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The Energy Exascale Earth System Model (E3SM) is a new coupled Earth system model sponsored by the U.S Department of Energy. Here we present E3SM global simulations using active ocean and sea ice that are driven by the Coordinated Ocean‐ice Reference Experiments II (CORE‐II) interannual atmospheric forcing data set. The E3SM ocean and sea ice components are MPAS‐Ocean and MPAS‐Seaice, which use the Model for Prediction Across Scales (MPAS) framework and run on unstructured horizontal meshes. For this study, grid cells vary from 30 to 60 km for the low‐resolution mesh and 6 to 18 km at high resolution. The vertical grid is a structured z‐star coordinate and uses 60 and 80 layers for low and high resolution, respectively. The lower‐resolution simulation was run for five CORE cycles (310 years) with little drift in sea surface temperature (SST) or heat content. The meridional heat transport (MHT) is within observational range, while the meridional overturning circulation at 26.5°N is low compared to observations. The largest temperature biases occur in the Labrador Sea and western boundary currents (WBCs), and the mixed layer is deeper than observations at northern high latitudes in the winter months. In the Antarctic, maximum mixed layer depths (MLD) compare well with observations, but the spatial MLD pattern is shifted relative to observations. Sea ice extent, volume, and concentration agree well with observations. At high resolution, the sea surface height compares well with satellite observations in mean and variability. Key Points The Energy Exascale Earth System Model (E3SM) is a new climate model by the U.S. Department of Energy E3SM ocean and ice components use unstructured horizontal meshes for variable‐resolution simulations The 310‐year E3SM simulations agree well with observations in ocean currents and sea ice coverage

In urban microclimate research, ground-based thermography is used to gain insight into the spatial distribution of surface temperatures of various materials. Taking snapshots over a certain time span helps experts to observe the temporal thermo-radiative behavior of the monitored surface elements and therefore supports decisions on possible optimizations, e.g., improving the thermal comfort in a neighborhood. Appropriate visualization techniques facilitate decision-making and are thus crucial in the optimization process. In this study, we present a tool that eases the extraction of thermo-radiative features from multi-temporal thermographs taken from a monitored scene. Assisted by our tool, users can identify, choose, and register thermo-radiative features for each time step according to their individual research needs. The features’ temporal development is then visualized using a directed graph that encodes topological events as well as each feature’s size and summarizing statistics. To enhance this summary, a comprehensive animated sequence emphasizes the spatiotemporal behavior of the most significant thermo-radiative features. Salient developments are visually embedded and highlighted in the original infrared images, which are blended in an animation from time step to time step. Since we enable the user to interact with the data in a flexible way, noisy and low resolution image data sets can also be processed.

The Energy Exascale Earth System Model (E3SM) is a new coupled Earth system model sponsored by the US Department of Energy. Here we present E3SM global simulations using active ocean and sea ice that are driven by the CORE–II inter–annual atmospheric forcing data set. The E3SM ocean and sea–ice components are MPAS–Ocean and MPAS–Seaice, which use the Model for Prediction Across Scales (MPAS) framework and run on unstructured horizontal meshes. For this study, grid cells vary from 30 to 60 km for the low resolution mesh and 6 to 18 km at high resolution. The vertical grid is a structured z–star coordinate and uses 60 and 80 layers for low and high resolution, respectively. The lower resolution simulation was run for five CORE cycles (310 years) with little drift in sea surface temperature or heat content. The meridional heat transport is within observational range, while the meridional overturning circulation at 26.5° N is low compared to observations. The largest temperature biases occur in the Labrador Sea and western boundary currents, and the mixed layer is deeper than observations at northern high latitudes in the winter months. In the Antarctic, maximum mixed layer depths (MLD) compare well with observations, but the spatial MLD pattern is shifted relative to observations. Sea–ice extent, volume and concentration agree well with observations. At high resolution, the sea surface height compares well with satellite observations in mean and variability.

In today's manufacturing processes, optical measurement techniques are becoming increasingly popular for on-line quality control. This fast and cheap technique enables manufacturers to not only check single points given by an inspection plan, but entire surfaces. This paradigm change brings new possibilities as well as new challenges to the inspection process. We devised software and technologies that achieve a seamless integration of optical measurement techniques into the existing workflow in the production process from design and prototyping up to series production. These techniques go far beyond the simple measuring of structural dimensions. The system permits the management and storage of the complete history of measurements. Hence, trends in deviations from the desired quality or functionality can be determined early and easily. This helps to implement corrective actions even before the produced structures fail to meet the specifications. Using a safe and decentralized server architecture using https, all data is available across business units and plants. Additionally, we developed highly interactive visualization and data exploration tools which enable expert users to fast and easily evaluate the measured data. With these techniques and visualization tools, we combine the advantages of optical measurements with the established evaluation of tactile measurements.

