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1. Congenital Generalised Hypertrophy of Feet

Author

Agarwal AK, Srivastava PK, and Kumar D

Subjects
Congenital Hypertrophy, macrodactyly, Medicine
Abstract

Local hypertrophy, gigantism or overgrowth of hand, foot,part of it (Macrodactyly) or of full extremity are commonlyseen in Klippel Trenaunay Parkes Weber Syndrome.However congenital generalized hypertrophy of feet is arare presentation and a search of the literature revealedone case report in a 25 year old female, a similar case isbeing presented here.

Published
2009

2. Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability

Author

Feleke, R, Jazayeri, D, Abouzeid, M, Powell, KL, Srivastava, PK, O'Brien, TJ, Jones, NC, Johnson, MR, Feleke, R, Jazayeri, D, Abouzeid, M, Powell, KL, Srivastava, PK, O'Brien, TJ, Jones, NC, and Johnson, MR

Abstract

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied-inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar

Published
2022

26. BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases

Author

Papathanassiu, AE, Ko, JH, Imprialou, M, Bagnati, M, Srivastava, PK, Vu, HA, Cucchi, D, McAdoo, SP, Ananieva, EA, Mauro, C, Behmoaras, JV, Medical Research Council (MRC), and Kidney Research UK

Subjects
EXPRESSION, Male, POLARIZATION, Science, Citric Acid Cycle, Drug Evaluation, Preclinical, Arthritis, Rheumatoid, Glomerulonephritis, BRANCHED-CHAIN AMINOTRANSFERASE, Leucine, Animals, Humans, Hydro-Lyases, Transaminases, ALTERNATIVE ACTIVATION, Science & Technology, EXPERIMENTAL GLOMERULONEPHRITIS, GLUCOSE-METABOLISM, Succinates, Arthritis, Experimental, SUCCINATE-DEHYDROGENASE, Rats, Multidisciplinary Sciences, Mice, Inbred C57BL, GENE-1, Mice, Inbred DBA, Macrophages, Peritoneal, Science & Technology - Other Topics, ITACONATE, DENDRITIC CELL
Abstract

Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors; however, the function of BCATs in macrophages is unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity. Selective inhibition of BCAT1 activity results in decreased oxygen consumption and glycolysis. This decrease is associated with reduced IRG1 levels and itaconate synthesis, suggesting involvement of BCAA catabolism through the IRG1/itaconate axis within the tricarboxylic acid cycle in activated macrophages. ERG240 suppresses production of IRG1 and itaconate in mice and contributes to a less proinflammatory transcriptome signature. Oral administration of ERG240 reduces the severity of collagen-induced arthritis in mice and crescentic glomerulonephritis in rats, in part by decreasing macrophage infiltration. These results establish a regulatory role for BCAT1 in macrophage function with therapeutic implications for inflammatory conditions.

Published
2017

27. A Bayesian Approach for Analysis of Whole-Genome Bisulfite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation

Author

Rackham, OJL, Langley, SR, Oates, T, Vradi, E, Harmston, N, Srivastava, PK, Behmoaras, J, Dellaportas, P, Bottolo, L, and Petretto, E

Subjects
REGULATORY ELEMENTS, MACROPHAGE ACTIVATION, Investigations, Bayesian statistics, Rats, Inbred WKY, Sensitivity and Specificity, WGBS, Glomerulonephritis, Animals, TRANSCRIPTION, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Promoter Regions, Genetic, GENE-EXPRESSION, Genetics & Heredity, 0604 Genetics, Science & Technology, DNA methylation, Genome, fungi, food and beverages, High-Throughput Nucleotide Sequencing, Membrane Proteins, Bayes Theorem, Sequence Analysis, DNA, REGIONS, Rats, MODEL, Rats, Inbred Lew, STATISTICAL-METHODS, INFERENCE, CRESCENTIC GLOMERULONEPHRITIS, Life Sciences & Biomedicine, Statistical Genetics and Genomics, Developmental Biology
Abstract

Whole-genome bisulphite sequencing (WGBS) can identify important methylation differences between diseased and healthy samples. However, results from..., DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulfite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome while taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method’s efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600 bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis), and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.

