Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients.

Detailed knowledge of human B-cell development is crucial for the proper interpretation of inborn errors of immunity and malignant diseases. It is of interest to understand the kinetics of protein expression changes during development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human samples from healthy individuals with the aim of describing all B-cell developmental trajectories.

Online and Offline Behavior Change Techniques to Promote a Healthy Lifestyle: A Qualitative Study.

Combined lifestyle interventions (CLI) are focused on guiding clients with weight-related health risks into a healthy lifestyle. CLIs are most often delivered through face-to-face sessions with limited use of eHealth technologies. To integrate eHealth into existing CLIs, it is important to identify how behavior change techniques are being used by health professionals in the online and offline treatment of overweight clients.

The expansion of human T-betCD21 B cells is T cell dependent.

Accumulation of human CD21 B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21 B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-betCD21 B cells.

Water Professionals Reflect on Pandemic Response.

The COVID-19 pandemic has posed the greatest challenge to the water sector in the 21st century. A recent roundtable discussion offers insights from a range of water professionals on the challenges they've faced and the strategies they've used to maintain operations.

Dissection of the Pre-Germinal Center B-Cell Maturation Pathway in Common Variable Immunodeficiency Based on Standardized Flow Cytometric EuroFlow Tools.

Introduction: Common Variable Immunodeficiency (CVID) is characterized by defective antibody production and hypogammaglobulinemia. Flow cytometry immunophenotyping of blood lymphocytes has become of great relevance for the diagnosis and classification of CVID, due to an impaired differentiation of mature post-germinal-center (GC) class-switched memory B-cells (MBC) and severely decreased plasmablast/plasma cell (Pb) counts. Here, we investigated in detail the pre-GC B-cell maturation compartment in blood of CVID patients.

A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26-104/RFASE in Patients with Advanced Solid Malignancies.

Lessons Learned: The novel therapeutic vaccine hVEGF /RFASE was found to be safe and well tolerated in patients with cancer. hVEGF /RFASE failed to induce seroconversion against native hVEGF and, accordingly, neither a decrease in circulating vascular endothelial growth factor (VEGF) levels nor clinical benefit was observed. Remarkably, hVEGF /RFASE induced VEGF -neutralizing antibodies in a nonhuman primate model.

Delineating Human B Cell Precursor Development With Genetically Identified PID Cases as a Model.

B-cell precursors (BCP) arise from hematopoietic stem cells in bone marrow (BM). Identification and characterization of the different BCP subsets has contributed to the understanding of normal B-cell development. BCP first rearrange their immunoglobulin (Ig) heavy chain (IGH) genes to form the pre-B-cell receptor (pre-BCR) complex together with surrogate light chains.

Teachers' and students' perceptions on barriers and facilitators for eHealth education in the curriculum of functional exercise and physical therapy: a focus groups study.

Background: Despite the growing importance of eHealth it is not consistently embedded in the curricula of functional exercise and physical therapy education. Insight in barriers and facilitators for embedding eHealth in education is required for the development of tailored strategies to implement eHealth in curricula. This study aims to identify barriers/facilitators perceived by teachers and students of functional exercise/physical therapy for uptake of eHealth in education.

Factors associated with willingness to use eRehabilitation after stroke: A cross-sectional study among patients, informal caregivers and healthcare professionals.

Objective: Despite the increasing availability of eRehabilitation, its use remains limited. The aim of this study was to assess factors associated with willingness to use eRehabilitation.

Design: Cross-sectional survey.

How to improve eRehabilitation programs in stroke care? A focus group study to identify requirements of end-users.

Background: A user-centered design approach for eHealth interventions improves their effectiveness in stroke rehabilitation. Nevertheless, insight into requirements of end-users (patients/informal caregivers and/or health professionals) for eRehabilitation is lacking. The aim of this study was to identify end-user requirements for a comprehensive eHealth program in stroke rehabilitation.

EuroFlow-Based Flowcytometric Diagnostic Screening and Classification of Primary Immunodeficiencies of the Lymphoid System.

Guidelines for screening for primary immunodeficiencies (PID) are well-defined and several consensus diagnostic strategies have been proposed. These consensus proposals have only partially been implemented due to lack of standardization in laboratory procedures, particularly in flow cytometry. The main objectives of the EuroFlow Consortium were to innovate and thoroughly standardize the flowcytometric techniques and strategies for reliable and reproducible diagnosis and classification of PID of the lymphoid system.

The EuroFlow PID Orientation Tube for Flow Cytometric Diagnostic Screening of Primary Immunodeficiencies of the Lymphoid System.

