Myosteatosis in a systemic inflammation-dependent manner predicts favorable survival outcomes in locally advanced esophageal cancer

Increased adiposity and its attendant metabolic features as well as systemic inflammation have been associated with prognosis in locally advanced esophageal cancer (LAEC). However, whether myosteatosis and its combination with systemic inflammatory markers are associated with prognosis of esophageal cancer is unknown. Our study aimed to investigate the influence of myosteatosis and its association with systemic inflammation on progression-free survival (PFS) and overall survival (OS) in LAEC patients treated with definitive chemoradiotherapy (dCRT). We retrospectively gathered information on 123 patients with LAEC submitted to dCRT at the University of Campinas Hospital. Computed tomography (CT) images at the level of L3 were analyzed to assess muscularity and adiposity. Systemic inflammation was mainly measured by calculating the neutrophil-to-lymphocyte ratio (NLR). Median PFS for patients with myosteatosis (n = 72) was 11.0 months vs 4.0 months for patients without myosteatosis (n = 51) (hazard ratio [HR]: 0.53; 95% confidence interval [CI], 0.34-0.83; P = .005). Myosteatosis was also independently associated with a favorable OS. Systemic inflammation (NLR > 2.8) was associated with a worse prognosis. The combination of myosteatosis with systemic inflammation revealed that the subgroup of patients with myosteatosis and without inflammation presented less than half the risk of disease progression (HR: 0.47; 95% CI: 0.26-0.85; P = .013) and death (HR: 0.39; 95% CI, 0.21-0.72; P = .003) compared with patients with inflammation. This study demonstrated that myosteatosis without systemic inflammation was independently associated with favorable PFS and OS in LAEC patients treated with dCRT81669676976FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2018/23428-

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

EpIG‐DB: A database of vascular epiphyte assemblages in the Neotropics

Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil‐rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large‐scale distribution patterns. EpIG‐DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG‐DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG‐DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up‐to‐date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG‐DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG‐DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes

Genetic Evidence Supporting the Association of Protease and Protease Inhibitor Genes with Inflammatory Bowel Disease: A Systematic Review

As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family