Publications by authors named "Anup Singh"

256 Publications

Geographic tongue.

CMAJ 2021 Sep;193(36):E1424

Department of Otolaryngology and Head and Neck Surgery (Prasanth, Singh), Andaman and Nicobar Islands Institute of Medical Sciences, Port Blair, India

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http://dx.doi.org/10.1503/cmaj.202855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443279PMC
September 2021

A prospective observational safety study on ChAdOx1 nCoV-19 corona virus vaccine (recombinant) use in healthcare workers- first results from India.

EClinicalMedicine 2021 Aug 23;38:101038. Epub 2021 Jul 23.

Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.

Background: We provide the first post-approval safety analysis of COVISHIELD in health care workers (HCWs) in northern India.

Methods: This continuing prospective observational study (February 2021 to May 2022) enrolled participants ≥18 years receiving COVISHIELD vaccination. Primary outcome was safety and reactogenicity. Categories (FDA toxicity grading) and outcomes of adverse events following immunization (AEFIs) were recorded, causality assessment performed, and risk factors analysed.

Findings: We present the results of an interim analysis of 804 participants. AEFIs following first dose were reported in 321 (40%; systemic involvement in 248). Among 730 participants who completed a 7-day follow-up post second dose, AEFIs occurred in 115 (15.7%; systemic in 99). Majority of AEFIs were mild-moderate and resolved spontaneously. Serious AEFIs, leading to hospitalization was noticed in 1 (0.1%) participant with suspicion of immunization stress related response (ISRR). AEFIs of grade 3 severity (FDA) were recorded in 4 participants (0.5%). No deaths were recorded. Regression analysis showed increased risk of AEFIs in younger individuals, a two times higher odds in females, those with hypertension or with history of allergy; and three times higher odds in individuals with hypothyroidism.

Interpretation: COVISHIELD carries an overall favourable safety profile with AEFI rates much less than reported for other adenoviral vaccines. Females, those with hypertension, individuals with history of allergy and hypothyroidism may need watchful vaccine administration. This being an interim analysis and based on healthcare workers who may not reflect the general population demographics, larger inclusive studies are warranted for confirming the findings.

Funding: No funding support.
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http://dx.doi.org/10.1016/j.eclinm.2021.101038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413251PMC
August 2021

Editorial for "Analysis of MR Signs to Distinguish Between ARCO Stages 2 and 3A in Osteonecrosis of the Femoral Head".

Authors:
Anup Singh

J Magn Reson Imaging 2021 Sep 3. Epub 2021 Sep 3.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

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http://dx.doi.org/10.1002/jmri.27916DOI Listing
September 2021

Unusual cause of recalcitrant epistaxis.

BMJ Case Rep 2021 Aug 16;14(8). Epub 2021 Aug 16.

Department of Otorhinolaryngology and Head & Neck Surgery, Medanta - The Medicity, Gurugram, Haryana, India.

Nosebleeds are among the most familiar presentations to the emergency department as well as otorhinolaryngologic outpatient services. Bleeding from nasal septal branches of the anterior ethmoid artery (AEA) is common and can be effectively controlled endoscopically. However, the bleeding from a pseudoaneurysm involving the nasal septal branches of AEA is extremely rare and can be troublesome to control using endoscopic methods. We report an adult patient presenting with profuse nasal bleeding postroad traffic accident due to the formation of AEA septal branch pseudoaneurysm. The patient required repeated nasal packing, and the diagnosis was revealed using digital subtraction angiography. Since profuse active bleeding precluded endoscopic visualisation, an external approach had to be adopted to ligate the AEA to control the bleeding. We discuss the management options and nuances for this rare cause of the troublesome nasal bleeding.
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http://dx.doi.org/10.1136/bcr-2021-244231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370496PMC
August 2021

Plant single-cell solutions for energy and the environment.

Commun Biol 2021 08 12;4(1):962. Epub 2021 Aug 12.

Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

Progress in sequencing, microfluidics, and analysis strategies has revolutionized the granularity at which multicellular organisms can be studied. In particular, single-cell transcriptomics has led to fundamental new insights into animal biology, such as the discovery of new cell types and cell type-specific disease processes. However, the application of single-cell approaches to plants, fungi, algae, or bacteria (environmental organisms) has been far more limited, largely due to the challenges posed by polysaccharide walls surrounding these species' cells. In this perspective, we discuss opportunities afforded by single-cell technologies for energy and environmental science and grand challenges that must be tackled to apply these approaches to plants, fungi and algae. We highlight the need to develop better and more comprehensive single-cell technologies, analysis and visualization tools, and tissue preparation methods. We advocate for the creation of a centralized, open-access database to house plant single-cell data. Finally, we consider how such efforts should balance the need for deep characterization of select model species while still capturing the diversity in the plant kingdom. Investments into the development of methods, their application to relevant species, and the creation of resources to support data dissemination will enable groundbreaking insights to propel energy and environmental science forward.
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http://dx.doi.org/10.1038/s42003-021-02477-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361165PMC
August 2021

Device for Assessing Knee Joint Dynamics During Magnetic Resonance Imaging.

J Magn Reson Imaging 2021 Aug 9. Epub 2021 Aug 9.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

Background: Knee assessment with and without load using magnetic resonance imaging (MRI) can provide information on knee joint dynamics and improve the diagnosis of knee joint diseases. Performing such studies on a routine MRI-scanner require a load-exerting device during scanning. There is a need for more studies on developing loading devices and evaluating their clinical potential.

Purpose: Design and develop a portable and easy-to-use axial loading device to evaluate the knee joint dynamics during the MRI study.

Study Type: Prospective study.

Subjects: Nine healthy subjects.

Field Strength/sequence: A 0.25 T standing-open MRI and 3.0 T MRI. PD-T -weighted FSE, 3D-fast-spoiled-gradient-echo, FS-PD, and CartiGram sequences.

Assessment: Design and development of loading device, calibration of loads, MR safety assessment (using projectile angular displacement, torque, and temperature tests). Scoring system for ease of doing. Qualitative (by radiologist) and quantitative (using structural similarity index measure [SSIM]) image-artifact assessment. Evaluation of repeatability, comparison with various standing stances load, and loading effect on knee MR parameters (tibiofemoral bone gap [TFBG], femoral cartilage thickness [FCT], tibial cartilage thickness [TCT], femoral cartilage T -value [FCT2], and tibia cartilage T -value [TCT2]). The relative percentage change (RPC) in parameters due to the device load was computed.

Statistical Test: Pearson's correlation coefficient (r).

Results: The developed device is conditional-MR safe (details in the manuscript and supplementary materials), 15 × 15 × 45 cm dimension, and <3 kg. The ease of using the device was 4.9/5. The device introduced no visible image artifacts, and SSIM of 0.9889 ± 0.0153 was observed. The TFBG intraobserver variability (absolute difference) was <0.1 mm. Interobserver variability of all regions of interest was <0.1 mm. The load exerted by the device was close to the load during standing on both legs in 0.25 T scanner with r > 0.9. Loading resulted in RPC of 1.5%-11.0%, 7.9%-8.5%, and -1.5% to 13.0% in the TFBG, FCT, and TCT, respectively. FCT2 and TCT2 were reduced in range of 1.5-2.7 msec and 0.5-2.3 msec due to load.

Data Conclusion: The proposed device is conditionally MR safe, low cost (material cost < INR 6000), portable, and effective in loading the knee joint with up to 50% of body weight.

Evidence Level: 1 TECHNICAL EFFICACY: Stage 1.
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http://dx.doi.org/10.1002/jmri.27877DOI Listing
August 2021

Microfabrication of a Chamber for High-Resolution, In Situ Imaging of the Whole Root for Plant-Microbe Interactions.

Int J Mol Sci 2021 Jul 23;22(15). Epub 2021 Jul 23.

Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Fabricated ecosystems (EcoFABs) offer an innovative approach to in situ examination of microbial establishment patterns around plant roots using nondestructive, high-resolution microscopy. Previously high-resolution imaging was challenging because the roots were not constrained to a fixed distance from the objective. Here, we describe a new 'Imaging EcoFAB' and the use of this device to image the entire root system of growing at high resolutions (20×, 40×) over a 3-week period. The device is capable of investigating root-microbe interactions of multimember communities. We examined nine strains of with different fluorescent constructs to . and individual cells on root hairs were visible. Succession in the rhizosphere using two different strains of was examined, where the second addition was shown to be able to establish in the root tissue. The device was suitable for imaging with different solid media at high magnification, allowing for the imaging of fungal establishment in the rhizosphere. Overall, the Imaging EcoFAB could improve our ability to investigate the spatiotemporal dynamics of the rhizosphere, including studies of fluorescently-tagged, multimember, synthetic communities.
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http://dx.doi.org/10.3390/ijms22157880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348081PMC
July 2021

A comprehensive evaluation and impact of normalization of generalized tracer kinetic model parameters to characterize blood-brain-barrier permeability in normal-appearing and tumor tissue regions of patients with glioma.

