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The increased susceptibility to infections of neonates is caused by an immaturity of the immune system as a result of both qualitative and quantitative differences between neonatal and adult immune cells. With respect to B cells, neonatal antibody responses are known to be decreased. Accountable for this is an altered composition of the neonatal B cell compartment towards more immature B cells. However, it remains unclear whether the functionality of individual neonatal B cell subsets is altered as well. In the current study we therefore compared phenotypical and functional characteristics of corresponding neonatal and adult B cell subpopulations. No phenotypic differences could be identified with the exception of higher IgM expression in neonatal B cells. Functional analysis revealed differences in proliferation, survival, and B cell receptor signaling. Most importantly, neonatal B cells showed severely impaired class-switch recombination (CSR) to IgG and IgA. This was associated with increased expression of miR-181b in neonatal B cells. Deficiency of miR-181b resulted in increased CSR. With this, our results highlight intrinsic differences that contribute to weaker B cell antibody responses in newborns.
Background: Right ventricular (RV) dysfunction is frequently observed in patients with aortic stenosis (AS). Nevertheless, assessment of regional RV deformation is yet not performed. The aim of the study was to analyze the impact of moderate and severe AS on global and regional RV function by a multisegmental approach using tissue Doppler imaging (TDI).
Methods: In 50 patients (Group I – AS [n = 25] and Group II – normal controls [n = 25]), additional echocardiographic views of the RV were prospectively performed. The TDI sample volume was placed in the basal myocardial region of the anterior (RV-anterior), inferior (RV-inferior), and free RV wall (RV-free wall) to assess the following parameters: S'RV, E'RV, and A'RV waves; IVCTRV; IVRTRV; and myocardial performance index (MPIRV).
esults: In AS patients, left ventricular (LV) mass index, left atrial (LA) volume index, and LV end-diastolic pressure were significantly increased. Moreover, AS patients had higher systolic pulmonary artery pressure (sPAP) and lower values for PV AccT (P < 0.0001), but TAPSE was not different between the two groups (P = 0.062). In AS patients, IVRTRV-anterior, IVRTRV-inferior, and IVRTRV-freewall and MPIRV were statistically increased (P < 0.0001). A significant correlation between IVRTRV (evaluated at all three regions) and the parameters including sPAP, PV AccT, and ELV/e'LV ratio was observed in AS. A strong correlation was observed between IVRTRV-freewall/inferior and AS severity by evaluation of velocities, gradient, and aortic valve area (P < 0.0001).
Conclusions: The present study reports a correlation between the severity of AS and the increase of IVRTRV and MPIRV. Thus, a distinct analysis of RV performance is important for echocardiographic evaluation of patients with AS.
Co-design of a trustworthy AI system in healthcare: deep learning based skin lesion classifier
(2021)
This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.