As a crop for the new millennium Bambara groundnut (Vigna subterranea L. Verdc.) considered as leading legumes in the tropical regions due to its versatile advantages. The main intent of this study ...was to find out the high yielding potential genotypes and considering these genotypes to develop pure lines for commercial cultivation in Malaysia. Considering the 14 qualitative and 27 quantitative traits of fifteen landraces the variation and genetic parameters namely, variability, heritability, genetic advance, characters association, and cluster matrix were determined. ANOVA revealed significant variation for all the agronomic traits (except plant height). Among the accessions, highly significant differences (P ≤ 0.01) were found for almost all the traits excluding fifty percent flowering date, seed length, seed width. The 16 traits out of the 27 quantitative traits had a coefficient of variation (CV) ≥ 20%. A positive and intermediate to perfect highly significant association (r = 0.23 to 1.00; P < 0.00) was found between yield and its related traits. The trait dry seed weight per plant (g) had the highest GCV = 59.91% and PCV = 59.57% whereas the trait fresh pod weight (99.55%), dry seed weight (98.86%), and yield (98.10%) were highly heritable. The genetic advance recorded the highest for dry seed weight (122.01%) and lowest (3.97%) for plant height. To validate the genetic disparity, an unweighted pair-group produce with arithmetic mean (UPGMA), principal component analysis (PCA), heatmap, and H'-index was performed considering 27 quantitative traits. The constructed dendrogram showed five distinct groups of accessions. Genotypes G2, G3, and G9 from Group IV consider as promising lines which gave 70.05% higher mean yield compared to grand mean yield (1180 kg ha
) with desirable traits. Group II had a maximum number of accessions while group III and group V had one of each. However, findings declared that the availability of genetic variance will be beneficial for this crop improvement through cross breeding as well as the plant breeders to prefer desirable traits in V. subterranea L. Verdc. for further breeding purposes.
Summary Background In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly ...and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. Methods RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America. Eligible patients (aged ≥18 years) with polycythaemia vera, no palpable splenomegaly, and hydroxyurea resistance or intolerance were stratified by their hydroxyurea therapy status (resistance vs intolerance) and randomly assigned (1:1) by an interactive response technology provider using a validated system to receive either oral ruxolitinib 10 mg twice daily or investigator-selected best available therapy (hydroxyurea at the maximum tolerated dose, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment). Investigators and patients were not masked to treatment assignment; however, the study sponsor was masked to treatment assignment until database lock. The primary endpoint was the proportion of patients achieving haematocrit control at week 28. Analyses were done according to an intention-to-treat principle, including data from all patients randomly assigned to treatment. This study is registered with ClinicalTrials.gov ( NCT02038036 ) and is ongoing but not recruiting patients. Findings Between March 25, 2014, and Feb 11, 2015, of 173 patients assessed for eligibility, 74 patients were randomly assigned to receive ruxolitinib and 75 to receive best available therapy. At randomisation, best available therapy included hydroxyurea (37 49% of 75 in the best available therapy group), interferon or pegylated interferon (ten 13% of 75), pipobroman (five 7% of 75), lenalidomide (one 1% of 75), no treatment (21 28% of 75), and other (one 1% of 75). Haematocrit control was achieved in 46 (62%) of 74 ruxolitinib-treated patients versus 14 (19%) of 75 patients who received best available therapy (odds ratio 7·28 95% CI 3·43–15·45; p<0·0001). The most frequent haematological adverse events of any grade were anaemia (ten 14% of 74 in the ruxolitinib group vs two 3% of 75 in the best available therapy group) and thrombocytopenia (two 3% vs six 8%). No cases of grade 3–4 anaemia or thrombocytopenia occurred with ruxolitinib; one patient (1%) reported grade 3–4 anaemia and three patients (4%) reported grade 3–4 thrombocytopenia in the group receiving best available therapy. Frequent grade 3–4 non-haematological adverse events were hypertension (five 7% of 74 vs three 4% of 75) and pruritus (0 of 74 vs two 3% of 75). Serious adverse events occurring in more than 2% of patients in either group, irrespective of cause, included thrombocytopenia (none in the ruxolitinib group vs two 3% of 75 in the best available therapy group) and angina pectoris (two 3% of 74 in the ruxolitinib group vs none in the best available therapy group). Two deaths occurred, both in the best available therapy group. Interpretation RESPONSE-2 met its primary endpoint. The findings of this study indicate that ruxolitinib could be considered a standard of care for second-line therapy in this post-hydroxyurea patient population. Funding Novartis.
As a new crop in Malaysia, forty-four Bambara groundnut (Vigna subterranea L. verdc.) genotypes were sampled from eleven distinct populations of different origins to explore the genetic structure, ...genetic inconsistency, and fixation index. The Bambara groundnut, an African underutilized legume, has the capacity to boost food and nutrition security while simultaneously addressing environmental sustainability, food availability, and economic inequalities. A set of 32 ISSRs were screened out of 96 primers based on very sharp, clear, and reproducible bands which detected a total of 510 loci with an average of 97.64% polymorphism. The average calculated value of PIC = 0.243, RP = 5.30, H = 0.285, and MI = 0.675 representing the efficiency of primer set for genetic differentiation among the genotypes. The ISSR primers revealed the number of alleles (Na = 1.97), the effective number of alleles (Ne = 1.38), Nei's genetic diversity (h = 0.248), and a moderate level of gene flow (Nm = 2.26) across the genotypes studied. The estimated Shannon's information index (I = 0.395) indicates a high level of genetic variation exists among the accessions. Based on Nei's genetic dissimilarity a UPMGA phylogenetic tree was constructed and grouped the entire genotypes into 3 major clusters and 6 subclusters. PCA analysis revealed that first principal component extracted maximum variation (PC1 = 13.92%) than second principal component (PC2 = 12.59%). Bayesian model-based STRUCTURE analysis assembled the genotypes into 3 (best ΔK = 3) genetic groups. The fixation-index (Fst) analysis narrated a very great genetic diversity (Fst = 0.19 to 0.40) exists within the accessions of these 3 clusters. This investigation specifies the effectiveness of the ISSR primers system for the molecular portrayal of V. subterranea genotypes that could be used for genetic diversity valuation, detection, and tagging of potential genotypes with quick, precise, and authentic measures for this crop improvement through effective breeding schemes.
In a breeding program, studies of genotypic and phenotypic relationships among agricultural crop traits are useful to design, evaluate, and develop selection criteria for desirable traits. Using path ...coefficient analysis, the present study was executed to estimate the phenotypic, genotypic, and environmental correlation coefficients between yield and yield-related traits and to determine the direct and indirect effects of yield-related traits on yield per plant. A total of 30 genotypes of Vigna subterranea were studied under tropical conditions at two sites over two planting seasons (considered as four environments). The experiment at each site used a randomized complete block design with three replicates. Data were collected on vegetative and yield component attributes. Based on analysis of variance, pooled results showed that there were positive and highly significant differences (p ≤ 0.01) among the 30 genotypes for all attributes studied. Highly significant and positive strong correlation at phenotypic level was observed for dry seed weight (0.856), hundred seed weight (0.754), fresh pod weight (0.789), and total pod weight (0.626) with yield in kg per hectare, while moderate positive correlations were observed for harvest cut (0.360) and days to maturity (0.356). However, a perfect positive correlation was observed for the dry weight of pods with seed yield. In contrast, days to 50% flowering (- 0.350) showed a negative significant relationship with yield per hectare. The dried pod weight attribute (1.00) had a high positive direct effect on yield. Fresh pod weight had the greatest indirect effect on yield per hectare, followed by the number of total pods by dry pod weight. As a result, dry pod weight, hundred seed weight, number of total pods, and fresh pod weight could be used as selection criteria to improve the seed yield of Bambara groundnut (Vigna subterranea).
RESPONSE-2 is a phase 3 study comparing the efficacy and safety of ruxolitinib with the best available therapy (BAT) in hydroxyurea-resistant/hydroxyurea-intolerant polycythemia vera (PV) patients ...without palpable splenomegaly. This analysis evaluated the durability of the efficacy and safety of ruxolitinib after patients completed the visit at week 80 or discontinued the study. Endpoints included proportion of patients achieving hematocrit control (< 45%), proportion of patients achieving complete hematologic remission (CHR) at week 28, and the durability of hematocrit control and CHR. At the time of analysis, 93% (69/74) of patients randomized to ruxolitinib were receiving ruxolitinib; while in the BAT arm, 77% (58/75) of patients crossed over to ruxolitinib after week 28. No patient remained on BAT by week 80. Among patients who achieved a hematocrit response at week 28, the probability of maintaining response up to week 80 was 78% in the ruxolitinib arm. At week 80, durable CHR was achieved in 18 patients (24%) in the ruxolitinib arm versus 2 patients (3%) in the BAT arm. The safety profile of ruxolitinib was consistent with previous reports. These data support that ruxolitinib treatment should be considered also as a standard of care for hydroxyurea-resistant/hydroxyurea-intolerant PV patients without palpable splenomegaly.
Aliskiren, an Oral Renin Inhibitor, Provides Dose-Dependent Efficacy and Sustained 24 Hour Blood Pressure Control in Patients With Hypertension Byung-Hee Oh, Jerry Mitchell, James R. Herron, Jenny ...Chung, Mahmudul Khan, Deborah L. Keefe The efficacy of the novel renin inhibitor aliskiren was investigated in a randomized, double-blind, placebo-controlled, dose-ranging study in 672 patients with mild-to-moderate hypertension. Patients were randomized to receive aliskiren 150, 300, or 600 mg or placebo once daily for 8 weeks. Aliskiren 150, 300, and 600 mg significantly reduced office blood pressure by 13.0/10.3, 14.7/11.1, and 15.8/12.5 mm Hg (systolic/diastolic), respectively, compared with 3.8/4.9 mm Hg with placebo (p < 0.0001). The blood-pressure-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal. Aliskiren was well tolerated. Aliskiren provides significant antihypertensive efficacy with no rebound effects on blood pressure after treatment withdrawal.
Ruxolitinib was well tolerated and superior to best available therapy (including interferon IFN) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving ...polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients) and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at
clinicaltrials.gov
.
The stability and high yielding of Vigna subterranea L. Verdc. genotype is an important factor for long-term development and food security. The effects of G × E interaction on yield stability in 30 ...Bambara groundnut genotypes in four different Malaysian environments were investigated in this research. The experiment used a randomized complete block design with three replications in each environment. Over multiple harvests, yield component traits such as the total number of pods per plant, fresh pods weight (g), hundred seeds weight (g), and yield per hectare were evaluated in the main and off-season in 2020 and 2021. Stability tests for multivariate stability parameters were performed based on analyses of variance. For all the traits, the pooled analysis of variance revealed highly significant (p < 0.01) variations between genotypes, locations, seasons, and genotypes by environment (G × E interaction). A two-dimensional GGE biplot was generated using the first two principal components (axis 1 and axis 2), which accounted for 94.97% and 3.11% difference in GEI for yield per hectare, respectively. Season and location were found to be the most significant causes of yield heterogeneity, accounting for 31.13% and 14.02% of overall G + E + G × E variation, respectively, according to the combined study of variance. The GGE biplot revealed that the three winning genotypes G1, G3, and G5 appear across environments whereas AMMI model exposed genotypes viz G18, G14, G7, G3, G1, and G5 as best performer. Based on ideal genotype ranking genotype G1 was the best performer, with a high mean yield and high stability in the tested environment. According to the AEC line, genotypes G1 and G3 were extremely stable, while genotypes G2 and G4 were low stable, with a high average yielding per hectare. A GGE and AMMI biplot graphically showed the interrelationships between the tested environment and genotypes, classified genotypes into three categories as well as simplifying visual evaluations, according to this investigation. According to our results, breeding could improve yield production, and the genotypes discovered could be recommended for commercial cultivation.
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