Magn Reson Imaging 2021 Nov 24;83:77-88. Epub 2021 Jul 24.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India; Department of Biomedical Engineering, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Rationale And Objectives: To comprehensively evaluate robustness and variations of DCE-MRI derived generalized-tracer-kinetic-model (GTKM) parameters in healthy and tumor tissues and impact of normalization in mitigating these variations on application to glioma.

Materials (patients) And Methods: A retrospective study included pre-operative 31 high-grade-glioma(HGG), 22 low-grade-glioma(LGG) and 33 follow-up data from 10 patients a prospective study with 4 HGG subjects. Voxel-wise GTKM was fitted to DCE-MRI data to estimate K, v, v. Simulations were used to evaluate noise sensitivity. Variation of parameters with-respect-to arterial-input-function (AIF) variation and data length were studied. Normalization of parameters with-respect-to mean values in gray-matter (GM) and white-matter (WM) regions (GM-Type-2, WM-Type-2) and mean curves (GM-Type-1, WM-Type-1) were also evaluated. Co-efficient-of-variation(CoV), relative-percentage-error (RPE), Box-Whisker plots, bar graphs and t-test were used for comparison.

Results: GTKM was fitted well in all tissue regions. K and v in contrast-enhancing (CE) has shown improved noise sensitivity in longer data. v was reliable in all tissues. Mean AIF and C(t) peaks showed ~38% and ~35% variations. During simulation, normalizations have mitigated variations due to changes in AIF amplitude in K and v. v was less sensitive to normalizations. CoV of K and v has reduced ~70% after GM-Type-1 normalization and ~80% after GM-Type-2 normalization, respectively. GM-Type-1 (p = 0.003) and GM-Type-2 (p = 0.006) normalizations have significantly improved differentiation of HGG and LGG using K.

Conclusion: K and v can be reliably estimated in normal-appearing brain tissues and can be used for normalization of corresponding parameters in tumor tissues for mitigating inter-subject variability due to errors in AIF. Normalized K and v provided improved differentiation of HGG and LGG.
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http://dx.doi.org/10.1016/j.mri.2021.07.005DOI Listing
November 2021

Model for in-vivo estimation of stiffness of tibiofemoral joint using MR imaging and FEM analysis.

J Transl Med 2021 07 19;19(1):310. Epub 2021 Jul 19.

Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, New Delhi, 110016, India.

Background: Appropriate structural and material properties are essential for finite-element-modeling (FEM). In knee FEM, structural information could extract through 3D-imaging, but the individual subject's tissue material properties are inaccessible.

Purpose: The current study's purpose was to develop a methodology to estimate the subject-specific stiffness of the tibiofemoral joint using finite-element-analysis (FEA) and MRI data of knee joint with and without load.

Methods: In this study, six Magnetic Resonance Imaging (MRI) datasets were acquired from 3 healthy volunteers with axially loaded and unloaded knee joint. The strain was computed from the tibiofemoral bone gap difference (ΔmBGFT) using the knee MR images with and without load. The knee FEM study was conducted using a subject-specific knee joint 3D-model and various soft-tissue stiffness values (1 to 50 MPa) to develop subject-specific stiffness versus strain models.

Results: Less than 1.02% absolute convergence error was observed during the simulation. Subject-specific combined stiffness of weight-bearing tibiofemoral soft-tissue was estimated with mean values as 2.40 ± 0.17 MPa. Intra-subject variability has been observed during the repeat scan in 3 subjects as 0.27, 0.12, and 0.15 MPa, respectively. All subject-specific stiffness-strain relationship data was fitted well with power function (R = 0.997).

Conclusion: The current study proposed a generalized mathematical model and a methodology to estimate subject-specific stiffness of the tibiofemoral joint for FEM analysis. Such a method might enhance the efficacy of FEM in implant design optimization and biomechanics for subject-specific studies. Trial registration The institutional ethics committee (IEC), Indian Institute of Technology, Delhi, India, approved the study on 20th September 2017, with reference number P-019; it was a pilot study, no clinical trail registration was recommended.
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http://dx.doi.org/10.1186/s12967-021-02977-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287773PMC
July 2021

Characterization of Arsenic-Resistant Klebsiella pneumoniae RnASA11 from Contaminated Soil and Water Samples and Its Bioremediation Potential.

