Identification of prognostic and susceptibility markers in chronic myeloid leukemia using next generation sequencing

Background: Incidence of Chronic Myeloid Leukemia (CML) is continuously increasing and expected to reach 100,000 patients every year by 2030. Though the discovery of Imatinib Mesylate (IM) has brought a paradigm shift in CML treatment, 20% patients show resistance to this tyrosine kinase inhibiter (TKI). Therefore, it is important to identify markers, which can predict the occurrence and prognosis of CML. Clinical Exome Sequencing, panel of more than 4800 genes, was performed in CML patients to identify prognostic and susceptibility markers in CML.Methods: Enrolled CML patients (n=18) were segregated as IM responders (n=10) and IM failures (n=8) as per European Leukemia Net (ELN), 2013 guidelines. Healthy controls (n=5) were also enrolled. DNA from blood of subjects was subjected to Next Generation Sequencing. Rare mutations present in one patient group and absent in another group were considered as prognostic markers, whereas mutations present in more than 50% patients were considered as susceptibility markers.Result: Mutations in genes associated with cancer related functions were found in different patient groups. Four variants: rs116201358, rs4014596, rs52897880 and rs2274329 in C8A, UNC93B1, APOH and CA6 genes, respectively, were present in IM responders; whereas rs4945 in MFGE8 was present in IM failures. Mutations in HLA-DRB1 (rs17878951), HLA-DRB5 (rs137863146), RPHN2 (rs193179333), CYP2F1 (rs116958555), KCNJ12 (rs76684759) and FUT3 (rs151218854) were present as susceptibility markers.Conclusion: The potential genetic markers discovered in this study can help in predicting response to IM as frontline therapy. Susceptibility markers may also be used as panel for individuals prone to have CML.Keywords: Chronic Myeloid Leukemia, Genetic Markers, Next Generation Sequencing (NGS

Physiological traits reveal potential for identification of droughttolerant mungbean[Vigna radiata (L.)Wilczek] genotypes undermoderate soil-moisture deficit

Not AvailableCanopy temperature is an important physiological trait usedfor screening drought tolerance in several crop plants.Mungbean being often exposed to post-flowering drought,we evaluated a set of 48 genotypes for variability in post-flowering canopy temperature and its association with roottraits and other physiological parameters contributing todrought tolerance under soil-moisture deficit stressconditions. Overall, canopy temperature depressionrevealed significant association with seed yield. Root traitslike number of lateral branches and dry root weight exhibitedsignificant negative correlation with canopy temperature.Leaf SPAD readings were positively associated with grainyield and most of the high SPAD genotypes maintainedhot canopies under drought. Some genotypes withcontrasting variation in SPAD levels (DMG-1050 and SML-1628) maintained their photosystem PSII health at par.Moreover, cool canopy was no guarantee for better PSIIhealth or vice versa. This study identified some cool canopygenotypes (VC-6173-C, IC-325770 and ML-2082) and agenotype (DMG-1050) with novel trait combinations likehigh SPAD and better PSII health despite high canopytemperature which can be used as donors in mungbeanbreeding programs. Present study explores geneticvariation in these adaptation traits contributing to plantperformance under soil-moisture deficit stress conditionsand potential of physiological breeding approaches forgenetic enhancement of this legume cropICA

Trends in characteristics and outcomes of hospitalized young patients undergoing coronary artery bypass grafting in the United States, 2004 to 2018

Background: Data are limited about young adults\u27 characteristics and outcomes undergoing coronary artery bypass grafting (CABG). Methods and Results: We used the National Inpatient Sample database to identify adults aged 18 to 45 years who underwent CABG between 2004 and 2018. The data were weighted to generate national estimates of the entire US hospitalized population. We identified 110 463 CABG cases, equivalent to 62.2 per 1 000 000 person-years; 27.1% were women, and 70.2% were White adults. Overall, annual CABG volume per 1 000 000 significantly decreased from 87.3 in 2004 to 45.7 in 2018. The prevalence of obesity, diabetes mellitus, hypertension, drug abuse, and chronic medical conditions increased over time. Overall, inpatient mortality was 1.76%; ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, heart failure, peripheral vascular disease, renal failure, and valvular surgery were associated with higher inpatient mortality. Women had higher inpatient mortality than men (2.29% versus 1.57%), and Black patients had higher deaths than White patients (2.86% versus 1.58%). Inpatient mortality remained stable overall, according to sex, race, or clinical indication of CABG. However, the mean length of stay (8.4 days in 2004 to 9.5 days in 2018) and inflation-adjusted cost of care ($40 522.8 in 2004 to$52 434.2 in 2018) significantly increased during the study period.Conclusions: Despite the increased burden of cardiometabolic risk factors, the inpatient mortality in young adults undergoing CABG remained stable during the last 15 years. However, CABG volumes have decreased, but length of stay and inflation-adjusted costs have increased over time