Expert Panel Curation of 113 Primary Mitochondrial Disease Genes for the Leigh Syndrome Spectrum

OBJECTIVE: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes. METHODS: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene-Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS. RESULTS: The GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31/114 gene-disease relationships curated (27%); moderate for 38 (33%); limited for 43 (38%); and 2 as disputed (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 autosomal dominant, and 3 X-linked. INTERPRETATION: GDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multi-system organ surveillance, recurrence risk counselling, reproductive choice, natural history studies and eligibility for interventional clinical trials. This article is protected by copyright. All rights reserved

Alterações musculares e esqueléticas cervicais em mulheres disfônicas

Termo clínico, a disfonia envolve a todas as transformações e dificuldades durante a emissão vocal, as quais resultam no impedimento da produção normal da voz. Pacientes como esse problema, podem apresentar desequilíbrio da musculatura crâniocervical e laríngea e lesão orgânica subjacente. A disfonia resulta em modificações fonatórias, limitando atividades diárias relacionadas ao uso da voz, impactando na vida social e na qualidade de vida do indivíduo. Este estudo teve como objetivo analisar alterações musculares e esqueléticas cervicais em mulheres com disfonia, conforme identificado na literatura científica sobre o tema. Para isso, realizou-se uma revisão integrativa de literatura, selecionando estudos nas bases de dados Literatura Latino-americana e do Caribe em Ciências da Saúde (Lilacs) e Medical Literature Analysis and Retrieval System Online (Medline). A partir da análise qualitativa dos resultados, concluiu-se que dor intensa na região posterior do pescoço e na laringe se manifestam em mulheres disfônicas. Contribuem para isso a função prejudicada da articulação cervical e alterações da amplitude de movimento cervical. Com isso, compreende-se que o abuso vocal e o mau uso da voz como fatores mais comuns para a disfonia

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Os principais tipos e manifestações da Cirrose Hepática: uma atualização clínica

Introdução: A cirrose hepática é um processo patológica crônico, considerado a hepatopatia mais comum, definido como a conversão difusa morfoestrutural por nódulos de arquitetura anômalo envoltos por fibrose. Objetivou-se descrever os tipos mais relevantes de cirrose e suas devidas manifestações. Metodologia: Trata-se de uma revisão bibliográfica, fundamentada nas plataformas do SciELO, PubMed, Scopus, utilizando os termos “hepatical cirrhosis”, “liver disease” e “hepatocellular insufficiency” a qual através da revisão narrativa, abordou amplamente a respeito da contextualização da cirrose e as principais etiologias. Resultados e Discussão: Foi analisado que tal condição afeta qualquer faixa etária, sexo, etnia e independe da classe socioeconômica, mas as diversas etiologias impõem um perfil epidemiológico específico conforme a aparição. As principais origens abordam o tipo alcoólico, hepatite, aplicação crônica de alguns fármacos e esteatose gordurosa ou não. Ademais, estima-se que estas afetam a anatomofuncionalidade do órgão responsável por grande parte da homeostase, culminando em diversas manifestações clínicas.  Conclusão: A cirrose é uma consequência grave de fatores de base em estágio avançado, a qual devido ao seu curso geralmente silencioso culmina no desenvolvimento e progressão clínica. Neste contexto, a atenção aos fatores predisponentes como alimentação rica em lipídios, estilismo, negligência a exames de rotina, sedentarismo e obesidade contribuem constituem medidas eficazes de prevenção primária.&nbsp

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Role of the diffusion-weighted sequence (DWI) in the imaging surveillance for the characterization of recurrences of embryonal tumors in the central nervous system

A ressonância magnética tem papel fundamental no diagnóstico dos tumores do sistema nervoso central. Singular ênfase é dada à sequência ponderada em difusão, a qual tem destacado auxílio no diagnóstico dos tumores embrionários do sistema nervoso central, particularmente na faixa etária pediátrica. No entanto, a efetiva relevância desta sequência para a diferenciação dos diversos subtipos de tumores primários do encéfalo, bem como a sua utilidade diagnóstica na detecção de recidiva dos tumores embrionários não é, ainda hoje, bem estabelecida. Assim, os objetivos deste estudo foram (1) criar um fluxograma que colabore no diagnóstico inicial de tumores embrionários, com auxílio da sequência de difusão, particularmente quando localizados no cerebelo e na faixa etária pediátrica, (2) comparar a sequência de difusão e as demais sequências da ressonância magnética convencional para a detecção de recidiva dos tumores embrionários do sistema nervoso central e (3) avaliar as propriedades da sequência de difusão e da sequência T1 após o uso do agente de contraste paramagnético nas lesões induzidas por radiação. Duas análises retrospectivas e distintas foram realizadas neste trabalho. A primeira análise incluiu a avaliação dos estudos de ressonância magnética em cento e quarenta e oito (148) crianças com diagnóstico histológico e molecular de tumores cerebelares pediátricos. Os respectivos tumores foram avaliados por diferentes sequências de imagem, bem como análise demográfica, seguindo um fluxograma previamente instituído, que incluiu a sequência ponderada em difusão como o núcleo da diferenciação desses tumores para obtenção de um diagnóstico final mais preciso. Com base na análise destes casos, o fluxograma apresentou uma relativa adequada acurácia na identificação da maioria dos diagnósticos dos tumores cerebelares. Um segundo fluxograma (fluxograma modificado) foi então por nós proposto, baseado nos resultados obtidos pela nossa casuística, que apresentou um significativo aumento da acurácia quando comparado ao anterior, incluindo também uma excelente razão de verossimilhança para a diferenciação da maioria dos grupos histológicos e moleculares dos tumores embrionários cerebelares, entre outros. A segunda análise do nosso estudo incluiu a avaliação retrospectiva dos exames de ressonância magnética em cinquenta e seis (56) pacientes com tumor embrionário do sistema nervoso central. Esses estudos foram avaliados por meio da análise separada das sequências (1) ponderadas em difusão, (2) conjunto de sequências convencionais (T1, T2 / FLAIR e T1 pós-contraste) e (3) sequências ponderadas em T1 pós-contraste de forma isolada. A sensibilidade para detecção de recidiva foi calculada para cada um dos grupos de imagem pré-estabelecidos. Uma análise descritiva por paciente também foi realizada. A sensibilidade de detecção de recidiva nodular focal pela sequência ponderada em difusão (96%) foi significativamente maior que as demais sequências da ressonância magnética convencional (77%) e que a sequência pós-contraste isolada (51%) (p = 0,0003 e p < 0,0001). Na análise de recidiva por paciente, nenhum diagnóstico foi perdido pela avaliação da sequência de difusão. As demais sequências de ressonância magnética convencional perderam dois (2) diagnósticos e a sequência póscontraste isolada perdeu oito (8). Em conclusão, o estudo de ressonância magnética, em especial a sequência ponderada em difusão, mostrou-se essencial para diferenciação dos diversos subtipos de tumores encefálicos pediátricos, na detecção aprimorada de recidiva focal em pacientes com tumores embrionários do sistema nervoso central e fundamental em auxiliar na diferenciação entre as lesões decorrentes de recidiva tumoral e as lesões radioinduzidas no contexto de tumores embrionáriosMagnetic resonance imaging has a fundamental role in the diagnosis of tumors of the central nervous system. Singular emphasis is given to the diffusion-weighted sequence, which has an essential role in the diagnosis of embryonal tumors, particularly in the pediatric age group. However, the real relevance of this sequence in differentiating the subtypes of primary brain tumors, as well as its diagnostic utility in detecting recurrence of embryonal tumors, is still not well-established. The aims of this study are (1) to create a flowchart that improves the capability of a correct diagnosis of brain tumors, particularly those affecting the cerebellum during childhood, with the support of the diffusion-weighted sequence, (2) compare the diffusion sequence with the other conventional magnetic resonance sequences in detecting the recurrence of embryonal tumors of the central nervous system, and (3) to evaluate the properties of the diffusion and T1 sequence after injection of the paramagnetic agent in the analysis of radiationinduced lesions. For these purposes, two retrospective analyses were performed from two different pediatric cohorts. The first one included magnetic resonance imaging of 148 children with cerebellar tumors confirmed molecularly and histologically. These tumors were evaluated by separate imaging and demographic analysis following a pre-designed step-by-step flowchart which includes diffusion-weighted imaging sequence as the core of the stratification of these tumors to obtain a correct final diagnosis. Based on analysis of our cohort, we have confirmed that the pre-designed flowchart was reliable in identifying most diagnoses. However, a few discrepancies between literature and our results were also observed. In order to obtain a more accurate flowchart, our group has submitted modifications in the flowchart, and, subsequently, a modified flowchart with an overall increased accuracy was created. The modified flowchart showed a good likelihood ratio for most of the histologic and molecular groups of embryonal tumors among others. The second imaging analysis of our study included a retrospective review of fifty-six patients with the diagnosis of an embryonal tumor of the central nervous system. These tumors were evaluated by separate sequences of magnetic resonance imaging including (1) diffusion-weighted sequences, (2) set of conventional sequences (T1, T2 / FLAIR, and T1 post-contrast), and (3) post-contrast T1 sequence alone. The sensitivity for detecting recurrence was calculated for each of the pre-established image groups. A descriptive analysis per patient was also performed. Sensitivity of detection of focal nodular recurrence by the diffusion-weighted sequence (96%) was significantly higher than the other conventional magnetic resonance sequences (77%) and the postcontrast sequence alone (51%) (p = 0.0003 ep < 0.0001). In the analysis of recurrence per patient, no diagnosis was missed by assessing the diffusion sequence. The other conventional MRI sequences missed two diagnoses and the isolated analysis of the postcontrast sequence missed eight diagnoses. In conclusion, the magnetic resonance study, particularly, the diffusion-weighted image sequence, proved to be essential in the differentiation of the diverse subtypes of pediatric brain tumors, particularly embryonal tumors; improves the detection of focal recurrence in patients with embryonal tumors of the central nervous system; and can assist in the differentiation between tumor recurrence and radioinduced lesion

AMAZONIA CAMTRAP: a dataset of mammal, bird, and reptile species recorded with camera traps in the Amazon forest

The Amazon forest has the highest biodiversity on earth. However, information on Amazonian vertebrate diversity is still deficient and scattered across the published, peer-reviewed and grey literature and in unpublished raw data. Camera traps are an effective non-invasive method of surveying vertebrates, applicable to different scales of time and space. In this study, we organized and standardized camera trap records from different Amazon regions to compile the most extensive dataset of inventories of mammal, bird and reptile species ever assembled for the area. The complete dataset comprises 154,123 records of 317 species (185 birds, 119 mammals and 13 reptiles) gathered from surveys from the Amazonian portion of eight countries (Brazil, Bolivia, Colombia, Ecuador, French Guiana, Peru, Suriname and Venezuela). The most frequently recorded species per taxa were: mammals - Cuniculus paca (11,907 records); birds - Pauxi tuberosa (3,713 records); and reptiles - Tupinambis teguixin (716 records). The information detailed in this data paper opens-up opportunities for new ecological studies at different spatial and temporal scales, allowing for a more accurate evaluation of the effects of habitat loss, fragmentation, climate change and other human-mediated defaunation processes in one of the most important and threatened tropical environments in the world. The dataset is not copyright restricted; please cite this data-paper when using its data in publications and we also request that researchers and educators inform us of how they are using this data