Publications by authors named "Satya Prakash"

377 Publications

Outcomes of multisystem inflammatory syndrome in children temporally related to COVID-19: a longitudinal study.

Rheumatol Int 2021 Oct 19. Epub 2021 Oct 19.

All India Institute of Medical Sciences, New Delhi, India.

To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.
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http://dx.doi.org/10.1007/s00296-021-05030-yDOI Listing
October 2021

Synthesis and characterization of peptide conjugated human serum albumin nanoparticles for targeted cardiac uptake and drug delivery.

PLoS One 2021 30;16(9):e0254305. Epub 2021 Sep 30.

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Montreal, QC, Canada.

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483410PMC
September 2021

Dissecting the genetic history of the Roman Catholic populations of West Coast India.

Hum Genet 2021 Oct 23;140(10):1487-1498. Epub 2021 Aug 23.

CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 500007, India.

Migration and admixture history of populations have always been curious and an interesting theme. The West Coast of India harbours a rich diversity, bestowing various ethno-linguistic groups, with many of them having well-documented history of migrations. The Roman Catholic is one such distinct group, whose origin was much debated. While some historians and anthropologists relating them to ancient group of Gaud Saraswat Brahmins, others relating them for being members of the Jews Lost Tribes in the first Century migration to India. Historical records suggests that this community was later forcibly converted to Christianity by the Portuguese in Goa during the Sixteenth Century. Till date, no genetic study was done on this group to infer their origin and genetic affinity. Hence, we analysed 110 Roman Catholics from three different locations of West Coast of India including Goa, Kumta and Mangalore using both uniparental and autosomal markers to understand their genetic history. We found that the Roman Catholics have close affinity with the Indo-European linguistic groups, particularly Brahmins. Additionally, we detected genetic signal of Jews in the linkage disequilibrium-based admixture analysis, which was absent in other Indo-European populations, who are inhabited in the same geographical regions. Haplotype-based analysis suggests that the Roman Catholics consist of South Asian-specific ancestry and showed high drift. Ancestry-specific historical population size estimation points to a possible bottleneck around the time of Goan inquisition (fifteenth century). Analysis of the Roman Catholics data along with ancient DNA data of Neolithic and bronze age revealed that the Roman Catholics fits well in a basic model of ancient ancestral composition, typical of most of the Indo-European caste groups of India. Mitochondrial DNA (mtDNA) analysis suggests that most of the Roman Catholics have aboriginal Indian maternal genetic ancestry; while the Y chromosomal DNA analysis indicates high frequency of R1a lineage, which is predominant in groups with higher ancestral North Indian (ANI) component. Therefore, we conclude that the Roman Catholics of Goa, Kumta and Mangalore regions are the remnants of very early lineages of Brahmin community of India, having Indo-Europeans genetic affinity along with cryptic Jewish admixture, which needs to be explored further.
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http://dx.doi.org/10.1007/s00439-021-02346-4DOI Listing
October 2021

Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy.

Genes Dev 2021 Sep 12;35(17-18):1256-1270. Epub 2021 Aug 12.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA.

Chemotherapy with cisplatin becomes limiting due to toxicity and secondary malignancies. In principle, therapeutics could be improved by targeting translesion synthesis (TLS) polymerases (Pols) that promote replication through intrastrand cross-links, the major cisplatin-induced DNA adduct. However, to specifically target malignancies with minimal adverse effects on normal cells, a good understanding of TLS mechanisms in normal versus cancer cells is paramount. We show that in normal cells, TLS through cisplatin intrastrand cross-links is promoted by Polη- or Polι-dependent pathways, both of which require Rev1 as a scaffolding component. In contrast, cancer cells require Rev1-Polζ. Our findings that a recently identified Rev1 inhibitor, JH-RE-06, purported to specifically disrupt Rev1 interaction with Polζ to block TLS through cisplatin adducts in cancer cells, abrogates Rev1's ability to function with Y family Pols as well, implying that by inactivating Rev1-dependent TLS in normal cells, this inhibitor will exacerbate the toxicity and tumorigenicity of chemotherapeutics with cisplatin.
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http://dx.doi.org/10.1101/gad.348662.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415319PMC
September 2021

Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure.

Pharmaceuticals (Basel) 2021 Jul 19;14(7). Epub 2021 Jul 19.

Department of Biomedical Engineering, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.

Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetics with a mean retention time of 123.7 min, half-life of 101.3 min, and clearance rate of 0.24 L/(kg*h). The targeted formulation also significantly improved ejection fraction and fractional shortening parameters thus improving cardiac function. This study demonstrates a new approach in delivering inotropic drugs such as milrinone for superior treatment of congestive heart failure.
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http://dx.doi.org/10.3390/ph14070697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308836PMC
July 2021

Physicochemical controls on the initiation of phytoplankton bloom during the winter monsoon in the Arabian Sea.

Sci Rep 2021 06 29;11(1):13448. Epub 2021 Jun 29.

Indian National Centre for Ocean Information Services, Ministry of Earth Sciences, Government of India, Hyderbad, 500090, India.

Occurrence of phytoplankton bloom in the northern Arabian Sea (NAS) during the winter monsoon is perplexing. The convective mixing leads to a deeper and well-oxygenated (> 95% saturation) mixed layer. We encountered low chlorophyll conditions though the nutrient conditions were favorable for a bloom. The mean ratio of silicate (Si) to DIN (Dissolved Inorganic Nitrogen: nitrate + nitrite + ammonium) in the euphotic zone was 0.52 indicating a "silicate-stressed" condition for the proliferation of diatoms. Also, the euphotic depth was much shallower (~ 49 m) than the mixed layer (~ 110 m) suggesting the Sverdrup critical depth limitation in the NAS. We show that the bloom in this region initiates only when the mixed layer shoals towards the euphotic zone. Our observations further suggest that two primary factors, the stoichiometric ratio of nutrients, especially the Si/DIN ratio, in the mixed layer and re-stratification of the upper water column, govern the phytoplankton blooming in NAS during the later winter monsoon. The important finding of the present study is that the Sverdrup's critical depth limitation gives rise to the observed low chl-a concentration in the NAS, despite having enough nutrients.
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http://dx.doi.org/10.1038/s41598-021-92897-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242075PMC
June 2021

Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.

Nat Commun 2021 06 29;12(1):4020. Epub 2021 Jun 29.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3'-terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3'-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.
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http://dx.doi.org/10.1038/s41467-021-24317-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241999PMC
June 2021

DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ.

J Biol Chem 2021 07 10;297(1):100868. Epub 2021 Jun 10.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address:

In a previous study, we showed that replication through the N1-methyl-deoxyadenosine (1-MeA) adduct in human cells is mediated via three different Polι/Polθ, Polη, and Polζ-dependent pathways. Based on biochemical studies with these Pols, in the Polι/Polθ pathway, we inferred a role for Polι in the insertion of a nucleotide (nt) opposite 1-MeA and of Polθ in extension of synthesis from the inserted nt; in the Polη pathway, we inferred that this Pol alone would replicate through 1-MeA; in the Polζ pathway, however, the Pol required for inserting an nt opposite 1-MeA had remained unidentified. In this study, we provide biochemical and genetic evidence for a role for Polλ in inserting the correct nt T opposite 1-MeA, from which Polζ would extend synthesis. The high proficiency of purified Polλ for inserting a T opposite 1-MeA implicates a role for Polλ-which normally uses W-C base pairing for DNA synthesis-in accommodating 1-MeA in a syn confirmation and forming a Hoogsteen base pair with T. The potential of Polλ to replicate through DNA lesions by Hoogsteen base pairing adds another novel aspect to Polλ's role in translesion synthesis in addition to its role as a scaffolding component of Polζ. We discuss how the action mechanisms of Polλ and Polζ could be restrained to inserting a T opposite 1-MeA and extending synthesis thereafter, respectively.
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http://dx.doi.org/10.1016/j.jbc.2021.100868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260881PMC
July 2021

Baculoviruses in Gene Therapy and Personalized Medicine.

Biologics 2021 28;15:115-132. Epub 2021 Apr 28.

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, H3A 2B4, Canada.

This review will outline the role of baculoviruses in gene therapy and future potential in personalized medicine. Baculoviruses are a safe, non-toxic, non-integrative vector with a large cloning capacity. Baculoviruses are also a highly adaptable, low-cost vector with a broad tissue and host tropism due to their ability to infect both quiescent and proliferating cells. Moreover, they only replicate in insect cells, not mammalian cells, improving their biosafety. The beneficial properties of baculoviruses make it an attractive option for gene delivery. The use of baculoviruses in gene therapy has advanced significantly, contributing to vaccine production, anti-cancer therapies and regenerative medicine. Currently, baculoviruses are primarily used for recombinant protein production and vaccines.  This review will also discuss methods to optimize baculoviruses protein production and mammalian cell entry, limitations and potential for gene therapy and personalized medicine. Limitations such as transient gene expression, complement activation and virus fragility are discussed in details as they can be overcome through further genetic modifications and other methods. This review concludes that baculoviruses are an excllent candidate for gene therapy, personalized medicine and other biotherapeutic applications.
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http://dx.doi.org/10.2147/BTT.S292692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088983PMC
April 2021

Variable response to therapeutic plasma exchange in pediatric anti-NMDA receptor encephalitis.

