COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits

Peer reviewe

—The Power of CLV: Managing Customer Lifetime Value at IBM

Customer management activities at firms involve making consistent decisions over time, about: (a) which customers to select for targeting, (b) determining the level of resources to be allocated to the selected customers, and (c) selecting customers to be nurtured to increase future profitability. Measurement of customer profitability and a deep understanding of the link between firm actions and customer profitability are critical for ensuring the success of the above decisions. We present the case study of how IBM used customer lifetime value (CLV) as an indicator of customer profitability and allocated marketing resources based on CLV. CLV was used as a criterion for determining the level of marketing contacts through direct mail, telesales, e-mail, and catalogs for each customer. In a pilot study implemented for about 35,000 customers, this approach led to reallocation of resources for about 14% of the customers as compared to the allocation rules used previously (which were based on past spending history). The CLV-based resource reallocation led to an increase in revenue of about $20 million (a tenfold increase) without any changes in the level of marketing investment. Overall, the successful implementation of the CLV-based approach resulted in increased productivity from marketing investments. We also discuss the organizational and implementation challenges that surrounded the adoption of CLV in this firm.customer relationship management, customer lifetime value, field experiment, return on marketing contacts, missing value imputation

Der goalballspezifische Leistungstest TAMP: Entwicklung und Evaluation einer virtuellen Ballwurfmaschine

Höner O, Hermann T. Der goalballspezifische Leistungstest TAMP: Entwicklung und Evaluation einer virtuellen Ballwurfmaschine. In: Ehrlenspiel F, Beckmann J, maier S, Heiss C, Waldenmayer D, eds. Diagnostik und Intervention - Bridging the gap ; 39. Jahrestagung der Arbeitsgemeinschaft für Sportpsychologie. München: Czwalina; 2007: 74-74.In dem paralympischen Sportspiel Goalball ist die auditive Wahrnehmung des rollenden Klingelballs die dominante Informationsquelle für Defensivaktionen. In der Konsequenz bilden audiomotorische Fähigkeiten eine zentrale Leistungskomponente, für die jedoch – nach einer Befragung von 22 Nationaltrainern während der EM 2005 – keine goalballspezifische Diagnostik existiert. In einem BISp-Forschungsprojekt wird die Methode der interaktiven Sonifikation zur Entwicklung eines goalballspezifischen Leistungstests „TAMP“ (Test for audiomotor performance) genutzt und dieser mit der deutschen Goalball-Nationalmannschaft validiert

Mielopatia compressiva por lipoma de células fusiformes infiltrativo em cão Compressive myelopathy by infiltrative spindle cell lipoma in a dog

Relata-se um caso de lipoma de células fusiformes infiltrativo diagnosticado em cadela com sinais neurológicos de ataxia proprioceptiva, reação postural ausente no membro pélvico direito, paraparesia fracamente ambulatória e dor à palpação sobre as vértebras torácicas craniais. A mielografia demonstrou compressão extradural do lado direito sobre a quinta vértebra torácica. À necropsia foi observado neoplasma que invadia o canal vertebral na quarta e quinta vértebras torácicas com compressão acentuada da medula espinhal. Microscopicamente, foram observados adipócitos neoplásicos bem diferenciados, com áreas de células fusiformes, diagnosticado como lipoma de células fusiformes infiltrativo. A avaliação por imuno-histoquímica, com anticorpo anti-CD34, revelou positividade principalmente nas áreas fusiformes do lipoma.A female dog was referred presenting neurological signs of proprioceptive ataxy, proprioceptive deficit in the right pelvic limb, mild ambulatory paresis and spinal pain during the palpation in thoracic vertebrae. It was observed a right extradural compression of spinal cord over fourth and fifth thoracic vertebrae by spinal myelography. During necropsy evaluation, it was observed a neoplasm which infiltrated in the spinal canal in the fourth and fifth thoracic vertebrae with marked compression of the spinal cord. Microscopically there were well differentiated neoplasic adipocytes, with areas of spindle cells, diagnosed as infiltrative spindle cell lipoma. The immunohistochemical staining revealed positive CD34 cells mainly in the areas of spindle cells lipoma