Curr Microbiol 2021 Aug 7;78(8):3258-3267. Epub 2021 Jul 7.

Department of Agricultural Microbiology, College of Agriculture, Indira Gandhi Krishi Viswavidyalaya, Raipur, CG, India.

Rapid industrialization and intensive agriculture activities have led to a rise in heavy metal contamination all over the world. Chhattisgarh (India) being an industrial state, the soil and water are thickly contaminated with heavy metals, especially from arsenic (As). In the present study, we isolated 108 arsenic-resistant bacteria (both from soil and water) from different arsenic-contaminated industrial and mining sites of Chhattisgarh to explore the bacterial gene pool. Further, we screened 24 potential isolates out of 108 for their ability to tolerate a high level of arsenic. The sequencing of the 16S rRNA gene of bacterial isolates revealed that all these samples belong to different diverse genera including Bacillus, Enterobacter, Klebsiella, Pantoea, Acinetobacter, Cronobacter, Pseudomonas and Agrobacterium. The metal tolerance ability was determined by amplification of arsB (arsenite efflux gene) and arsC (arsenate reductase gene) from chromosomal DNA of isolated RnASA11, which was identified as Klebsiella pneumoniae through in silico analysis. The bacterial strains RpSWA2 and RnASA11 were found to tolerate 600 mM As (V) and 30 mM As (III) but the growth of strain RpSWA2 was slower than RnASA11. Furthermore, atomic absorption spectroscopy (AAS) of the sample obtained from bioremediation assay revealed that Klebsiella pneumoniae RnASA11 was able to reduce the arsenic concentration significantly in the presence of arsenate (44%) and arsenite (38.8%) as compared to control.
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http://dx.doi.org/10.1007/s00284-021-02602-wDOI Listing
August 2021

A multiplexed nanostructure-initiator mass spectrometry (NIMS) assay for simultaneously detecting glycosyl hydrolase and lignin modifying enzyme activities.

Sci Rep 2021 Jun 3;11(1):11803. Epub 2021 Jun 3.

Joint BioEnergy Institute, Emeryville, CA, 94608, USA.

Lignocellulosic biomass is composed of three major biopolymers: cellulose, hemicellulose and lignin. Analytical tools capable of quickly detecting both glycan and lignin deconstruction are needed to support the development and characterization of efficient enzymes/enzyme cocktails. Previously we have described nanostructure-initiator mass spectrometry-based assays for the analysis of glycosyl hydrolase and most recently an assay for lignin modifying enzymes. Here we integrate these two assays into a single multiplexed assay against both classes of enzymes and use it to characterize crude commercial enzyme mixtures. Application of our multiplexed platform based on nanostructure-initiator mass spectrometry enabled us to characterize crude mixtures of laccase enzymes from fungi Agaricus bisporus (Ab) and Myceliopthora thermophila (Mt) revealing activity on both carbohydrate and aromatic substrates. Using time-series analysis we determined that crude laccase from Ab has the higher GH activity and that laccase from Mt has the higher activity against our lignin model compound. Inhibitor studies showed a significant reduction in Mt GH activity under low oxygen conditions and increased activities in the presence of vanillin (common GH inhibitor). Ultimately, this assay can help to discover mixtures of enzymes that could be incorporated into biomass pretreatments to deconstruct diverse components of lignocellulosic biomass.
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http://dx.doi.org/10.1038/s41598-021-91181-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175421PMC
June 2021

Unusual cause of dysphagia and dysphonia.

BMJ Case Rep 2021 Jun 2;14(6). Epub 2021 Jun 2.

Department of Otorhinolaryngology and Head and Neck Surgery, Medanta The Medicity, Gurgaon, Haryana, India.

