Using the role model approach to optimise caregiver administration of sulfadoxine-pyrimethamine amodiaquine to children aged 3-59 months in Burkina Faso, Chad and Togo: findings from an evaluation.

Background: Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo.

Barriers to the quality delivery of seasonal malaria chemoprevention in Chad and Burkina Faso: a qualitative exploration of caregivers and community distributors' perspectives.

Background: Recommended since 2012 by the World Health Organization (WHO), seasonal malaria chemoprevention (SMC) is a community-based intervention to prevent malaria in children in African regions where malaria transmission follows a seasonal pattern. Following the publication of consolidated WHO guidelines for malaria, SMC is expected to reach more children in new geographies in future years. Though SMC has been shown to reduce malaria-related morbidity and mortality, there is potential for quality improvement of the intervention implementation.

Protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of brain tumors.

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections.

Exploring existing malaria services and the feasibility of implementing community engagement approaches amongst conflict-affected communities in Cameroon: a qualitative study.

Background: Cameroon is one of the countries with the highest burden of malaria. Since 2018, there has been an ongoing conflict in the country, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of this study was to understand the current situation regarding access to malaria services in Cameroon to inform the design of interventions to remove barriers and encourage the use of available services.

A formative cross-sectional study to assess caregiver's health-seeking behaviour and knowledge surrounding malaria, and understand the burden of malaria among children under-five in conflict-affected communities of Cameroon.

Background: Malaria remains a major global health problem often worsened by political instability and armed conflict. The purpose of the study was to explore community knowledge, attitudes and practices on malaria prevention, and to understand the burden of malaria and health-seeking behaviours of caregivers of children under-five in conflict-affected communities of the South West and Littoral Regions of Cameroon.

Methods: A cross-sectional survey involving internally displaced persons (IDPS), host population, and their children under-five was conducted across 80 communities.

The Virtual Child.

We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life.

Developmental basis of SHH medulloblastoma heterogeneity.

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development.

Optimizing the role of 'lead mothers' in seasonal malaria chemoprevention (SMC) campaigns: formative research in Kano State, northern Nigeria.

Background: Seasonal malaria chemoprevention (SMC) is a safe and effective intervention for preventing malaria in children under 5 years of age. Lead mothers are community health volunteers that help caregivers comply with monthly administration of anti-malarial drugs during SMC campaigns. The lead mother approach is used in several SMC implementing states across Nigeria, but there is lack of evidence about their roles and how effective they are.

Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells.

Background Aims: The targeting of solid cancers with chimeric antigen receptor (CAR) T cells faces many technological hurdles, including selection of optimal target antigens. Promising pre-clinical and clinical data of CAR T-cell activity have emerged from targeting surface antigens such as GD2 and B7H3 in childhood cancer neuroblastoma. Anaplastic lymphoma kinase (ALK) is expressed in a majority of neuroblastomas at low antigen density but is largely absent from healthy tissues.

Mechanosensitive brain tumor cells construct blood-tumor barrier to mask chemosensitivity.

Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2 tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries.

Health related quality of life trajectories after stereotactic radiosurgery for brain metastases: a systematic review.

Purpose: Health related quality of life (HRQoL) is often used as an outcome measure of cancer treatment. Stereotactic radiosurgery (SRS) is a mainstay treatment of brain metastases (BMs) with constantly improving treatment envelope. The goal of this systematic review was to evaluated HRQoL trajectories after SRS, identify important predictors of HRQoL after SRS, and to evaluate clinical importance of post-SRS HRQoL trajectories of BM patients treated with SRS.

Delivery of seasonal malaria chemoprevention with enhanced infection prevention and control measures during the COVID-19 pandemic in Nigeria, Burkina Faso and Chad: a cross-sectional study.

Background: Seasonal malaria chemoprevention (SMC) is a WHO-recommended intervention for children aged 3-59 months living in areas of high malaria transmission to provide protection against malaria during the rainy season. Operational guidelines were developed, based on WHO guidance, to support countries to mitigate the risk of coronavirus disease 2019 (COVID-19) transmission within communities and among community distributors when delivering SMC.

Methods: A cross-sectional study to determine adherence to infection prevention and control (IPC) measures during two distribution cycles of SMC in Nigeria, Chad and Burkina Faso.

Extending Delivery of Seasonal Malaria Chemoprevention to Children Aged 5-10 Years in Chad: A Mixed-Methods Study.

Background: To prevent malaria among children aged 3-59 months in areas with high seasonal transmission, seasonal malaria chemoprevention (SMC) is recommended. In Chad, there is evidence of SMC administration to children aged older than 5 years (referred to as "leakage"). This study aimed to understand the reasons for leakage and explore the feasibility and acceptability of extending the delivery of SMC to children aged 5-10 years in Chad.

Extending seasonal malaria chemoprevention to five cycles: a pilot study of feasibility and acceptability in Mangodara district, Burkina Faso.

Background: Seasonal malaria chemoprevention (SMC) involves administering antimalarial drugs at monthly intervals during the high malaria transmission period to children aged 3 to 59 months as recommended by the World Health Organization. Typically, a full SMC course is administered over four monthly cycles from July to October, coinciding with the rainy season. However, an analysis of rainfall patterns suggest that the malaria transmission season is longer and starting as early as June in the south of Burkina Faso, leading to a rise in cases prior to the first cycle.

Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment.

Relapsed medulloblastoma (rMB) accounts for a considerable, and disproportionate amount of childhood cancer deaths. Recent advances have gone someway to characterising disease biology at relapse including second malignancies that often cannot be distinguished from relapse on imaging alone. Furthermore, there are now multiple international early-phase trials exploring drug-target matches across a range of high-risk/relapsed paediatric tumours.

Health management information system (HMIS) data quality and associated factors in Massaguet district, Chad.

Background: Quality data from Health Management Information Systems (HMIS) are important for tracking the effectiveness of malaria control interventions. However, HMIS data in many resource-limited settings do not currently meet standards set by the World Health Organization (WHO). We aimed to assess HMIS data quality and associated factors in Chad.

Causes of Death and End-of-Life Care in Patients With Intracranial High-Grade Gliomas: A Retrospective Observational Study.

Background And Objectives: To understand patterns of care and circumstances surrounding end of life in patients with intracranial gliomas.

Methods: We retrospectively analyzed end-of-life circumstances in patients with intracranial high-grade gliomas at Columbia University Irving Medical Center who died from January 2014 to February 2019, including cause of death, location of death, and implementation of comfort measures and resuscitative efforts.

Results: There were 152 patients (95 men, 57 women; median age at death 61.

Community health worker knowledge, attitudes and practices towards COVID-19: Learnings from an online cross-sectional survey using a digital health platform, UpSCALE, in Mozambique.

Healthcare workers (HCWs) are at the frontline of the Coronavirus Disease 2019 (COVID-19) pandemic response, yet there is a paucity of literature on their knowledge, attitudes and practices (KAP) in relation to the pandemic. Community Health Workers (CHWs) in Mozambique are known locally as agentes polivalentes elementares (APEs). While technical guidance surrounding COVID-19 is available to support APEs, communicating this information has been challenging due to restrictions on travel, face-to-face group meetings and training, imposed from May to August 2020.

Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma.

Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27).

Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma.

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor α2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain.

Stalled developmental programs at the root of pediatric brain tumors.

Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics.

Childhood cerebellar tumours mirror conserved fetal transcriptional programs.

Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells.