Kumar Welch (baboonmint56)

Applying the DTF model to predict missing entries in our drug-cell line tensor, we identified novel synergistic drug combinations for 10 cell lines from the 5 cancer types. A literature survey showed that some of these predicted drug synergies have been identified in vivo or in vitro. Thus, the DTF model could be a valuable in silico tool for prioritizing novel synergistic drug combinations. AVAILABILITY Source code and data is available at https//github.com/ZexuanSun/DTF-Drug-Synergy. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Invasive meningococcal disease clusters occur amongst university students and may reflect higher carriage prevalence amongst this population. We aimed to measure meningococcal carriage prevalence, acquisition and risk factors amongst first-year university students in South Africa, a middle-income country. METHODS In summer to autumn 2017, after consenting to participate, we collected oropharyngeal swabs and questionnaires on carriage risk factors and tested students for HIV infection at two universities, during registration week (survey one) and 6-8 weeks later (survey two). Meningococci were detected by culture and polymerase chain reaction. RESULTS We enrolled 2120 students at registration. Mean age was 18.5 years, 59% (1252/2120) were female and 0.8% (16/1984) were HIV-infected. Seventy-eight percent of students returned for survey two (1655/2120).Amongst the cohort, carriage prevalence was 4.7% (77/1655) at registration; increasing to 7.9% (130/1655) at survey two 5.0% (83) acquired new carriage, 2.8% (47) had persistent carriage, 1.8% (30) cleared the initial carriage and 90.3% (1495) remained carriage-free. At both surveys, non-genogroupable meningococci predominated, followed by genogroups Y, B, W and C. On multinomial analysis risk factors for carriage acquisition included attending nightclubs (adjusted relative risk ratio (aRRR) 2.1 (95%CI=1.1-4.0)), having intimate kissing partners (aRRR 1.8 (95%CI=1.1-2.9)) and being HIV-infected (aRRR 5.0 (95%CI=1.1-24.4)). CONCLUSION Meningococcal carriage amongst first-year university students increased after two months. Social-behavioural risk factors were associated with increased carriage for all analyses. HIV-infection was associated with carriage acquisition. Until vaccination programmes become mandatory in South African universities, data suggest that HIV-infected students could benefit most from meningococcal vaccination. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.The bispecific antibody Emicizumab is increasingly used for hemophilia A-treatment. However, its specificity for human factors IX and X (FIX, FX) has limited its in vivo functional analysis to primate models of acquired hemophilia. Here we describe a novel mouse model allowing to examine Emicizumab function. Briefly, FVIII-deficient mice receive Emicizumab intravenously 24h before performing a tail clip-bleeding model. A second infusion with human FIX and FX is administered 5 min before bleeding. This approach generates consistent levels of Emicizumab (0.7-19 mg/dL for 0.5-10 mg/kg dose) and of both FIX and FX (85 and 101 U/dL respectively, after dosing 100 U/kg). Plasmas from these mice display FVIII-like activity in a diluted aPTT and in thrombin generation assays, similar to human samples containing Emicizumab. Emicizumab doses of 1.5 mg/kg and higher significantly reduced blood loss in a tail clip-bleeding model using FVIII-deficient mice. However, reduction was incomplete compared to mice treated with human FVIII concentrate, and no difference in efficacy between doses was observed. From this model, we deducted a FVIII-like activity of Emicizumab that corresponds to a dose of 4.5 U FVIII/kg (i.e. 9.0 U/dL). Interestingly, combine