Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer.

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces.

Protection against Marburg Virus and Sudan Virus in NHP by an Adenovector-Based Trivalent Vaccine Regimen Is Correlated to Humoral Immune Response Levels.

The Marburg virus (MARV) and Sudan virus (SUDV) belong to the filovirus family. The sporadic human outbreaks occur mostly in Africa and are characterized by an aggressive disease course with high mortality. The first case of Marburg virus disease in Guinea in 2021, together with the increased frequency of outbreaks of Ebola virus (EBOV), which is also a filovirus, accelerated the interest in potential prophylactic vaccine solutions against multiple filoviruses.

Potential Biomarkers, Risk Factors, and Their Associations with IgE-Mediated Food Allergy in Early Life: A Narrative Review.

Food allergy (FA) affects the quality of life of millions of people worldwide and presents a significant psychological and financial burden for both national and international public health. In the past few decades, the prevalence of allergic disease has been on the rise worldwide. Identified risk factors for FA include family history, mode of delivery, variations in infant feeding practices, prior diagnosis of other atopic diseases such as eczema, and social economic status.

The Impact of the Availability of Immunotherapy on Patterns of Care in Stage III NSCLC: A Dutch Multicenter Analysis.

Introduction: Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available.

The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring.

The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria.

Psychosocial needs of patients and spouses justify a position of psychosocial health professionals in the multidisciplinary care for Parkinson's disease.

Introduction: Living a life with Parkinson's Disease (PD) is a challenge for both patients and spouses. Patients have to cope with an increasing limitation in all domains of their daily life and spouses need to adjust to these changes. The focus of this study is on exploring, both quantitatively and qualitatively, the psychosocial needs of both patients with PD and spouses.

Nutritional Interventions to Prevent the Development of Atopic Diseases: A Focus on Cow's Milk Allergy.

In the western world the prevalence of atopic diseases such as food allergies is increasing highly significantly. One of the earliest and most prevalent food allergies occurring in the first year of life is cow's milk allergy. No treatment is available and only avoidance of the cow's milk allergens prevents the occurrence of an allergic reaction.

The Architecture of Contemporary Care Networks for Rare Movement Disorders: Leveraging the ParkinsonNet Experience.

In this paper, we present a universal model for implementing network care for persons living with chronic diseases, specifically those with rare movement disorders. Building on our longstanding experience with ParkinsonNet, an integrated care network for persons living with Parkinson's disease or a form of atypical parkinsonism, we provide a series of generic, supportive building blocks to (re)design comparable care networks. We discuss the specific challenges related to rare movement disorders and how these challenges can inform a tailored implementation strategy, using the basic building blocks to offer practical guidance.

Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer.

Purpose: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer.

Methods: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands.

Surprising impact of stromal TIL's on immunotherapy efficacy in a real-world lung cancer study.

Introduction: Immune checkpoint inhibitors (ICI), such as anti-PD-1 agents, have become part of the standard of care treatment of advanced non-small cell lung cancer (NSCLC). Predictive biomarkers are needed to identify patients that benefit from anti-PD-1 treatments. Tumor infiltrating lymphocytes (TILs) and PD-L1 are major players in the ICI mechanism of action.

Factors influencing multi-disciplinary tumor board recommendations in stage III non-small cell lung cancer.

Objectives: Treatment patterns in patients with stage III non-small cell lung cancer (NSCLC) vary considerably between countries, for reasons that are not well understood. We studied factors influencing treatment decision-making at thoracic multidisciplinary tumor boards (MDT's) and outcome for patients treated between 2015-2017, at a regional network comprising 5 hospitals.

Materials And Methods: Details of all patients, including comorbidities, with stage III NSCLC were collected in an ethics-approved database.

Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy.

Immunoglobulin E (IgE)-mediated allergy against cow's milk protein fractions such as whey is one of the most common food-related allergic disorders of early childhood. Histone acetylation is an important epigenetic mechanism, shown to be involved in the pathogenesis of allergies. However, its role in food allergy remains unknown.

Functional definition of a transcription factor hierarchy regulating T cell lineage commitment.

T cell factor 1 (Tcf1) is the first T cell-specific protein induced by Notch signaling in the thymus, leading to the activation of two major target genes, and . Tcf1 deficiency results in partial arrests in T cell development, high apoptosis, and increased development of B and myeloid cells. Phenotypically, seemingly fully T cell-committed thymocytes with Tcf1 deficiency have promiscuous gene expression and an altered epigenetic profile and can dedifferentiate into more immature thymocytes and non-T cells.

What Goals Do Patients and Oncologists Have When Starting Medical Treatment for Metastatic Lung Cancer?