The central role played by cerebrospinal-fluid (CSF) examinations including antineuronal autoantibody (Ab) testing is increasingly recognized in psychiatry. The rationale of this study was to present a multimodally investigated group of patients. In total, 992 patients were analyzed for CSF alterations: 456 patients with schizophreniform and 536 with affective syndromes. Ab measurement included testing for established antineuronal IgG-Abs against intracellular antigens in serum (Yo/Hu/Ri/cv2[CRMP5]/Ma1/Ma2/SOX1/TR[DNER]/Zic4/amphiphysin/GAD65) and for cell surface antigens in the CSF (NMDAR/AMPA-1/2-R/GABA-B-R/LGI1/CASPR2/DPPX). In 30 patients with “red flags” for autoimmune psychosis, “tissue tests” were performed. Additional diagnostics included MRI and EEG analyses. CSF white-blood-cell counts were increased in 4% and IgG indices in 2%; CSF-specific oligoclonal bands were detected in 4%; overall, 8% displayed signs of neuroinflammation. In addition, 18% revealed increased albumin quotients. Antineuronal Abs against intracellular antigens were detected in serum in 0.6%. Antineuronal Abs against established cell surface antigens were detected in serum of 1% and in the CSF of 0.3% (CSF samples were only questionably positive). Abnormal IgG binding in “tissue tests” was detected in serum of 23% and in CSF of 27%. In total, 92% of the Ab-positive patients demonstrated at least one sign of brain involvement in additional diagnostics using CSF, MRI, EEG, and FDG-PET. In summary, CSF basic analyses revealed signs of blood–brain-barrier dysfunction and neuroinflammation in relevant subgroups of patients. Established antineuronal IgG-Abs were rare in serum and even rarer in the CSF. “Tissue tests” revealed frequent occurrences of Ab-binding; therefore, novel antineuronal Abs could play a relevant role in psychiatry.

In the revised diagnostic classification systems ICD-11 and DSM-5, secondary, organic forms of obsessive-compulsive disorder (OCD) are implemented as specific nosological entities. Therefore, the aim of this study was to clarify whether a comprehensive screening approach, such as the Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD), is beneficial for detecting organic OCD forms. The FDP-OCD includes advanced laboratory tests, an expanded magnetic resonance imaging (MRI) protocol, and electroencephalography (EEG) investigations as well as automated MRI and EEG analyses. Cerebrospinal fluid (CSF), [18F]fluorodeoxyglucose positron emission tomography, and genetic analysis were added for patients with suspected organic OCD. The diagnostic findings of the first 61 consecutive OCD inpatients (32 female and 29 male; mean age: 32.7 ± 12.05 years) analyzed using our protocol were investigated. A probable organic cause was assumed in five patients (8%), which included three patients with autoimmune OCD (one patient with neurolupus and two with specific novel neuronal antibodies in CSF) and two patients with newly diagnosed genetic syndromes (both with matching MRI alterations). In another five patients (8%), possible organic OCD was detected (three autoimmune cases and two genetic cases). Immunological serum abnormalities were identified in the entire patient group, particularly with high rates of decreased “neurovitamin” levels (suboptimal vitamin D in 75% and folic acid in 21%) and increased streptococcal (in 46%) and antinuclear antibodies (ANAs; in 36%). In summary, the FDP-OCD screening led to the detection of probable or possible organic OCD forms in 16% of the patients with mostly autoimmune forms of OCD. The frequent presence of systemic autoantibodies such as ANAs further support the possible influence of autoimmune processes in subgroups of patients with OCD. Further research is needed to identify the prevalence of organic OCD forms and its treatment options.

Recruiting the endogenous editing enzyme adenosine deaminase acting on RNA (ADAR) with tailored guide RNAs for adenosine-to-inosine (A-to-I) RNA base editing is promising for safely manipulating genetic information at the RNA level. However, the precision and efficiency of editing are often compromised by bystander off-target editing. Here, we find that in 5′-U A N triplets, which dominate bystander editing, G•U wobble base pairs effectively mitigate off-target events while maintaining high on-target efficiency. This strategy is universally applicable to existing A-to-I RNA base-editing systems and complements other suppression methods such as G•A mismatches and uridine (U) depletion. Combining wobble base pairing with a circularized format of the CLUSTER approach achieves highly precise and efficient editing (up to 87%) of a disease-relevant mutation in the Mecp2 transcript in cell culture. Virus-mediated delivery of the guide RNA alone realizes functional MeCP2 protein restoration in the central nervous system of a murine Rett syndrome model with editing yields of up to 19% and excellent bystander control in vivo. Using G•U wobble base pairs at specific loci increases RNA base-editing precision and efficiency.

