizes to the perinuclear space, whereas the N-terminus is directed to the nucleoplasm, interacting with the spermiogenesis-specific lamin B3. We found that SUN4 forms heteromeric assemblies with SUN3 in vivo and regulates SUN3 expression. Together, our results contribute to a better understanding of the specific function of SUN4 at the spermatid nucleo-cytoplasmic junction and the process of sperm-head formation., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability., (© 2022. The Author(s).)

High-entropy oxide (HEO) superconductors have been developed since very recently. Different superconductors can be produced in the form of a high-entropy compound, including REBa 2 Cu 3 O 7- δ (REBCO). However, until now, mainly bulk samples (mostly in polycrystalline form) have been reported. In this work, the first CSD-grown high-entropy (HE) REBCO nanocomposite films were successfully synthesized. In particular, high-quality Gd 0.2 Dy 0.2 Y 0.2 Ho 0.2 Er 0.2 Ba 2 Cu 3 O 7- δ nanocomposite films with 12 mol% BaHfO 3 nanoparticles were grown on SrTiO 3 substrates. The X-ray diffraction patterns show a near-perfect c -axis oriented grain growth. Both T c and 77 K J sf c , 91.9 K and 3.5 MA cm -2 , respectively, are comparable with the values of the single-RE REBCO films. Moreover, at low temperatures, specifically at 30 K, the J c values are larger than those of the single-RE samples. A transmission electron microscopy (TEM) study, including energy-dispersive X-ray spectroscopy (EDXS) measurements, reveals that the different RE 3+ ions are distributed homogeneously in the matrix without forming clusters. This distribution causes point-like pinning centres that explain the superior performances of these samples at low temperatures. Although still seen as a proof-of-concept for the feasibility of preparing such films, these results demonstrate that the HE REBCO films are a promising option for the future fabrication of high-performance coated conductors. In the investigated B - T range, however, their J c values are still lower than those of other, medium-entropy REBCO films, which shows that an optimization of the composition of the HE REBCO films is needed to maximize their performance., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Recent studies show an association of Parkin RBR E3 ubiquitin protein ligase (PARK2) copy number variations (CNVs) with attention deficit hyperactivity disorder (ADHD). The aim of our pilot study to investigate gene expression associated with PARK2 CNVs in human-derived cellular models. We investigated gene expression in fibroblasts, hiPSC and dopaminergic neurons (DNs) of ADHD PARK2 deletion and duplication carriers by qRT PCR compared with healthy and ADHD cell lines without PARK2 CNVs. The selected 10 genes of interest were associated with oxidative stress response (TP53, NQO1, and NFE2L2), ubiquitin pathway (UBE3A, UBB, UBC, and ATXN3) and with a function in mitochondrial quality control (PINK1, MFN2, and ATG5). Additionally, an exploratory RNA bulk sequencing analysis in DNs was conducted. Nutrient deprivation as a supplementary deprivation stress paradigm was used to enhance potential genotype effects. At baseline, in fibroblasts, hiPSC, and DNs, there was no significant difference in gene expression after correction for multiple testing. After nutrient deprivation in fibroblasts NAD(P)H-quinone-dehydrogenase 1 (NQO1) expression was significantly increased in PARK2 CNV carriers. In a multivariate analysis, ubiquitin C (UBC) was significantly upregulated in fibroblasts of PARK2 CNV carriers. RNA sequencing analysis of DNs showed the strongest significant differential regulation in Neurontin (NNAT) at baseline and after nutrient deprivation. Our preliminary results suggest differential gene expression in pathways associated with oxidative stress, ubiquitine-proteasome, immunity, inflammation, cell growth, and differentiation, excitation/inhibition modulation, and energy metabolism in PARK2 CNV carriers compared to wildtype healthy controls and ADHD patients., (© 2022 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)