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1.
  • 2021
  • swepub:Mat__t
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2.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Abelev, Betty, et al. (author)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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5.
  • Kumar, Rakesh, et al. (author)
  • Rice husk biochar-A novel engineered bio-based material for transforming groundwater-mediated fluoride cycling in natural environments
  • 2023
  • In: Journal of Environmental Management. - : Elsevier BV. - 0301-4797 .- 1095-8630. ; 343
  • Journal article (peer-reviewed)abstract
    • Biochar, a promising carbon-rich and carbon-negative material, can control water pollution, harness the synergy of sustainable development goals, and achieve circular economy. This study examined the performance feasibility of treating fluoride-contaminated surface and groundwater using raw and modified biochar synthesized from agricultural waste rice husk as problem-fixing renewable carbon-neutral material. Physicochemical characterizations of raw/modified biochars were investigated using FESEM-EDAX, FTIR, XRD, BET, CHSN, VSM, pHpzc, Zeta potential, and particle size analysis were analyzed to identify the surface morphology, functional groups, structural, and electrokinetic behavior. In fluoride (Fˉ) cycling, performance feasibility was tested at various governing factors, contact time (0–120 min), initial Fˉ levels (10–50 mg L−1), biochar dose (0.1–0.5 g L−1), pH (2–9), salt strengths (0–50 mM), temperatures (301–328 K), and various co-occurring ions. Results revealed that activated magnetic biochar (AMB) possessed higher adsorption capacity than raw biochar (RB) and activated biochar (AB) at pH 7. The results indicated that maximum Fˉ removal (98.13%) was achieved using AMB at pH 7 for 10 mg L−1. Electrostatic attraction, ion exchange, pore fillings, and surface complexation govern Fˉ removal mechanisms. Pseudo-second-order and Freundlich were the best fit kinetic and isotherm for Fˉ sorption, respectively. Increased biochar dose drives an increase in active sites due to Fˉ level gradient and mass transfer between biochar-fluoride interactions, which reported maximum mass transfer for AMB than RB and AB. Fluoride adsorption using AMB could be described through chemisorption processes at room temperature (301 K), though endothermic sorption follows the physisorption process. Fluoride removal efficiency reduced, from 67.70% to 53.23%, with increased salt concentrations from 0 to 50 mM NaCl solutions, respectively, due to increased hydrodynamic diameter. Biochar was used to treat natural fluoride-contaminated surface and groundwater in real-world problem-solving measures, showed removal efficiency of 91.20% and 95.61%, respectively, for 10 mg L−1 Fˉ contamination, and has been performed multiple times after systematic adsorption-desorption experiments. Lastly, techno-economic analysis was analyzed for biochar synthesis and Fˉ treatment performance costs. Overall, our results revealed worth output and concluded with recommendations for future research on Fˉ adsorption using biochar.
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6.
  • Sharma, Vinay, et al. (author)
  • Expression, purification, characterization and in silico analysis of newly isolated hydrocarbon degrading bleomycin resistance dioxygenase
  • 2020
  • In: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 47:1, s. 533-544
  • Journal article (peer-reviewed)abstract
    • In the present investigation, we report cloning, expression, purification and characterization of a novel Bleomycin Resistance Dioxygenase (BRPD). His-tagged fusion protein was purified to homogeneity using Ni-NTA affinity chromatography, yielding 1.2 mg of BRPD with specific activity of 6.25 U mg−1 from 600 ml of E. coli culture. Purified enzyme was a dimer with molecular weight ~ 26 kDa in SDS-PAGE and ~ 73 kDa in native PAGE analysis. The protein catalyzed breakdown of hydrocarbon substrates, including catechol and hydroquinone, in the presence of metal ions, as characterized via spectrophotometric analysis of the enzymatic reactions. Bleomycin binding was proven using the EMSA gel retardation assay, and the putative bleomycin binding site was further determined by in silico analysis. Molecular dynamic simulations revealed that BRPD attains octahedral configuration in the presence of Fe2+ ion, forming six co-ordinate complexes to degrade hydroquinone-like molecules. In contrary, in the presence of Zn2+ ion BRPD adopts tetrahedral configuration, which enables degradation of catechol-like molecules.
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7.
  • Abelev, Betty, et al. (author)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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8.
  • Gupta, Ankit, et al. (author)
  • Reconstruction of Bacterial and Viral Genomes from Multiple Metagenomes.
  • 2016
  • In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 7:April
  • Journal article (peer-reviewed)abstract
    • Several metagenomic projects have been accomplished or are in progress. However, in most cases, it is not feasible to generate complete genomic assemblies of species from the metagenomic sequencing of a complex environment. Only a few studies have reported the reconstruction of bacterial genomes from complex metagenomes. In this work, Binning-Assembly approach has been proposed and demonstrated for the reconstruction of bacterial and viral genomes from 72 human gut metagenomic datasets. A total 1156 bacterial genomes belonging to 219 bacterial families and, 279 viral genomes belonging to 84 viral families could be identified. More than 80% complete draft genome sequences could be reconstructed for a total of 126 bacterial and 11 viral genomes. Selected draft assembled genomes could be validated with 99.8% accuracy using their ORFs. The study provides useful information on the assembly expected for a species given its number of reads and abundance. This approach along with spiking was also demonstrated to be useful in improving the draft assembly of a bacterial genome. The Binning-Assembly approach can be successfully used to reconstruct bacterial and viral genomes from multiple metagenomic datasets obtained from similar environments.
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10.
  • Huang, Hongyun, et al. (author)
  • Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
  • 2018
  • In: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
  • Research review (peer-reviewed)abstract
    • Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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11.