Published
2017

29. Identification of ceruloplasmin as a gene that affects susceptibility to glomerulonephritis through macrophage function

Author

Chen, T, Rotival, M, Behmoaras, JV, Chiu, LY, Bagnati, M, Jo, JH, Srivastava, PK, Petretto, E, Pusey, CD, Lai, PC, Aitman, TJ, Cook, HT, Behmoaras, J, Wellcome Trust, Kidney Research UK, Medical Research Council (MRC), and Imperial College London

Subjects
0604 Genetics, QTL, fine mapping, positional cloning, Genetics of Immunity, eQTL, glomerulonephritis, macrophages, Developmental Biology
Abstract

Crescentic glomerulonephritis (Crgn) is a complex disorder where macrophage activity and infiltration are significant effector causes. In previous linkage studies using the uniquely susceptible Wistar Kyoto (WKY) rat strain, we have identified multiple crescentic glomerulonephritis QTL (Crgn) and positionally cloned genes underlying Crgn1 and Crgn2, which accounted for 40% of total variance in glomerular inflammation. Here, we have generated a backcross (BC) population (n = 166) where Crgn1 and Crgn2 were genetically fixed and found significant linkage to glomerular crescents on chromosome 2 (Crgn8, LOD = 3.8). Fine mapping analysis by integration with genome-wide expression QTLs (eQTLs) from the same BC population identified ceruloplasmin (Cp) as a positional eQTL in macrophages but not in serum. Liquid chromatography-tandem mass spectrometry confirmed Cp as a protein QTL in rat macrophages. WKY macrophages overexpress Cp and its downregulation by RNA interference decreases markers of glomerular proinflammatory macrophage activation. Similarly, short incubation with Cp results in a strain-dependent macrophage polarization in the rat. These results suggest that genetically determined Cp levels can alter susceptibility to Crgn through macrophage function and propose a new role for Cp in early macrophage activation.

Published
2017

30. Genome-wide analysis of differential RNA editing in epilepsy

Author

Srivastava, PK, Bagnati, M, Delahaye-Duriez, A, KO, J-H, Rotival, M, Langley, SR, Shkura, K, Mazzuferi, M, Danis, B, Eyll, JV, Foerch, P, Behmoaras, J, Kaminski, RM, Petretto, E, Johnson, MR, Commission of the European Communities, Medical Research Council (MRC), UCB Biopharma SPRL, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Genetics & Heredity, Biochemistry & Molecular Biology, Science & Technology, INTELLECTUAL DISABILITY, Bioinformatics, GENE SET ANALYSIS, WIDESPREAD RNA, 11 Medical And Health Sciences, 06 Biological Sciences, HUMAN CANCERS, DNA-SEQUENCE DIFFERENCES, HUMAN TRANSCRIPTOME, Biotechnology & Applied Microbiology, DE-NOVO MUTATIONS, MOUSE STRAINS, TEMPORAL-LOBE EPILEPSY, Life Sciences & Biomedicine, PILOCARPINE MODEL
Abstract

The recoding of genetic information through RNA editing contributes to proteomic diversity, but the extent and significance of RNA editing in disease is poorly understood. In particular, few studies have investigated the relationship between RNA editing and disease at a genome-wide level. Here, we developed a framework for the genome-wide detection of RNA sites that are differentially edited in disease. Using RNA-sequencing data from 100 hippocampi from mice with epilepsy (pilocarpine–temporal lobe epilepsy model) and 100 healthy control hippocampi, we identified 256 RNA sites (overlapping with 87 genes) that were significantly differentially edited between epileptic cases and controls. The degree of differential RNA editing in epileptic mice correlated with frequency of seizures, and the set of genes differentially RNA-edited between case and control mice were enriched for functional terms highly relevant to epilepsy, including “neuron projection” and “seizures.” Genes with differential RNA editing were preferentially enriched for genes with a genetic association to epilepsy. Indeed, we found that they are significantly enriched for genes that harbor nonsynonymous de novo mutations in patients with epileptic encephalopathy and for common susceptibility variants associated with generalized epilepsy. These analyses reveal a functional convergence between genes that are differentially RNA-edited in acquired symptomatic epilepsy and those that contribute risk for genetic epilepsy. Taken together, our results suggest a potential role for RNA editing in the epileptic hippocampus in the occurrence and severity of epileptic seizures.

