Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target

Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data. Drug sensitivity profiling further demonstrates the role of the JAK-STAT pathway in the pathogenesis of NK-cell malignancies, identifying NK cells to be highly sensitive to JAK and BCL2 inhibition compared to other hematopoietic cell lineages. Our results provide insight into ANKL genetics and a framework for application of targeted therapies in NK-cell malignancies

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Electroreduction of Some Azomethinc Compounds at Copper & Copper Amalgam Cathodes

176-17

Improvement in catalytic activity of molybdenum oxide by incorporation of Ni(II) ions

657-660The electrical conductivity (&sigma;) measurements of various molybdena samples containing different mol % Ni2+ reveal an increase in &sigma; when 2-propanol vapor is admitted in the gas feed. IR and XRD analysis indicate a solid state reaction between MoO3 and NiO in different ratios around 500&deg;C. &nbsp;Molybdena containing 70 mol % Ni2+ shows the formation of NiMoO4 spinel. The catalytic activity of molybdena samples containing different mol % Ni2+, calcined at 500&deg;C, has been investigated via the catalytic decomposition of 2-propanol. It is observed that % conversion or the selectivity of the catalysts, for the dehydration of 2-propanol td propylene, increases with increase in Ni2+ content of molybdena catalysts up to 70 mol % Ni2+. A suitable mechanism has been proposed to explain the observed results

Catalytic activity of pure copper oxide and samples containing different concentrations of aluminium oxide in heterogeneous decomposition of hydrogen peroxide

860-863The catalytic activities of pure CuO and of CuO samples containing different concentrations of Al3+ ions have been determined using the heterogeneous catalytic decomposition of H2O2. The activity has been correlated with various physicochemical properties. Experimental evidence shows that Al3+ is responsible for lowering the charge carrier concentration (positive holes) which affects the capability of the surface for oxygen adsorption. This has a decisive role in the decomposition reaction. A suitable mechanism has been proposed to explain the observed results

Metal-loaded silica catalysts for dehydrogenation of cycloparaffins

75-78The dehydrogenation of cyclohexane and methylcyclohexane has been studied using a micropulse reactor technique on Pt/SiO2, Ni/ SiO2 and V/ SiO2 catalysts. Monoatomic ensemble is the active center in the systems studied. The dehydrogenation activity has been found to be affected by the metal content and the textural properties of the catalyst sample. The dehydrogenation has been found to be a first-order reaction. The rate determining-step of the dehydrogenation process has been also discussed

The effect of the thermal treatment on the decomposition and catalytic properties of pure and doped cobalt oxide

470-475The influence of Zr4+-doping on the thermal decomposition of cobalt carbonate has been studied using DTA and TG techniques. Zr4+-doping slightly retards the decomposition of CoCO3 and increases the thermal stability of Co3O4. The textural characteristics, i.e., the specific surface area, the total pore volume and the mean pore radius have been determined from nitrogen adsorption isotherms measured at -196ᵒC. The results obtained indicate that the textural properties of pure cobalt oxide are influenced by doping with Zr4+ in the temperature range studied. The rate of catalytic decomposition of H2O2 changes with both the doping percentage and dehydration temperatures of pure and doped cobalt oxide samples

Structural and textural properties of some supported nickel catalysts

1046- 1051Nickel/alumina, nickel/alumina-chromia and nickel/chromia supported catalysts have been prepared by impregnation method. The DTA and X-ray techniques have been used to investigate the influence of the support on the formation of the active phase. It is found that alumina, alumina-chromia and chromia affect the formation of nickel oxide and/or nickel metal. The surface areas and pore structures have been determined using low temperature nitrogen adsorption technique. The results indicate that the addition of nickel to alumina, alumina-chromia and chromia changes the textural properties of the supports. Nickel promotes both activation and sintering of the supports