Isolated functional tricuspid regurgitation: how to define patients at risk for event?

Aims: Functional tricuspid regurgitation (TR) is a turning point in cardiac diseases. Symptoms typically appear late. The optimal timing for proposing a valve repair remains a challenge.

Functional tricuspid regurgitation: A clustering analysis and prognostic validation of three echocardiographic phenotypes in an external cohort.

Background: Functional tricuspid regurgitation (FTR) is an independent risk factor for morbidity and mortality. New pathophysiological concepts but also new therapeutic options are justifying new knowledges for characterizing FTRs and their prognoses.

Aim: To study echocardiographic criteria associated with prognosis in FTR-patients using a clustering method in two cohorts.

Functional linkage of gene fusions to cancer cell fitness assessed by pharmacological and CRISPR-Cas9 screening.

Many gene fusions are reported in tumours and for most their role remains unknown. As fusions are used for diagnostic and prognostic purposes, and are targets for treatment, it is crucial to assess their function in cancer. To systematically investigate the role of fusions in tumour cell fitness, we utilized RNA-sequencing data from 1011 human cancer cell lines to functionally link 8354 fusion events with genomic data, sensitivity to >350 anti-cancer drugs and CRISPR-Cas9 loss-of-fitness effects.

ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks.

Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens in cells treated with the DNA topoisomerase I inhibitor topotecan. Thus, we here establish that inactivating terminal components of the non-homologous end-joining (NHEJ) machinery or of the BRCA1-A complex specifically confer topotecan resistance to ATM-deficient cells.

Unsupervised correction of gene-independent cell responses to CRISPR-Cas9 targeting.

Background: Genome editing by CRISPR-Cas9 technology allows large-scale screening of gene essentiality in cancer. A confounding factor when interpreting CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes within copy number amplified regions of the genome. We have developed the computational tool CRISPRcleanR which is capable of identifying and correcting gene-independent responses to CRISPR-Cas9 targeting.

Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics.

Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic, and transcriptomic landscape of the primary tumor including point mutations, copy number alterations, and mutational signatures.

GDSCTools for mining pharmacogenomic interactions in cancer.

Motivation: Large pharmacogenomic screenings integrate heterogeneous cancer genomic datasets as well as anti-cancer drug responses on thousand human cancer cell lines. Mining this data to identify new therapies for cancer sub-populations would benefit from common data structures, modular computational biology tools and user-friendly interfaces.

Results: We have developed GDSCTools: a software aimed at the identification of clinically relevant genomic markers of drug response.

Evolution and development of monocot stomata.

Premise Of The Study: Leaves of monocots are typically linear with parallel venation, though a few taxa have broad leaves. Studies of stomatal patterning and development in monocots required updating in the context of rapidly improving knowledge of both the phylogenetic and development-genetic context of monocots that facilitate studies of character evolution.

Methods: We used an existing microscope-slide collection to obtain data on stomatal structure across all the major monocot clades, including some species with relatively broad leaves.

Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients.

Aim: To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A () -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC).

Methods: A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time.