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Additionally, VIRIDIC can group viruses into clusters, based on user-defined intergenomic similarity thresholds. The sensitivity of VIRIDIC is given by the BLASTN. Thus, it is able to capture relationships between viruses having in common even short genomic regions, with as low as 65% similarity. Below this similarity level, protein-based analyses should be used, as they are the best suited to capture distant relationships. VIRIDIC is available at viridic.icbm.de, both as a web-service and a stand-alone tool. It allows fast analysis of large phage genome datasets, especially in the stand-alone version, which can be run on the user's own servers and can be integrated in bioinformatics pipelines. VIRIDIC was developed having viruses of Bacteria and Archaea in mind; however, it could potentially be used for eukaryotic viruses as well, as long as they are monopartite.Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from four schools in Wondo Gennet and Hawella Tula districts were screened for Schistosoma mansoni and STHs infection. The overall prevalence of S. mansoni infection was 25.8% (range between schools 11.6% to 54.1%), with light (19.1%), moderate (5.3%), and heavy (1.4%) infection intensities. A total of 61.6% S. mansoni-infected children were STH co-infected. The overall prevalence of STHs infection was 54.7% (range between schools 30.6-71.0%), with moderate-to-heavy intensity infections being 16.3%. Ascaris lumbricoides was the most prevalent 45% (95% CI, 43.5-47) followed by Trichuris trichiura 25.3% (95% CI, 23.8-26.9) and hookworm 6.1% (95% CI, 5.3-7). A total of 33.7% of STHs-infected children had A. lumbricoides and T. trichiura co-infections. S. mansoni infection was significantly associated with school and STHs co-infection (p less then 0.001). STH infection was correlated with school and younger age (p less then 0.001). Despite repeated PC, S. mansoni and STH infection remain significant health problems, and the WHO target to control schistosomiasis and eliminate STH by 2020 may not be achieved. Intensified control and prevention measures, including drug efficacy surveillance, is recommended.The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.Lung cancer is the major cause of cancer-associated death worldwide, and development of new therapeutic drugs is needed to improve treatment outcomes. Three-dimensional (3D) tumorspheroids offer many advantages over conventional two-dimensional cell cultures due to the similarities to in vivo tumors. We found that isoharringtonine, a natural product purified from Cephalotaxus koreana Nakai, significantly inhibited the growth of tumorspheroids with NCI-H460 cells in a dose-dependent manner and induced apoptotic cell death in our 3D cell culture system. On the other hand, A549 tumorspheroids displayed low sensitivity to isoharringtonine-induced apoptosis. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor known to regulate proliferation and apoptosis of cancer cells. We observed that knockdown of NR4A1 dramatically increased isoharringtonine-induced cancer cell death in A549 tumorspheroids by activating the intrinsic apoptosis pathway. Furthermore, treatment with combined isoharringtonine and iNR4A1 significantly inhibited multivulva formation in a Caenorhabditis elegans model and tumor development in a xenograft mouse model. Taken together, our data suggest that isoharringtonine is a potential natural product for treatment of non-small cell lung cancers, and inhibition of NR4A1 sensitizes cancer cells to anti-cancer treatment.Diabetic patients are at increased risk of developing foot ulcers which may cause bone infections associated with a high probability of both amputation and mortality. Therefore, prompt diagnosis and adequate treatment are of key importance. In our Diabetic Foot Unit, effective multidisciplinary treatment of osteomyelitis secondary to diabetes involves the application of a gentamicin-eluting calcium sulphate/hydroxyapatite bone graft substitute to fill residual bone voids after debridement. The data of all patients treated with the gentamicin-eluting calcium sulphate/hydroxyapatite bone graft substitute for diabetic foot infections with ulcer formation and osteomyelitis at metatarsals, calcaneus and hindfoot at our institute from July 2013 to September 2016 were retrospectively collected and evaluated. A total of 35 patients were included in this retrospective single-arm case series and were either continuously followed up for at least one year or until healing was confirmed. Nineteen lesions affected the distal row of tarsus/talus, ten the calcaneus and a further six were located at the metatarsals. While all of the metatarsal lesions had healed at 1-year follow-up, the healing rate in the hindfoot region was lower with 62.5% at the calcaneus and 72.2% at the distal tarsus and talus at 12 months, respectively. The overall cure rate for ulcerous bone infection was 81.3%. read more In two calcaneal lesions (25%) and two lesions of distal tarsus/talus (11.1%) amputation was considered clinically necessary. Promising results were achieved in the treatment of diabetic foot infections with soft tissue ulcers by a multidisciplinary approach involving extensive debridement followed by adequate dead space management with a resorbable gentamicin-eluting bone graft substitute.

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