Transfus Clin Biol 2021 Aug 8;28(3):287-290. Epub 2021 Apr 8.

Department of Transfusion Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. Electronic address:

Introduction: Anti-NMDA receptor encephalitis in an acute form generally presents with abnormal movements and psychiatric symptoms. Therapeutic plasma exchange has been considered to be one of the first line treatment options. This report highlights the role of plasma exchange in anti-NMDA receptor encephalitis in pediatric patients.

Methods: This is a retrospective analysis of four cases of a severe form of encephalitis due to anti-NMDA receptor antibody. All these four patients were evaluated for clinical and laboratory profile before plasma exchange. Plasma exchange was performed with Cobe Spectra Version 7.0(Terumo BCT, USA), and 5% albumin and fresh frozen plasma were used as replacement fluid.

Results: A total of 20 procedures (range: 2-8/patient) were performed on four patients on an alternate day basis. Slow recovery and long-term hospitalization (range: 25-70 days) was observed in all these patients and may be due to delayed initiation of plasma exchange. One patient was lost in follow up while another one had fatal consequences after one month of discharge from the hospital.

Conclusion: Early diagnosis and timely initiation of therapeutic plasma exchange along with immunosuppressive therapy hasten the recovery, duration of hospitalization and yield a better outcome.
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http://dx.doi.org/10.1016/j.tracli.2021.03.006DOI Listing
August 2021

Challenges and actions to the environmental management of Bio-Medical Waste during COVID-19 pandemic in India.

Heliyon 2021 Mar 19;7(3):e06313. Epub 2021 Feb 19.

Centre for Ecological Economics and Natural Resources (CEENR), Institute for Social and Economic Change (ISEC), Nagarabhavi, Bangalore 560 072, India.

The outbreak of COVID-19 has engendered a global health crisis along with diverse impacts on economy, society and environment. Efforts to combat this pandemic have also significantly shot-up the quantity of Bio-medical Waste (BMW) generation. Safe disposal of large quantity of BMW has been gradually posing a major challenge. BMW management is mostly implemented at municipal level following regulatory guidelines defined by respective states and the Union. This article is a narrative of the status of BMW generation, management and regulation in India in the context of COVID-19 crisis. The article is based on comparative analysis of data on BMW generation and management from authentic sources, a systematic literature review and review of news reports. In the current pandemic situation where media has been playing a significant role in highlighting all the concerns related to COVID-19 spread and management. Assessing the ground situation regarding effectiveness of prevailing BMW management facilities, requirement and suggestions can provide insights to the subject with policy implications for India and countries as well. The discussion has been built on different dimensions of BMW management during the pandemic including existing infrastructures, capacity utilisation, policy guidelines, operational practices and waste-handlers aspects. The results on state-wise analysis of reported BMW quantity and active COVID-19 patients also reveal some non-linear relationship between the two variables. Delhi, the National Capital is situated at a better position in terms of BMW management as compared to other studied states. The findings are expected to provide valuable insights to the policy makers and other relevant authorities to evaluate adequateness as well as efficiency quotients of entire BMW management landscape. Some of the critical observations of this article are also expected to offer impetus for enhancing national disaster preparedness in future.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962757PMC
March 2021

Loss and Reappearance of A Antigen After Chemotherapy Leading to Blood Group Discrepancy in Acute Myeloid Leukemia: A Case Report.

Lab Med 2021 Sep;52(5):509-513

Department of Transfusion Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.

A male patient aged 11 years diagnosed with acute myeloid leukemia presented with complaints of fever, lethargy, and bleeding manifestations. On ordering red blood cells and platelet transfusion, his blood group was tested. Blood group discrepancy was observed in that forward grouping showed the O Rh D positive blood group and reverse grouping revealed the A Rh D positive. The patient's previous blood group record was O Rh D positive, and he had a transfusion history of O Rh D positive red blood cells and platelets in other hospital. Initial immunohematological workup results, including adsorption and heat elution, were consistent with the O Rh D-positive blood group, but further workups on follow-up after the commencement of chemotherapy showed that his original blood group was A Rh D positive, in which the A antigen expression was previously masked by the underlying disease condition of the patient. Hence, the correlation of laboratory results with clinical details and case history is an essential step in resolving such blood group discrepancies.
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http://dx.doi.org/10.1093/labmed/lmab008DOI Listing
September 2021

Nanoparticles in the Food Industry and Their Impact on Human Gut Microbiome and Diseases.

Int J Mol Sci 2021 Feb 16;22(4). Epub 2021 Feb 16.

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.

The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher's ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases.
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http://dx.doi.org/10.3390/ijms22041942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920074PMC
February 2021

Brassica juncea leaf cuticle proteome analysis shows myrosinase protein, antifreeze activity, and post-translationally modified secretory proteins.

Plant Physiol Biochem 2021 Apr 19;161:234-247. Epub 2021 Feb 19.

Molecular Physiology and Proteomics Laboratory, Department of Botany, University of Delhi, Delhi, 110007, India. Electronic address:

Plant cuticle, the site of perception of stress signals, is an extracellular hydrophobic barrier that covers the epidermis of the above-ground parts. This lipidic layer has been explored for its cutin and wax composition. However, reports on the cuticle proteins are scanty. Therefore, leaf cuticle proteins of Brassica juncea isolated using organic solvents (chloroform-methanol, 2:1(v/v)) were analyzed using gel based and quantitative shotgun proteomics. Out of 615 proteins identified, 27% (169) had signal peptides supporting extracellular localization. Bioinformatics tool, QuickGO predicted the involvement of these proteins in catabolism (21%), peptidase activity (13%), oxidoreductase (12%), defense response (9%), fatty acid binding (9%), nutrient reservoir activity (8%), chitin binding (7%) and lipid transport (2%). Myrosinase-catalyzed glucosinolate hydrolysis releases bioactive compounds, which contribute to plant defense. This system is termed as "mustard oil bomb". Myrosinase and its associating protein, GDSL esterase/lipase ESM1 (involved in cuticle structuring and defense) were detected in the cuticle. GDSL-esterase/lipase ESM1 and β-glucanase (an antifreeze protein) showed in vitro activity. Analysis of cuticle extract by nanoliter osmometer-phase contrast microscopy detected antifreeze activity due to non-protein component. Post-translational modification analysis using PTM viewer predicted N-glycosylation (66%), N-terminal proteolysis (40%), and phosphorylation (32%) to be the dominant modification in the classical secretory proteins. N-glycosylation of myrosinase and GDSL esterase/lipase, ESM1 was confirmed by Con A affinoblotting. This study not only identified leaf cuticle proteins, but also laid the foundation for exploring the extracellular glucosinolate-myrosinase system, PTM crosstalk, and antifreeze activity as stress adaptive strategies in B. juncea.
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http://dx.doi.org/10.1016/j.plaphy.2021.02.012DOI Listing
April 2021

Centrifugal Therapeutic Plasma Exchange in Pediatric Patients.

Indian J Pediatr 2021 08 2;88(8):757-763. Epub 2021 Feb 2.

Department of Transfusion Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Objective: To assess the safety of centrifugal therapeutic plasma exchange (TPE) in pediatric patients.

Methods: The authors did a retrospective analysis of all TPE procedures performed in pediatric patients over a period of 19 y (2001-2019). Procedures were done on different apheretic devices, daily or on alternate days depending on the clinical condition of the patient. Adverse events during the procedure were noted and analyzed.

Results: A total of 672 TPE (with mean of 6.77 ± 4.85) procedures were performed for 99 pediatric patients with different indications like hematological (n = 68), renal (n = 12), neurology (n = 18) and hepatology (n = 1). The mean age was 7.00 ± 3.11 y and weight was 20.72 ± 9.17 kg. Adverse events (AEs) were observed during 34 (5%) procedures, most common were allergic reactions to replacement fluid (2.24%) followed by hypotension (1.04%), symptomatic hypocalcemia (1.04%), line occlusion (0.59%), and febrile non hemolytic transfusion reaction (0.41%). A significant correlation of AEs was observed with weight (p = 0.045), total blood volume of the patient (p = 0.04), increasing number of procedures (p = 0.000) and replacement fluid [Fresh frozen plasma (FFP)] (p = 0.04). All AEs were managed as per departmental standard operating procedures (SOPs) completing procedures successfully except one which was abandoned. No mortality was observed during the procedures.

Conclusion: TPE is a safe therapeutic modality in pediatric patients when performed under expert technical supervision with proper SOPs in place.
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http://dx.doi.org/10.1007/s12098-020-03657-6DOI Listing
August 2021

A novel role of DNA polymerase λ in translesion synthesis in conjunction with DNA polymerase ζ.

