Terkildsenvestergaard1408

Significant advances in tumor sequencing have led to an explosion in our knowledge of the genetic complexity of cancer. For many cancers, the selection of a targetable alteration is not readily apparent, especially when confronted with mutational variants of unknown significance. The complex clinical landscape of MEK mutations illustrates the need for improved methods to identify those patients, independent of tumor histology, who would benefit from treatment with a MAP kinase pathway inhibitor. In this issue of Cancer Research, Hanrahan and colleagues adopt an in silico platform to attempt to distinguish benign MEK mutations from those that are functional and, therefore, most likely to be therapeutically actionable.See related article by Hanrahan et al., p. 4233.

Emergency Medical Services (EMS) are expected to be affected by a pandemic outbreak. However, the available data about trends and extents of these effects is limited.

We analyzed numbers of ambulance calls for all 136 diagnosis codes used by Magen David Adom (MDA), Israel's national EMS during 121days between January 01 and April 30, 2020.

There was an increase in calls for COVID-19 symptoms (cough, fever, throat pain). This trend followed the same shape as the curve for confirmed COVID-19 patients. Trends were found to increase for calls not followed by transport to the hospital as well as in calls for mental or psychiatric causes. Simultaneously, there was a decrease in calls for cardiovascular issues, pneumonia, and all injuries.

Understanding these correlations may allow better preparedness of the EMS and a better response towards the public needs in the period of an epidemic or a pandemic.

Understanding these correlations may allow better preparedness of the EMS and a better response towards the public needs in the period of an epidemic or a pandemic.Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications.Nursing students are increasingly undertaking paid work while studying and most choose paid work in health care or hospitality. This paper is drawn from a larger sequential exploratory mixed-method study which examined the relationship between students working while studying nursing and the impact on academic performance. In this paper, we explored first year nursing students' perceptions of communication skills gained through paid work. Using a qualitative exploratory design, 50 first year commencing nursing students from four nursing schools (3 Australia; 1 New Zealand) were interviewed. Inductive thematic analysis was used which identified two themes (i) recognising the value of learning interpersonal communication skills and; (ii)opportunities to develop effective interpersonal communication skills. Paid work provides interpersonal communication skills; active listening, being present and interacting while multi-tasking and emotion management. Undergraduate education providers need to recognise the benefits of paid work for students, including enhancing interpersonal skills.

The root of Gentiana dahurica Fisch (called Qin-Jiao in China), a traditional Chinese medicine, is used in China to treat alcoholic liver disease (ALD), but there has been no scientific report on the treatment of ALD.

To investigate the therapeutic effects of Gentiana dahurica Fisch ethanol extract (GDEE) on ALD and to reveal its possible mechanism of action using RNA sequencing.

The model of ALD was established by continuous gavage with alcohol in mice, and GDEE was used to treat ALD. Pathological observation (HE staining, oil red O staining) and biochemical indicators were performed to evaluate liver tissue lesions and efficacy of GDEE. RNA sequencing analysis of liver tissues was carried out to elucidate the pathogenesis of ALD and the mechanism of hepatoprotective effect by GDEE. The RNA sequencing results were verified by detecting mRNA and protein expressions of acetyl coenzyme A carboxylase α (Acacα), fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1A (Cpt1a) by quantitative real-tile acid metabolism. In the validation experiments, the Acacα, Fasn and Cpt1a expressions quantified by real-time PCR and Western blot were consistent with the RNA sequencing results.

GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.

GDEE can alleviate liver damage and steatosis in ALD mice, and its mechanism of action may be related to the process of regulating triglycerides and cholesterol.AP-002 is a novel, gallium-based, anti-cancer oral compound in clinical development for cancer patients with bone metastases. We examined the effects of AP-002 on osteoclastogenesis, fusion, and osteogenesis. AP-002 exhibited a dramatic effect on osteoclast function without causing osteoclast cell death. The expression of tartrate-resistant acid phosphatase and cathepsin K mRNA levels was down-regulated in RAW264.7 cells treated with AP-002 in the presence of soluble receptor activator of NF-κB ligand. AZD2281 cell line AP-002 was also found to block the fusion of osteoclasts from RAW264.7 cells. AP-002 had a similar inhibitory effect on RANKL-induced mouse primary bone marrow monocytes fusion. Human blood monocytes treated with AP-002 failed to form TRAcP/ACP5-positive cells. AP-002 caused these inhibitory effects without causing osteoclast cell death, which was in contrast to zoledronic acid controls. Furthermore, unlike zoledronic acid, AP-002 did not inhibit Rac1 activation. Gene expression analysis by microarrays showed that AP-002 significantly reverses the effects of RANKL-induced gene expression.