Forestier's disease is an idiopathic noninflammatory condition associated with enthesopathy leading to hyperostosis of the vertebrae and peripheral skeletal system. The disease tends to affect elderly individuals and remains asymptomatic in most of the cases. Uncommonly, the patient may present with upper aerodigestive symptomatology, usually dysphagia. In elderly individuals, the disease may closely mimic upper aerodigestive tract malignancy, which should be actively excluded. In our patient, the hypopharyngeal soft tissue distortions created by the bony hypertrophy shifted the clinicoradiological suspicion towards malignant pathology. The current case presents the diagnostic dilemma associated with the disease and the need to keep the possibility of severe cervical bony hypertrophy as a cause of upper aerodigestive symptoms in mind.
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http://dx.doi.org/10.1136/bcr-2021-243060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174514PMC
June 2021

A semi-automatic framework based upon quantitative analysis of MR-images for classification of femur cartilage into asymptomatic, early OA, and advanced-OA groups.

J Orthop Res 2021 May 31. Epub 2021 May 31.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

To develop a semi-automatic framework for quantitative analysis of biochemical properties and thickness of femur cartilage using magnetic resonance (MR) images and evaluate its potential for femur cartilage classification into asymptomatic (AS), early osteoarthritis (OA), and advanced OA groups. In this study, knee joint MRI data (fat suppressed-proton density-weighted and multi-echo T2-weighted images) of eight AS-volunteers (data acquired twice) and 34 OA patients including 20 early OA (16 Grade-I and 4 Grade-II), 14 advanced-OA (Grade-III) were acquired at 3.0T MR scanner. Modified Outerbridge classification criteria was performed for the clinical evaluation of data by an experienced radiologist. Cartilage segmentation, T2-mapping, 2D-WearMap generation, and subregion analysis were performed semi-automatically using in-house developed algorithms. The intraclass correlation coefficient (ICC) and coefficient of variation (CV) were computed for testing the reproducibility of T2 values. One-way analysis of variance with Tukey-Kramer post hoc test was performed for evaluating the differences among the groups. The performance of individual T2 and thickness, as well as their combination using logistic regression, were evaluated with receiver operating characteristics (ROC) curve analysis. The interscan agreement based on the ICC index was 0.95 and the CV was 2.45 ± 1.33%. T2 mean of values greater than 75th percentile showed sensitivity and specificity of 94.1% and 81.3% (AUC = 0.93, cut-off value = 47.9 ms) in differentiating AS volunteers versus OA group, while sensitivity and specificity of 90.0% and 81.3% (AUC = 0.90, cut-off value = 47.9 ms) in differentiating AS volunteers versus early OA groups, respectively. In the differentiation of early OA versus advanced-OA group, ROC results of combination (T2 and thickness) showed the highest sensitivity and specificity of 85.7%, and 70.0% (AUC = 0.79, cut-off value = 0.39) compared with individual T2 and thickness features, respectively. A computer-aided quantitative evaluation of femur cartilage degeneration showed promising results and can be used to assist clinicians in diagnosing OA.
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http://dx.doi.org/10.1002/jor.25109DOI Listing
May 2021

Sinonasal polyposis complicated with extradural abscess and lateral rectus palsy.

BMJ Case Rep 2021 May 26;14(5). Epub 2021 May 26.

ENT & Head and neck surgery, All India Institute of Medical Sciences, New Delhi, India.

Sinogenic intracranial and orbital complications are infrequent complications of chronic rhinosinusitis with nasal polyposis (CRSwNP), leading to potentially fatal intracranial and orbital sequelae. The mortality and morbidity associated with these complications remain high despite the widespread use of antibiotics. We report a patient with CRSwNP presenting with acute onset extradural empyema and sixth nerve palsy in whom the diagnosis was delayed, necessitating early surgical intervention. Our case shows that delay in management and underdiagnosis of sinusitis with nasal polyposis can lead to devastating complications. A high index of suspicion, early recognition of the clinical findings and radiological evaluation with contrast-enhanced CT of paranasal sinuses, orbit and brain are essential to rule out fatal complications associated with CRSwNP. Timely endoscopic intervention and the use of antibiotics can lead to good outcomes, even in complicated cases.
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http://dx.doi.org/10.1136/bcr-2021-242667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160177PMC
May 2021

Worsening anasarca on a child with severe steroid-dependent nephrotic syndrome without proteinuria: Answers.

Pediatr Nephrol 2021 May 25. Epub 2021 May 25.

Department of Pediatrics, Monmouth Medical Center, Long Branch, NJ, USA.

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http://dx.doi.org/10.1007/s00467-021-05124-6DOI Listing
May 2021

Worsening anasarca on a child with severe steroid-dependent nephrotic syndrome without proteinuria: Questions.