Life Sci Alliance 2021 04 29;4(4). Epub 2021 Jan 29.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA

By extending synthesis opposite from a diverse array of DNA lesions, DNA polymerase (Pol) ζ performs a crucial role in translesion synthesis (TLS). In yeast and cancer cells, Rev1 functions as an indispensable scaffolding component of Polζ and it imposes highly error-prone TLS upon Polζ. However, for TLS that occurs during replication in normal human cells, Rev1 functions instead as a scaffolding component of Pols η, ι, and κ and Rev1-dependent TLS by these Pols operates in a predominantly error-free manner. The lack of Rev1 requirement for Polζ function in TLS in normal cells suggested that some other protein substitutes for this Rev1 role. Here, we identify a novel role of Polλ as an indispensable scaffolding component of Polζ. TLS studies opposite a number of DNA lesions support the conclusion that as an integral component, Polλ adapts Polζ-dependent TLS to operate in a predominantly error-free manner in human cells, essential for genome integrity and cellular homeostasis.
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http://dx.doi.org/10.26508/lsa.202000900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898466PMC
April 2021

The Microbiome and Alzheimer's Disease: Potential and Limitations of Prebiotic, Synbiotic, and Probiotic Formulations.

Front Bioeng Biotechnol 2020 14;8:537847. Epub 2020 Dec 14.

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, QC, Canada.

The Microbiome has generated significant attention for its impacts not only on gastrointestinal health, but also on signaling pathways of the enteric and central nervous system via the microbiome gut-brain axis. In light of this, microbiome modulation may be an effective therapeutic strategy for treating or mitigating many somatic and neural pathologies, including neurodegenerative disorders. Alzheimer's disease (AD) is a chronic neurodegenerative disease that interferes with cerebral function by progressively impairing memory, thinking and learning through the continuous depletion of neurons. Although its etiopathogenesis remains uncertain, recent literature endorses the hypothesis that probiotic, prebiotic and synbiotic supplementation alters AD-like symptoms and improves many of its associated disease biomarkers. Alternatively, a dysfunctional microbiota impairs the gut epithelial barrier by inducing chronic gastric inflammation, culminating in neuroinflammation and accelerating AD progression. The findings in this review suggest that probiotics, prebiotics or synbiotics have potential as novel biological prophylactics in treatment of AD, due to their anti-inflammatory and antioxidant properties, their ability to improve cognition and metabolic activity, as well as their capacity of producing essential metabolites for gut and brain barrier permeability.
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http://dx.doi.org/10.3389/fbioe.2020.537847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771210PMC
December 2020

Tn Red cell polyagglutination in a healthy blood donor: A case report.

Transfus Apher Sci 2021 Feb 24;60(1):103013. Epub 2020 Nov 24.

All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. Electronic address:

Introduction: Polyagglutination is a rare entity in immunohematology and unusually presents in a healthy blood donor. The general presentation was described in the literature in association with bacterial infections, which result in the exposure of crypt antigens. Nowadays, polyagglutination is rarely detected due to the use of monoclonal antisera. Our case report describes the presence of Tn polyagglutination in a healthy adult blood donor with no prior history of any infection in the recent past.

Methods: Immunohematology work-up for incompatible cross-match was done in the serology lab using commercially procured antisera and column agglutination gel card (Tulip Diagnostics India Pvt. Ltd, Goa, India). The three cell-screening panel was procured commercially (ID Dia cell I, II, III; Bio-Rad, Switzerland), and in-house lectin was prepared as per the standard method.

Result: We have come across a case of incompatible cross-match with negative antibody screen, auto-control, and Negative direct coombs test. Cross-match with multiple adult serum and cord serum gives us a clue towards polyagglutination. Further, Polyagglutination was confirmed serologically using anti-A1 lectin and later concludes of Tn type by lectin prepared in-house from Salvia Sclarea.

Conclusion: Resolution of incompatible cross-match in a case of polyagglutination needs a skilled workforce and rare reagents. Identification of reason for incompatibility helps in an early issue of blood units.
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http://dx.doi.org/10.1016/j.transci.2020.103013DOI Listing
February 2021

A baseline investigation of phytoplankton pigment composition in contrasting coastal ecosystems of north-western Bay of Bengal.

Mar Pollut Bull 2020 Nov 25;160:111708. Epub 2020 Sep 25.

Department of Marine Sciences, Berhampur University, Ganjam 760007, India.

A baseline investigation of the chromatographic characterization of phytoplankton pigments with complementing microscopy was conducted in Mahanadi estuary, Chilika lagoon, and coastal waters off Gopalpur along the east coast of India. Marker pigments specific to different phytoplankton groups have been discerned in these contrasting coastal ecosystems. A total of 16 phytoplankton pigments were identified. Irrespective of seasons, Chilika lagoon was characterized by a high concentration of zeaxanthin, indicating the predominance of picocyanobacteria. Zeaxanthin and fucoxanthin were the major diagnostic pigments in Mahanadi estuary during monsoon and other seasons, respectively. In coastal waters off Gopalpur, algal blooms resulted in a higher concentration of fucoxanthin during pre-monsoon and monsoon season. The pigment ratios were comparatively higher for Chilika lagoon than for Mahanadi estuary and off Gopalpur, irrespective of seasons. The present study highlights the advantages of the chromatography technique in identifying small-sized phytoplankton in coastal ecosystems in comparison to conventional microscopy.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111708DOI Listing
November 2020

A review of the clinical applications of ketamine in pediatric oncology.

Pediatr Blood Cancer 2021 01 31;68(1):e28785. Epub 2020 Oct 31.

Division of Pediatric Oncology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Ketamine is a dissociative anesthetic agent with excellent analgesic properties and a favorable safety profile. The feasibility and efficacy of various routes of administration have been established, including intravenous (IV), intramuscular (IM), oral, intranasal, rectal, and transdermal routes. The advent of newer anesthetic agents has led to a decline in the use of ketamine as an anesthetic, but its utility in short-term sedation and analgesia has expanded. Its value for chronic pain management in children with cancer is being increasingly recognized but requires more evidence. The use of topical ketamine is largely in investigational stages. Medical use of ketamine is, to a great extent, free from significant long-term neurological side effects. The objective of this review is to provide a brief account of the pharmacology of ketamine and primarily focus on the clinical applications of ketamine in pediatric oncology.
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http://dx.doi.org/10.1002/pbc.28785DOI Listing
January 2021

Comparison of medication acceptance of intranasal midazolam administered by parents versus doctors in children - A randomized trial.

Indian J Pharmacol 2020 Jul-Aug;52(4):254-259

Department of Anaesthesiology and CC, JIPMER, Puducherry, India.

Background: The positive effects of midazolam as a premedication in pediatric patients are well documented. Although there are many studies regarding the route and dosage of administration, literature does not have any evidence on the outcome of medication acceptance based on the person administering the drug.

Aim: The aim of this study was to compare the medication acceptance and preoperative anxiolysis of intranasal midazolam administered by parents and anesthesiologists.

Materials And Methods: This prospective randomized study was conducted in sixty children belonging to the American Society of Anesthesiologists Class 1 or 2 belonging to either sex, aged between 1 and 9 years, undergoing elective surgeries. Group P received intranasal midazolam administered by parents, whereas Group D received intranasal midazolam administered by doctors. Various scores were assessed.

Results: Children were more sedated in Group P. Clinically, medication acceptance was better in Group P when compared with Group D, but a statistically significant difference in medication acceptance was seen only in patients who are >4 years of age. Parental separation, Ramsay Sedation Score, and mask acceptance were better in Group P than in Group D.

Conclusion: Intranasal midazolam when given by parents produces better preoperative anxiolysis and easier parental separation as compared with administration by a medical staff.
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http://dx.doi.org/10.4103/ijp.IJP_418_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722905PMC
October 2021

Polymeric Microspheres Containing Human Vocal Fold Fibroblasts for Vocal Fold Regeneration.

Laryngoscope 2021 08 17;131(8):1828-1834. Epub 2020 Oct 17.

Department of Mechanical Engineering, Faculty of Engineering, McGill University, Montreal, Quebec, Canada.

Objective: Most acellular injectable biomaterials for vocal fold (VF) wound treatment have limited regenerative potential due to their fast enzymatic degradation and limited recruitment of native cells postinjection. The injection of cells as therapeutic treatment often results in apoptosis due to stresses within the needle and the immune response of the host. Degradable microspheres may improve treatment effectiveness by increasing cell residence time, shielding cells during injection, and offering early protection against the immune system response. The objective of the present study was to investigate the potential of human VF fibroblasts encapsulated in polymeric microspheres as an injectable therapeutic treatment in vitro.

Methods: Alginate, alginate-poly-L-lysine, and alginate-chitosan microspheres were fabricated using electrospraying and characterized in terms of biocompatibility, swelling, and mechanical properties as well as cytokine production.

Results: Alginate microspheres were found to have the most desirable properties for VF regeneration. They were resistant to mechanical challenges. They were found to have a stiffness similar to that reported for native VF-lamina propria. They were found to be biocompatible and increased the proliferation of fibroblasts. Human VF fibroblasts encapsulated in alginate microspheres induced the production of interleukin (IL)-8 and IL-4 at 24 hours.

