BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand–Cambodia border. Slowly clearing in fections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the “propeller” region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)

One in 6 temporary ileostomies constructed during an elective anterior resection for rectal cancer was not closed. Patients should be told before the index surgery that there is a risk of nonclosure and possible complications associated with permanent ileostomy.

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The long noncoding RNA NR2F1-AS1 has been found to promote the development of hepatocellular carcinoma and endometrial cancer. In this study, we measured NR2F1-AS1 expression in osteosarcoma (OS), determined the involvement of NR2F1-AS1 in the malignant properties of OS, and investigated the underlying mechanisms. NR2F1-AS1 was found to be upregulated in OS tumors and cell lines. The increased NR2F1-AS1 level was closely associated with advanced clinical stage and distant metastasis in patients with OS. Patients with OS in an NR2F1-AS1 high-expression group demonstrated significantly shorter overall survival than did patients in an NR2F1-AS1 low-expression group. NR2F1-AS1 knockdown inhibited OS cell proliferation, migration, and invasion and promoted cell cycle arrest and apoptosis in vitro and slowed tumor growth in vivo. NR2F1-AS1 was found to function as a competing endogenous RNA by directly sponging microRNA-483-3p (miR-483-3p) and upregulating its target oncogene forkhead box A1 (FOXA1). Finally, rescue experiments revealed that knockdown of miR-483-3p and recovery of FOXA1 expression both attenuated the influence of the NR2F1-AS1 knockdown on OS cells. Thus, NR2F1-AS1 plays an oncogenic role in OS through sponging miR-483-3p and thereby upregulating FOXA1, suggesting an additional target for osteosarcoma therapeutics.