Pediatr Nephrol 2021 May 25. Epub 2021 May 25.

Department of Pediatrics, Monmouth Medical Center, Long Branch, NJ, USA.

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http://dx.doi.org/10.1007/s00467-021-05109-5DOI Listing
May 2021

CXCR4 intracellular protein promotes drug resistance and tumorigenic potential by inversely regulating the expression of Death Receptor 5.

Cell Death Dis 2021 05 8;12(5):464. Epub 2021 May 8.

Division of Cancer Biology, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.

Chemokine receptor CXCR4 overexpression in solid tumors has been strongly associated with poor prognosis and adverse clinical outcome. However, blockade of CXCL12-CXCR4 signaling axis by inhibitors like Nox-A12, FDA approved CXCR4 inhibitor drug AMD3100 have shown limited clinical success in cancer treatment. Therefore, exclusive contribution of CXCR4-CXCL12 signaling in pro-tumorigenic function is questionable. In our pursuit to understand the impact of chemokine signaling in carcinogenesis, we reveal that instead of CXCR4-CXCL12 signaling, presence of CXCR4 intracellular protein augments paclitaxel resistance and pro-tumorigenic functions. In search of pro-apoptotic mechanisms for CXCR4 mediated drug resistance; we discover that DR5 is a new selective target of CXCR4 in breast and colon cancer. Further, we detect that CXCR4 directs the differential recruitment of transcription factors p53 and YY1 to the promoter of DR5 in course of its transcriptional repression. Remarkably, inhibiting CXCR4-ligand-mediated signals completely fails to block the above phenotype. Overexpression of different mutant versions of CXCR4 lacking signal transduction capabilities also result in marked downregulation of DR5 expression in colon cancer indeed confirms the reverse relationship between DR5 and intracellular CXCR4 protein expression. Irrespective of CXCR4 surface expression, by utilizing stable gain and loss of function approaches, we observe that intracellular CXCR4 protein selectively resists and sensitizes colon cancer cells against paclitaxel therapy in vitro and in vivo. Finally, performing TCGA data mining and using human breast cancer patient samples, we demonstrate that expression of CXCR4 and DR5 are inversely regulated. Together, our data suggest that targeting CXCR4 intracellular protein may be critical to dampen the pro-tumorigenic functions of CXCR4.
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http://dx.doi.org/10.1038/s41419-021-03730-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106681PMC
May 2021

Regarding Use of Povidone Iodine to Reduce Nasopharyngeal Viral Load in Patients With COVID-19.

JAMA Otolaryngol Head Neck Surg 2021 07;147(7):680-681

Department of Otorhinolaryngology and Head & Neck Surgery, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1001/jamaoto.2021.0683DOI Listing
July 2021

Penumbra quantification from MR SWI-DWI mismatch and its comparison with MR ASL PWI-DWI mismatch in patients with acute ischemic stroke.

NMR Biomed 2021 07 20;34(7):e4526. Epub 2021 Apr 20.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

In acute-ischemic-stroke patients, penumbra assessment plays a significant role in treatment outcome. MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch ratio can provide penumbra assessment. Recently reported studies have shown the potential of susceptibility-weighted imaging (SWI) in the qualitative assessment of penumbra. We hypothesize that quantitative penumbra assessment using SWI-DWI can provide an alternative to the PWI-DWI approach and this can also reduce the overall scan-time. The purpose of the current study was to develop a framework for accurate quantitative assessment of penumbra using SWI-DWI and its validation with PWI-DWI-based quantification. In the current study, the arterial-spin-labelling (ASL) technique has been used for PWI. This retrospective study included 25 acute-ischemic-stroke patients presenting within 24 hours of the last noted baseline condition of stroke onset. Eleven patients also had follow-up MRI within 48 hours. MRI acquisition comprised DWI, SWI, pseudo-continuous-ASL (pCASL), FLAIR and non-contrast-angiography sequences. A framework was developed for the enhancement of prominent hypo-intense vein signs followed by automatic segmentation of the SWI penumbra ROI. Apparent-diffusion-coefficient (ADC) maps and cerebral-blood-flow (CBF) maps were computed. The infarct core ROI from the ADC map and the ASL penumbra ROI from CBF maps were segmented semiautomatically. The infarct core volume, SWI penumbra volume (SPV) and pCASL penumbra volume were computed and used to calculate mismatch ratios and . The Dice coefficient between the SWI penumbra ROI and ASL penumbra ROI was 0.96 ± 0.07. correlated well (r = 0.90, p < 0.05) with , which validates the hypothesis of accurate penumbra assessment using the SWI-DWI mismatch ratio. Moreover, a significant association between high SPV and the presence of vessel occlusion in the MR angiogram was observed. Follow-up data showed salvation of penumbra tissue (location and volumes predicted by proposed framework) by treatments. Additionally, functional-outcome analysis revealed 93.3% of patients with > 1 benefitted from revascularization therapy. Overall, the proposed automated quantitative assessment of penumbra using the SWI-DWI mismatch ratio performs equivalently to the ASL PWI-DWI mismatch ratio. This approach provides an alternative to the perfusion sequence required for penumbra assessment, which can reduce scan time by 17% for the protocol without a perfusion sequence.
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http://dx.doi.org/10.1002/nbm.4526DOI Listing
July 2021