Patients with autoimmune encephalitis - who often have accompanying psychiatric symptoms - frequently have electroencephalography (EEG) changes and normal conventional magnetic resonance imaging (MRI) findings. The aim of this paper was to analyze automated EEG and morphometric MRI findings in psychiatric patients with suspected autoimmune psychosis (AP) spectrum syndromes versus controls and the correlation of MRI measures with EEG, cerebrospinal fluid (CSF), and psychometric/neuropsychological findings. In total, forty patients were included. Suspected AP spectrum syndromes were defined broadly based on the autoimmune psychiatric syndrome concept. All patients showed signs of an autoimmune process. That is, upon further diagnostic testing, they tested at least positive for well-characterized neuronal antibodies, novel central nervous system antibodies, or well-characterized systemic antibodies with brain involvement. For EEG, thirty-seven matched patient-control pairs, and for structural MRI, thirty-five patients and matched controls, were available. EEG analysis for intermittent rhythmic delta/theta activity (IRDA/IRTA) was performed using independent component analysis. MRI scans were analyzed using FreeSurfer (7.2) for the subcortical measures and CAT12 for cortical thickness and global volumes. Patients did not show significantly increased IRDA/IRTA rates. Regarding brain volumes, there was a significant decrease in grey matter volume/total intracranial volume (TIV) (p=0.027) and a significant increase in CSF/TIV (p=0.027), which remained significant after correction for multiple comparisons. Further differences with lower white matter volume/TIV, reduced cortical thickness in the left parahippocampal and transversotemporal gyri and an increase in the volume of the left lateral ventricle of patients did not remain significant after correcting for multiple testing. White blood cell counts in the CSF of the whole patient group correlated positively with increased hippocampal volumes. Brain volumes did not correlate with psychometric scales, but with several neuropsychological scores. Autoantibody-associated suspected AP spectrum syndromes seem to be associated with slight global grey matter volume reductions and secondary increased CSF volumes. Associations between hippocampal volume increases and inflammatory CSF markers could, in contrast, reflect edematous swelling within the limbic system. Further multimodal imaging studies of more homogeneous AP groups might be promising to detect morphometric correlates.

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a neuropsychiatric disorder with additional psychiatric features caused by NMDA-R immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF). This report presents the follow-up of a patient in whom we assumed mild NMDA-R encephalitis in the first psychotic episode. A patient with a prior episode of an acute polymorphic psychotic syndrome relapsed five and a half years later following a severe COVID-19 infection. Serum NMDA-R antibodies were again detected with a titer of max. 1:320 using fixed-cell-based assays, but conventional magnetic resonance imaging (MRI), electroencephalography (EEG), and CSF findings were largely normal. NMDA-R antibody levels in serum decreased to 1:80 after approximately one month without immunotherapy. [ F]fluorodeoxyglucose positron emission tomography (FDG-PET) still revealed pronounced metabolism of the association cortices (clearly more pronounced in the first episode with an encephalitis-like pattern at that time). Advanced MRI analyses including diffusion microstructure imaging (DMI) showed frontal and thalamic microstructural alterations compatible with edematization (but also far less accentuated than in the first episode). Further advanced antibody tests of CSF (approx. 1 month after symptom onset) using a live-cell-based and different tissue-based assays were negative for NMDA-R IgG antibodies. Research mass spectrometry of the CSF identified neurotransmitter-precursor shortages, increased turnover of tryptophan into quinolinic acid, and low-glucose/lactate levels. Immunotherapy (performed after the initial assumption of an autoimmune cause) with steroids led to clinical improvement of residual symptoms. After approximately three months, NMDA-R IgG serum antibodies were no longer detectable; however, FDG-PET/DMI follow-up revealed no relevant changes. The international consensus criteria for a probable/definite diagnosis of NMDA-R encephalitis or autoimmune psychosis were not fulfilled, especially as no NMDA-R IgG antibodies were identified in CSF using different antibody assays and EEG/CSF routine findings were inconspicuous. NMDA-R encephalitis was therefore not diagnosed (as initially suspected). Independent of the NMDA-R IgG antibodies, there were possible signs of an autoimmune process. For a better understanding of similar patients, multimodal diagnostic approaches including complementary antibody tests could be promising.

Cognitive impairment is an important constraint for PwPD with Parkinson’s disease (PwPD). Digital assessments potentially provide more accessible measurements and obtain a richer set of data than traditional paper–pencil-based instruments. Open-source generation can support the availability of comparable assessments in different cohorts. A digital, tablet-based cognitive assessment (DiCo) comprising 13 distinct tests was implemented as an open-source tool, expanding on available frameworks. Commonly used tests were selected to cover response inhibition, cognitive flexibility, attention, and working memory. After extensive usability testing, the DiCo was applied in participants without overt cognitive impairment. 97 participants (43% women) completed the entire DiCo. Clustering of DiCo feature correlations and conditional dependencies indicated a predominantly mutual organization of cognitive performance in PwPD. Exploratory factor analysis identified five interrelated latent factors. Most factors were derived from individual tests and correlated moderately with traditional neuropsychological tests and questionnaires. Machine learning identified a test of working memory (N-back) as the most predictive feature for the Montreal Cognitive Assessment. Latent profile analysis revealed four cognitive subgroups, mainly reflecting severity. The open-source digital cognitive assessment established in this study showed good usability by PwPD. The observed overlap between individual DiCo features and MoCA and FAB scores may inform future reduced task sets for research or selected clinical settings.