In our study, multivariate regression indicated the following clinical and laboratory characteristics upon admission were independently associated with the development of severe dengue: (1) age >40 years, (2) persistent vomiting, (3) absolute atypical lymphocyte >300 cells per μL, and (4) lactate level ≥2.0 mmol/L. In addition, patients with severe dengue commonly presented with severe plasma leakage and severe organ involvement. Age >40 years was independently associated with severe dengue in our study, consistent with a previous retrospective analysis from France, which reported that plasma leakage was the most common presentation for adults with severe dengue and that an age of >37 years predicted plasma leakage [ 14]. Our results also suggest that persistent vomiting at admission could be used to predict the development of severe dengue, which is similar to a finding of a previous multicenter study showing that persistent vomiting was one of the warning signs for severe dengue [ 31]. Although the sensitivity of persistent vomiting for identifying severe dengue in adults was very low (6.0–23.0 %), the specificity was as high as 93.0–96.0 % and the negative predictive value was 82.0–97.0 % [ 32, 33]. Okorie ON, Dellinger P. Lactate: biomarker and potential therapeutic target. Crit Care Clin. 2011;27(2):299–326. Max Turbo Frequency refers to the maximum single-core processor frequency that can be achieved with Intel® Turbo Boost Technology. See www.intel.com/technology/turboboost/ for more information and applicability of this technology. Give it a try now with a similar division by 2. What is the Quotient and Remainder of 1150 Divided by 2? Here we provide you with the result of the division with remainder, also known as Euclidean division, including the terms in a nutshell:

Watts DM, Porter KR, Putvatana P, Vasquez B, Calampa C, Hayes CG, et al. Failure of secondary infection with American genotype dengue 2 to cause dengue haemorrhagic fever. Lancet. 1999;354(9188):1431–4.Leung, D. et al. Integrative analysis of haplotype-resolved epigenomes across human tissues. Nature 518, 350–354 (2015). Lonsdale, J. et al. The Genotype-Tissue Expression (GTEx) project. Nat. Genetics 45, 580–585 (2013). Regarding laboratory findings on admission, patients having >300 cells/μL of absolute atypical lymphocytes could be used to predict the development of severe dengue as patients with severe dengue had significantly greater levels of absolute atypical lymphocytes than patients with non-severe dengue. These findings are similar to those of a previous Thai study showing that atypical lymphocytes among patients with dengue were correlated with the presence of CD19 + B lymphocytes [ 34]. After a secondary dengue infection, atypical lymphocytes could indicate an augmented immune response attempting to control the spread of dengue-infected cells [ 35]. Simultaneously, these antibodies could enhance the entry of the dengue virus into macrophages and dendritic cells whereupon the virus would replicate [ 36]. Previous reports have also indicated that patients with higher dengue viremia have higher disease severity [ 37]. Liu, L. et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 27, 1067–1080 (2018).

Lee VJ, Lye DC, Sun Y, Fernandez G, Ong A, Leo YS. Predictive value of simple clinical and laboratory variables for dengue hemorrhagic fever in adults. J Clin Virol. 2008;42(1):34–9. The architecture of a CPU refers to its general design, from process size to cache capacity to the functioning of datapaths. Each generation of CPU tends to be built using a different, more advanced microarchitectural blueprint. For example, the CPUs we’ll be taking a look at today are based on Haswell architecture, which was superseded in 2014 by Broadwell, followed by Airmont and Skylake…all the way through to the most recently announced, Lunar Lake.Gallagher EJ, Rodriguez K, Touger M. Agreement between peripheral venous and arterial lactate levels. Ann Emerg Med. 1997;29(4):479–83. World Health Organization (WHO). Global strategy for dengue prevention and control 2012–2020. Geneva: WHO; 2012. Aung KL, Thanachartwet V, Desakorn V, Chamnanchanunt S, Sahassananda D, Chierakul W, et al. Factors associated with severe clinical manifestation of dengue among adults in Thailand. Southeast Asian J Trop Med Public Health. 2013;44:602–12.

The laboratory investigations including complete blood count, blood chemistries, and peripheral venous lactate were performed at patient admission. All dengue patients in this study received standard care according to WHO guidelines [ 8]. Patient data including baseline characteristics, clinical parameters, and laboratory findings were recorded in a pre-defined case-report form. Severity of dengue was summarized on the date of discharge according to the WHO’s 2009 definition [ 8]. Case definition of dengue Grossman, R. L. et al. Toward a shared vision for cancer genomic data. N. Engl. J. Med. 375, 1109–1112 (2016). Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000;181(1):2–9. Zhang, X. et al. Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nat. Genet. 48, 176–182 (2016).Dajani EZ, Islam K. Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J Physiol Pharmacol. 2008;59 Suppl 2:117–33. Blood samples for peripheral venous lactate were collected from veins of upper extremities without the use of a tourniquet. We placed 2 ml of blood in a vacutainer containing sodium fluoride and immediately placed the sample on ice. Samples were sent to the laboratory and lactate levels were tested within 10 min of being drawn using a colorimetric assay (Roche/Hitashi cobas c systems, USA) according to the manufacturer’s instructions. The coefficient of variation in lactate assay levels in the central laboratory of the Hospital for Tropical Diseases is estimated to be 1.1 %. Sample-size calculation a, Heatmap illustrating cell death measured by propidium iodide staining ( z score). Cancer cells were treated with increasing doses of FK-866 for 72 h. b, Intracellular measurement of NAD + levels. c, Immunoblotting for cleaved caspase-3, in salvage-dependent cancer cells treated with 10 nM FK-866 for 72 h. Cells were supplemented with exogenous NAD + (200 µM) or with the indicated precursors (NM, NMR, NR, NA) at a dose of 500 µM. d, Cell viability of non-cancer and cancer cells (PH-amp and sal-dep) stably silenced with shRNA against NMRK1, treated with increasing doses of FK-866 for 72 h. e, Schematic overview of experiment. OV4 PH-amp (top) and H460 Sal-dep (bottom) cells stably expressing shRNA against the target gene NMRK1 were implanted subcutaneously. f, Tumour volume of nude mice bearing stably engineered OV4 PH-amp cells implanted subcutaneously. Tumour volume was monitored over a 24-day period. Mice were injected intraperitoneally with FK-866 twice daily. g, Intratumoral NAD + measurement of nude mice bearing stably engineered OV4 PH-amp tumours, taken at the end of experiment on day 24. h, Immunoblotting for cleaved caspase-3 as a measure of cell death and to test for protein abundance for NMRK1 in tumour tissues obtained from the indicated tumour types. Representative blots are from one of two independent experiments. Both biological replicates showed similar results. Actin was used as a loading control. Data are representative of three ( b, d), eight ( f) or six ( g) independent biological replicates from independent experiments. Data in scatter plots ( b, g) are mean ± s.d., with P values determined by one-way ANOVA with Tukey’s multiple comparisons test. For cell viability data ( d), P values were determined by two-tailed unpaired Student’s t-test. Data in f are mean tumour volume ± s.e.m. ( n = 8 tumours/cohort), with P values determined by two-way ANOVA on repeated measurements over time. For gel source data, see Supplementary Fig. 1. Gurvich OL, Tuohy TM, Howard MT, Finkel RS, Medne L, Anderson CB, et al. DMD pseudoexon mutations: splicing efficiency, phenotype, and potential therapy. Ann Neurol. 2008;63:81–9.