The Usefulness of Chest CT Imaging in Patients With Suspected or Diagnosed COVID-19: A Review of Literature.

Chest 2021 08 20;160(2):652-670. Epub 2021 Apr 20.

Department of Pulmonary and Critical Care Medicine, Lenox Hill Hospital, Northwell Health Physician Partners, New York, NY. Electronic address:

The COVID-19 pandemic has had devastating medical and economic consequences globally. The severity of COVID-19 is related, in a large measure, to the extent of pulmonary involvement. The role of chest CT imaging in the management of patients with COVID-19 has evolved since the onset of the pandemic. Specifically, the description of CT scan findings, use of chest CT imaging in various acute and subacute settings, and its usefulness in predicting chronic disease have been defined better. We performed a review of published data on CT scans in patients with COVID-19. A summary of the range of imaging findings, from typical to less common abnormalities, is provided. Familiarity with these findings may facilitate the diagnosis and management of this disease. A comparison of sensitivity and specificity of chest CT imaging with reverse-transcriptase polymerase chain reaction testing highlights the potential role of CT imaging in difficult-to-diagnose cases of COVID-19. The usefulness of CT imaging to assess prognosis, to guide management, and to identify acute pulmonary complications associated with SARS-CoV-2 infection is highlighted. Beyond the acute stage, it is important for clinicians to recognize pulmonary parenchymal abnormalities, progressive fibrotic lung disease, and vascular changes that may be responsible for persistent respiratory symptoms. A large collection of multi-institutional images were included to elucidate the CT scan findings described.
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http://dx.doi.org/10.1016/j.chest.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056836PMC
August 2021

Specialized Plant Growth Chamber Designs to Study Complex Rhizosphere Interactions.

Front Microbiol 2021 26;12:625752. Epub 2021 Mar 26.

Climate and Ecosystem Sciences, Earth and Environmental Sciences Area, Lawrence Berkeley National Laboratory, Berkeley, CA, United States.

The rhizosphere is a dynamic ecosystem shaped by complex interactions between plant roots, soil, microbial communities and other micro- and macro-fauna. Although studied for decades, critical gaps exist in the study of plant roots, the rhizosphere microbiome and the soil system surrounding roots, partly due to the challenges associated with measuring and parsing these spatiotemporal interactions in complex heterogeneous systems such as soil. To overcome the challenges associated with study of rhizosphere interactions, specialized plant growth chamber systems have been developed that mimic the natural growth environment. This review discusses the currently available lab-based systems ranging from widely known rhizotrons to other emerging devices designed to allow continuous monitoring and non-destructive sampling of the rhizosphere ecosystems in real-time throughout the developmental stages of a plant. We categorize them based on the major rhizosphere processes it addresses and identify their unique challenges as well as advantages. We find that while some design elements are shared among different systems (e.g., size exclusion membranes), most of the systems are bespoke and speaks to the intricacies and specialization involved in unraveling the details of rhizosphere processes. We also discuss what we describe as the next generation of growth chamber employing the latest technology as well as the current barriers they face. We conclude with a perspective on the current knowledge gaps in the rhizosphere which can be filled by innovative chamber designs.
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http://dx.doi.org/10.3389/fmicb.2021.625752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032546PMC
March 2021

An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population.

Metab Brain Dis 2021 06 2;36(5):957-968. Epub 2021 Mar 2.

