Parental Strategies to Promote Mental Health in Digital Citizens of Grades 6-8

The research conducted in this study was done to discern the best parental strategies to promote mental health in digital citizens of grades 6-8. The world of technology is very dynamic, and often these days children are advancing much faster than their parents. The purpose of this research study was to keep parents informed and educated of the latest trends, tools, and dangers in the digital world today. To achieve this goal the researchers held four online workshops over the course of two months to provide parents the tools necessary to raise responsible digital citizens. The results of the study proved that the workshops provided parents the knowledge they needed to promote digital citizens in the middle school aged child. The majority of the results from the comparison of the pre and post assessment survey were statistically significant with 90 - 95% certainty depending on the question. In the future, the researchers believe the effectiveness of the development of digital citizenship among middle school students would be improved if their families were introduced to the topic earlier in their educational journey, such as elementary school. Another recommendation would be yearly workshops to continue growth and understanding of digital citizenship. In conclusion, the data collected from the post survey indicates that overall, parents/guardians became empowered and knowledgeable in digital citizenship and were able to better guide their middle school aged child to become responsible digital citizens

Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy

Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing life-long therapy to a global population of over 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Hyper-AdaC: Adaptive clustering-based hypergraph representation of whole slide images for survival analysis

International audienceThe emergence of deep learning in the medical field has popularized the development of models to predict survival outcomes from histopathology images in precision oncology. Graph-based formalism has opened interesting perspectives for generating informative representations, as they can be context-aware and model local and global topological structures in the tumor’s microenvironment. However, the critical issue in using graph representations lies in their generalizability. They can suffer from overfitting due to their large sizes or high discrepancies between nodes due to random sampling from WSI. In addition, standard graph formulations are limited to pairwise interactions, which can sometimes fail to represent the reality observed in histopathology and hinder the interpretability of those interactions. In this work, we present Hyper-AdaC, an adaptive clustering-based hypergraph representation to model high-order correlations among different regions of the WSIs while being compact enough to help graph neural networks generalize in the case of survival prediction. We evaluate our approach on 5 different public available cancer datasets. Our method outperforms most state-of-the-art graph-based methods for survival prediction with WSIs, creating a more efficient and robust alternative to other graph representations. Moreover, due to our formulation, attention maps are depicted at different resolutions depending on the tissue characteristics of each WSI. The code is available at: https://github.com/HakimBenkirane/Hyper-adaC

Hyper-AdaC: Adaptive clustering-based hypergraph representation of whole slide images for survival analysis

International audienceThe emergence of deep learning in the medical field has popularized the development of models to predict survival outcomes from histopathology images in precision oncology. Graph-based formalism has opened interesting perspectives for generating informative representations, as they can be context-aware and model local and global topological structures in the tumor’s microenvironment. However, the critical issue in using graph representations lies in their generalizability. They can suffer from overfitting due to their large sizes or high discrepancies between nodes due to random sampling from WSI. In addition, standard graph formulations are limited to pairwise interactions, which can sometimes fail to represent the reality observed in histopathology and hinder the interpretability of those interactions. In this work, we present Hyper-AdaC, an adaptive clustering-based hypergraph representation to model high-order correlations among different regions of the WSIs while being compact enough to help graph neural networks generalize in the case of survival prediction. We evaluate our approach on 5 different public available cancer datasets. Our method outperforms most state-of-the-art graph-based methods for survival prediction with WSIs, creating a more efficient and robust alternative to other graph representations. Moreover, due to our formulation, attention maps are depicted at different resolutions depending on the tissue characteristics of each WSI. The code is available at: https://github.com/HakimBenkirane/Hyper-adaC

ATP8A2-related disorders as recessive cerebellar ataxia

International audienceATP8A2-related disorders are autosomal recessive conditions that associate encephalopathy with or without hypotonia, psychomotor delay, abnormal movements, chorea, tremor, optic atrophy and cerebellar atrophy (CARMQ4). Through a multi-centric collaboration, we identified six point mutations (one splice site and five missense mutations) involving ATP8A2 in six individuals from five families. Two patients from one family with the homozygous p.Gly585Val mutation had a milder presentation without encephalopathy. Expression and functional studies of the missense mutations demonstrated that protein levels of four of the five missense variants were very low and lacked phosphatidylserine-activated ATPase activity. One variant p.Ile215Leu, however, expressed at normal levels and displayed phospholipid-activated ATPase activity similar to the non-mutated protein. We therefore expand for the first time the phenotype related to ATP8A2 mutations to less severe forms characterized by cerebellar ataxia without encephalopathy and suggest that ATP8A2 should be analyzed for all cases of syndromic or non-syndromic recessive or sporadic ataxia