Conclusion: The alginate microspheres fabricated in this study were found to offer potential advantages, as cell delivery tool. This study highlights the importance of combining biomaterials and cells to expedite the wound-healing process through cytokine production. Future work is aimed to further analysis of the wound-healing properties the microspheres.

Level Of Evidence: NA Laryngoscope, 131:1828-1834, 2021.
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http://dx.doi.org/10.1002/lary.29118DOI Listing
August 2021

Blink detection and magnetic force generation for correction of lagophthalmos, with specific regard to implant compatibility testing.

Orbit 2020 Oct 3:1-10. Epub 2020 Oct 3.

Department of Ophthalmology and Visual Sciences, McGill University Health Center, Montreal, Quebec, Canada.

Purpose: The overall goal was to restore a normal and synchronous blink in unilateral lagophthalmos. We describe the biocompatibility profiling of a novel ferromagnetic implant used for electromagnetic eyelid force generation.

Methods: A non-contact blink detection system and an electromagnetic stimulation system were designed and tested. A modified Lester-Burch speculum equipped with strain gauge technology was used in blinking force measurement. Samarium-cobalt magnets were prototyped and coated with parylene-C. Biocompatibility testing was performed using NIH/3T3 mouse fibroblast cells with MTT colorimetric assay cytotoxic quantification.

Outcome Measures: Cellular viability and interleukin concentrations.

Results: Our system was capable of detecting 95.5 ± 3.6% of blinks in various lighting conditions. Using our force measuring device, the difference between non-paralyzed and paralyzed orbicularis oculi (OO) for normal and forceful blinking closure was 40.4 g and 101.9 g, respectively. A 16.6 × 5.0 × 1.5 mm curved shaped samarium cobalt eyelid implant was successfully developed and showed a reproducible blink at 100 ms with full corneal coverage with external eyelid taping. Compared to gold weights, parylene-C coated samarium cobalt implants showed not only excellent cell viability (82.0 ± 4.9% vs. 88.4 ± 0.9%, respectively, .05), but also below detection threshold for pro-inflammatory marker concentrations (interleukin-6 < 2 pg/mL and interleukin-10 < 3 pg/mL).

Conclusions: We demonstrated excellent biocompatibility of our parylene-C coated samarium cobalt implants. We believe that our novel approach can improve the quality-of-life of affected individuals and provides new understanding of blinking biomechanics.
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http://dx.doi.org/10.1080/01676830.2020.1826544DOI Listing
October 2020

Comment on "Delayed adverse events in male plateletpheresis donors: Initial insights on donor safety".

J Clin Apher 2021 02 24;36(1):221-222. Epub 2020 Sep 24.

Department of Transfusion Medicine, All India Institute of Medical Sciences, Bhubaneswar, India.

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http://dx.doi.org/10.1002/jca.21837DOI Listing
February 2021

Standoff pump-probe photothermal detection of hazardous chemicals.

Sci Rep 2020 09 14;10(1):15053. Epub 2020 Sep 14.

Banaras Hindu University, Varanasi, 221005, India.

A novel pump-probe Photothermal methodology using Quartz Tuning Fork (QTF) detector has been demonstrated for the first time. A tunable mid-IR Quantum Cascade Laser (QCL) and a CW fixed wavelength visible laser have been used as the pump and probe beam respectively. The developed Photothermal (PT) technique is based on Quartz Tuning Fork (QTF) detector for the detection of hazardous/explosive molecules adsorbed on plastic surface and also in aerosols form. PT spectra of various trace molecules in the fingerprinting mid- infrared spectral band 7-9 µm from distance of 25 m have been recorded. The PT spectra of explosives RDX, TNT and Acetone have been recorded at very low quantities. Acetone is the precursor of explosive Tri-Acetone Tri-Phosphate (TATP). The experimentations using pump and probe lasers, exhibit detection sensitivity of less than 5 μg/cm for RDX, TNT powders and of ~ 200 nl quantity for Nitrobenzene (NB) and Acetone (in liquid form) adsorbed on surfaces, from a distance of ~ 25 m. The sensitivity of the same order achieved from a distance of 15 m by using only a mid-IR tunable pump laser coupled to QTF detector. Thus the pump-probe PT technique is more sensitive in comparison to single tunable QCL pump beam technique and it is better suited for standoff detection of hazardous chemicals for homeland security as well as for forensic applications.
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http://dx.doi.org/10.1038/s41598-020-71937-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490358PMC
September 2020

Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.

