The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia

Evaluation of CO2-doped blends in single-stage with IHX and parallel compression refrigeration architectures

CO2 is the standard for medium to large-sized commercial applications, as it combines security and low environmental impact. However, it requires the use of advanced and complex cycles. Recently, CO2-doping (the addition of a small quantity of another fluid) has attracted scientific attention, as when CO2 is mixed with fluids with higher critical temperatures, the optimum operation moves to subcritical, providing COP increments in relation to pure-CO2 operation. This work, from a theoretical perspective, evaluates CO2-doping with the fluids R-152a, R-1234yf, R-1234ze(E) and R-1233zd(E) considering the two most used CO2 cycles: the base cycle with an internal heat exchanger (IHX) and the cycle with parallel compression (PC), fractionation taking place. The work analyses the COP improvements for an evaporating level of -10°C and from 10 to 40°C of environment temperature. Predicted maximum COP increments reach up to 5.8% for the IHX cycle and 10.0% for the PC cycle

BCR::ABL1 levels at first month after TKI discontinuation predict subsequent maintenance of treatment-free remission: A study from the “GRUPPO TRIVENETO LMC”

We analyzed BCR::ABL1 expression at stop and in the first month after discontinuation in 168 chronic myeloid leukemia patients who stopped imatinib or 2nd generation tyrosine kinase inhibitors (2G-TKIs) while in sustained deep molecular response. Patients were divided among those who maintained response (group 1, n = 123) and those who lost major molecular response (group 2, n = 45). Mean BCR::ABL1 RNA levels 1 month after discontinuation were higher in group 2 than in group 1 (p = 0.0005) and the difference was more evident 2 months after stop (p < 0.0001). The same trend was found both for imatinib and 2G-TKIs. A receiver operating characteristic (ROC) analysis to determine a threshold value of BCR::ABL1 at 1 month after discontinuation identified a cut-off value of 0.0051%, with 92.2% specificity, 31.7% sensitivity and a likelihood ratio of 4.087

Finding footy : female fan socialization and Australian rules football

The question of how, irrespective of gender, a person becomes a sports fan has been absent in sociological studies of sports supporters. Distinct from other studies of sport spectatorship that focus on the practices of already existing (and overwhelmingly male) fans, our research is the first to consider how women become supporters, and in doing so, it begins to redress the significant under-representation of women in sports fan research. From interviews with female supporters of the Australian Football League (AFL), this article identifies and critically assesses the modes by which women come to support sport. We propose four categories to explain the different ways women accomplish fandom, focusing on the importance of strong social ties and doxic actions in this process. The events, experiences and social relations that inform women\u27s first encounters with AFL offers a template for the wider consideration of women as social agents in the sporting landscape

Acute rhabdomyolysis and delayed pericardial effusion in an Italian patient with Ebola virus disease : a case report

Background: During the 2013-2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA. Case presentation: In May 2015, a 37-year old male nurse contracted Ebola virus disease in Sierra Leone. After Ebola virus detection in plasma, he was medically-evacuated to Italy. At admission, rhabdomyolysis was clinically and laboratory-diagnosed and was treated with aggressive hydration, oral favipiravir and intravenous investigational monoclonal antibodies against Ebola virus. The recovery clinical phase was complicated by a febrile thrombocytopenic syndrome with pericardial effusion treated with corticosteroids for 10days and indomethacin for 2months. No evidence of recurrence is reported. Conclusions: A febrile thrombocytopenic syndrome with pericardial effusion during the recovery phase of EVD appears to be uncommon. Clinical improvement with corticosteroid treatment suggests that an immune-mediated mechanism contributed to the pericardial effusion

Ice thermal energy storage for electricity peak shaving in a commercial refrigeration/HVAC unit

An ice thermal energy storage is adopted in the HVAC plant of a supermarket, to shave peaks in electricity use. Ice is formed at night-time by employing the commercial refrigeration system, which is considerably part-loaded during the shop closing time. During daytime, the thermal storage is discharged and operated in parallel to a water chiller, to produce chilled water for air conditioning purposes. The whole system is modelled, to look for the most effective control rule in an attempt to match energy efficiency and the need to comply with a threshold in the electricity use