  • Huang, Hongyun, et al. (author)
  • The 2022 yearbook of neurorestoratology
  • 2023
  • In: JOURNAL OF NEURORESTORATOLOGY. - : Tsinghua University Press. - 2324-2426. ; 11:2
  • Research review (peer-reviewed)abstract
    • There was much progress in the field of Neurorestoratology in the year of 2022. It included highlighting advances in understanding the pathogenesis of neurological diseases, neurorestorative mechanisms, and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology. There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease (AD) pathology. The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found. Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse, limited or failing bidirectional cholinergic upregulation in early cognitive impairment, or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD. Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation, immunomodulation, neurogenesis, neural network or circuitry reconstruction, neuroprotection, nervous structural repair, and neuroplasticity. Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials. However, mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke, spinal cord injury (SCI), and amyotrophic lateral sclerosis in randomized, double-blind, placebo-controlled clinical trials (RDPCTs). Clinical treatments through neurostimulation/neuromodulati on and the brain-computer/ machine interface yielded positive results in AD, Parkinson's disease, stroke, SCI, cerebral palsy, and other diseases in RDPCTs. Neurorestorative surgery, pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs. Thus, this year, additional guidelines, assessment scales, and standards were set up or revised. These included guidelines of clinical neurorestorative treatments for brain trauma (2022 China version), clinical cell therapy guidelines for neurorestoration (IANR/CANR 2022), SCI or dysfunction quality of life rating scale (SCIDQLRS) (IANR 2022 version). Neurorestorative effects of varying therapeutic stra-tegies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases. Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.
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12.
  • Sharma, Ashok K., et al. (author)
  • Prediction of peptidoglycan hydrolases- a new class of antibacterial proteins.
  • 2016
  • In: BMC Genomics. - : BioMed Central. - 1471-2164. ; 17:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The efficacy of antibiotics against bacterial infections is decreasing due to the development of resistance in bacteria, and thus, there is a need to search for potential alternatives to antibiotics. In this scenario, peptidoglycan hydrolases can be used as alternate antibacterial agents due to their unique property of cleaving peptidoglycan cell wall present in both gram-positive and gram-negative bacteria. Along with a role in maintaining overall peptidoglycan turnover in a cell and in daughter cell separation, peptidoglycan hydrolases also play crucial role in bacterial pathophysiology requiring development of a computational tool for the identification and classification of novel peptidoglycan hydrolases from genomic and metagenomic data.RESULTS: In this study, the known peptidoglycan hydrolases were divided into multiple classes based on their site of action and were used for the development of a computational tool 'HyPe' for identification and classification of novel peptidoglycan hydrolases from genomic and metagenomic data. Various classification models were developed using amino acid and dipeptide composition features by training and optimization of Random Forest and Support Vector Machines. Random Forest multiclass model was selected for the development of HyPe tool as it showed up to 71.12 % sensitivity, 99.98 % specificity, 99.55 % accuracy and 0.80 MCC in four different classes of peptidoglycan hydrolases. The tool was validated on 24 independent genomic datasets and showed up to 100 % sensitivity and 0.94 MCC. The ability of HyPe to identify novel peptidoglycan hydrolases was also demonstrated on 24 metagenomic datasets.CONCLUSIONS: The present tool helps in the identification and classification of novel peptidoglycan hydrolases from complete genomic or metagenomic ORFs. To our knowledge, this is the only tool available for the prediction of peptidoglycan hydrolases from genomic and metagenomic data.AVAILABILITY: http://metagenomics.iiserb.ac.in/hype/ and http://metabiosys.iiserb.ac.in/hype/ .
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13.
  • Sharma, Ashok K., et al. (author)
  • Woods : A fast and accurate functional annotator and classifier of genomic and metagenomic sequences
  • 2015
  • In: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 106:1, s. 1-6
  • Journal article (peer-reviewed)abstract
    • Functional annotation of the gigantic metagenomic data is one of the major time-consuming and computationally demanding tasks, which is currently a bottleneck for the efficient analysis. The commonly used homology-based methods to functionally annotate and classify proteins are extremely slow. Therefore, to achieve faster and accurate functional annotation, we have developed an orthology-based functional classifier 'Woods' by using a combination of machine learning and similarity-based approaches. Woods displayed a precision of 98.79% on independent genomic dataset, 96.66% on simulated metagenomic dataset and >97% on two real metagenomic datasets. In addition, it performed >87 times faster than BLAST on the two real metagenomic datasets. Woods can be used as a highly efficient and accurate classifier with high-throughput capability which facilitates its usability on large metagenomic datasets.
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14.
  • Sharma, Pushpa Kumari, et al. (author)
  • Adsorptive behavior of Fe/Zn-modified nanobiochar for arsenic removal from naturally contaminated groundwater
  • 2023
  • In: Groundwater for Sustainable Development. - : Elsevier BV. - 2352-801X. ; 23, s. 101011-
  • Journal article (peer-reviewed)abstract
    • Global groundwater is frequently discovered to have high arsenic (As) concentrations, critically endangered and potentially toxic to aquatic organisms and humans. This work investigates As(V) adsorption using raw nanobiochar (RnBC) and activated magnetic nanobiochar (AMnBC), which are synthesized via pre-treating rice straw biomass with ZnCl2 and FeCl3 and pyrolyzing at 500 °C, followed by ball milling. The highest adsorption capacity for AMnBC and RnBC was 130 μg/g and 38.67 μg/g, respectively, at alkaline water chemistry to mimic natural groundwater conditions. Different functional groups contributed by modifications are evident with As(V) adsorption using RnBC and AMnBC. Multilayer chemisorption may explain the adsorption of As(V) on biochar surfaces, as Freundulich isotherm and pseudo-second-order kinetic model are suggested. The synthesis cost for AMnBC and RnBC was $0.0147/g and $0.0099/g, respectively, which helped to determine the most effective and efficient method for As(V) adsorption. In this study, natural As-contaminated groundwater collected from Patna, Bihar (India), was treated for As(V) removal using AMnBC in natural environments. Thus, this study recommends that cost-effective modified biochar can effectively be used for As(V) elimination from naturally contaminated groundwater as well as surface water.