Published
2017

37. Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group.

Author

Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A, Yuh L, Gupta R, Srivastava PK, C-100-21 Study Group, Testori, Alessandro, Richards, Jon, Whitman, Eric, Mann, G Bruce, Lutzky, Jose, and Camacho, Luis

Published
2008
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38. Characterization of diabetes mellitus in South African hamsters (Mystromys albicaudatus)

Author

Townsend Jf, Vorbedk Ml, Srivastava Pk, Schmidt G, and Stuhlman Ra

Subjects
Glycosuria, Blood Glucose, Male, medicine.medical_specialty, Diabetic ketoacidosis, Endocrinology, Diabetes and Metabolism, Kidney, Diabetic Ketoacidosis, chemistry.chemical_compound, Polyuria, Internal medicine, Diabetes mellitus, Cricetinae, Internal Medicine, medicine, Diabetes Mellitus, Animals, Pancreas, Glycogen, business.industry, Age Factors, Ketones, medicine.disease, Disease Models, Animal, Polyphagia, Endocrinology, chemistry, Liver, Hyperglycemia, Karyotyping, Ketonuria, Female, medicine.symptom, business, Polydipsia
Abstract

Spontaneous diabetes mellitus has been studied inMystromys albicaudatus (South African hamster) at the University of Missouri, Columbia Medical Center since its original discovery here in 1969. Thus far, characteristics established as part of the diabetic syndrome in this species included hyperglycemia, glucosuria, ketonuria, polyuria, polyphagia and polydipsia with variations in age of onset, degree of severity, and rate of progression. In addition, decreased glucose tolerance has been demonstrated and statistical analyses of data collected indicated that diabetes mellitus inM. albicaudatus has a polygenic, nonsex-linked mode of inheritance. — Histologic findings involving the pancreas, kidneys, and liver were found to be positively correlated to diagnostic parameters as well as to their degree of severity and duration. Pancreatic lesions includedΒ-cell vacuolization, glycogen infiltration, nuclear pyknosis, margination of organelles, andΒ-cell death.

Published
1974

39. A teen-ager with 46,X,del(X)(q21)

Author

Townsend Jf, McDavid Re, Fristoe F, and Srivastava Pk

Subjects
Adult, endocrine system, congenital, hereditary, and neonatal diseases and abnormalities, X Chromosome, endocrine system diseases, Somatic cell, Centromere, Turner Syndrome, Medicine, Humans, Primary amenorrhea, Amenorrhea, X chromosome, Chromosome Aberrations, Sex Chromosomes, business.industry, Chromosome, Karyotype, General Medicine, Anatomy, Chromatin, Sex Chromatin, External genitalia, Karyotyping, Female, Chromosome Deletion, business
Abstract

A 19-year-old woman has a chromosome constitution of 46,X,del (X) (pter leads to q21:). X chromatin masses seen in buccal smears were fewer and smaller than normal. The deleted X has more darkly stained regions around the centromere, and the short arm is also shorter. She is 155.5 cm tall and the breasts are normally developed, as are the external genitalia; however, she had primary amenorrhea. There are no evocative somatic malformation of Turner's syndrome.

Published
1979

40. A Bayesian Approach for Analysis of Whole-Genome Bisulphite Sequencing Data Identifies Disease-Associated Changes in DNA Methylation

Author

Rackham, OJL, Langley, Oates, T, Vradi, E, Harmston, N, Srivastava, PK, Behmoaras, J, Dellaportas, P, Bottolo, L, and Petretto, E

Subjects
WGBS, DNA methylation, Bayesian statistics, glomerulonephritis, 3. Good health
Abstract

DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method's efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1,000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis) and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.

41. Heavy Metal Soil Contamination Detection Using Combined Geochemistry and Field Spectroradiometry in the United Kingdom

Author

Lamine, S, Petropoulos, GP, Brewer, P, Bachari, NEI, Srivastava, PK, Manevski, K, Kalaitzidis, C, Macklin, Mark, Lamine, S, Petropoulos, GP, Brewer, P, Bachari, NEI, Srivastava, PK, Manevski, K, Kalaitzidis, C, and Macklin, Mark

Abstract

Technological advances in hyperspectral remote sensing have been widely applied in heavy metal soil contamination studies, as they are able to provide assessments in a rapid and cost-effective way. The present work investigates the potential role of combining field and laboratory spectroradiometry with geochemical data of lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd) in quantifying and modelling heavy metal soil contamination (HMSC) for a floodplain site located in Wales, United Kingdom. The study objectives were to: (i) collect field- and lab-based spectra from contaminated soils by using ASD FieldSpec® 3, where the spectrum varies between 350 and 2500 nm; (ii) build field- and lab-based spectral libraries; (iii) conduct geochemical analyses of Pb, Zn, Cu and Cd using atomic absorption spectrometer; (iv) identify the specific spectral regions associated to the modelling of HMSC; and (v) develop and validate heavy metal prediction models (HMPM) for the aforementioned contaminants, by considering their spectral features and concentrations in the soil. Herein, the field- and lab-based spectral features derived from 85 soil samples were used successfully to develop two spectral libraries, which along with the concentrations of Pb, Zn, Cu and Cd were combined to build eight HMPMs using stepwise multiple linear regression. The results showed, for the first time, the feasibility to predict HMSC in a highly contaminated floodplain site by combining soil geochemistry analyses and field spectroradiometry. The generated models help for mapping heavy metal concentrations over a huge area by using space-borne hyperspectral sensors. The results further demonstrated the feasibility of combining geochemistry analyses with filed spectroradiometric data to generate models that can predict heavy metal concentrations.

42. Heavy metals soil contamination detection using combined geochemistry and ASD Field Spectrometry over a highly contaminated floodplain site in the United Kingdom

Author

Lamine, S, Petropoulos, G, Brewer, P, Srivastava, PK, Manevski, K, Prashant, K, Kalaitzidis, C, Macklin, Mark, Lamine, S, Petropoulos, G, Brewer, P, Srivastava, PK, Manevski, K, Prashant, K, Kalaitzidis, C, and Macklin, Mark

Abstract

Technological advances in hyperspectral remote sensing have been widely applied in heavy metal soil contamination studies, as they are able to provide assessments in a rapid and cost-effective way. The present work investigates the potential role of combining field and laboratory spectroradiometry with geochemical data of lead (Pb), zinc (Zn), copper (Cu) and cadmium (Cd) in quantifying and modelling heavy metal soil contamination (HMSC) for a floodplain site located in Wales, United Kingdom. The study objectives were to: (i) collect field- and lab-based spectra from contaminated soils by using ASD FieldSpec® 3, where the spectrum varies between 350 and 2500 nm; (ii) build field- and lab-based spectral libraries; (iii) conduct geochemical analyses of Pb, Zn, Cu and Cd using atomic absorption spectrometer; (iv) identify the specific spectral regions associated to the modelling of HMSC; and (v) develop and validate heavy metal prediction models (HMPM) for the aforementioned contaminants, by considering their spectral features and concentrations in the soil. Herein, the field- and lab-based spectral features derived from 85 soil samples were used successfully to develop two spectral libraries, which along with the concentrations of Pb, Zn, Cu and Cd were combined to build eight HMPMs using stepwise multiple linear regression. The results showed, for the first time, the feasibility to predict HMSC in a highly contaminated floodplain site by combining soil geochemistry analyses and field spectroradiometry. The generated models help for mapping heavy metal concentrations over a huge area by using space-borne hyperspectral sensors. The results further demonstrated the feasibility of combining geochemistry analyses with filed spectroradiometric data to generate models that can predict heavy metal concentrations.

