Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies.

Automated manufacture of ΔNPM1 TCR-engineered T cells for AML therapy.

Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure.

Individual and environmental determinants of serum ferritin levels: A structural equation model.

Background And Objectives: Serum ferritin levels are increasingly being used to assess iron stores. Considerable variation in ferritin levels within and between individuals has been observed, but our current understanding of factors that explain this variation is far from complete. We aim to combine multiple potential determinants in an integrative model, and investigate their relative importance and potential interactions.

Identification of patient-specific CD4 and CD8 T cell neoantigens through HLA-unbiased genetic screens.

Cancer neoantigens that arise from tumor mutations are drivers of tumor-specific T cell responses, but identification of T cell-recognized neoantigens in individual patients is challenging. Previous methods have restricted antigen discovery to selected HLA alleles, thereby limiting the breadth of neoantigen repertoires that can be uncovered. Here, we develop a genetic neoantigen screening system that allows sensitive identification of CD4 and CD8 T cell-recognized neoantigens across patients' complete HLA genotypes.

Mortality among rough sleepers, squatters, residents of homeless shelters or hotels and sofa-surfers: a pooled analysis of UK birth cohorts.

Background: Homelessness encompasses a wide spectrum of experience. Rough sleepers and people attending homeless shelters have been found to be at an increased risk of mortality. It is unclear whether risks are also elevated in those squatting, living temporarily in low-cost hotels or 'sofa-surfing' with friends or family members.

Donation-induced iron depletion is significantly associated with low hemoglobin at subsequent donations.

Background: Blood donation is associated with a loss of hemoglobin (Hb)-bound iron. Hb levels recover relatively fast by using stored iron. However, it takes more time to replenish iron stores, potentially resulting in iron deficiency.

T cells expanded from renal cell carcinoma display tumor-specific CD137 expression but lack significant IFN-γ, TNF-α or IL-2 production.

Metastatic renal cell carcinoma (RCC) has a poor prognosis. Recent advances have shown beneficial responses to immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies. As only a subset of RCC patients respond, alternative strategies should be explored.

Stroke in COVID-19: A systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.

Aims: We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.

Dietary intake of heme iron is associated with ferritin and hemoglobin levels in Dutch blood donors: results from Donor InSight.

Whole blood donors, especially frequently donating donors, have a risk of iron deficiency and low hemoglobin levels, which may affect their health and eligibility to donate. Lifestyle behaviors, such as dietary iron intake and physical activity, may influence iron stores and thereby hemoglobin levels. We aimed to investigate whether dietary iron intake and questionnaire-based moderate-to-vigorous physical activity were associated with hemoglobin levels, and whether ferritin levels mediated these associations.

Challenges in Establishing Pure Lung Cancer Organoids Limit Their Utility for Personalized Medicine.

Clinical implementation of tumor organoids for personalized medicine requires that pure tumor organoids can be reliably established. Here, we present our experience with organoid cultures from >70 non-small cell lung cancer (NSCLC) samples. We systematically evaluate several methods to identify tumor purity of organoids established from intrapulmonary tumors.

Lifestyle behaviours are not associated with haemolysis: results from Donor InSight.

Background: Lifestyle behaviours such as physical activity, sedentary behaviour and dietary habits have been shown to influence blood lipid levels, and both lifestyle and blood lipids may be associated with haemolysis during storage of blood products. We aimed to investigate whether lifestyle behaviours are associated with degree of haemolysis in red cell concentrates (RCC), and if such associations are mediated by low-density lipoprotein (LDL) cholesterol and triglyceride levels.

Materials And Methods: Cross-sectional analyses were performed in data from 760 Dutch blood donors participating in Donor InSight, an observational cohort study.

Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with an immune-engaged T cell profile.

Non-small cell lung cancer (NSCLC) is the second most prevalent type of cancer. With the current treatment regimens, the mortality rate remains high. Therefore, better therapeutic approaches are necessary.

Urban-rural differences in the association between blood lipids and characteristics of the built environment: a systematic review and meta-analysis.