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15.
  • Sharma, Yashpal, et al. (author)
  • Fabrication of conducting electrospun nanofibers scaffold for three-dimensional cells culture
  • 2012
  • In: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 51:4, s. 627-631
  • Journal article (peer-reviewed)abstract
    • Electrospinning is a versatile method to fabricate nanofibers of a range of polymeric and composite materials suitable as scaffolds for tissue engineering applications. In this study, we report the fabrication and characterization of polyaniline-carbon nanotube/poly(N-isopropyl acrylamide-co-methacrylic acid) (PANI-CNT/PNIPAm-co-MAA) composite nanofibers and PNIPAm-co-MAA nanofibers suitable as a three-dimensional (3D) conducting smart tissue scaffold using electrospinning. The chemical structure of the resulting nanofibers was characterized with FUR and H-1 NMR spectroscopy. The surface morphology and average diameter of the nanofibers were observed by SEM. Cellular response of the nanofibers was studied with mice L929 fibroblasts. Cell viability was checked on 7th day of cell culture by double staining the cells with calcein-AM and PI dye. PANI-CNT/PNIPAm-co-MAA composite nanofibers were shown the highest cell growth and cell viability as compared to PNIPAm-co-MAA nanofibers. Cell viability in the composite nanofibers was obtained in order of 98% that indicates the composite nanofibers provide a better environment as a 3D scaffold for the cell proliferation and attachment suitable for tissue engineering applications.
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16.
  • Tiwari, Ashutosh, et al. (author)
  • Influence of poly(N-isopropylacrylamide)-CNT-polyaniline three-dimensional electrospun microfabric scaffolds on cell growth and viability
  • 2013
  • In: Biopolymers. - : John Wiley & Sons. - 0006-3525 .- 1097-0282. ; 99:5, s. 334-341
  • Journal article (peer-reviewed)abstract
    • This study investigates the effect on: 1) the bulk surface; and 2) the three-dimensional non-woven microfabric scaffolds of poly(N-isopropylacylamide)-CNT-polyaniline on growth and viability of  mice fibroblast cells L929. The poly(N-isopropylacylamide)-CNT-polyaniline was prepared using coupling chemistry and electrospinning was then used for the fabrication of responsive, nonwoven microfabric scaffolds. The electrospun microfabrics were assembled in regular three-dimensional scaffolds with OD: 400-500 mm; L: 6-20 cm. Mice fibroblast cells L929 were seeded on the both poly(N-isopropylacylamide)-CNT-polyaniline bulk surface as well as non-woven microfabric scaffolds. Excellent cell proliferation and viability was observed on poly(N-isopropylacylamide)-CNT-polyaniline non-woven microfabric matrices in compare to poly(N-isopropylacylamide)-CNT-polyaniline bulk and commercially available Matrigel™ even with a range of cell lines up to 168 h. Temperature dependent cells detachment behaviour was observed on the poly(N-isopropylacylamide)-CNT-polyaniline scaffolds by varying incubation at below lower critical solution temperature (LCST) of poly(N-isopropylacylamide). The results suggest that poly(N-isopropylacylamide)-CNT-polyaniline non-woven microfabrics could be used as a smart matrices for applications in tissue engineering.
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17.
  • Diwan, Vishal, et al. (author)
  • Understanding Healthcare Workers Self-Reported Practices, Knowledge and Attitude about Hand Hygiene in a Medical Setting in Rural India
  • 2016
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
  • Journal article (peer-reviewed)abstract
    • Aim To describe self-reported practices and assess knowledge and attitudes regarding hand hygiene among healthcare workers in a rural Indian teaching hospital. Setting A rural teaching hospital and its associated medical and nursing colleges in the district of Ujjain, India. Method The study population consisted of physicians, nurses, teaching staff, clinical instructors and nursing students. Self-administered questionnaires based on the World Health Organization Guidelines on Hand Hygiene in Healthcare were used. Results Out of 489 healthcare workers, 259 participated in the study (response rate = 53%). The proportion of healthcare workers that reported to 'always' practice hand hygiene in the selected situations varied from 40-96% amongst categories. Reported barriers to maintaining good hand hygiene were mainly related to high workload, scarcity of resources, lack of scientific information and the perception that priority is not given to hand hygiene, either on an individual or institutional level. Previous training on the topic had a statistically significant association with self-reported practice (p = 0.001). Ninety three per cent of the respondents were willing to attend training on hand hygiene in the near future. Conclusion Self-reported knowledge and adherence varied between situations, but hand hygiene practices have the potential to improve if the identified constraints could be reduced. Future training should focus on enhancing healthcare workers' knowledge and understanding regarding the importance of persistent practice in all situations.
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19.
  • Fresard, Laure, et al. (author)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Journal article (peer-reviewed)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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20.
