Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8+ T Cell Epitopes

Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV) acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8+ T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVFTL peptide (GIL), formulated with WIV. By screening various concentrations of GIL and WIV, we found that both components contributed to the GIL-specific T cell response. Whereas co-localization of the peptide antigen and WIV adjuvant was found to be important, neither physical association between peptide and WIV nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We furthermore show that WIV may adjuvate T cell responses to a variety of peptides, using pools of either conserved wild-type influenza peptides or chemically altered peptide ligands. This study shows the potential of WIV as an adjuvant for influenza peptides. The simple formulation process and the solid safety record of WIV make this an attractive adjuvant for T cell peptides, and may also be used for non-influenza antigens

CerebNet: A fast and reliable deep-learning pipeline for detailed cerebellum sub-segmentation

Quantifying the volume of the cerebellum and its lobes is of profound interest in various neurodegenerative and acquired diseases. Especially for the most common spinocerebellar ataxias (SCA), for which the first antisense oligonculeotide-base gene silencing trial has recently started, there is an urgent need for quantitative, sensitive imaging markers at pre-symptomatic stages for stratification and treatment assessment. This work introduces CerebNet, a fully automated, extensively validated, deep learning method for the lobular segmentation of the cerebellum, including the separation of gray and white matter. For training, validation, and testing, T1-weighted images from 30 participants were manually annotated into cerebellar lobules and vermal sub-segments, as well as cerebellar white matter. CerebNet combines FastSurferCNN, a UNet-based 2.5D segmentation network, with extensive data augmentation, e.g. realistic non-linear deformations to increase the anatomical variety, eliminating additional preprocessing steps, such as spatial normalization or bias field correction. CerebNet demonstrates a high accuracy (on average 0.87 Dice and 1.742mm Robust Hausdorff Distance across all structures) outperforming state-of-the-art approaches. Furthermore, it shows high test-retest reliability (average ICC >0.97 on OASIS and Kirby) as well as high sensitivity to disease effects, including the pre-ataxic stage of spinocerebellar ataxia type 3 (SCA3). CerebNet is compatible with FreeSurfer and FastSurfer and can analyze a 3D volume within seconds on a consumer GPU in an end-to-end fashion, thus providing an efficient and validated solution for assessing cerebellum sub-structure volumes. We make CerebNet available as source-code (https://github.com/Deep-MI/FastSurfer)

Using co-authorship networks to map and analyse global Neglected Tropical Disease research with an affiliation to Germany

Neglected tropical disease research has changed considerably in recent decades, and the German government is committed to addressing its past neglect of NTD research. Our aim was to use an innovative social network analysis of bibliometric data to map neglected tropical disease research networks that are inside of and affiliated with Germany, thereby enabling data-driven health policy decision-making. We created and analysed co-author networks from publications in the SCOPUS database, with a focus on five diseases. We found that Germany's share of global publication output for NTDs is approximately half that of other medical research fields. Furthermore, we identified institutions with prominent NTD research within Germany and strong research collaborations between German institutions and partners abroad, mostly in other high-income countries. This allowed an assessment of strong collaborations for further development, e.g., for research capacity strengthening in low-income-countries, but also for identifying missed opportunities for collaboration within the network. Through co-authorship network analysis of individual researcher networks, we identified strong performers by using classic bibliometric parameters, and we identified academic talent by social network analysis parameters on an individual level

Suppression of circulating IgD+CD27+ memory B cells in infants living in a malaria-endemic region of Kenya

Background: Plasmodium falciparum infection leads to alterations in B cell subset distribution. During infancy, development of peripheral B cell subsets is also occurring. However, it is unknown if infants living a malaria endemic region have alterations in B cell subsets that is independent of an age effect. Methods: To evaluate the impact of exposure to P. falciparum on B cell development in infants, flow cytometry was used to analyse the distribution and phenotypic characteristic of B cell subsets in infant cohorts prospectively followed at 12, 18 and 24 months from two geographically proximate regions in western Kenya with divergent malaria exposure i.e. Kisumu (malaria-endemic, n = 24) and Nandi (unstable malaria transmission, n = 21). Results: There was significantly higher frequency and absolute cell numbers of CD19+ B cells in Kisumu relative to Nandi at 12(p = 0.0440), 18(p = 0.0210) and 24 months (p = 0.0493). No differences were observed between the infants from the two sites in frequencies of naïve B cells (IgD+CD27-) or classical memory B cells (IgD-CD27+). However, immature transitional B cells (CD19+CD10+CD34-) were higher in Kisumu relative to Nandi at all three ages. In contrast, the levels of non-class switched memory B cells (CD19+IgD+CD27+) were significantly lower overall in Kisumu relative to Nandi at significantly at 12 (p = 0.0144), 18 (p = 0.0013) and 24 months (p = 0.0129). Conclusions: These data suggest that infants living in malaria endemic regions have altered B cell subset distribution. Further studies are needed to understand the functional significance of these changes and long-term impact on ability of these infants to develop antibody responses to P. falciparum and heterologous infections

The Rotterdam Study: 2012 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

Meßkunst für Kinder von 8 bis 12 Jahren, die ihren Verstand schärfen wollen

A.F.E. Jacobi, ...Aus dem Vorbesitz der Naturforschenden Gesellschaft in Zürich Exemplar der ZB Züric

Disputatio Theologica, De Termino Vitae Humanae

Quam in florentissima Academia Salana, Praeside ... Dn. Joh. Ernesto Gerhardo ... Publico examini sistit Autor Matthias Jacobi, Dantiscanus. Ad d. 25. Iunii Anno MDCLXIV. ...Nicht identisch mit VD17 12:174100E (abweichender Fingerprint