43. Agenesis of the lungs

Author

Pant, MC, primary, Srivastava, PK, additional, Sinha, KN, additional, Agrawal, GN, additional, Agrawal, PK, additional, Tripathi, AK, additional, and Agrawal, DK, additional

Published
1989
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45. "Efficient novel fungal-enriched biochar formulation for hexavalent chromium bioremediation".

Author

Dubey P, Roy A, Mishra S, Naseem M, Farooqui A, Patel A, Singh PC, and Srivastava PK

Abstract

Chromium (Cr), a key element in industrial processes such as leather tanning, poses severe environmental hazards, particularly its hexavalent form, Cr(VI), which is highly toxic and prevalent in tannery effluents/sludge. The persistence and toxicity of Cr(VI) necessitate the development of effective remediation strategies to mitigate its environmental impact. This study investigated the potential of Trichoderma yunnanense (NBRICRF_97) and its combination with 0.5% sugarcane bagasse biochar (SBC) for the reduction of Cr(VI). The results demonstrated that T. yunnanense alone achieved a 91.04% reduction of 50 mg L -1 Cr(VI) within 72 h. Combined with 0.5% SBC, the reduction efficiency increased to 99.65% within 48 h. However, the efficiency decreased at higher concentrations (200 mg L -1 ). The combination also improved fungal growth and increased extracellular ChrR enzyme activity (13.07 U mg -1 protein compared to the control). Total glutathione activity was boosted by 161.07% at 100 mg L -1 Cr(VI). Antioxidant enzymes (SOD, POD, CAT) and proline mitigated oxidative stress and FTIR analysis revealed changes in fungal cell wall functional groups (-OH and -NH) upon Cr(VI) exposure. SEM-EDX confirmed chromium deposition on fungal surfaces. These results underscore the Cr(VI) detoxification capabilities of T. yunnanense and the synergistic benefits of SBC, suggesting a promising bioremediation strategy for Cr(VI)-contaminated environments. The integration of T. yunnanense with SBC offers a sustainable and cost-effective approach for the bioremediation of Cr(VI)-contaminated sites, with potential for implementation in large-scale environmental cleanup efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Published
2024
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46. Prediction of COVID-19 severity using machine learning.

Author

Karaduzovic-Hadziabdic K, Adilovic M, Zhang L, Lumley AI, Shah P, Shoaib M, Satagopam V, Srivastava PK, Emanueli C, Greco S, Madè A, Padro T, Domingo P, Lustrek M, Scholz M, Rosolowski M, Jordan M, Benczik B, Ágg B, Ferdinandy P, Baker AH, Fagherazzi G, Ollert M, Michel J, Sanchez G, Firat H, Brandenburger T, Martelli F, Badimon L, and Devaux Y

Subjects
Humans, SARS-CoV-2, Male, Female, Middle Aged, COVID-19 diagnosis, COVID-19 epidemiology, Machine Learning, Severity of Illness Index
Published
2024
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47. Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study.

Author

van Vliet EA, Scheper M, Mills JD, Puhakka N, Szydlowska K, Ferracin M, Lovisari F, Soukupova M, Zucchini S, Srivastava PK, Johnson MR, Lukasiuk K, Gorter JA, Aronica E, Pitkänen A, and Simonato M

Abstract

Objective: Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult., Methods: Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long-term video-electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome-wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers., Results: Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model-specific manner. One miRNA, miR-3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, p < .05)., Significance: Identified plasma miRNAs and isomiRs are mostly etiology-specific rather than common prognostic biomarkers of epileptogenesis. These data imply that in preclinical and clinical studies, it may be necessary to identify specific biomarkers for different epilepsy etiologies. Importantly, circulating miRNAs like miR-3085 with high negative predictive value for epileptogenesis in different etiologies could be useful candidates for initial screening purposes of epileptogenesis risk., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Published
2024
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48. Predicting in-hospital mortality among patients admitted with a diagnosis of heart failure: a machine learning approach.