  • Grover, Sandeep, et al. (author)
  • Replication of a Novel Parkinson's Locus in a European Ancestry Population
  • 2021
  • In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:7, s. 1689-1695
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A recently published East Asian genome-wide association study of Parkinson;s disease (PD) reported 2 novel risk loci, SV2C and WBSCR17.OBJECTIVES: The objective of this study were to determine whether recently reported novel SV2C and WBSCR17 loci contribute to the risk of developing PD in European and East Asian ancestry populations.METHODS: We report an association analysis of recently reported variants with PD in the COURAGE-PD cohort (9673 PD patients; 8465 controls) comprising individuals of European and East Asian ancestries. In addition, publicly available summary data (41,386 PD patients; 476,428 controls) were pooled.RESULTS: Our findings confirmed the role of the SV2C variant in PD pathogenesis (rs246814, COURAGE-PD PEuropean = 6.64 × 10-4 , pooled PD P = 1.15 × 10-11 ). The WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian pooled population only (P = 1.16 × 10-8 ).CONCLUSIONS: Our comprehensive study provides an up-to-date summary of recently detected novel loci in different PD populations and confirmed the role of SV2C locus as a novel risk factor for PD irrespective of the population or ethnic group analyzed. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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21.
  • Jena, Manoj Kumar, et al. (author)
  • Molecular complexity of mammary glands development : a review of lactogenic differentiation in epithelial cells
  • 2023
  • In: Artificial Cells, Nanomedicine and Biotechnology. - 2169-1401. ; 51:1, s. 491-508
  • Journal article (peer-reviewed)abstract
    • The mammary gland is a dynamic organ with various physiological processes like cellular proliferation, differentiation, and apoptosis during the pregnancy-lactation-involution cycle. It is essential to understand the molecular changes during the lactogenic differentiation of mammary epithelial cells (MECs, the milk-synthesizing cells). The MECs are organized as luminal milk-secreting cells and basal myoepithelial cells (responsible for milk ejection by contraction) that form the alveoli. The branching morphogenesis and lactogenic differentiation of the MECs prepare the gland for lactation. This process is governed by many molecular mediators including hormones, growth factors, cytokines, miRNAs, regulatory proteins, etc. Interestingly, various signalling pathways guide lactation and understanding these molecular transitions from pregnancy to lactation will help researchers design further research. Manipulation of genes responsible for milk synthesis and secretion will promote augmentation of milk yield in dairy animals. Identifying protein signatures of lactation will help develop strategies for persistent lactation and shortening the dry period in farm animals. The present review article discusses in details the physiological and molecular changes occurring during lactogenic differentiation of MECs and the associated hormones, regulatory proteins, miRNAs, and signalling pathways. An in-depth knowledge of the molecular events will aid in developing engineered cellular models for studies related to mammary gland diseases of humans and animals.
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22.
  • Joshi, Sudhir Chandra, et al. (author)
  • “How Can the Patients Remain Safe, If We Are Not Safe and Protected from the Infections”? A Qualitative Exploration among Health-Care Workers about Challenges of Maintaining Hospital Cleanliness in a Resource Limited Tertiary Setting in Rural India
  • 2018
  • In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 15:9
  • Journal article (peer-reviewed)abstract
    • Background: Health care-associated infections (HAIs) result in treatment delays as well as failures and financial losses not only to patients but also to the treating hospital and overall health-care delivery system. Due to hospital-acquired infections, there are problems of increase in morbidity and mortality, additional diagnostic and therapeutic interventions and ultimately antimicrobial resistance. Proper understanding among health-care workers about the ill effects of HAIs is very important to address this issue. The present study is a qualitative exploration aimed at understanding various aspects of hospital environmental hygiene and Infection prevention control program, by exploring the staff perception regarding the challenges, facilitators and barriers as well as feasible measures towards improvement in a rural tertiary teaching hospital in central India.Method: A qualitative study was conducted using 10 focus group discussions (FGDs) among five different professional groups, which included hospital administrators, doctors, nurses, environmental cleaning staff, and undergraduate medical students. The FGD guide included the following topics: (1) opinion about the status of cleanliness, (2) concepts and actual practices prevailing of hospital environmental hygiene, (3) Barriers, constraints, and problems in maintaining hospital environmental hygiene, (4) Suggestions for improvements. The data were analyzed manually using the content (thematic) analysis method.Results: Two themes were identified: Theme 1: “Prevailing practices and problems related to hospital surface/object contamination and hospital infection control”. Theme 2: “Measures suggested for improving hospital cleanliness within the existing constraints”. The participants emphasized the influence of resource constraints and needed inputs. They brought up the consequent prevailing practices and problems related, on one hand, to various stakeholders (service consumers, hospital personnel including the management), on the other, to specific infection prevention and control processes. They also suggested various measures for improvement.Conclusions: The study has revealed prevailing practices, problems, and suggested measures related to hospital environmental hygiene, particularly hospital cleanliness and HAI prevention and control processes. These insights and assertions are important for developing future behavioral and structural interventions in resource-limited settings. This study recommends a nationwide reliable HAI surveillance system and a robust infection prevention and control program in each health-care institution.
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23.
  • Joshi, Sudhir Chandra, et al. (author)
  • Staff Perception on Biomedical or Health Care Waste Management : A Qualitative Study in a Rural Tertiary Care Hospital in India
  • 2015
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
  • Journal article (peer-reviewed)abstract
    • Background Health care or biomedical waste, if not managed properly, can be of high risk to the hospital staff, the patients, the community, public health and the environment, especially in low and middle income settings where proper disposal norms are often not followed. Our aim was to explore perceptions of staff of an Indian rural tertiary care teaching hospital on hospital waste management. Method A qualitative study was conducted using 10 focus group discussions (FGDs), with different professional groups, cleaning staff, nurses, medical students, doctors and administrators. The FGD guide included the following topics: (i) role of Health Care Waste Management (HCWM) in prevention of health care associated infections, (ii) awareness of and views about HCWM-related guidelines/legislation, (iii) current HCWM practices, (iv) perception and preparedness related to improvements of the current practices, and (v) proper implementation of the available guidelines/legislation. The FGDs were recorded, transcribed verbatim, translated to English (when conducted in Hindi) and analysed using content analysis. Results Two themes were identified: Theme (A), 'Challenges in integration of HCWM in organizational practice,' with the categories (I) Awareness and views about HCWM, (II) Organizational practices regarding HCWM, and (III) Challenges in Implementation of HCWM; and Theme (B), 'Interventions to improve HCWM,' with three categories, (I) Educational and motivational interventions, (II) Organizational culture change, and (III) Policy-related interventions. Conclusion A gap between knowledge and actual practice regarding HCWM was highlighted in the perception of the hospital staff. The participants suggested organizational changes, training and monitoring to address this. The information generated is relevant not merely to the microsystem studied but to other institutions in similar settings.
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24.
  • Khare, Shweta, et al. (author)
  • Antibiotic Prescribing by Informal Healthcare Providers for Common Illnesses : A Repeated Cross-Sectional Study in Rural India
  • 2019
  • In: Antibiotics. - : MDPI. - 2079-6382. ; 8:3
  • Journal article (peer-reviewed)abstract
    • Informal healthcare providers (IHCPs) are predominant healthcare providers in rural India, who prescribe without formal training. Antibiotic prescription by IHCPs could provide crucial information for controlling antibiotic resistance. The aim of this study is to determine the practices and seasonal changes in antibiotic prescribing for common illnesses by IHCPs. A repeated cross-sectional study was conducted over 18 months, covering different seasons in the rural demographic surveillance site, at Ujjain, India. Prescriptions given to outpatients by 12 IHCPs were collected. In total, 15,322 prescriptions for 323 different complaint combinations were analyzed, of which 11,336 (74%) included antibiotics. The results showed that 14,620 (95%) of antibiotics prescribed were broad spectrum and the most commonly prescribed were fluoroquinolones (4771,31%), followed by penicillin with an extended spectrum (4119,27%) and third-generation cephalosporin (3069,20%). Antibiotics were prescribed more frequently in oral and dental problems (1126,88%), fever (3569,87%), and upper respiratory tract infections (3273, 81%); more during the monsoon season (2350,76%); and more frequently to children (3340,81%) than to adults (7996,71%). The study concludes that antibiotics were the more commonly prescribed drugs compared to other medications for common illnesses, most of which are broad-spectrum antibiotics, a situation that warrants further investigations followed by immediate and coordinated efforts to reduce unnecessary antibiotic prescriptions by IHCPs.
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25.
  • Khare, Shweta, et al. (author)
  • Determinants and pathways of healthcare-seeking behaviours in under-5 children for common childhood illnesses and antibiotic prescribing : a cohort study in rural India
  • 2021
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:12
  • Journal article (peer-reviewed)abstract
    • Objectives To explore the healthcare-seeking pathways, antibiotic prescribing and determine the sociodemographic factors associated with healthcare-seeking behaviour (HSB) of caregivers for common illnesses in under-5 (U-5) children in rural Ujjain, India.Study design Prospective cohort study.Study setting and study sample The cohort included 270 U-5 children from selected six villages in rural demographic surveillance site, of the R.D. Gardi Medical College, Ujjain, Madhya Pradesh, India. A community-based cohort was visited two times weekly for over 113 weeks (August 2014 to October 2016) to record the HSB of caregivers using HSB diaries. Sociodemographic information was also solicited.Primary and secondary outcome measures Primary outcomes: first point of care, healthcare-seeking pathway and quantify antibiotic prescribing for the common acute illnesses.Secondary outcome HSB risk factors were determined using mixed-effects multinomial logistic regression.Results A total of 60 228 HSB follow-up time points for 270 children were recorded with a total of 2161 acute illness episodes. The most common illnesses found were respiratory tract infections (RTI) (69%) and gastrointestinal tract infections (8%). No healthcare was sought in 33% of illness episodes, mostly for RTIs. The most common healthcare-seeking pathway was to informal healthcare providers (IHCPs, 49% of illness episodes). The adjusted relative risk for obtaining no treatment, home treatment and treatment by IHCPs was higher for RTIs (aRR=11.54, 1.82 and 1.29, respectively), illiterate mothers (aRR=2.86, 2.38 and 1.93, respectively), and mothers who were homemakers (aRR=2.90, 4.17 and 2.10, respectively). Socioeconomic status was associated with HSB, with the highest aRR for no treatment in the lowest two socioeconomic quintiles (aRR=6.59 and 6.39, respectively). Antibiotics were prescribed in 46% (n=670/1450) illness episodes and the majority (85%, n=572/670) were broad spectrum.Conclusion In our rural cohort for many acute episodes of illnesses, no treatment or home treatment was done, which resulted in overall reduced antibiotic prescribing. The most common healthcare-seeking pathway was to visit IHCPs, which indicates that they are major healthcare providers in rural areas. Most of the antibiotics were prescribed by IHCPs and were commonly prescribed for illnesses where they were not indicated.
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26.
  • Kumar, A. Naresh, et al. (author)
  • Upgrading the value of anaerobic fermentation via renewable chemicals production : A sustainable integration for circular bioeconomy
  • 2022
  • In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 806, part 1
  • Research review (peer-reviewed)abstract
    • The single bioprocess approach has certain limitations in terms of process efficiency, product synthesis, and effective resource utilization. Integrated or combined bioprocessing maximizes resource recovery and creates a novel platform to establish sustainable biorefineries. Anaerobic fermentation (AF) is a well-established process for the transformation of organic waste into biogas; conversely, biogas CO2 separation is a challenging and cost-effective process. Biological fixation of CO2 for succinic acid (SA) mitigates CO2 separation issues and produces commercially important renewable chemicals. Additionally, utilizing digestate rich in volatile fatty acid (VFA) to produce medium-chain fatty acids (MCFAs) creates a novel integrated platform by utilizing residual organic metabolites. The present review encapsulates the advantages and limitations of AF along with biogas CO2 fixation for SA and digestate rich in VFA utilization for MCFA in a closed-loop approach. Biomethane and biohydrogen process CO2 utilization for SA production is cohesively deliberated along with the role of biohydrogen as an alternative reducing agent to augment SA yields. Similarly, MCFA production using VFA as a substrate and function of electron donors namely ethanol, lactate, and hydrogen are comprehensively discussed. A road map to establish the fermentative biorefinery approach in the framework of AF integrated sustainable bioprocess development is deliberated along with limitations and factors influencing for techno-economic analysis. The discussed integrated approach significantly contributes to promote the circular bioeconomy by establishing carbon-neutral processes in accord with sustainable development goals.
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27.
  • Kumar, Rakesh, et al. (author)
  • Co-transport and deposition of fluoride using rice husk-derived biochar in saturated porous media : Effect of solution chemistry and surface properties
  • 2023
  • In: Environmental Technology & Innovation. - : Elsevier BV. - 2352-1864. ; 30
  • Journal article (peer-reviewed)abstract
    • Fluoride (F-) contamination in water is a global health concern, threatening the well-being of millions. This study investigated the role of ZnCl2/FeCl3-rice husk-modified biochar (Zn-BC and Zn/Fe-BC) in treating F--contaminated surface and groundwater under the influence of varying solution chemistry, co-existing ions, and biochar-amended through column transport experiments. Modified biochar showed maximum F- adsorp-tion, 99.01% and 91.90% using Zn/Fe-BC and Zn-BC, respectively, than 85.87% using raw biochar (R-BC). Raw/modified biochars were characterized with FESEM-EDAX, FTIR, XRD, particle size, surface area, electro-kinetic potential, and point of zero charge analyses. Langmuir and pseudo-second-order kinetic could explain that F--biochar interactions are dominated by chemisorption at ambient temperature while physisorption at higher temperatures. The influence of salt concentrations and co-occurring ions reduced F- sorption using Zn/Fe-BC. Increased salt strengths led to reduced electrophoretic mobility of biochar particles, i.e., biochar-biochar particles attract each other and increase the hydrodynamic diameter, which ultimately reduces the active sites on biochar for F- adsorption. Co-transport and deposition of biochar and F- in saturated porous media revealed lower mobility of biochar, and maximum F- adsorption was observed at 10 mM salt strength. Biochar transport is governed by electrostatic interactions, whereas F- transport mainly occurs through chemisorption. In rural areas, hand pumps and tube wells are generally used as source of potable water for drinking and cooking purposes; thus, biochar-mediated sand columns can be utilized for defluoridation. Thus, Zn/Fe-BC can be utilized as a potential bio-adsorbent for F--contaminated natural surface and groundwater with optimum preparation and treatment costs.
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28.
  • Kumar, Rakesh, et al. (author)
  • Micro(nano)plastics pollution and human health : How plastics can induce carcinogenesis to humans?
  • 2022
  • In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 298, s. 134267-
  • Journal article (peer-reviewed)abstract
    • Microplastics (MPs) and nanoplastics (NPs) are key indicators of the plasticine era, widely spread across different ecosystems. MPs and NPs become global stressors due to their inherent physicochemical characteristics and potential impact on ecosystems and humans. MPs and NPs have been exposed to humans via various pathways, such as tap water, bottled water, seafood, beverages, milk, fish, salts, fruits, and vegetables. This paper highlights MPs and NPs pathways to the food chains and how these plastic particles can cause risks to human health. MPs have been evident in vivo and vitro and have been at health risks, such as respiratory, immune, reproductive, and digestive systems. The present work emphasizes how various MPs and NPs, and associated toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), impact human health. Polystyrene (PS) and polyvinyl chloride (PVC) are common MPs and NPs, reported in human implants via ingestion, inhalation, and dermal exposure, which can cause carcinogenesis, according to Agency for Toxic Substances and Disease Registry (ATSDR) reports. Inhalation, ingestion, and dermal exposure-response cause genotoxicity, cell division and viability, cytotoxicity, oxidative stress induction, metabolism disruption, DNA damage, inflammation, and immunological responses in humans. Lastly, this review work concluded with
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29.
  • Lundborg, Cecilia Stalsby, et al. (author)
  • Protocol : a 'One health' two year follow-up, mixed methods study on antibiotic resistance, focusing children under 5 and their environment in rural India
  • 2015
  • In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15
  • Journal article (peer-reviewed)abstract
    • Background: Antibiotic resistance has been referred to as 'the greatest malice of the 21st century' and a global action plan was adopted by the World Health Assembly in 2015. There is a wealth of independent studies regarding antibiotics and resistant bacteria in humans, animals and their environment, however, integrated studies are lacking, particularly ones that simultaneously also take into consideration the health related behaviour of participants and healthcare providers. Such, 'One health' studies are difficult to implement, because of the complex teamwork that they entail. This paper describes the protocol of a study that investigates 'One health' issues regarding antibiotic use and antibiotic resistance in children and their environment in Indian villages. Methods/Design: Both quantitative and qualitative studies are planned for a cohort of children, from 6 villages, and their surrounding environment. Repeated or continues data collection is planned over 2 years for quantitative studies. Qualitative studies will be conducted once. Studies include parents' health seeking behavior for their children (1-3 years of age at the onset), prescribing pattern of formal and informal healthcare providers, analysis of phenotypic antibiotic resistance of Escherichia coli from samples of stool from children and village animals, household drinking water, village source water and waste water, and investigation on molecular mechanisms governing resistance. Analysis of interrelationship of these with each other will also be done as basis for future interventions. Ethics approval has been obtained from the Institutional Ethics Committee R.D. Gardi Medical College, Ujjain, India (No: 2013/07/17-311). Discussion: The findings of the study presented in this protocol will add to our knowledge about the multi-factorial nature of causes governing antibiotic use and antibiotic resistance from a 'One health' perspective. Our study will be the first of its kind addressing antibiotic use and resistance issues related to children in a One-health approach, particularly for rural India.
