Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Law experience 2022: embates políticos e democráticos e seus desdobramentos jurídicos

Em ano eleitoral decidimos trazer a comunidade em geral Esta Obra com diversos artigos sobre a temática das eleições e os embates democráticos, por meio de um diálogo entre discentes e docentes da FAE Centro universitário e, também, com participantes externos. Pelo terceiro ano consecutivo, esta obra faz parte da estruturação da disciplina de Pesquisa científica no FAE LAW EXPERIENCE, na qual ministro, e tem por objetivo despertar a paixão pela técnica na pesquisa científica em direito e, no calor dos embates democráticos, conseguimos afastar as opiniões pessoais para trazer uma obra qualificada sobre o tema. Como resultado material desta experiência, tivemos em 2020 o evento e a obra “Law Experience 2020: Direitos Fundamentais e a era Tecnológica”, com comunicados científicos e artigos científicos. No ano de 2021, realizando o evento “Law Experience 2021 – Jurisdição Constitucional e Direitos Fundamentais”, que também resultou nessa obra, em diálogo também com a disciplina da Professora Luciana Ferreira. Agora, apresentamos a obra “Embates Políticos e Democráticos e seus desdobramentos jurídicos: III Livro Law Experience” como resultado dessa troca também com a professora Luciana. Assim, participaram ativamente do processo de idealização, elaboração, editoração e coordenação os discentes: Ana Luísa Alves Pinto, Ana Luiza de Paiva, Ana Luiza Fachini, Aryadne Izabelle dos Santos Santana, Bernardo Afonso Nora, Luiza Mandelli, Maria Julia Silveira, Marcos Arthur Montes Ribeiro Francisco Chagas, Matheus Dalgallo Camargo, Victoria Midori Deguchi Teramoto e Vinícius Braga Machado, que trouxeram temas audaciosos para este projeto. A presente obra está composta primeiramente pelos resumos científicos produzidos em sala de aula, demonstrando o avanço que tiveram na disciplina e, posteriormente os artigos científicos, estes tanto de discentes da FAE como externos. A Aluna Victoria Midori produziu primeiramente resumo “A influência das decisões proferidas pelo Supremo Tribunal Federal (STF) no financiamento privado em campanhas eleitorais” e, posteriormente, evoluiu para o segundo resumo “A influência das decisões proferidas pelo Supremo Tribunal Federal (STF) no financiamento privado em campanhas eleitorais: análise da ADI 4650/2015” em que analisou a referida ADI. Os alunos Bernardo Afonso Nora e Marcos Arthur Montes Ribeiro Francisco Chaves partiram do primeiro resumo “Coligações e estratégias partidárias nas eleições” para depois apresentarem uma análise a partir da jurisprudência no segundo resumo: “Coligações e estratégias partidárias nas eleições”. Os alunos Matheus Dalgallo Camargo e Vinicius Braga Machado trouxeram o resumo consolidado no tema: “Análise acerca da discussão legislativa e judicial em torno do voto impresso auditável”. As alunas Ana Luísa Alves Pinto e Luiza Mandelli trouxeram a pesquisa “Federalismo, Covid e STF: uma análise crítica do enfrentamento à pandemia no Brasil”. As alunas Ana Fachini e Aryadne Santana trouxeram primeiramente a pesquisa “Análise jurisprudencial da restrição à liberdade de expressão no âmbito político por meio da ADI 5.122/DF” e avançaram para o segundo resumo: “Democracia em tensão: proteção e restrição à liberdade de expressão no âmbito político”. Por fim, as alunas Ana Luiza de Paiva e Maria Julia Silveira discutiram o tema inquieto da prisão em segunda instância: “A (in)constitucionalidade da prisão em segunda instância e o princípio da presunção de inocência”. Finalizado este primeiro bloco esta coletânea traz os artigos científicos que foram submetidos por acadêmicos da FAE e externos em capítulos. O primeiro capítulo aborda sobre os Embates Democráticos e seus desdobramentos jurídicos e é composto por cinco artigos: Luiz Guilherme Schinzel traz o tema atual “O fim da paz perpétua: a guerra na Ucrânia e a crise da democracia no Brasil e no mundo”; Felipe Gomes Mano e Sofia Covas Russi trazem o largo debate: “Democracia, direitos humanos e cidadania para além do estado: crise da democracia neoliberal e superação”; o autor Udo Guilherme Lutz aborda um tema pouco explorado: “O caso do DIFAL nas operações do ICMS e o respeito ao Princípio da Anterioridade: embate econômico e político contra a “literalidade” interpretativa”; e, por fim, Julio de Oliveira Pighi retoma o tema da prisão em segunda instância: “Constitucionalidade ou inconstitucionalidade da prisão em Segunda Instância” e as alunas Ana Luiza de Paiva e Maria Julia Silveira abordam de forma aprofundada essa temática no artigo: “A prisão em segunda instância no ordenamento jurídico brasileiro e a insegurança jurídica gerada entre a tensão dos poderes”. O segundo capítulo trata do Âmbito eleitoral e seus nuances e é composto por nove artigos: o primeiro de Miriam Olivia Knopik Ferraz e Marcelo Reviglio Bertoncini discutindo o tema “O financiamento coletivo de campanhas eleitorais: perspectivas para a democratização das eleições”; o trabalho de Leonardo Francisco Navarrete de Andrade – Lucas Salazar Serena – Vítor Hilzendeger de Oliveira instiga os leitores por meio do tema “São as empresas as reais vilãs do financiamento político?”; o terceiro artigo de Georgia Hutter Gamper Reis; Guilherme Lehi de Souza Gaertner; e Stephanie Smalarz Jansen aborda o tema das fake News: “Fake news e eleições: análise entre censura, liberdade de expressão, e a visão do STF”; o quarto artigo é de Wadson Lima Vieira; Anderson Jordan Alves Abreu e trata sobre “Sistema do conflito: a relação entre o presidencialismo de coalizão e a instabilidade governamental do Estado brasileiro”; o quinto artigo da acadêmica Victoria Midori Deguchi Teramoto aprofunda o tema “O STF: financiamento eleitoral de campanha e a caixa de pandora – análise da ADI 4650”; o sexto artigo dos acadêmicos Bernardo Afonso Nora e Marcos Arthur Montes Ribeiro Francisco Chaves aborda o tema “Coligações e estratégias partidárias nas eleições (entendimento e decisões do stf sobre as coligações partidárias – ADI 7021)”; o sétimo artigo de Matheus Dalgallo Camargo; Vinicius Braga Machado discute o tema “Análise acerca da discussão legislativa e judicial em torno do voto impresso auditável”; o oitavo trabalho de Ana Luísa Alves Pinto; Luiza Mandelli retoma o tema do federalismo “Federalismo, Covid e STF: uma análise crítica do enfrentamento à pandemia no Brasil”; por fim, Ana Fachini e Aryadne Santana apresentam o tema “Democracia em tensão: proteção e restrição à liberdade de expressão na esfera eleitoral”. Diante da exposição dos trabalhos que foram submetidos, é possível observar uma grande diferenciação, se comparada às Obras anteriores do Law Experience. Nesta edição o tema é afunilado para a temática eleitoral, apresentando, contudo, outros trabalhos que também abordam temas atuais do direito. Consolidamos por meio dessa abordagem uma edição especial, marcada temporalmente, com discussões que transpassam somente essas eleições, mas fundam discussões para as próximas e para o fortalecimento da democracia

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation