Machine learning method using position-specific mutation based classification outperforms one hot coding for disease severity prediction in haemophilia 'A'.

Haemophilia is an X-linked genetic disorder in which A and B types are the most common that occur due to absence or lack of protein factors VIII and IX, respectively. Severity of the disease depends on mutation. Available Machine Learning (ML) methods that predict the mutational severity by using traditional encoding approaches, generally have high time complexity and compromised accuracy. In this study, Haemophilia 'A' patient mutation dataset containing 7784 mutations was processed by the proposed Position-Specific Mutation (PSM) and One-Hot Encoding (OHE) technique to predict the disease severity. The dataset processed by PSM and OHE methods was analyzed and trained for classification of mutation severity level using various ML algorithms. Surprisingly, PSM outperformed OHE, both in terms of time efficiency and accuracy, with training and prediction time improvement in the range of approximately 91 to 98% and 80 to 99% respectively. The severity prediction accuracy also improved by using PSM with different ML algorithms.

Purification, characterization and synthetic application of a thermally stable laccase from Hexagonia tenuis MTCC-1119.

A thermally stable laccase was purified from the culture filtrate of Hexagonia tenuis MTCC-1119. The method involved concentration of the culture filtrate by ammonium sulphate precipitation and an anion-exchange chromatography on diethylaminoethyl (DEAE) cellulose. The sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and native polyacrylamide gel electrophoresis (native-PAGE) both gave single protein bands, indicating that the enzyme preparation was pure. The molecular mass of the enzyme determined from SDS-PAGE analysis was 100 kDa. The purification fold and percentage recovery of the enzyme activity were 12.75 and 30.12%, respectively. The pH and the temperature optima were 3.5 and 45 degrees C, respectively. The enzyme was most stable at pH 4.0 when exposed for 1 h. Using 2,6-dimethoxyphenol (DMP), 2,2 [azino-bis-(3-ethylbonzthiazoline-6-sulphonic acid) diammonium salt] (ABTS) and 3,5-dimethoxy-4-hydroxybenzaldehyde azine (syringaldazine) as the substrates, the K(m), k(cat) and k(cat)/K(m) values of the laccase were 80 µM, 2.54 s(-1), 3.17 x 10(4) M(-1)s(-1), 36 µM, 2.54 s(-1), 7.05 x 10(4) M(-1)s(-1) and 87 µM, 2.54 s(-1), 2.92 x 10(4) M(-1)s(-1), respectively. The purified laccase was finally used for the selective biotransformation of aromatic methyl group to aldehyde group in presence of diammonium salt of ABTS as the mediator and products were characterized by HPLC, IR and 1H NMR. The percentage yields of these transformed products were > 91%.

AYURAKSHA, a prophylactic Ayurvedic immunity boosting kit reducing positivity percentage of IgG COVID-19 among frontline Indian Delhi police personnel: A non-randomized controlled intervention trial.

Objective: The world continues to face the COVID-19 crisis, and efforts are underway to integrate traditional medicine interventions for its effective management. The study aimed to determine the efficacy of the "AYURAKSHA" kit in terms of post-interventional percentage of COVID-19 IgG positivity, immunity levels, and quality of life (QoL) against COVID-19. Method: This was a non-randomized controlled, prospective intervention trial, done after the distribution of 80,000 AYURAKSHA kits (constituent of Sanshamani Vati, AYUSH Kadha, and Anu Taila) among Delhi police participants in India. Among 47,827 participants, the trial group (n = 101) was evaluated with the positivity percentage of IgG COVID-19 and Immune Status Questionnaire (ISQ) scores as a primary outcome and the WHO Quality of Life Brief Version (QOL BREF) scores along with hematological parameters as a secondary outcome in comparison to the control group (n = 71). Results: The data showed that the percentage of COVID-19 IgG positivity was significantly lower in the trial group (17.5 %) as compared to the control group (39.4 %, p = 0.003), indicating the lower risk (55.6%) of COVID-19 infection in the trial group. The decreased incidence (5.05%) and reduced mortality percentage (0.44%) of COVID-19 among Delhi police officers during peak times of the pandemic also corroborate our findings. The ISQ score and WHO-QOL BREF tool analysis showed the improved scores in the trial group when compared with the controls. Furthermore, no dysregulated blood profile and no increase in inflammation markers like C-reactive protein, erythrocyte sedimentation rate, Interleukin-6 (IL-6) were observed in the trial group. However, significantly enhanced (p = 0.027) IL-6 levels and random blood sugar levels were found in the control group (p = 0.032), compared to a trial group (p = 0.165) post-intervention. Importantly, the control group showed more significant (p = 0.0001) decline in lymphocyte subsets CD3+ (% change = 21.04), CD4+ (% change = 20.34) and CD8+ (% change = 21.54) levels than in trial group, confirming more severity of COVID-19 infection in the control group. Conclusion: The AYURAKSHA kit is associated with reduced COVID-19 positivity and with a better quality of life among the trial group. Hence, the study encourages in-depth research and future integration of traditional medicines for the prevention of the COVID-19 pandemic. Clinical trial registration: http://ctri.nic.in/, identifier: CTRI/2020/05/025171.

Metabolite Diversity and Metabolic Genome-Wide Marker Association Studies (Mgwas) for Health Benefiting Nutritional Traits in Pearl Millet Grains.

As efforts are made to increase food security, millets are gaining increasing importance due to their excellent nutritional credentials. Among the millets, pearl millet is the predominant species possessing several health benefiting nutritional traits in its grain that are helpful in mitigating chronic illnesses such as type-2 diabetes and obesity. In this paper, we conducted metabolomic fingerprinting of 197 pearl millet inbred lines drawn randomly from within the world collection of pearl millet germplasm and report the extent of genetic variation for health benefitting metabolites in these genotypes. Metabolites were extracted from seeds and assessed using flow infusion high-resolution mass spectrometry (FIE-HRMS). Metabolite features (m/z), whose levels significantly differed among the germplasm inbred lines, were identified by ANOVA corrected for FDR and subjected to functional pathway analysis. A number of health-benefiting metabolites linked to dietary starch, antioxidants, vitamins, and lipid metabolism-related compounds were identified. Metabolic genome-wide association analysis (mGWAS) performed using the 396 m/z as phenotypic traits and the 76 K SNP as genotypic variants identified a total of 897 SNPs associated with health benefiting nutritional metabolite at the -log p-value ≤ 4.0. From these associations, 738 probable candidate genes were predicted to have an important role in starch, antioxidants, vitamins, and lipid metabolism. The mGWAS analysis focused on genes involved in starch branching (α-amylase, ß-amylase), vitamin-K reductase, UDP-glucuronosyl, and UDP-glucosyl transferase (UGTs), L-ascorbate oxidase, and isoflavone 2'-monooxygenase genes, which are known to be linked to increases in human health benefiting metabolites. We demonstrate how metabolomic, genomic, and statistical approaches can be utilized to pinpoint genetic variations and their functions linked to key nutritional properties in pearl millet, which in turn can be bred into millets and other cereals crops using plant breeding methods.

Identifying Anti-Oxidant Biosynthesis Genes in Pearl Millet [Pennisetum glaucum (L.) R. Br.] Using Genome-Wide Association Analysis.

Pearl millet [Pennisetum glaucum (L.) R Br.] is an important staple food crop in the semi-arid tropics of Asia and Africa. It is a cereal grain that has the prospect to be used as a substitute for wheat flour for celiac patients. It is an important antioxidant food resource present with a wide range of phenolic compounds that are good sources of natural antioxidants. The present study aimed to identify the total antioxidant content of pearl millet flour and apply it to evaluate the antioxidant activity of its 222 genotypes drawn randomly from the pearl millet inbred germplasm association panel (PMiGAP), a world diversity panel of this crop. The total phenolic content (TPC) significantly correlated with DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity (% inhibition), which ranged from 2.32 to 112.45% and ferric-reducing antioxidant power (FRAP) activity ranging from 21.68 to 179.66 (mg ascorbic acid eq./100 g). Genome-wide association studies (GWAS) were conducted using 222 diverse accessions and 67 K SNPs distributed across all the seven pearl millet chromosomes. Approximately, 218 SNPs were found to be strongly associated with DPPH and FRAP activity at high confidence [-log (p) > 3.0-7.4]. Furthermore, flanking regions of significantly associated SNPs were explored for candidate gene harvesting. This identified 18 candidate genes related to antioxidant pathway genes (flavanone 7-O-beta-glycosyltransferase, GDSL esterase/lipase, glutathione S-transferase) residing within or near the association signal that can be selected for further functional characterization. Patterns of genetic variability and the associated genes reported in this study are useful findings, which would need further validation before their utilization in molecular breeding for high antioxidant-containing pearl millet cultivars.

A study of triggers of migraine in India.

OBJECTIVE: To evaluate the migraine triggers in consecutive patients and correlate these with demographic and clinical variables. DESIGN: A prospective study. SETTING: Tertiary care teaching hospital. SUBJECT AND METHODS: A total of 182 patients with migraine were included whose age ranged between 14 to 58 years and 131 were females. Duration of migraine ranged between 6 and 260 months. Endogenous and exogenous migraine triggers were inquired using a questionnaire. Severity of migraine, associated symptoms, and functional disability were recorded. Presence of trigger was correlated with various demographic and clinical variables. RESULTS: Migraine triggers were present in 160 (87.9%) patients and included emotional stress in 70%, fasting in 46.3%, physical exhaustion or traveling in 52.5%, sleep deprivation in 44.4%, menstruation in 12.8%, and weather changes in 10.1% patients. Multiple triggers (>2) were present in 34.4% patients. CONCLUSION: The triggers in the Indian migraine patients are similar to other populations but for dietary factors.

Harnessing Finger Millet to Combat Calcium Deficiency in Humans: Challenges and Prospects.

Humans require more than 20 mineral elements for healthy body function. Calcium (Ca), one of the essential macromineral, is required in relatively large quantities in the diet for maintaining a sound overall health. Young children, pregnant and nursing women in marginalized and poorest regions of the world, are at highest risk of Ca malnutrition. Elderly population is another group of people most commonly affected by Ca deficiency mainly in the form of osteoporosis and osteopenia. Improved dietary intake of Ca may be the most cost-effective way to meet such deficiencies. Finger millet [Eleusine coracana (L.) Gaertn.], a crop with inherently higher Ca content in its grain, is an excellent candidate for understanding genetic mechanisms associated with Ca accumulation in grain crops. Such knowledge will also contribute toward increasing Ca contents in other staple crops consumed on daily basis using plant-breeding (also known as biofortification) methods. However, developing Ca-biofortified finger millet to reach nutritional acceptability faces various challenges. These include identifying and translating the high grain Ca content to an adequately bioavailable form so as to have a positive impact on Ca malnutrition. In this review, we assess some recent advancements and challenges for enrichment of its Ca value and present possible inter-disciplinary prospects for advancing the actual impact of Ca-biofortified finger millet.

Dietary Interventions for Type 2 Diabetes: How Millet Comes to Help.

Diabetes has become a highly problematic and increasingly prevalent disease world-wide. It has contributed toward 1.5 million deaths in 2012. Management techniques for diabetes prevention in high-risk as well as in affected individuals, beside medication, are mainly through changes in lifestyle and dietary regulation. Particularly, diet can have a great influence on life quality for those that suffer from, as well as those at risk of, diabetes. As such, considerations on nutritional aspects are required to be made to include in dietary intervention. This review aims to give an overview on the general consensus of current dietary and nutritional recommendation for diabetics. In light of such recommendation, the use of plant breeding, conventional as well as more recently developed molecular marker-based breeding and biofortification, are discussed in designing crops with desired characteristics. While there are various recommendations available, dietary choices are restricted by availability due to geo-, political-, or economical- considerations. This particularly holds true for countries such as India, where 65 million people (up from 50 million in 2010) are currently diabetic and their numbers are rising at an alarming rate. Millets are one of the most abundant crops grown in India as well as in Africa, providing a staple food source for many poorest of the poor communities in these countries. The potentials of millets as a dietary component to combat the increasing prevalence of global diabetes are highlighted in this review.

A comparison of migraine patients with and without allodynic symptoms.

BACKGROUND: Although the association of symptoms of allodynia with migraine have been reported, there is a paucity of studies on Asians. AIMS: To evaluate allodynic symptoms in migraine patients and its relationship with various clinical variables. METHODS: Consecutive migraine patients meeting the International Headache Society criteria were evaluated. Frequency, duration of illness, precipitating factors and severity of headache, associated symptoms, and functional disability were noted. Presence of allodynic symptoms and its distribution were recorded and correlated with demographic and clinical variables. RESULTS: One hundred eighty-two consecutive patients with migraine without aura were included. Mean age was 30.7 years and 51 of the patients were males. Allodynic symptoms were present in 57.1%, which were triggered by various stimuli. In majority of patients, allodynic symptoms were induced by multiple stimuli. Symptoms of allodynia were restricted to the initial site of headache in 32.7%, holocranial in 46.2% and cephalic and extracephalic in 21.1% patients. Duration, frequency of migraine attacks, and functional disability were significantly associated with allodynic symptoms. Rizatriptan resulted in better relief of headache at 2 hours compared with ibuprofen in allodynic patients. CONCLUSIONS: Allodynic symptoms occurred in 57.1% patients with migraine. In allodynic patients with moderate-to-severe headache, rizatriptan resulted in greater pain relief compared with ibuprofen. These results need further confirmation in larger study.

Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.

The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with <8 attacks/months were included. One hundred and fifty-five migraine patients were randomised to rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.