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30.
  • Lundgren, Markus, et al. (author)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Journal article (peer-reviewed)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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31.
  • Mungai, Isaac Gikandi, et al. (author)
  • Identifying the know-do gap in evidence-based neonatal care practices among informal health care providers-a cross-sectional study from Ujjain, India
  • 2020
  • In: BMC Health Services Research. - : BMC. - 1472-6963. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background More than a quarter of global neonatal deaths are reported from India, and a large proportion of these deaths are preventable. However, in the absence of robust public health care systems in several states in India, informal health care providers (IHCPs) with no formal medical education are the first contact service providers. The aim of this study was to assess the knowledge of IHCPs in basic evidence-based practices in neonatal care in Ujjain district and investigated factors associated with differences in levels of knowledge. Methods A cross-sectional survey was conducted using a questionnaire with multiple-choice questions covering the basic elements of neonatal care. The total score of the IHCPs was calculated. Multivariate quantile regression model was used to look for association of IHCPs knowledge score with: the practitioners' age, years of experience, number of patients treated per day, and whether they attended children in their practice. Results Of the 945 IHCPs approached, 830 (88%) participated in the study. The mean +/- SD score achieved was 22.3 +/- 7.7, with a median score of 21 out of maximum score of 48. Although IHCPs could identify key tenets of enhancing survival chances of neonates, they scored low on the specifics of cord care, breastfeeding, vitamin K use to prevent neonatal hemorrhage, and identification and care of low-birth-weight babies. The practitioners particularly lacked knowledge about neonatal resuscitation, and only a small proportion reported following up on immunizations. Results of quantile regression analysis showed that more than 5 years of practice experience and treating more than 20 patients per day had a statistically significant positive association with the knowledge score at higher quantiles (q75(th) and q90th) only. IHCPs treating children had significantly better scores across quantiles accept at the highest quantile (90(th)). Conclusions The present study highlighted that know-do gap exists in evidence-based practices for all key areas of neonatal care tested among the IHCPs. The study provides the evidence that some IHCPs do possess knowledge in basic evidence-based practices in neonatal care, which could be built upon by future educational interventions. Targeting IHCPs can be an innovative way to reach a large rural population in the study setting and to improve neonatal care services.
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32.
  • Nadda, Ashok Kumar, et al. (author)
  • Chemistry of CO2-phillic materials in enzyme-based hybrid interfacial systems : Implications, strategies and applications
  • 2023
  • In: Fuel processing technology. - : Elsevier BV. - 0378-3820 .- 1873-7188. ; 250
  • Journal article (peer-reviewed)abstract
    • Carbon dioxide (CO2) emissions from a variety of sources, such as transportation, fossil fuel burning, and cement manufacturing facilities, are widely regarded to be the root cause of global warming. The rising CO2 levels call for immediate improvements in CO2 capture, extraction, and utilization technology. Methods for capturing and converting CO2 into useful products have included the use of microbial enzymes, nonporous materials, metal -organic frameworks (MOFs), chemicals, and hybrid membranes. However, these methods possess limitations that make the scale up and commercialization challenging. Scientists are concentrating on maximizing CO2 utilization by incorporating CO2-philic components into enzyme-chemical-material combinations, due to the high solubility of CO2. Here, the focus is on the chemistry of CO2-phillic materials, enzymes and biomolecules engaged in CO2 conversion, and the hybrid micro-reactors that contain material and enzymes integrating together to convert the CO2 into value-added products (organic acids, bioelectricity, carbonates, carbamates, methane, methanol, etc.). The difficulties and obstacles inherent in creating and sustaining such systems have also been highlighted.
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33.
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34.
  • Sharma, Ashok, et al. (author)
  • Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort
  • 2016
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3, s. 0152476-0152476
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prospective cohort study.METHODS: A total of 424,788 newborns from the US and European general populations and first-degree relatives with type 1 diabetes were screened for specific HLA genotypes. Of these, 21,589 carried 1 of the 9 HLA genotypes associated with increased risk for type 1 diabetes and celiac disease; we followed 8676 of the children in a 15 y prospective follow-up study. Genotype analyses were performed on 6010 children using the Illumina ImmunoChip. Levels of tTGA were measured in serum samples using radio-ligand binding assays; diagnoses of celiac disease were made based on persistent detection of tTGA and biopsy analysis. Data were analyzed using Cox proportional hazards analyses.RESULTS: We found 54 single-nucleotide polymorphisms (SNPs) in 5 genes associated with celiac disease (TAGAP, IL18R1, RGS21, PLEK, and CCR9) in time to celiac disease analyses (10-4>P>5.8x10-6). The hazard ratios (HR) for the SNPs with the smallest P values in each region were 1.59, 1.45, 2.23, 2.64, and 1.40, respectively. Outside of regions previously associated with celiac disease, we identified 10 SNPs in 8 regions that could also be associated with the disease (P<10-4). A SNP near PKIA (rs117128341, P = 6.5x10-8, HR = 2.8) and a SNP near PFKFB3 (rs117139146, P<2.8x10-7, HR = 4.9) reached the genome-wide association threshold in subjects from Sweden. Analyses of time to detection of tTGA identified 29 SNPs in 2 regions previously associated with celiac disease (CTLA4, P = 1.3x10-6, HR = 0.76 and LPP, P = 2.8x10-5, HR = .80) and 6 SNPs in 5 regions not previously associated with celiac disease (P<10-4); non-HLA genes are therefore involved in development of tTGA.CONCLUSIONS: In conclusion, using a genetic analysis of a large international cohort of children, we associated celiac disease development with 5 non-HLA regions previously associated with the disease and 8 regions not previously associated with celiac disease. We identified 5 regions associated with development of tTGA. Two loci associated with celiac disease progression reached a genome-wide association threshold in subjects from Sweden.
