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Stopping the COVID-19 pandemic and its socio-economic consequences is only possible with a multifaceted strategy, including mass vaccination. Studies have been conducted mainly in adults, and data on the pediatric population is relatively limited. However, it appears that vaccination in children and adolescents is highly effective and safe. Despite the apparent benefits of vaccinating this age group, there are some medical and ethical concerns. Based on the above considerations, the European Academy of Paediatrics (EAP) and the European Confederation of Primary Care Pediatricians (ECPCP) assessed the current situation and presented recommendations for international and national authorities, pediatricians, and pediatric societies regarding vaccination against SARS-CoV-2 in children and adolescents.

Diffuse midline glioma (DMG) is an incurable malignancy with the highest mortality rate among pediatric brain tumors. While radiotherapy and chemotherapy are the most common treatments, these modalities have limited promise. Due to their diffuse nature in critical areas of the brain, the prognosis of DMG remains dismal. DMGs are characterized by unique phenotypic heterogeneity and histological features. Mutations of H3K27M, TP53, and ACVR1 drive DMG tumorigenesis. Histological artifacts include pseudopalisading necrosis and vascular endothelial proliferation. Mouse models that recapitulate human DMG have been used to study key driver mutations and the tumor microenvironment. DMG consists of a largely immunologically cold tumor microenvironment that lacks immune cell infiltration, immunosuppressive factors, and immune surveillance. While tumor-associated macrophages are the most abundant immune cell population, there is reduced T lymphocyte infiltration. Immunotherapies can stimulate the immune system to find, attack, and eliminate cancer cells. However, it is critical to understand the immune microenvironment of DMG before designing immunotherapies since differences in the microenvironment influence treatment efficacy. To this end, our review aims to overview the immune microenvironment of DMG, discuss emerging insights about the immune landscape that drives disease pathophysiology, and present recent findings and new opportunities for therapeutic discovery.

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.

Background: The COVID-19 pandemic presented unique challenges for endoscopic skull base surgery (ESBS) given the elevated viral load in the nasopharynx and aerosolization of particles inherent to the endoscopic endonasal approach (EEA). Furthermore, reports and anecdotes shared within the skull base surgeon community suggesting potential elevated risk of COVID-19 transmission during ESBS led to an abundance of precaution and scrutiny regarding endonasal procedures during the pandemic. The Mount Sinai Hospital is a busy ESBS center located in New York City, the United States COVID-19 pandemic epicenter. We report a case series describing the early experience of resuming ESBS during the COVID-19 pandemic, including systems for case selection, surgical precautions and modifications, and patient outcomes. Methods: All consecutive ESBS cases and deferred surgical cases were identified prospectively within the first three-week period after resumption of urgent scheduled surgery. Data regarding indications, pre-surgical screening, operative results, and postoperative course were collected retrospectively. All data are presented using descriptive statistics. Results: With the study time frame, 14 patients underwent ESBS. Four patients had surgery deferred. The mean age was 57. The most common pathology was pituitary tumor, in 57% of patients. Visual symptoms precipitated the urgency in 36% of cases. All patients underwent COVID-19 screening with a minimum of one SARSCoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) nasal swab within 48 hours preceding surgery. All patients tested negative. There were no intraoperative complications. Median length of stay was two days. A total of 14% of patients experienced postoperative complications. Mean follow-up was 100.9 days. Conclusions: Due to its relatively low morbidity and potential short length of stay, ESBS is adaptable to unique pandemic challenges such as bed scarcity and exposure minimization. As endoscopic centers return to normal operations during the COVID-19 era, standard testing, case selection algorithms, and systematic surgical precautions and modifications can enable a safe resumption of ESBS.

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Abstract Background Genomic rearrangements exert a heavy influence on the molecular landscape of cancer. New analytical approaches integrating somatic structural variants (SSVs) with altered gene features represent a framework by which we can assign global significance to a core set of genes, analogous to established methods that identify genes non-randomly targeted by somatic mutation or copy number alteration. While recent studies have defined broad patterns of association involving gene transcription and nearby SSV breakpoints, global alterations in DNA methylation in the context of SSVs remain largely unexplored. Results By data integration of whole genome sequencing, RNA sequencing, and DNA methylation arrays from more than 1400 human cancers, we identify hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of a somatic structural variant (SSV) breakpoint is recurrently associated with altered expression or DNA methylation, respectively, independently of copy number alterations. CGIs with SSV-associated increased methylation are predominantly promoter-associated, while CGIs with SSV-associated decreased methylation are enriched for gene body CGIs. Rearrangement of genomic regions normally having higher or lower methylation is often involved in SSV-associated CGI methylation alterations. Across cancers, the overall structural variation burden is associated with a global decrease in methylation, increased expression in methyltransferase genes and DNA damage response genes, and decreased immune cell infiltration. Conclusion Genomic rearrangement appears to have a major role in shaping the cancer DNA methylome, to be considered alongside commonly accepted mechanisms including histone modifications and disruption of DNA methyltransferases.

