Validation of 4D flow CMR against simultaneous invasive hemodynamic measurements: a swine study

The purpose of this study was to compare invasively measured aorta fow with 2D phase contrast fow and 4D fow measurements by cardiovascular magnetic resonance (CMR) imaging in a large animal model. Nine swine (mean weight 63±4 kg) were included in the study. 4D fow CMR exams were performed on a 1.5T MRI scanner. Flow measurements were performed on 4D fow images at the aortic valve level, in the ascending aorta, and main pulmonary artery. Simultaneously, fow was measured using an invasive fow probe, placed around the ascending aorta. Additionally, standard 2D phase contrast fow and 2D left ventricular (LV) volumetric data were used for comparison. The correlations of cardiac output (CO) between the invasive fow probe, and CMR modalities were strong to very strong. CO measured by 4D fow CMR correlated better with the CO measured by the invasive fow probe than 2D fow CMR fow and volumetric LV data (4D fow CMR: Spearman’s rho = 0.86 at the aortic valve level and 0.90 at the ascending aorta level; 2D fow CMR: 0.67 at aortic valve level; LV measurements: 0.77). In addition, there tended to be a correlation between mean pulmonary artery fow and aorta fow with 4D fow (Spearman’s rho=0.65, P=0.07), which was absent in measurements obtained with 2D fow CMR (Spearman’s rho=0.40, P=0.33). This study shows that aorta fow can be accurately measured by 4D fow CMR compared to simultaneously measured invasive fow. This helps to further validate the quantitative reliability of this technique

Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge

Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. We investigated their role at nasal mucosa following allergen challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on nasal immune cells from nasal biopsies cells from 30 allergic rhinitis and 27 non-allergic subjects before and after repeated nasal allergen challenge. Biopsies of patients showed infiltrating inflammatory HLA-DRhi/CD14+ and CD16+ monocytes and proallergic transcriptional changes in resident CD1C+/CD1A+ conventional dendritic cells (cDC)2 following challenge. In contrast, non-allergic individuals displayed distinct innate MPS responses to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (MDSC: HLA-DRlow/CD14+ monocytes) and cDC2 expressing inhibitory/tolerogenic transcripts. These divergent patterns were confirmed in ex vivo stimulated MPS nasal biopsy cells. Thus, we identified not only MPS cell clusters involved in airway allergic inflammation but also highlight novel roles for non-inflammatory innate MPS responses by MDSC to allergens in non-allergic individuals. Future therapies should address MDSC activity as treatment for inflammatory airway diseases.</p

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Updating of the Gaussian graphical model through targeted penalized estimation

Updating of the Gaussian graphical model via shrinkage estimation is studied. This shrinkage is towards a nonzero parameter value representing prior quantitative information. Once new data become available, the previously estimated parameter needs updating. Shrinkage provides the means to this end, using the latter as a shrinkage target to acquire an updated estimate. The process of iteratively updating the Gaussian graphical model in shrinkage fashion is shown to yield an improved fit and an asymptotically unbiased and consistent estimator. The workings of updating via shrinkage are elucidated by linking it to Bayesian updating and through the inheritance by the update of eigen-properties of the previous estimate. The effect of shrinkage on the moments and loss of the estimator are pointed out. Practical issues possibly hampering updating are identified and solutions outlined. The presented updating procedure is illustrated through the reconstruction of a gene–gene interaction network using transcriptomic data

Abnormal EEG synchronisation in heavily drinking students

OBJECTIVE: In alcoholics, grey and white brain matter is damaged. In addition, functional brain connectivity as measured by EEG coherence is abnormal. We investigated whether heavily drinking students, although drinking for a shorter period than alcoholics, already show differences in functional connectivity compared to light-drinking controls. METHODS: EEG was recorded in 11 light and 11 heavy male student drinkers during eyes closed, and eyes closed plus mental rehearsal of pictures. Functional connectivity was assessed with the Synchronisation Likelihood method. RESULTS: Heavily drinking students had more synchronisation in the theta (4-8 Hz) and gamma (30-45 Hz) band than lightly drinking students during eyes closed, both with and without a mental-rehearsal task. CONCLUSIONS: Heavy student drinkers have increases in EEG synchronisation that are indicative of changes in hippocampal-neocortical connectivity. SIGNIFICANCE: Heavy student drinkers show differences in functional connectivity as compared to their lightly drinking counterparts, even though they have a relatively short drinking history

Mirror therapy: fMRI pilot study on mirror-induced visual illusions

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Helminth infections drive heterogeneity in human type 2 and regulatory cells

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A genetic analysis of relative growth rate and underlying components in Hordeum spontaneum

Abstract Species from productive and unproductive habitats differ inherently in their relative growth rate (RGR) and a wide range of correlated quantitative traits. We investigated the genetic basis of this trait complex, and specifically assessed whether it is under the control of just one or a few genes that can act as &apos;master switches&apos; by simultaneously affecting a range of traits in the complex. To address this problem, we crossed two Hordeum spontaneum lines originating from two habitats that differ in productivity. The F 3 offspring, in which parental alleles are present in different combinations due to recombination and segregation, was analysed for RGR and its underlying components (leaf area ratio, unit leaf rate, photosynthesis, respiration), as well as a number of other physiological and morphological parameters. For this intra-specific comparison, we found a complex of positively and negatively correlated traits, which was quite similar to what is generally observed across species. A quantitative trait loci (QTL) analysis showed three major and one minor QTL for RGR. Most other variables of the growth-trait complex showed fewer QTLs that were typically scattered over various locations on the genome. Thus, at least in H. spontaneum, we found no evidence for regulation of the trait complex by one or two master switches