In the rapidly evolving field of primary immunodeficiencies (PID), the EuroFlow consortium decided to develop a PID orientation and screening tube that facilitates fast, standardized, and validated immunophenotypic diagnosis of lymphoid PID, and allows full exchange of data between centers. Our aim was to develop a tool that would be universal for all lymphoid PIDs and offer high sensitivity to identify a lymphoid PID (without a need for specificity to diagnose particular PID) and to guide and prioritize further diagnostic modalities and clinical management. The tube composition has been defined in a stepwise manner through several cycles of design-testing-evaluation-redesign in a multicenter setting.

Precursor B-cell development in bone marrow of Good syndrome patients.

Good syndrome is an immunodeficiency presenting with thymoma, hypogammaglobulinemia and almost absent B cells. To investigate the origin of the B-cell lymphopenia in these patients, we studied B cell differentiation in the bone marrow of Good syndrome patients. We found very low numbers of precursor B cells in bone marrow of Good syndrome patients and a differentiation arrest after the pro-B-cell stage; this is different from other agammaglobulinemia patients with a defect in pre B-cell receptor signaling.

A 3-Year-Old Girl With a Mediastinal Mass.

A 3-year-old girl was referred to a pediatric pulmonologist for dyspnea and recurrent upper respiratory tract infections (RTIs). The patient was born full term to unrelated Dutch parents after an uneventful pregnancy and birth. The year before presentation, she had suffered from pneumonia and > 10 upper RTIs.

Why the uptake of eRehabilitation programs in stroke care is so difficult-a focus group study in the Netherlands.

Background: The uptake of eRehabilitation programs in stroke care is insufficient, despite the growing availability. The aim of this study was to explore which factors influence the uptake of eRehabilitation in stroke rehabilitation, among stroke patients, informal caregivers, and healthcare professionals.

Methods: A qualitative focus group study with eight focus groups (6-8 participants per group) was conducted: six with stroke patients/informal caregivers and two with healthcare professionals involved in stroke rehabilitation (rehabilitation physicians, physical therapists, occupational therapists, psychologists, managers).

What is Important in E-health Interventions for Stroke Rehabilitation? A Survey Study among Patients, Informal Caregivers and Health Professionals.

Incorporating user requirements in the design of e-rehabilitation interventions facilitates their implementation. However, insight into requirements for e-rehabilitation after stroke is lacking. This study investigated which user requirements for stroke e-rehabilitation are important to stroke patients, informal caregivers, and health professionals.

Deficiencies in the CD19 complex.

Signaling via the CD19-complex, consisting of CD19, CD81, CD21 and CD225, is critically important for B-cell development, differentiation and maturation. In this complex, each protein has its own distinct function. Over the past decade, 15 patients with antibody deficiency due to deficiencies in the CD19-complex have been described.

Adherence of stroke patients with an online brain training program: the role of health professionals' support.

Background Computer-based cognitive rehabilitation is used to improve cognitive functioning after stroke. However, knowledge on adherence rates of stroke patients is limited. Objective To describe stroke patients' adherence with a brain training program using two frequencies of health professionals' supervision.

Exhaustion of the CD8 T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta.

Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8 T cells was suggested to contribute to APDS pathogenesis.

A safety and immunogenicity study of immunization with hVEGF/RFASE in cynomolgus monkeys.

Introduction: Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF. hVEGF/RFASE is based on the truncated protein hVEGF as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant.

Selection and validation of antibody clones against IgG and IgA subclasses in switched memory B-cells and plasma cells.

The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry.

Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma.

Background: Based on the tumor-driven concomitant activation of angiogenesis and coagulation we conducted a phase I combination study of sunitinib with the low molecular weight heparin dalteparin in patients with metastatic clear cell renal cell carcinoma (ccRCC).

Materials And Methods: Patients received standard treatment with sunitinib (50 mg daily, 4 weeks on, 2 weeks off). During the second week of no sunitinib in the first cycle (week 6) patients received dalteparin monotherapy (in escalating doses).

The patient perspective on the use of information and communication technologies and e-health in rehabilitation.

Introduction: Success of e-health relies on the extent to which the related technology, such as the electronic device, is accepted by its users. However, there has been limited research on the patients' perspective on use of e-health-related technology in rehabilitation care.

Objective: To explore the usage of common electronic devices among rehabilitation patients with access to email and investigate their preferences regarding their usage in rehabilitation.

Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections.

Background: Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway.

Methods: We studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis.