On the interplay of temporal resolution power and spatial suppression in their prediction of psychometric intelligence.

As a measure of the brain's temporal fine-tuning capacity, temporal resolution power (TRP) explained repeatedly a substantial amount of variance in psychometric intelligence. Recently, spatial suppression, referred to as the increasing difficulty in quickly perceiving motion direction as the size of the moving stimulus increases, has attracted particular attention, when it was found to be positively related to psychometric intelligence. Due to the conceptual similarities of TRP and spatial suppression, the present study investigated their mutual interplay in the relation to psychometric intelligence in 273 young adults to better understand the reasons for these relationships. As in previous studies, psychometric intelligence was positively related to a latent variable representing TRP but, in contrast to previous reports, negatively to latent and manifest measures of spatial suppression. In a combined structural equation model, TRP still explained a substantial amount of variance in psychometric intelligence while the negative relation between spatial suppression and intelligence was completely explained by TRP. Thus, our findings confirmed TRP to be a robust predictor of psychometric intelligence but challenged the assumption of spatial suppression as a representation of general information processing efficiency as reflected in psychometric intelligence. Possible reasons for the contradictory findings on the relation between spatial suppression and psychometric intelligence are discussed

Contrast-Enhanced Magnetic Resonance Angiography Using a Novel Elastin-Specific Molecular Probe in an Experimental Animal Model

Objectives. The aim of this study was to test the potential of a new elastin-specific molecular agent for the performance of contrast-enhanced first-pass and 3D magnetic resonance angiography (MRA), compared to a clinically used extravascular contrast agent (gadobutrol) and based on clinical MR sequences. Materials and Methods. Eight C57BL/6J mice (BL6, male, aged 10 weeks) underwent a contrast-enhanced first-pass and 3D MR angiography (MRA) of the aorta and its main branches. All examinations were on a clinical 3 Tesla MR system (Siemens Healthcare, Erlangen, Germany). The clinical dose of 0.1 mmol/kg was administered in both probes. First, a time-resolved MRA (TWIST) was acquired during the first-pass to assess the arrival and washout of the contrast agent bolus. Subsequently, a high-resolution 3D MRA sequence (3D T1 FLASH) was acquired. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated for all sequences. Results. The elastin-specific MR probe and the extravascular imaging agent (gadobutrol) enable high-quality MR angiograms in all animals. During the first-pass, the probes demonstrated a comparable peak enhancement (300.6 +/- 32.9 vs. 288.5 +/- 33.1, p > 0.05). Following the bolus phase, both agents showed a comparable intravascular enhancement (SNR: 106.7 +/- 11 vs. 102.3 +/- 5.3; CNR 64.5 +/- 7.4 vs. 61.1 +/- 7.2, p > 0.05). Both agents resulted in a high image quality with no statistical difference (p > 0.05). Conclusion. The novel elastin-specific molecular probe enables the performance of first-pass and late 3D MR angiography with an intravascular contrast enhancement and image quality comparable to a clinically used extravascular contrast agent

Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: Simultaneous assessment of plaque inflammation and extracellularmatrix remodeling

Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE-/-) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls' Prussian-blue-stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions

Dataset of prostate MRI annotated for anatomical zones and cancer

In the present work, we present a publicly available, expert-segmented representative dataset of 158 3.0 Tesla biparametric MRIs [1]. There is an increasing number of studies investigating prostate and prostate carcinoma segmentation using deep learning (DL) with 3D architectures [2], [3], [4], [5], [6], [7]. The development of robust and data-driven DL models for prostate segmentation and assessment is currently limited by the availability of openly available expert-annotated datasets [8], [9], [10]. The dataset contains 3.0 Tesla MRI images of the prostate of patients with suspected prostate cancer. Patients over 50 years of age who had a 3.0 Tesla MRI scan of the prostate that met PI-RADS version 2.1 technical standards were included. All patients received a subsequent biopsy or surgery so that the MRI diagnosis could be verified/matched with the histopathologic diagnosis. For patients who had undergone multiple MRIs, the last MRI, which was less than six months before biopsy/surgery, was included. All patients were examined at a German university hospital (Charité Universitätsmedizin Berlin) between 02/2016 and 01/2020. All MRI were acquired with two 3.0 Tesla MRI scanners (Siemens VIDA and Skyra, Siemens Healthineers, Erlangen, Germany). Axial T2W sequences and axial diffusion-weighted sequences (DWI) with apparent diffusion coefficient maps (ADC) were included in the data set. T2W sequences and ADC maps were annotated by two board-certified radiologists with 6 and 8 years of experience, respectively. For T2W sequences, the central gland (central zone and transitional zone) and peripheral zone were segmented. If areas of suspected prostate cancer (PIRADS score of ≥ 4) were identified on examination, they were segmented in both the T2W sequences and ADC maps. Because restricted diffusion is best seen in DWI images with high b-values, only these images were selected and all images with low b-values were discarded. Data were then anonymized and converted to NIfTI (Neuroimaging Informatics Technology Initiative) format

MEDBERT.de: A Comprehensive German BERT Model for the Medical Domain

This paper presents medBERTde, a pre-trained German BERT model specifically designed for the German medical domain. The model has been trained on a large corpus of 4.7 Million German medical documents and has been shown to achieve new state-of-the-art performance on eight different medical benchmarks covering a wide range of disciplines and medical document types. In addition to evaluating the overall performance of the model, this paper also conducts a more in-depth analysis of its capabilities. We investigate the impact of data deduplication on the model's performance, as well as the potential benefits of using more efficient tokenization methods. Our results indicate that domain-specific models such as medBERTde are particularly useful for longer texts, and that deduplication of training data does not necessarily lead to improved performance. Furthermore, we found that efficient tokenization plays only a minor role in improving model performance, and attribute most of the improved performance to the large amount of training data. To encourage further research, the pre-trained model weights and new benchmarks based on radiological data are made publicly available for use by the scientific community.Comment: Keno K. Bressem and Jens-Michalis Papaioannou and Paul Grundmann contributed equall

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Can the resting state peak alpha frequency explain the relationship between temporal resolution power and psychometric intelligence?

The temporal resolution power (TRP) hypothesis states that individuals with higher TRP, as reflected by a higher performance on several psychophysical timing tasks, perform better on intelligence tests due to their ability to process information faster and coordinate their mental operations more effectively. It is proposed that these differences in TRP are related to the rate of a master clock based on neural oscillations. The present study aimed to investigate whether the peak alpha frequency (PAF) measured via electroencephalography (EEG) reflects a psychophysiological measure of this rate and its potential role in explaining the relationship between TRP and psychometric intelligence. A sample of 129 young adults (M = 23.0, SD = 3.1) completed a short version of Raven's Advanced Progressives Matrices and three timing tasks. PAF was measured using EEG before each timing task during two resting states with eyes closed (EC) and eyes open (EO), respectively. From these PAF measurements, four latent PAF variables were extracted, differing in resting state (EC, EO) and electrode cluster (frontal/central, parietal/occipital). The results confirmed a strong association between TRP and psychometric intelligence (r = .56, p < .01), as previously reported in other studies. Additionally, we found a positive association between intelligence and a latent PAF variable extracted from frontal/central electrodes in the EO resting state conditions (r = .27, p < .05). However, there was no association between TRP and PAF. This indicates that PAF does not reflect the underlying psychophysiological mechanism that links TRP to intelligence. (PsycInfo Database Record (c) 2023 APA, all rights reserved)