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35.
  • Sharma, Ashok, et al. (author)
  • Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort
  • 2018
  • In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 89, s. 90-100
  • Journal article (peer-reviewed)abstract
    • Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip. Cox proportional hazards analyses were performed to discover the SNPs associated with the risk for IA, T1D, or both. Three regions were associated with the risk of developing any persistent confirmed islet autoantibody: one known region near SH2B3 (HR = 1.35, p = 3.58 × 10-7) with Bonferroni-corrected significance and another known region near PTPN22 (HR = 1.46, p = 2.17 × 10-6) and one novel region near PPIL2 (HR = 2.47, p = 9.64 × 10-7) with suggestive evidence (p < 10-5). Two known regions (PTPN22: p = 2.25 × 10-6, INS; p = 1.32 × 10-7) and one novel region (PXK/PDHB: p = 8.99 × 10-6) were associated with the risk for multiple islet autoantibodies. First appearing islet autoantibodies differ with respect to association. Two regions (INS: p = 5.67 × 10-6 and TTC34/PRDM16: 6.45 × 10-6) were associated if the fist appearing autoantibody was IAA and one region (RBFOX1: p = 8.02 × 10-6) was associated if the first appearing autoantibody was GADA. The analysis of T1D identified one region already known to be associated with T1D (INS: p = 3.13 × 10-7) and three novel regions (RNASET2, PLEKHA1, and PPIL2; 5.42 × 10-6 > p > 2.31 × 10-6). These results suggest that a number of low frequency variants influence the risk of developing IA and/or T1D and these variants can be identified by large prospective cohort studies using a survival analysis approach.
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36.
  • Sharma, L Ajitkumar, et al. (author)
  • Molecular magnetic properties of two-copper(II) containing complexes [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)(2)(2+) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)](2) - An EPR study
  • 2004
  • In: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier BV. - 1386-1425 .- 1873-3557. ; 60:7, s. 1593-1600
  • Journal article (peer-reviewed)abstract
    • Electron paramagnetic resonance (EPR) investigations were conducted on [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)12 21 (1) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)](2) (2) respectively, in the temperature range 300-77 K. Fine structure characteristics of S = 1 system, was observed in both complexes with zero field splitting of 0.0525 and 0.0225 cm(-1), respectively, suggesting the formation of dimeric complexes. The presence of the half-field signal (DeltaM(s)= +/-2), in the complex 1, further confirmed the formation of dimer. The temperature dependence of EPR signal intensity has given evidence for the ferromagnetic (FM) coupling between the two Cu2+ ions. The isotropic exchange interaction constants J, were evaluated from this and were found out to be similar to57 and similar to27 cm(-1), respectively, for the complexes I and 2. The photoacoustic spectra of these complexes had shown a band around 26,400 cm(-1) characteristic of metal-metal bonding giving an independent support for the existence of dimeric Cu2+ species. The high magnetic moment values at room temperature for complex I (2.68mu(B)) and complex 2 (2.00mu(B)), obtained from the magnetic susceptibility measurements, support the formation of ferromagnetically coupled Cu2+ dimers.
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37.
  • Sharma, Suchinder, 1982, et al. (author)
  • Understanding the Reasons for Variations in Luminescence Sensitivity of Natural Quartz Using Spectroscopic and Chemical Studies
  • 2017
  • In: Proceedings of the Indian National Science Academy. - : Indian National Science Academy. - 0370-0046. ; 83:3, s. 645-653
  • Journal article (peer-reviewed)abstract
    • Natural quartz from diverse provenances exhibit variations in their luminescence sensitivity (photon flux/mg.Gy) that span over ten orders of magnitude. A range of factors (such as crystallization/recrystallization process, irradiation, thermal and optical history) that modify luminescence sensitivity have been considered to explain such differences in luminescence sensitivity. However, a clearly definable/identifiable reason is still awaited; such as, these large variations in luminescence sensitivity are related to commonly occurring luminescence quenchers/enhancers in natural quartz lattice. Towards this, quartz mineral grains extracts from different provenances and from varied depositional environments were examined spectroscopically using Fourier Transform infra-red spectroscopy (FTIR), optically stimulated luminescence (OSL), photoluminescence (PL), time resolved PL (TRPL) decay, thermoluminescence (TL) and the trace element analysis. The present study exhibited an anti-correlation between OSL sensitivity and water content in quartz (estimated through integrated intensity of normalized FTIR signal in the wave number region 3000-3600 cm(-1)), such that a sensitivity change of over 5 orders of magnitude corresponded to a change in integrated water absorption signal by 5 times, but in opposite direction. PL and TRPL results enabled further insights.
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38.
  • Törn, Carina, et al. (author)
  • Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
  • 2016
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Journal article (peer-reviewed)abstract
    • A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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