Nat Struct Mol Biol 2020 10 17;27(10):913-924. Epub 2020 Aug 17.

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

DNA polymerase ζ (Polζ) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 Å) and without DNA (4.1 Å). Polζ displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31' Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein-protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Polζ's role in TLS and provide a framework for new cancer therapeutics.
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http://dx.doi.org/10.1038/s41594-020-0476-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554088PMC
October 2020

Does laparoscopic hernia repair affect the vascularity of testis?

J Family Med Prim Care 2020 May 31;9(5):2465-2468. Epub 2020 May 31.

Department of General Surgery, AIIMS Jodhpur, Jodhpur, Rajasthan, India.

Context: Laparoscopic hernia repair, despite its safety and effectivity is related to some drawbacks. Testicular complications are uncommon but serious among them. Testicular atrophy occurs in 0% to 2% of patients after hernioplasty.

Aim: In this study, we tried to evaluate the effects of laparoscopic total extraperitoneal (TEP) repair on testicular blood flow in Indian population by comparing the testicular perfusion in preoperative and postoperative status.

Settings And Design: A prospective study.

Subjects And Methods: A prospective study was conducted among adult male patients having an uncomplicated inguinal hernia. Preoperative and postoperative CDUS evaluation of testicular blood flow was done for each patient.

Statistical Analysis Used: Data were analyzed using the SPSS (SPSS, Chicago, IL, USA) software program.

Results: The resistive indexes of testicular, capsular, and intratesticular arteries of the operated and nonoperated side were similar preoperatively and did not differ ominously postoperatively.

Conclusion: Laparoscopic hernia surgery does not have any significant effect on testicular blood supply and can be advocated safely without any added risk of testicular atrophy.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_203_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380808PMC
May 2020

Ketamine mouthwash versus placebo in the treatment of severe oral mucositis pain in children with cancer: A randomized double-blind placebo-controlled trial.

Pediatr Blood Cancer 2020 09 10;67(9):e28573. Epub 2020 Jul 10.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Background And Aims: Oral mucositis (OM) is a common and distressing toxicity in children on chemotherapy. There are a limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in a few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children.

Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/mL solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events.

Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (P = 0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (P = 1.000). No significant adverse events were observed.

Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.
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http://dx.doi.org/10.1002/pbc.28573DOI Listing
September 2020

Microbial Medicine: Prebiotic and Probiotic Functional Foods to Target Obesity and Metabolic Syndrome.

Int J Mol Sci 2020 Apr 21;21(8). Epub 2020 Apr 21.

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.

Obesity has become a global epidemic and a public health crisis in the Western World, experiencing a threefold increase in prevalence since 1975. High-caloric diets and sedentary lifestyles have been identified as significant contributors to this widespread issue, although the role of genetic, social, and environmental factors in obesity's pathogenesis remain incompletely understood. In recent years, much attention has been drawn to the contribution of the gut microbiota in the development of obesity. Indeed, research has shown that in contrast to their healthier counterparts the microbiomes of obese individuals are structurally and functionally distinct, strongly suggesting microbiome as a potential target for obesity therapeutics. In particular, pre and probiotics have emerged as effective and integrative means of modulating the microbiome, in order to reverse the microbial dysbiosis associated with an obese phenotype. The following review brings forth animal and human research supporting the myriad of mechanisms by which the microbiome affects obesity, as well as the strengths and limitations of probiotic or prebiotic supplementation for the prevention and treatment of obesity. Finally, we set forth a roadmap for the comprehensive development of functional food solutions in combatting obesity, to capitalize on the potential of pre/probiotic therapies in optimizing host health.
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http://dx.doi.org/10.3390/ijms21082890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215979PMC
April 2020

Organocatalytic asymmetric addition of thioglycolates to o-quinone methides: a route to 5-substituted-5H-benzoxathiepine-2(3H)-ones.

Org Biomol Chem 2020 04;18(15):2828-2833

Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam 781039, India.

Herein we have developed the first enantioselective synthesis of 5-substituted-5H-benzoxathiepine-2(3H)-ones. 2-Sulfonylmethyl phenols and thioglycolates were employed as reaction partners in this method. The desired thia Michael products were obtained via bifunctional squaramide catalyzed conjugate addition reaction to in situ generated o-quinone methides and then basic hydrolysis followed by cyclization led to the formation of 5-substituted-5H-benzoxathiepine-2(3H)-ones. Broad scope and moderate to high enantioselectivities were observed for both products.
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http://dx.doi.org/10.1039/d0ob00568aDOI Listing
April 2020
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