Introduction: The built environment defines opportunities for healthy eating and physical activity and may thus be related to blood lipids. The aim of this study is to systematically analyse the scientific evidence on associations between built-environment characteristics and blood lipid levels in adults.

Methods: PubMed, EMBASE and Web of Science were searched for peer-reviewed papers on population-based studies up to 9 October 2017.

The association between population density and blood lipid levels in Dutch blood donors.

Background: In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior.

Dutch midwives' views on and experiences with woman-centred care - A Q-methodology study.

Background: Woman-centred care is a philosophy for midwifery care management of the childbearing woman. There is no mutually recognised internalised way in midwifery to provide woman-centred care.

Objective: To reveal midwives' distinct perspectives about woman-centred care.

Donor InSight: characteristics and representativeness of a Dutch cohort study on blood and plasma donors.

Background And Objectives: More insight into donor health and behaviour may contribute to more efficient and focused strategies regarding donor care and management. Donor InSight (DIS) is a Dutch cohort study of blood and plasma donors. We aimed to outline the objectives and methods of DIS, describe the cohort, and compare it to the active Dutch donor population.

What factors explain socioeconomic inequalities in adults' television-related sitting time?

Background: There are considerable socioeconomic inequalities in television-related sitting time, but there is little evidence for the explanatory mechanisms. We used a cohort of Belgian adults (25-60 years) and older adults (≥65 years) to examine the social cognitive, home environmental and health-related factors contributing to socioeconomic differences in television-related sitting.

Methods: We included 301 adults and 258 older adults (total n = 559).

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner.

Exploring the cross-sectional association between outdoor recreational facilities and leisure-time physical activity: the role of usage and residential self-selection.

Background: The availability of outdoor recreational facilities is associated with increased leisure-time physical activity (PA). We investigated how much of this association is attributable to selection effects, and explored whether usage of recreational facilities was an explanatory mechanism.

Methods: We analysed data from 5199 participants in the SPOTLIGHT survey residing in five European urban regions.

Woman-centered care 2.0: Bringing the concept into focus.

Introduction: Woman-centered care has become a midwifery concept with implied meaning. In this paper we aim to provide a clear conceptual foundation of woman-centered care for midwifery science and practice.

Methods: An advanced concept analysis was undertaken.

Viral dsRNA-activated human dendritic cells produce IL-27, which selectively promotes cytotoxicity in naive CD8+ T cells.

Viral recognition programs DCs to express Signal 3 molecules that promote the differentiation of effector CD8(+) T cells. Besides IL-12, another DC-derived IL-12 family member, IL-27, has been reported to contribute herein, but its specific role is not well understood. Here, we show that whereas IL-12 potently induces inflammatory cytokines (i.

CD5 costimulation induces stable Th17 development by promoting IL-23R expression and sustained STAT3 activation.

IL-17-producing CD4(+) T helper (Th17) cells are important for immunity against extracellular pathogens and in autoimmune diseases. The factors that drive Th17 development in human remain a matter of debate. Here we show that, compared with classic CD28 costimulation, alternative costimulation via the CD5 or CD6 lymphocyte receptors forms a superior pathway for human Th17-priming.

Cutting edge: virus selectively primes human langerhans cells for CD70 expression promoting CD8+ T cell responses.

The two outermost compartments of skin are populated by different Ag-presenting dendritic cell types. Epidermal Langerhans cells (LCs) are evolutionarily adapted to the continuous presence of harmless skin commensals by the selective lack of cell surface TLRs that sense bacteria. In this article, we analyze the ability of LCs and dermal dendritic cells (DDCs) to respond to virus infection.

Modeling acardiac twin pregnancies.

Acardiac twin pregnancies are a rare but severe complication of monochorionic twinning, where the acardiac twin lacks cardiac function but nevertheless grows during pregnancy because it is perfused by the pump twin through a set of placental arterioarterial and venovenous anastomoses. Because the acardiac twin's body is only perfused by the pump twin's arterial blood, acardiac twins have reduced blood oxygen saturation (SO(2)) levels. Furthermore, the pump twin has reduced blood oxygen saturation because the anastomoses merge the blood of the two twins.