Author

Jawadi Z, He R, Srivastava PK, Fonarow GC, Khalil SO, Krishnan S, Eskin E, Chiang JN, and Nsair A

Subjects
Humans, Female, Male, Aged, Middle Aged, Risk Assessment methods, Aged, 80 and over, Retrospective Studies, Prognosis, Stroke Volume physiology, Hospitalization statistics & numerical data, Risk Factors, Survival Rate trends, Heart Failure mortality, Heart Failure diagnosis, Machine Learning, Hospital Mortality trends
Abstract

Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in-hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th-75th percentile) was 70 (58-82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41-49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c-statistic (95% confidence interval) of 0.96 (0.95-0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in-hospital mortality. Models for those with HFrEF demonstrated a c-statistic of 0.96 (0.94-0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c-statistic of 0.95 (0.93-0.97), SN 87.4%, and SP 89.5% for predicting in-hospital mortality. The random forest model significantly outperformed logistic regression (c-statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c-statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines-Heart Failure risk score (c-statistic 0.69, SN 67%, and SP 63%); P < 0.001 for comparison. Machine learning models built from commonly recorded patient information can accurately predict in-hospital mortality among patients hospitalized with a diagnosis of heart failure., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2024
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49. Twist-Controlled Ferroelectricity and Emergent Multiferroicity in WSe 2 Bilayers.

Author

Hassan Y, Singh B, Joe M, Son BM, Ngo TD, Jang Y, Sett S, Singha A, Biswas R, Bhakar M, Watanabe K, Taniguchi T, Raghunathan V, Sheet G, Lee Z, Yoo WJ, Srivastava PK, and Lee C

Abstract

Recently, researchers have been investigating artificial ferroelectricity, which arises when inversion symmetry is broken in certain R-stacked, i.e., zero-degree twisted, van der Waals (vdW) bilayers. Here, the study reports the twist-controlled ferroelectricity in tungsten diselenide (WSe 2 ) bilayers. The findings show noticeable room temperature ferroelectricity that decreases with twist angle within the range 0° < θ < 3°, and disappears completely for θ ≥ 4°. This variation aligns with moiré length scale-controlled ferroelectric dynamics (0° < θ < 3°), while loss beyond 4° may relate to twist-controlled commensurate to non-commensurate transitions. This twist-controlled ferroelectricity serves as a spectroscopic tool for detecting transitions between commensurate and incommensurate moiré patterns. At 5.5 K, 3° twisted WSe 2 exhibits ferroelectric and correlation-driven ferromagnetic ordering, indicating twist-controlled multiferroic behavior. The study offers insights into twist-controlled coexisting ferro-ordering and serves as valuable spectroscopic tools., (© 2024 Wiley‐VCH GmbH.)

Published
2024
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50. Characterization and assessment of hydrological droughts using GloFAS streamflow data for the Narmada River Basin, India.

Author

Swain S, Mishra SK, Pandey A, Srivastava PK, and Nandi S

Subjects
India, Environmental Monitoring methods, Water Supply, Droughts, Rivers, Hydrology
Abstract

Hydrological droughts severely affect the demand of water for domestic water supply, irrigation, hydropower generation, and several other purposes. The pervasiveness and consequences of hydrological droughts necessitate a thorough investigation of their characteristics, which is hindered due to unavailability of continuous streamflow records at desirable resolutions. This study aims to assess the hydrological drought characteristics and their spatial distribution using high-resolution Global Flood Awareness System (GloFAS) v3.1 streamflow data for the period 1980 to 2020. Streamflow Drought Index (SDI) was used to characterize droughts at 3-, 6-, 9-, and 12-monthly timescales starting from June, i.e., the start of water year in India. GloFAS is found to capture the spatial distribution of streamflow and its seasonal characteristics. The number of hydrological drought years over the basin varied from 5 to 11 during the study duration, implying that the basin is prone to frequent abnormal water deficits. Interestingly, the hydrological droughts are more frequent in the eastern portion of the basin, i.e., the Upper Narmada Basin. The trend analysis of multi-scalar SDI series using non-parametric Spearman's Rho test exhibited increasing drying trends in the easternmost portions. The results were not similar for the middle and western portions of the basin, which may be due to presence of a large number of reservoirs in these regions and their systematic operations. This study highlights the importance of open-access global products that can be used for monitoring hydrological droughts, especially over ungauged catchments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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