Experimental evaluation of zeotropic refrigerants in a dedicated mechanical subcooling system in a CO2 cycle

Use of zeotropic blends in the dedicated mechanical subcooling system of a CO2 refrigeration system was suggested as a possible improvement due to matching of evaporating temperature with CO2 temperature profile during subcooling. This work has verified this possibility and has determined theoretically the best performing compositions of R-600, R-32 and CO2 with the base fluid R-152a. Then, the mixtures have been tested experimentally in a lab-test bench for constant heat load temperature for three heat rejection temperatures (25.1, 30.3 and 35.1\ub0C). Optimum conditions are measured (subcooling degree and heat rejection) and a COP increase of 1.4% has been obtained. The work, for the optimum conditions, analyses the operating parameters of the cycles and focus specially on the thermal parameters of the subcooler. It has been verified that the use of zeotropic mixtures allows to reduce irreversibilities in the cycle, as pointed out theoretically by Dai et al. (2018)

A TIME-RESOLVED ELECTRON-SPIN-RESONANCE STUDY OF MOBILE EXCITED TRIPLET-STATES IN THE ANTHRACENE-1,2,4,5-TETRACYANOBENZENE CRYSTAL

Mobile triplet excitations (excitons) in the antracene-1,2,4,5-tetracyanobenzene crystal are studied by analysing the e.s.r. transient nutation signals after laser pulse excitation. Values of the relaxation times T1 and T2 are measured as a function of the temperature and of the crystal orientation. Their values are discussed in terms of the time modulation of the fine tensor caused by the exciton and the lattice motion. In the phase stable at low temperature the crystal structure consists of magnetically inequivalent stacks of anthracene and tetracyanobenzene molecules and a detailed analysis of the variation of T2\u20131 with the crystal orientation gives an estimate of the interaction between anthracene molecules in adjacent stacks

A Novel ELISA-Based Peptide Biosensor Assay for Screening ABL1 Activity in vitro: A Challenge for Precision Therapy in BCR-ABL1 and BCR-ABL1 Like Leukemias

The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of BCR-ABL1 like acute lymphoblastic leukemia (ALL); TK inhibitors represent a useful therapeutic choice in these patients who respond poorly to conventional chemotherapy. Here we report a novel peptide biosensor (PABL)-ELISA assay to investigate ABL1 activity in four immortalized leukemic cell lines with different genetic background. The PABL sequence comprises an ABL1 tyrosine (Y) phosphorylation site and a targeting sequence that increases the specificity for ABL1; additional peptides (Y-site-mutated (PABL-F) and fully-phosphorylated (PPHOSPHO-ABL) biosensors) were included in the assay. After incubation with whole cell lysates, average PABL phosphorylation was significantly increased (basal vs. PABL phosphorylation: 6.84 ± 1.46% vs. 32.44 ± 3.25%, p-value < 0.0001, two-way ANOVA, Bonferroni post-test, percentages relative to PPHOSPHO-ABL in each cell line). Cell lines expressing ABL1-chimeric proteins (K562, ALL-SIL) presented the higher TK activity on PABL; a lower signal was instead observed for NALM6 and REH (p < 0.001 and p < 0.05 vs. K562, respectively). Phosphorylation was ABL1-mediated, as demonstrated by the specific inhibition of imatinib (p < 0.001 for K562, NALM6, ALL-SIL and p < 0.01 for REH) in contrast to ruxolitinib (JAK2-inhibitor), and occurred on the ABL1 Y-site, as demonstrated by PABL-F whose phosphorylation was comparable to basal levels. In order to validate this novel PABL-ELISA assay on leukemic cells isolated from patient’s bone marrow aspirates, preliminary analysis on blasts derived from an adult affected by chronic myeloid leukaemia (BCR-ABL1 positive) and a child affected by ALL (BCR-ABL1 negative) were performed. Phosphorylation of PABL was specifically inhibited after the incubation of BCR-ABL1 positive cell lysates with imatinib, but not with ruxolitinib. While requiring further optimization and validation in leukemic blasts to be of clinical interest, the PABL-based ELISA assay provides a novel in vitro tool for screening both the aberrant ABL1 activity in BCR-ABL1 like ALL leukemic cells and their potential response to TK inhibitors