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Abstract Antibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context. With this method we successfully identified 29 antibodies against K. pneumoniae, a dominant cause of hospital-acquired infections with increasing antibiotic resistance. Combining genetic tools and functional analyses, we reveal that the capacity of antibodies to activate complement on K. pneumoniae critically depends on their antigenic target. Furthermore, we find that antibody combinations can synergistically activate complement on K. pneumoniae by strengthening each other’s binding in an Fc-independent manner. Understanding the molecular basis of effective complement activation by antibody combinations to mimic a polyclonal response could accelerate the development of antibody-based therapies against problematic infections.

Summary: Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring.A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes.Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI.Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

This research explores the conceptual integration of Living Labs (LLs) into the Regional Innovation Ecosystem (RIE) to understand their potential as facilitators of Responsible Innovation. While previous studies explored the role of Living Labs, they lack comprehensive integration strategies for addressing wicked problems. A conceptual framework is developed to understand the main role, detailed functions, and key elements for integration. Seven expert interviews were conducted to develop the conceptual framework, using the Interuniversity Microelectronics Centre (imec) within the Flemish Innovation Ecosystem as empirical context. The findings emphasise Living Labs as central orchestrators, enabling user-centric innovation, real-world experimentation, and stakeholder engagement. We identify four key elements that facilitate the proposed integration: government policy and funding, strategic integration, formal collaborations, and proof of concept. These findings have implications for advancing the theoretical understanding of Living Labs' integration into the Regional Innovation Ecosystem, and for practitioners who aim to foster Responsible Innovation.

Antibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of tumors. Multiple strategies for viral epitope delivery have been shown to be effective. So far, most of these have relied on a free C-terminus of the immunogenic epitope for extracellular delivery. Here, we demonstrate that antibody-epitope conjugates (AECs) with genetically fused epitopes to the N-terminus of the antibody can also sensitize tumors for attack by virus-specific CD8+ T cells. AECs carrying epitopes genetically fused at the N-terminus of the light chains of cetuximab and trastuzumab demonstrate an even more efficient delivery of the T-cell epitopes compared to AECs with the epitope fused to the C-terminus of the heavy chain. We demonstrate that this increased efficiency is not caused by the shift in location of the cleavage site from the N- to the C-terminus, but by its increased proximity to the cell surface. We hypothesize that this facilitates more efficient epitope delivery. These findings not only provide additional insights into the mechanism of action of AECs but also broaden the possibilities for genetically fused AECs as an avenue for the redirection of multiple virus-specific T cells toward tumors.

Streptococcus suis is an opportunistic bacterial porcine pathogen that can cause severe disease in humans, most commonly meningitis and sepsis (1). Human S. suis infections occur both through direct contact [...]

Abstract Background Supermarket interventions are promising to promote healthier dietary patterns, but not all individuals may be equally susceptible. We explored whether the effectiveness of nudging and pricing strategies on diet quality differs by psychological and grocery shopping characteristics. Methods We used data of the 12-month Supreme Nudge parallel cluster-randomised controlled supermarket trial, testing nudging and pricing strategies to promote healthier diets. Participants were Dutch speaking adults aged 30–80 years and regular shoppers of participating supermarkets (n = 12) in socially disadvantaged neighbourhoods. Data on psychological characteristics (food-related behaviours; price sensitivity; food decision styles; social cognitive factors; self-control) and grocery shopping characteristics (time spent in the supermarket; moment of the day; average supermarket visits; shopping at other retailers; supermarket proximity) were self-reported at baseline. These characteristics were tested for their moderating effects of the intervention on diet quality (scored 0–150) in linear mixed models. Results We included 162 participants from intervention supermarkets and 199 from control supermarkets (73% female, 58 (± 10.8) years old, 42% highly educated). The interventions had no overall effect on diet quality. Only five out of 23 potential moderators were statistically significant. Yet, stratified analyses of these significant moderators showed no significant effects on diet quality for one of the subgroups and statistically non-significant negative effects for the other. Negative effects were suggested for individuals with lower baseline levels of meal planning (β − 2.6, 95% CI − 5.9; 0.8), healthy shopping convenience (β − 3.0, 95% CI − 7.2; 1.3), and healthy food attractiveness (β − 3.5, 95% CI − 8.3; 1.3), and with higher levels of price consciousness (β − 2.6, 95% CI − 6.2; 1.0) and weekly supermarket visits (β − 2.4, 95% CI − 6.8; 1.9). Conclusions Adults with varying psychological and grocery shopping characteristics largely seem equally (un)susceptible to nudging and pricing strategies. It might be that certain characteristics lead to adverse effects, but this is not plausible, and the observed negative effects were small and statistically non-significant and may be explained by chance findings. Verification of these findings is needed in real-world trials based on larger sample sizes and with the use of more comprehensive interventions. Trial registration Dutch Trial Register ID NL7064, 30th of May, 2018, https://onderzoekmetmensen.nl/en/trial/20990

School closures due to the COVID-19 pandemic raised concerns about increases in educational inequality. We examined the magnitude of the impact of the first school closure for vulnerable student groups in particular. This study was conducted among 886 Grade 3-5 students in the Netherlands in schools serving a high percentage of students from disadvantaged backgrounds. Piecewise growth analyses indicated that the school closures caused discontinuity in students' achievement growth on national standardized tests and led to an average learning loss of 2.47 months in mathematics and 2.35 in reading comprehension, exceeding the duration of the school closure. Findings suggest that school closures contribute to educational inequality and indicate which students may particularly need additional support to overcome the adverse consequences of the lockdowns.

Abstract The Karner blue butterfly, Plebejus (Lycaeides) samuelis, is an endangered North American climate change‐vulnerable species that has undergone substantial historical habitat loss and population decline. To better understand the species' genetic status and support Karner blue conservation, we sampled 116 individuals from 22 localities across the species' geographical range in Wisconsin (WI), Michigan (MI), Indiana (IN), and New York (NY). Using genomic analysis, we found that these samples were divided into three major geographic groups, NY, WI, and MI‐IN, with populations in WI and MI‐IN each further divided into three subgroups. A high level of inbreeding was revealed by inbreeding coefficients above 10% in almost all populations in our study. However, strong correlation between FST and geographical distance suggested that genetic divergence between populations increases with distance, such that introducing individuals from more distant populations may be a useful strategy for increasing population‐level diversity and preserving the species. We also found that Karner blue populations had lower genetic diversity than closely related species and had more alleles that were present only at low frequencies (

Summary: Airway epithelial cells represent the first line of defense against respiratory pathogens. Flagellin drives the motility of many mucosal pathogens and has been suggested as an immune enhancing adjunctive therapeutic in infections of the airways. This study leveraged single-cell RNA sequencing to determine cell-specific effects of flagellin in primary human bronchial epithelial cells growing in air-liquid interface. Seven cell clusters were identified, including ciliated cells, ionocytes, and several states of basal and secretory cells, of which only inflammatory basal cells and inflammatory secretory cells demonstrated a proportional increase in response to flagellin. Inflammatory secretory cells showed evidence of metabolic reprogramming toward aerobic glycolysis, while in inflammatory basal cells transcriptome profiles indicated enhanced oxidative phosphorylation. Inhibition of mTOR prevented the shift to glycolysis and reduced inflammatory gene transcription specifically in inflammatory secretory cells. These data demonstrate the functional heterogeneity of the human airway epithelium upon exposure to flagellin.