Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

The diagnosis of delirium in an acute-care hospital in Moscow: what does the Pandora’s box contain?

Olga N Tkacheva,1 Nadezda K Runikhina,1 Arkadiy L Vertkin,2 Irina V Voronina,1 Natalia V Sharashkina,1 Elen A Mkhitaryan,1 Valentina S Ostapenko,1 Elena A Prokhorovich,2 Tamar Freud,3 Yan Press3–5 1Russian Gerontology Clinical Research Center, Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation, 2Moscow State University of Medicine and Dentistry named after AI Evdokimov, Moscow, Russia; 3Department of Family Medicine, Faculty of Health Sciences, Sial Family Medicine and Primary Care Research Center, Ben-Gurion University of the Negev, 4Comprehensive Geriatric Assessment Unit, Clalit Health Care Services, Yassky Clinic, 5Community-Based Geriatric Unit, Division of Community Health, Ben-Gurion University of the Negev, Beer-Sheva, Israel Background: Delirium, a common problem among hospitalized elderly patients, is not usually diagnosed by doctors for various reasons. The primary aim of this study was to evaluate the effect of a short training course on the identification of delirium and the diagnostic rate of delirium among hospitalized patients aged ≥65 years. The secondary aim was to identify the risk factors for delirium. Methods: A prospective study was conducted in an acute-care hospital in Moscow, Russia. Six doctors underwent a short training course on delirium. Data collected included assessment by the confusion assessment method for the intensive care units, sociodemographic data, functional state before hospitalization, comorbidity, and hospitalization indices (indication for hospitalization, stay in intensive care unit, results of laboratory tests, length of hospitalization, and in-hospital mortality). Results: Delirium was diagnosed in 13 of 181 patients (7.2%) who underwent assessment. Cognitive impairment was diagnosed more among patients with delirium (30.0% vs 6.1%, P=0.029); Charlson comorbidity index was higher (3.6±2.4 vs 2.3±1.8, P=0.013); and Barthel index was lower (43.5±34.5 vs 94.1±17.0, P=0.000). The length of hospitalization was longer for patients with delirium at 13.9±7.3 vs 8.8±4.6 days (P=0.0001), and two of the 13 patients with delirium died during hospitalization compared with none of the 168 patients without delirium (P=0.0001). Conclusion: Although the rate of delirium was relatively low compared with studies from the West, this study proves that an educational intervention among doctors can bring about a significant change in the diagnosis of the condition. Keywords: delirium, elderly, inpatients, Russi