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Despite considerable recent advances in understanding and treating many other cancers, malignant brain tumors remain associated with low survival or severe long-term sequelae. Limited progress, including development of immunotherapies, relates in part to difficulties in accurately reproducing brain microenvironment with current preclinical models. The cellular interactions among resident microglia, recruited tumor-associated macrophages, stromal cells, glial cells, neurons, and cancer cells and how they affect tumor growth or behavior are emerging, yet many questions remain. MLN2238 The role of the blood-brain barrier, extracellular matrix components, and heterogeneity among tumor types and within different regions of a single tumor further complicate the matter. Here, we focus on brain microenvironment features impacted by tumor biology. We also discuss limits of current preclinical models and how complementary models, such as humanized animals and organoids, will allow deeper mechanistic insights on cancer biology, allowing for more efficient testing of therapeutic strategies, including immunotherapy, for brain cancers.Despite the central importance of the respiratory system, the exact mechanisms governing lung repair after severe injury remain unclear. The notion that alveolar type 2 cells (AT2s) self-renew and differentiate into alveolar type 1 cells (AT1s) does not fully encompass scenarios where these progenitors are severely affected by disease, e.g., H1N1 influenza or SARS-CoV-2 (COVID-19). Intrapulmonary p63+ progenitor cells, a rare cell type in mice but potentially encompassing more numerous classic basal cells in humans, are activated in such severe injury settings, proliferating and migrating into the injured alveolar parenchyma, providing a short-term “emergency” benefit. While the fate of these cells is controversial, most studies indicate that they represent a maladaptive repair pathway with a fate restriction toward airway cell types, rarely differentiating into AT2 or AT1 cells. Here, we discuss the role of intrapulmonary basal-like p63+ cells in alveolar regeneration and suggest a unified model to guide future studies.Little is known about the intrinsic specification of postnatal cerebellar neural stem cells (NSCs) and to what extent they depend on information from their local niche. Here, we have used an adapted cell preparation of isolated postnatal NSCs and live imaging to demonstrate that cerebellar progenitors maintain their neurogenic nature by displaying hallmarks of NSCs. Furthermore, by using this preparation, all the cell types produced postnatally in the cerebellum, in similar relative proportions to those observed in vivo, can be monitored. The fact that neurogenesis occurs in such organized manner in the absence of signals from the local environment, suggests that cerebellar lineage progression is to an important extent governed by cell-intrinsic or pre-programmed events. Finally, we took advantage of the absence of the niche to assay the influence of the vesicular nucleotide transporter inhibition, which dramatically reduced the number of NSCs in vitro by promoting their progression toward neurogenesis.Patients with gastroparesis often have signs and symptoms including nausea, vomiting, epigastric discomfort, and early satiety, thus leading to inadequate food intake and a high risk of malnutrition. There is a considerable scarcity of data about nutritional strategies for gastroparesis, and current practices rely on extrapolated evidence. Some approaches include the modification of food composition, food consistency, and food volume in the context of delayed gastric emptying. If the patient is unable to consume adequate calories through a solid food diet, stepwise nutritional interventions could include the use of liquid meals, oral nutrition supplements, enteral nutrition, and parenteral nutrition. This Review discusses the role, rationale, and current evidence of diverse nutritional interventions in the management of gastroparesis.

The 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.

In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for ant-2-, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021-0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.

The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.

US Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.

For the French translation of the abstract see Supplementary Materials section.

For the French translation of the abstract see Supplementary Materials section.

Seasonal influenza remains a substantial public health threat despite the availability of egg-derived and other vaccines. Plant-based manufacturing might address some of the limitations of current vaccines. We describe two phase 3 efficacy studies of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in plants, one in adults aged 18-64 years (the 18-64 study) and one in older people aged 65 years and older (the 65-plus study).

We did two randomised, observer-blind, multinational studies in the northern hemisphere in the 2017-18 (the 18-64 study) and 2018-19 (the 65-plus study) influenza seasons. The 18-64 study was done at 73 sites and the 65-plus study was done at 104 sites, both across Asia, Europe, and North America. In the 18-64 study, inclusion criteria were body-mass index less than 40 kg/m

; age 18-64 years at screening visit; and good health. In the 65-plus study, inclusion criteria were body-mass index of maximum 35 kg/m

; aged 65 years or older at screening visit; not living in a rehabilitation centre or care home; and no acute or evolving medical problems.