Background: Metastatic lung cancer is an incurable disease that can be treated with systemic therapy. These treatments might prolong survival and reduce symptoms, but they may also cause serious adverse effects. We studied the treatment goals of patients with metastasized lung cancer and their oncologists before starting systemic therapy, concordance between patients' and oncologists' goals, and feasibility of these goals.

Management of Cow's Milk Allergy from an Immunological Perspective: What Are the Options?

The immunological mechanism underlying Immunoglobuline E (IgE)-mediated cow's milk allergy has been subject to investigations for many years. Identification of the key immune cells (mast cells, B cells) and molecules (IgE) in the allergic process has led to the understanding that avoidance of IgE-crosslinking epitopes is effective in the reduction of allergic symptoms but it cannot be envisioned as a treatment. For the treatment and prevention of IgE-mediated cow's milk allergy, it is thought that the induction of a sustained state of immunological tolerance is needed.

Influence of orbital morphology on proptosis reduction and ocular motility after decompression surgery in patients with Graves' orbitopathy.

Purpose: Orbital decompression surgery is performed in patients with Graves' orbitopathy to treat dysthyroid optical neuropathy (DON) and reduce disfiguring proptosis. The intended proptosis reduction can deviate from the postoperative result and changes of motility with consecutive diplopia can occur. We performed a retrospective study to identify anatomical factors in computed tomography (CT), which influence the surgical effect and postoperative ocular motility and diplopia.

An inactivated poliovirus vaccine using Sabin strains produced on the serum-free PER.C6® cell culture platform is immunogenic and safe in a non-human primate model.

Background: The World Health Organization recommends the development of affordable next-generation inactivated poliovirus vaccines (IPV) using attenuated poliovirus Sabin strains. Previously, we introduced a novel PER.C6® cell culture platform, which allows for high yield production of an affordable trivalent Sabin IPV vaccine.

A comparative study between outbred and inbred rat strains for the use in in vivo IPV potency testing.

In vivo potency testing of inactivated poliovirus vaccines (IPV) is generally performed in rats, although no systematic investigation has identified the most appropriate rat strain for anti-poliovirus antibody quantification. We investigated humoral immune responses to IPV in five different rat strains to identify the most suitable strain. Three outbred (Wistar, Wistar Hannover, Sprague-Dawley) and two inbred rat strains (Fisher 344, Wistar Furth) were immunized intramuscularly with a full or one-fifth human dose of commercial IPV.

Discrete roles of canonical and non-canonical Wnt signaling in hematopoiesis and lymphopoiesis.

The mechanisms that regulate proliferation, fate decisions and differentiation of hematopoietic stem cells (HSC) and thymic stem cells are highly complex. Several signaling pathways including Wnt signaling have important roles during these processes. Both canonical and non-canonical Wnt signaling are important in normal and malignant hematopoiesis and lymphoid development, yet their precise roles are controversial.

The Quantity of Autocrine IL-2 Governs the Expansion Potential of CD8+ T Cells.

Adequate responsiveness of CD8(+) T cell populations is of utmost importance for the efficacy of many vaccines and immunotherapeutic strategies against intracellular pathogens and cancer. In this study, we show in mouse models that the relative number of IL-2-producing cells within Ag-specific CD8(+) T cell populations predicts the population expansion capacity upon challenge. We further demonstrate that IL-2 producers constitute the best responding subset.

T Cell factor 1 represses CD8+ effector T cell formation and function.

The Wnt-responsive transcription factor T cell factor 1 (Tcf1) is well known for its role in thymic T cell development and the formation of memory CD8(+) T cells. However, its role in the initial phases of CD8(+) T effector cell formation has remained unexplored. We report that high levels of Wnt signaling and Tcf1 are operational in naive and memory CD8(+) T cells, whereas Wnt signaling and Tcf1 were low in effector CD8(+) T cells.

TCF-1-mediated Wnt signaling regulates Paneth cell innate immune defense effectors HD-5 and -6: implications for Crohn's disease.

Wnt signaling regulates small intestinal stem cell maintenance and Paneth cell differentiation. In patients with ileal Crohn's disease (CD), a decrease of Paneth cell α-defensins has been observed that is partially caused by impaired TCF-4 and LRP6 function. Here we show reduced expression of the Wnt signaling effector TCF-1 (also known as TCF-7) in patients with ileal CD.

Wnt signaling in leukemias and myeloma: T-cell factors are in control.

Aberrant activation of the Wnt pathway has been implicated in the pathogenesis of many malignancies, especially solid tumors. During the past decade it also became clear that in hematological malignancies abnormal regulation of the Wnt pathway can either be causative or enhance disease progression, which will be discussed in detail in this review.

Canonical Wnt signaling negatively modulates regulatory T cell function.

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes.