Construction and validation of an algorithm to separate focal and generalised epilepsy using clinical variables: A comparison of machine learning approaches.

PURPOSE: Epilepsy type, whether focal or generalised, is important in deciding anti-seizure medication (ASM). In resource-limited settings, investigations are usually not available, so a clinical separation is required. We used a naïve Bayes approach to devise an algorithm to do this, and compared its accuracy with algorithms devised by five other machine learning methods. METHODS: We used data on 28 clinical variables from 503 patients attending an epilepsy clinic in India with defined epilepsy type, as determined by an epileptologist with access to clinical, imaging, and EEG data. We adopted a machine learning approach to select the most relevant variables based on mutual information, to train the model on part of the data, and then to evaluate it on the remaining data (testing set). We used a naïve Bayes approach and compared the results in the testing set with those obtained by several other machine learning algorithms by measuring sensitivity, specificity, accuracy, area under the curve, and Cohen's kappa. RESULTS: The six machine learning methods produced broadly similar results. The best naïve Bayes algorithm contained eleven variables, and its accuracy was 92.2% in determining epilepsy type (sensitivity 92.0%, specificity 92.7%). An algorithm incorporating the best eight of these variables was only slightly less accurate - 91.0% (sensitivity 89.6%, and specificity 95.1%) - and easier for clinicians to use. CONCLUSION: A clinical algorithm with eight variables is effective and accurate at separating focal from generalised epilepsy. It should be useful in resource-limited settings, by epilepsy-inexperienced doctors, to help determine epilepsy type and therefore optimal ASMs for individual patients, without the need for EEG or neuroimaging.

D-shaped fiber optic plasmonic sensors using planar and grating structures of silver and gold: design and analysis.

In this paper, a D-shaped optical fiber plasmonic sensor using planar and grating structures of silver and gold metals is simulated using the finite element method under the wave optics module of COMSOL Multiphysics. Performance defining parameters are based on (i) the transmittance curve, viz., resonance wavelength (λ r), shift in resonance wavelength (Δ λ r), minimum transmittance (T m i n ), and bandwidth (BW), and (ii) on electric field distribution of a surface plasmon wave, viz., penetration depth (PD) and propagation length (PL) obtained for the considered sensor structures. It is found that gold gives wider BW than silver (e.g., at 1.39 refractive index of the sample: 480% for the planar case and 241% for the grating case), which deteriorates sensor performance by degrading detection accuracy. However, gold gives higher Δ λ r than silver (at 1.40-1.39=0.01 change in refractive index of the sample: 18.33% for the planar case and 16.39% for the grating case), which improves sensor performance and enhances sensitivity. A grating slightly increases the BW and Δ λ r for both gold and silver. Further, with respect to silver, the sensor that contains gold demonstrates higher PD (e.g., 22.32% at 1.39 refractive index of the sample for the planar case) and lower PL (e.g., 22.74% at 1.39 refractive index of sample for the planar case). A grating increases the PD (e.g., 10% for silver at 1.39 refractive index of the sample), whereas it decreases the PL (e.g., 8.73% for silver at 1.39 refractive index of the sample). Lower PL signifies the localization of the field, whereas higher PD enables the sensor to detect larger molecules. Therefore, the sensor with grating metals provides better sensitivity with reduced detection accuracy for the detection of comparatively larger molecules.

An epilepsy type algorithm developed in India is accurate in Sudan: A prospective validation study.

PURPOSE: The effects of epilepsy are worse in lower- and middle-income countries (LMICs) where most people with epilepsy live, and where most are untreated. Correct treatment depends on determining whether focal or generalised epilepsy is present. EEG and MRI are usually not available to help so an entirely clinical method is required. We applied an eight-variable algorithm, which had been derived from 503 patients from India using naïve-Bayesian methods, to an adult Sudanese cohort with epilepsy. METHODS: There were 150 consecutive adult patients with known epilepsy type as defined by two neurologists who had access to clinical information, EEG and neuroimaging ("the gold standard"). We used seven of the eight variables, together with their likelihood ratios, to calculate the probability of focal as opposed to generalised epilepsy in each patient and compared that to the "gold standard". Sensitivity, specificity, accuracy, and Cohen's kappa statistic were calculated. RESULTS: Mean age was 28 years (range 17-49) and 53% were female. The accuracy of an algorithm comprising seven of the eight variables was 92%, with sensitivity of 99% and specificity of 72% for focal epilepsy. Cohen's kappa was 0.773, indicating substantial agreement. Ninety-four percent of patients had probability scores either less than 0.1 (generalised) or greater than 0.9 (focal). CONCLUSION: The results confirm the high accuracy of this algorithm in determining epilepsy type in Sudan. They suggest that, in a clinical condition like epilepsy, where a history is crucial, results in one continent can be applied to another. This is especially important as untreated epilepsy and the epilepsy treatment gap are so widespread. The algorithm can be applied to patients giving an individual probability score which can help determine the appropriate anti-seizure medication. It should give epilepsy-inexperienced doctors confidence in managing patients with epilepsy.

Morphological and molecular characterization of Lasiodiplodia theobromae associated with leaf spot and blight disease of Coscinium fenestratum (Gaertn.) Colebr.-a new host record from India.

Coscinium fenestratum is a medicinally significant critically endangered plant found in Western Ghats of India. The leaf spot and blight was observed in Kerala during 2021 with disease incidence of 40% in 20 assessed plants in 0.6 hectare. The associated fungus was isolated on potato dextrose agar medium. A total of six morpho-culturally identical isolates were isolated and morphologically identified. Based on morpho-cultural features, the fungus was identified at genus level as Lasiodiplodia sp., which was further authentically confirmed as Lasiodiplodia theobromae by molecular identification with a representative isolate (KFRIMCC 089) using multigene (ITS, LSU, SSU, TEF1-α, and TUB2) sequence analysis and concatenated phylogenetic analysis (ITS-TEF1-α-TUB2). Pathogenicity tests were also assessed in vitro and in vivo using mycelial disc and spore suspension of L. theobromae, and the isolated fungus's pathogenic behaviour was confirmed after re-isolation and morpho-cultural features. Literature survey reveals that there are no reports of L. theobromae on C. fenestratum from all over the world. Hence, C. fenestratum is being firstly reported as a new host record for L. theobromae from India.

Antibacterial, Antioxidant and Nutraceutical Potential of New Culinary-Medicinal Mushroom Russula lakhanpalii (Agaricomycetes) from India.

Russula lakhanpalii is a wild edible mushroom, collected from Pedkhal block of Pauri Garhwal, India. The nutritional composition, antioxidant activity (AOA), and antibacterial activity (ABA) of R. lakhanpalii were analyzed for the first time in this study. Dried fruiting bodies of R. lakhanpalii were reported to contain 17.7% ash, 10% crude fiber, 13.4% protein, 30.9% carbohydrate, and 5% unsaturated lipids. In addition, 10.22-72.56% DPPH scavenging activity also confirmed the good antioxidant nature of R. lakhanpalii. The methanolic extract of R. lakhanpalii fruiting bodies inhibited the growth of five pathogenic bacteria in vitro; Klebsiella pneumoniae (MTCC 4030), Micrococcus luteus (MTCC 1809), Staphylococcus aureus (MTCC 1144), Escherichia coli (MTCC 68), and Streptococcus pneumoniae (MTCC 655). The maximum and minimum zone of inhibitions (ZOIs) reported were 17.8 ± 1.04 mm (K. pneumoniae) and 11.16 ± 0.76 mm, (E. coli), respectively. The noticeable feature of the extract was the inhibition of erythromycin-resistant E. coli and M. luteus by it, which were resistant to 15 µg/disc concentration of erythromycin. Dietary components, antibacterial and antioxidant potentials of R. lakhanpalii suggested its nutraceutical and medicinal applications.

Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring.

OBJECTIVE: Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study. METHODS: In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207). RESULTS: One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46). SIGNIFICANCE: Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

Effective clinical classification of chronic epilepsy into focal and generalized: A cross sectional study.

PURPOSE: Investigations such as EEG and brain imaging are often difficult to obtain in primary care settings of resource-limited regions impacting millions of epilepsy patients. We wanted to test the hypothesis that classification of chronic epilepsy into focal and generalized based on clinical history and examination alone would be comparable to making such a classification with additional inputs from EEG and brain imaging. METHODS: Two investigators independently classified consecutive chronic epilepsy patients into focal, generalized and unclassified epilepsy. Investigator 1 made this determination using clinical history and examination alone whereas Investigator II additionally used EEG and brain imaging too. We calculated inter observer agreement between the two investigators and also looked at the predictors of focal and generalized epilepsy. RESULTS: Five hundred and twelve patients were recruited. Inter observer agreement between the two investigators in making the focal versus generalized classification was 96.8%, kappa 0.91 (p<0.0001). When EEG and neuroimaging findings were added to clinical information, there was a change in classification in 3.2% patients. Several predictors of focal and generalized epilepsy were identified. CONCLUSIONS: Classification of chronic epilepsy into focal and generalized can be done reliably in most patients using clinical information alone. Investigating chronic epilepsy patients with EEG and brain imaging may not be necessary in every patient. The results of our study are especially significant for epilepsy patients living in resource-limited regions where such investigations may not always be available.

Functional specialization of two paralogous TAF12 variants by their selective association with SAGA and TFIID transcriptional regulatory complexes.

TATA box-binding protein (TBP)-associated factors (TAFs), evolutionarily conserved from yeast to humans, play a central role during transcription initiation. A subset of TAF proteins is shared in transcription factor II D (TFIID) and SAGA transcription regulatory complexes. Although higher eukaryotes contain multiple TAF variants that specify tissue- and developmental stage-specific organization of TFIID or SAGA complexes, in unicellular genomes, however, each TAF is encoded by a single gene. Surprisingly, we found that the genome of Candida albicans, the predominant human fungal pathogen, contains two paralogous TAF12 genes, CaTAF12L and CaTAF12, encoding H2B-like histone-fold domain-containing variants. Of the available fungal genome sequences, only seven other closely related diploid pathogenic Candida genomes encode the two TAF12 paralogs. Using affinity purifications from C. albicans cell extracts, we demonstrate that CaTAF12L uniquely associates with the SAGA complex and CaTAF12 associates with the TFIID complex. We further show that CaTAF12, but not CaTAF12L, is essential for C. albicans growth. Conditional depletion of the two TAF12 variant proteins caused distinct cellular and colony phenotypes. Together our results define a specialized organization of the TAF12 variants and non-redundant roles for the two TAF12 variants in the unicellular C. albicans genome.

Serum high sensitivity C-reactive protein, nitric oxide metabolites, plasma fibrinogen, and lipid parameters in Indian type 2 diabetic males.

AIMS: Inflammation is postulated to play a role in diabetogenesis and its further vascular complications. The aim was to assess the inflammatory and lipid parameters in patients of type 2 diabetic mellitus with or without complication. MATERIAL AND METHODS: Serum high sensitivity C-reactive protein (hs-CRP), nitric oxide metabolite (NO(X)), fibrinogen, and lipid parameters were measured in eighty type 2 diabetic males (40-65 years) without (n=40, group B) and with complication (16 retinopathy, group C; 24 hypertension, group D); and compared with 40 healthy, age and sex matched nondiabetic males (group A) from the general population. RESULT: The mean age of subjects and fasting plasma glucose among groups A, B, and C+D were 51.0 ± 7.1 vs. 48.7 ± 5.7 vs. 50.2 ± 6.1 years (p>0.05); and 96.7 ± 10.4 vs. 134.3 ± 27.8 vs. 136.4 ± 29.8 mg/dl (p<0.001) respectively. Patients with retinopathy were older, with longer duration of diabetes, and high fasting plasma glucose (p<0.001). The mean hs-CRP, NO(X), fibrinogen, TC, TG, and LDL(C) varied significantly (p<0.001) between control and diabetics. hs-CRP, NO(X), and fibrinogen were found to be highest in retinopathy group whereas no significant (p>0.05) difference was noted between groups B and D in relation to hs-CRP and NO(X). TC and LDL(C) were significantly (p<0.001) high among group B patients. Significant positive correlation was observed between all three inflammatory markers in all categories of patients; between FPG, hs-CRP, and fibrinogen among patients with hypertension; between FPG, hs-CRP, and NO(X) in patients with retinopathy. However, none of the lipid parameters showed any significant correlation with any of the inflammatory markers in any group of patients studied. CONCLUSION: Low grade systemic inflammation, in association with dyslipidemia, plays a role in diabetogenesis and its complications.

Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes.

Set2-mediated methylation of histone H3 at Lys 36 (H3K36me) is a co-transcriptional event that is necessary for the activation of the Rpd3S histone deacetylase complex, thereby maintaining the coding region of genes in a hypoacetylated state. In the absence of Set2, H3K36 or Rpd3S acetylated histones accumulate on open reading frames (ORFs), leading to transcription initiation from cryptic promoters within ORFs. Although the co-transcriptional deacetylation pathway is well characterized, the factors responsible for acetylation are as yet unknown. Here we show that, in yeast, co-transcriptional acetylation is achieved in part by histone exchange over ORFs. In addition to its function of targeting and activating the Rpd3S complex, H3K36 methylation suppresses the interaction of H3 with histone chaperones, histone exchange over coding regions and the incorporation of new acetylated histones. Thus, Set2 functions both to suppress the incorporation of acetylated histones and to signal for the deacetylation of these histones in transcribed genes. By suppressing spurious cryptic transcripts from initiating within ORFs, this pathway is essential to maintain the accuracy of transcription by RNA polymerase II.