Physical activity through place attachment: Understanding perceptions of children and adolescents on urban places by using photovoice and walking interviews.

Public urban places and their environmental characteristics impact youth's physical activity (PA) through perceptions. The objective of this study was to use a qualitative participatory approach with children and adolescents to understand how their attachment to urban places perceived as PA-friendly or unfriendly is related to their PA behaviour. Ninety-three participants aged six to 17 from six neighbourhoods with varying objective walkability engaged in photovoice and walking interviews.

Engineering an inducible leukemia-associated fusion protein enables large-scale ex vivo production of functional human phagocytes.

Ex vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors.

Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets.

Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology.

Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32 nanoprotrusions deposit distinct plasma membrane patches onto target T cells.

Net-zero aviation: Transition barriers and radical climate policy design implications.

While air transport decarbonization is theoretically feasible, less attention has been paid to the complexity incurred in various 'transition barriers' that act as roadblocks to net-zero goals. A total of 40 barriers related to mitigation, management, technology and fuel transition, finance, and governance are identified. As these make decarbonization uncertain, the paper analyzes air transport system's growth, revenue, and profitability.

Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?

Background: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching.

Study Design And Methods: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021.

Novel NKG2D-directed bispecific antibodies enhance antibody-mediated killing of malignant B cells by NK cells and T cells.

The activating receptor natural killer group 2, member D (NKG2D) represents an attractive target for immunotherapy as it exerts a crucial role in cancer immunosurveillance by regulating the activity of cytotoxic lymphocytes. In this study, a panel of novel NKG2D-specific single-chain fragments variable (scFv) were isolated from naïve human antibody gene libraries and fused to the fragment antigen binding (Fab) of rituximab to obtain [CD20×NKG2D] bibodies with the aim to recruit cytotoxic lymphocytes to lymphoma cells. All bispecific antibodies bound both antigens simultaneously.

Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer.

Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types of cancer and may hold potential to also stimulate innate immune responses. A novel emerging potential target for immune checkpoint therapy is leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1).

Predictive value of molecular matching tools for the development of donor specific HLA-antibodies in patients undergoing lung transplantation.

Molecular matching is a new approach for virtual histocompatibility testing in organ transplantation. The aim of our study was to analyze whether the risk for de novo donor-specific HLA antibodies (dnDSA) after lung transplantation (LTX) can be predicted by molecular matching algorithms (MMA) and their combination. In this retrospective study we included 183 patients undergoing LTX at our center from 2012-2020.

Monitoring Blood Supply in Germany: A Regulatory Perspective.

Background And Objectives: A sufficient supply of safe, high-quality blood components for transfusion is essential to the healthcare system in Germany. The requirements for the current reporting system are laid down in the German Transfusion Act. The present work elaborates on the advantages and limitations of the current reporting system and investigates the feasibility of a pilot project that collects specific data on blood supply based on weekly reports.

Dual checkpoint blockade of CD47 and LILRB1 enhances CD20 antibody-dependent phagocytosis of lymphoma cells by macrophages.

Antibody-dependent cellular phagocytosis (ADCP) by macrophages, an important effector function of tumor targeting antibodies, is hampered by 'Don´t Eat Me!' signals such as CD47 expressed by cancer cells. Yet, human leukocyte antigen (HLA) class I expression may also impair ADCP by engaging leukocyte immunoglobulin-like receptor subfamily B (LILRB) member 1 (LILRB1) or LILRB2. Analysis of different lymphoma cell lines revealed that the ratio of CD20 to HLA class I cell surface molecules determined the sensitivity to ADCP by the combination of rituximab and an Fc-silent variant of the CD47 antibody magrolimab (CD47-IgGσ).

Emergency Use of Convalescent Plasma: Perception of the Regulatory Framework from a Clinical Perspective.

The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty.

Rapid, efficient and activation-neutral gene editing of polyclonal primary human resting CD4 T cells allows complex functional analyses.

CD4 T cells are central mediators of adaptive and innate immune responses and constitute a major reservoir for human immunodeficiency virus (HIV) in vivo. Detailed investigations of resting human CD4 T cells have been precluded by the absence of efficient approaches for genetic manipulation limiting our understanding of HIV replication and restricting efforts to find a cure. Here we report a method for rapid, efficient, activation-neutral gene editing of resting, polyclonal human CD4 T cells using optimized cell cultivation and nucleofection conditions of Cas9-guide RNA ribonucleoprotein complexes.

Tumor cell lysis and synergistically enhanced antibody-dependent cell-mediated cytotoxicity by NKG2D engagement with a bispecific immunoligand targeting the HER2 antigen.

Natural killer group 2 member D (NKG2D) plays an important role in the regulation of natural killer (NK) cell cytotoxicity in cancer immune surveillance. With the aim of redirecting NK cell cytotoxicity against tumors, the NKG2D ligand UL-16 binding protein 2 (ULBP2) was fused to a single-chain fragment variable (scFv) targeting the human epidermal growth factor receptor 2 (HER2). The resulting bispecific immunoligand ULBP2:HER2-scFv triggered NK cell-mediated killing of HER2-positive breast cancer cells in an antigen-dependent manner and required concomitant interaction with NKG2D and HER2 as revealed in antigen blocking experiments.

SIRPα-αCD123 fusion antibodies targeting CD123 in conjunction with CD47 blockade enhance the clearance of AML-initiating cells.

Background: Acute myeloid leukaemia (AML) stem cells (LSCs) cause disease relapse. The CD47 "don't eat me signal" is upregulated on LSCs and contributes to immune evasion by inhibiting phagocytosis through interacting with myeloid-specific signal regulatory protein alpha (SIRPα). Activation of macrophages by blocking CD47 has been successful, but the ubiquitous expression of CD47 on healthy cells poses potential limitations for such therapies.

[Update 2021: COVID-19 from the Perspective of Haematology and Haemostaseology].

Infection with SARS-CoV-2 has a profound influence on the hematopoetic system that mediates clinical symptoms and mortality. Several studies have shown that treatment of the cytokine storm (CRS) with anti-inflammatory drugs like dexamethasone and tocilizumab can significantly improve survival. Systematic reviews confirm the safety of convalescent plasma administration and offer initial indications of its effectiveness in certain groups.

Enhancement of epidermal growth factor receptor antibody tumor immunotherapy by glutaminyl cyclase inhibition to interfere with CD47/signal regulatory protein alpha interactions.

Integrin associated protein (CD47) is an important target in immunotherapy, as it is expressed as a "don't eat me" signal on many tumor cells. Interference with its counter molecule signal regulatory protein alpha (SIRPα), expressed on myeloid cells, can be achieved with blocking Abs, but also by inhibiting the enzyme glutaminyl cyclase (QC) with small molecules. Glutaminyl cyclase inhibition reduces N-terminal pyro-glutamate formation of CD47 at the SIRPα binding site.

Enhancing CDC and ADCC of CD19 Antibodies by Combining Fc Protein-Engineering with Fc Glyco-Engineering.

Background: Native cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody's Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies.

Epigenetic Compound Screening Uncovers Small Molecules for Reactivation of Latent HIV-1.

During infection with the human immunodeficiency virus type 1 (HIV-1), latent reservoirs are established that circumvent full eradication of the virus by antiretroviral therapy (ART) and are the source for viral rebound after cessation of therapy. As these reservoirs are phenotypically indistinguishable from infected cells, current strategies aim to reactivate these reservoirs, followed by pharmaceutical and immunological destruction of the cells. Here, we employed a simple and convenient cell-based reporter system, which enables sample handling under biosafety level (BSL)-1 conditions, to screen for compounds that were able to reactivate latent HIV-1.

The global scale, distribution and growth of aviation: Implications for climate change.

Prior to the COVID-19 crisis, global air transport demand was expected to triple between 2020 and 2050. The pandemic, which reduced global air travel significantly, provides an opportunity to discuss the scale, distribution and growth of aviation until 2018, also with a view to consider the climate change implications of a return to volume growth. Industry statistics, data provided by supranational organizations, and national surveys are evaluated to develop a pre-pandemic understanding of air transport demand at global, regional, national and individual scales.

[COVID-19 from the Perspective of Haematology and Haemostaseology].

Infection with SARS-COV-2 leads to a number of pathologies in the hematopoetic system that have significant impact on clinical symptoms and mortality. There are 3 stages of infection: (1) early upper respiratory tract infection with fever and lymphopenia (2) pulmonary phase and (3) hyperinflammatory phase with the clinical signs of organ failure such as ARDS/shock. Hyperinflammation, which is triggered by activation of T cells and monocytes/macrophages, is essential for organ pathologies.

Impact, Screening, and Therapy of HLA Antibodies in Patients before and after Lung Transplantation.

Since almost 30 years, lung transplantation is a considerable therapeutic option in patients suffering from end-stage lung disease. Up to now, the impact of donor-specific antibodies directed against donor HLA (human leukocyte antigen) before and after transplantation is still a matter of debate. As histocompatibility testing is not required for each patient according to the current national guidelines and Eurotransplant recommendations for lung transplantation, each transplantation unit has to establish a local protocol together with the tissue typing laboratory how to implement an immunological risk assessment strategy for their patients while enabling access to transplantation.