Abstract Background Over 1 billion people suffer from chronic respiratory diseases such as asthma, COPD, rhinitis and rhinosinusitis. They cause an enormous burden and are considered as major non-communicable diseases. Many patients are still uncontrolled and the cost of inaction is unacceptable. A meeting was held in Vilnius, Lithuania (March 23, 2018) under the patronage of the Ministry of Health and several scientific societies to propose multisectoral care pathways embedding guided self-management, mHealth and air pollution in selected chronic respiratory diseases (rhinitis, chronic rhinosinusitis, asthma and COPD). The meeting resulted in the Vilnius Declaration that was developed by the participants of the EU Summit on chronic respiratory diseases under the leadership of Euforea. Conclusion The Vilnius Declaration represents an important step for the fight against air pollution in chronic respiratory diseases globally and has a clear strategic relevance with regard to the EU Health Strategy as it will bring added value to the existing public health knowledge.

Vaccination has a significant impact on morbidity and mortality. High vaccination coverage rates are required to achieve herd protection against vaccine-preventable diseases. However, limited vaccine access and hesitancy among specific communities represent significant obstacles to this goal. This review provides an overview of critical factors associated with vaccination among disadvantaged groups in World Health Organisation European countries. Initial searches yielded 18,109 publications from four databases, and 104 studies from 19 out of 53 countries reporting 22 vaccine-preventable diseases were included. Nine groups representing the populations of interest were identified, and most of the studies focused on asylum seekers, refugees, migrants and deprived communities. Recall of previous vaccinations received was poor, and serology was conducted in some cases to confirm protection for those who received prior vaccinations. Vaccination coverage was lower among study populations compared to the general population or national average. Factors that influenced uptake, which presented differently at different population levels, included health service accessibility, language and vaccine literacy, including risk perception, disease severity and vaccination benefits. Strategies that could be implemented in vaccination policy and programs were also identified. Overall, interventions specific to target communities are vital to improving uptake. More innovative strategies need to be deployed to improve vaccination coverage among disadvantaged groups.

The COVID-19 pandemic and global lockdown have had drastic socioeconomic and psychological effects on countries and people, respectively. There has been limited access to health care and education. These negative consequences have had a significant impact on the well-being of children and adolescents. Therefore, the EAP and the ECPCP are requesting state, health, and education authorities as well as European pediatric societies and the healthcare professionals that special attention be given to this population and the problems they face as a result of the pandemic.

Objectives: After childcare and schools have been closed in March 2020 to prevent the spread of COVID-19, they were open again in most European countries after the summer holidays till early autumn. Aim of this study is to give an overview and to compare COVID-19 childcare and school containment policies in 19 European countries.Methods: We collected data on containment measures among delegates of the European Academy of Pediatrics (EAP), through an online, closed questionnaire in the second half of October 2020.Results: Most policy has been formulated for secondary education. In all three settings policy was most often formulated for individual hygiene, cleaning of surfaces, exclusion of sick children, ventilation, distance between children and between children and teachers. In secondary schools, policy is formulated on face masks in and outside the class. School closure, cancellation of physical education and class size reduction are measures for which the fewest countries have formulated national policies.Conclusion: We recommend to accompany the opening of children’s facilities and schools by surveillance studies that further clarify questions about control measures implemented to halt COVID-19 pandemic.

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2–4 h prior to induction to anesthesia.Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data.Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented.Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4.Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.

Despite the fact that the use of masks and respirators in adults has already reached a consensus in almost all countries and for situations in which they are recommended, this is not the case for the use of mask by children. This statement, regarding the usage of mask by children, has been jointly produced by the Association of Schools of Public Health in the European Region (ASPHER) and the European Academy of Paediatrics (EAP). It provides recommendations on the size of the mask, the material and ergonomics of children's masks. The authors also discuss the psychological dimension of children when they are asked to wear a mask. Moreover, they tackle the difficulties of children with disabilities.

In this work, we study the effect of elemental iodine as a halide intermediary in the synthesis of FePt3 nanoparticles using a co-reduction of Fe(acac)3 and (NH4)2PtCl2 with 1,2-hexadecanediol. Our study shows that elemental iodine facilitates the formation of FePt3 nanoparticles with the L12 structure. When iodine is not used, the as-made nanoparticles have mostly the disordered fcc FePt3 structure. The as-made nanoparticles are ferromagnetic and have a Curie temperature close to 380 K. Annealing of the as-made nanoparticles leads to an increased particle size and a transformation to the ordered L12 FePt3 phase. Nanoparticles annealed at 700°C for 30 minutes show a mixture of two magnetic phases, a ferromagnetic phase with a lower ordering temperature of ∼300 K and an antiferromagnetic phase with a Néel temperature around 135 K.

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.