Our results demonstrate that both the EMA binding and FC OF tests are useful as screening tests for the diagnosis of HS, but the cryohemolysis test has limited use due to its false positivity in IDA, with the Hb/MCHC ratio the most useful parameter for assessing the clinical severity of HS.

Macroautophagy (autophagy) is believed to maintain energy homeostasis by degrading unnecessary cellular components and molecules. Its implication in regulating cancer metabolism recently started to be uncovered. However, the precise roles of autophagy in cancer metabolism are still unclear. Here, we show that autophagy plays a critical role in glutamine metabolism, which is required for tumor survival. Pancreatic ductal adenocarcinoma (PDAC) cells require both autophagy and typical glutamine transporters to maintain intracellular glutamine levels. Glutamine deprivation, but not that of glucose, led to the activation of macropinocytosis-associated autophagy through TFEB induction and translocation into the nucleus. In contrast, glutamine uptake increased as a compensatory response to decreased intracellular glutamine levels upon autophagy inhibition. Moreover, autophagy inhibition and glutamine deprivation did not induce cell death, while glutamine deprivation dramatically activated apoptotic cell death upon autophagy inhibition. Interestingly, the addition of α-ketoglutarate significantly rescued the apoptotic cell death caused by the combination of the inhibition of autophagy with glutamine deprivation. Our data suggest that macropinocytosis-associated autophagy is a critical process providing glutamine for anaplerosis of the TCA cycle in PDAC. Thus, targeting both autophagy and glutamine metabolism to completely block glutamine supply may provide new therapeutic approaches to treat refractory tumors.

We extend the notion of cointegration for multivariate time series to a potentially infinite‐dimensional setting in which our time series takes values in a complex separable Hilbert space. In this setting, standard linear processes with nonzero long‐run covariance operator play the role of normalI()0 processes. We show that the cointegrating space for an normalI()1 process may be sensibly defined as the kernel of the long‐run covariance operator of its difference. The inner product of an normalI()1 process with an element of its cointegrating space is a stationary complex‐valued process. Our main result is a version of the Granger–Johansen representation theorem: we obtain a geometric reformulation of the Johansen I(1) condition that extends naturally to a Hilbert space setting, and show that an autoregressive Hilbertian process satisfying this condition, and possibly also a compactness condition, admits an normalI()1 representation.

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder that frequently involves the central nervous system (CNS). We compared the clinical characteristics, treatment, and prognosis of patients with HLH according to the degree of CNS involvement.MethodsThe clinical manifestations, initial laboratory data, treatment, and outcomes for 50 patients diagnosed with HLH and treated at Asan Medical Center between January 1995 and August 2011 were retrospectively reviewed and analyzed. CNS involvement was defined as the presence of neurological symptoms or an elevated white blood cell (WBC) count in the cerebrospinal fluid (CSF).ResultsAmong these 50 patients, 23 (46%) developed CNS disease. Among patients with CNS disease, 19 had neurological symptoms, including seizures, altered consciousness, facial palsy, dysarthria, and dysphagia. Four patients had elevated CSF WBC counts without neurological symptoms. Twelve patients had abnormal brain imaging results, including high signal intensity lesions on T2-weighted magnetic resonance imaging (MRI) findings, ventriculomegaly, hemorrhage, atrophy, and leptomeningeal enhancement. Patients with CNS disease had lower ferritin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels as well as reduced 5-year survival as compared to those without CNS disease.ConclusionCNS involvement is common among patients with HLH. Overall, patients with CNS disease achieve poorer outcomes than patients without CNS involvement. To improve outcomes, physicians must carefully monitor the neurological manifestations in patients with HLH and administer the appropriate course of intensified chemotherapy to patients with CNS disease.

Vine copulae provide a graphical framework in which multiple bivariate copulae may be combined in a consistent fashion to yield a more complex multivariate copula. In this article, we discuss the use of vine copulae to build flexible semiparametric models for stationary multivariate higher‐order Markov chains. We propose a new vine structure, the M‐vine, that is particularly well suited to this purpose. Stationarity may be imposed by requiring the equality of certain copulae in the M‐vine, while the Markov property may be imposed by requiring certain copulae to be independence copulae.

Bacillus anthracis has four plasmid possible virulence genotypes: pXO1+/pXO2+, pXO1+/pXO2-, pXO1-/pXO2+ or pXO1-/pXO2-. Due to the lack of a specific chromosomal marker for B. anthracis, differentiation of the pXO1-/pXO2- form of B. anthracis from closely related Bacillus cereus group species is difficult. In this study, we evaluate the ability of sspE, pXO1 and pXO2 primers to discriminate individual B. anthracis and the B. cereus group genotypes using multiplex real-time PCR and melting curve analysis. Optimal conditions for successful multiplex assays have been established. Purified DNAs from 38 bacterial strains including 11 strains of B. anthracis and 18 B. cereus group strains were analyzed. Nine of the B. cereus group near-neighbor strains were shown by multilocus sequence typing to be phylogenetically proximate to the B. anthracis clade. We have demonstrated that the four plasmid genotypes of B. anthracis and B. cereus group near-neighbors were differentially and simultaneously discriminated by this assay.

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Leukemic stem cells (LSCs) are root of clonal growth in acute myeloid leukemia (AML) and responsible for the propagation of leukemic blasts (LBs). LSCs are considered as CD34 + CD38- population among LBs and often express as CD123, CD44, or CD184, which are rarely expressed on normal hematopoietic stem cells and could be the potential therapeutic targets. Using multi-color flow cytometry, we analyzed the proportions of CD34 + CD38- LSCs and expression of CD123, CD44, and CD184 on LSCs in 63 patients with AML. The median proportion of LSCs was 1.3 % (0.0-33.1 %) at the time of diagnosis. Of all patients, 74.6 % of them had CD123-positive LSCs, all patients had CD44-positive LSCs, and 85.7 % had CD184-positive LSCs, respectively. The proportions of LSCs were significantly lower in the complete remission (CR) group compared with non-CR group (P = 0.006). The lower proportions of LSCs in CR group indicated that measurement of the proportion of LSCs might be helpful to predict the prognosis of AML.