Centre of Biomedical Research (CBMR), SGPGIMS Campus, Raibareli Road, Lucknow, Uttar Pradesh, 226014, India.

Mild cognitive impairment (MCI) is transition phase between cognitive decline and dementia. The current study aims to investigate altered metabolic pattern in plasma of MCI for potential biomarkers. MCI (N = 50) and healthy controls (HC, N = 50) age group 55-75 years were screened based on Mini Mental State Examination Test (MMSE) and diffusion tensor imaging (DTI imaging). The MMSE score of MCI was significantly lower (25.74 ± 1.83) compared to healthy control subjects (29 ± 1). The MCI patients exhibit significant changes in white matter integrity in the right frontal lobe, right temporal lobe, left frontal lobe, forcep major, fornix, corpus callosum. Further, the plasma samples of twenty seven MCI patients (N = 27) and twenty HC subjects (N = 20; having no significant differences in any demographics) were analyzed using H NMR based metabolomics approach. Consistent with many previous reports, the levels of several plasma metabolites were found to be elevated in MCI patients compared to healthy controls. Further univariate and multivariate ROC curve analyses provided three plasma metabolites as a diagnostic panel of biomarker for MCI; which are lysine, glycine, and glutamine. Overall, the results of this study will help to improve the diagnostic and prognostic strategies of MCI in addition to improving our understanding about disease pathogenesis. We believe that the over-nutritional metabolic phenotype of MCI needs to be targeted for developing future dietary interventions so that the progression of MCI can be limited. Metabolic derangements associated with Mild Cognitive Impairment.
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http://dx.doi.org/10.1007/s11011-021-00700-zDOI Listing
June 2021

Characterisation of prostate cancer using texture analysis for diagnostic and prognostic monitoring.

NMR Biomed 2021 06 27;34(6):e4495. Epub 2021 Feb 27.

Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

Automated classification of significant prostate cancer (PCa) using MRI plays a potential role in assisting in clinical decision-making. Multiparametric MRI using a machine-aided approach is a better step to improve the overall accuracy of diagnosis of PCa. The objective of this study was to develop and validate a framework for differentiating Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) grades (grade 2 to grade 5) of PCa using texture features and machine learning (ML) methods with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC). The study cohort included an MRI dataset of 59 patients with clinically proven PCa. Regions of interest (ROIs) for a total of 435 lesions were delineated from the segmented peripheral zones of DWI and ADC. Six texture methods comprising 98 texture features in total (49 each of DWI and ADC) were extracted from lesion ROIs. Random forest (RF) and correlation-based feature selection methods were applied on feature vectors to select the best features for classification. Two ML classifiers, support vector machine (SVM) and K-nearest neighbour, were used and validated by 10-fold cross-validation. The proposed framework achieved high diagnostic performance with a sensitivity of 85.25% ± 3.84%, specificity of 95.71% ± 1.96%, accuracy of 84.90% ± 3.37% and area under the receiver-operating characteristic curve of 0.98 for PI-RADS v2 grades (2 to 5) classification using the RF feature selection method and Gaussian SVM classifier with combined features of DWI + ADC. The proposed computer-assisted framework can distinguish between PCa lesions with different aggressiveness based on PI-RADS v2 standards using texture analysis to improve the efficiency of PCa diagnostic performance.
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http://dx.doi.org/10.1002/nbm.4495DOI Listing
June 2021

Virus-Encoded Complement Regulators: Current Status.

Viruses 2021 01 29;13(2). Epub 2021 Jan 29.

Complement Biology Laboratory, National Centre for Cell Science, S. P. Pune University Campus, Ganeskhind, Pune 411007, India.

Viruses require a host for replication and survival and hence are subjected to host immunological pressures. The complement system, a crucial first response of the host immune system, is effective in targeting viruses and virus-infected cells, and boosting the antiviral innate and acquired immune responses. Thus, the system imposes a strong selection pressure on viruses. Consequently, viruses have evolved multiple countermeasures against host complement. A major mechanism employed by viruses to subvert the complement system is encoding proteins that target complement. Since viruses have limited genome size, most of these proteins are multifunctional in nature. In this review, we provide up to date information on the structure and complement regulatory functions of various viral proteins.
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http://dx.doi.org/10.3390/v13020208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912105PMC
January 2021

Chasing the culprit in shadow - Sinonasal mucormycosis in an immunocompetent host.

Trop Doct 2021 Feb 10:49475521991354. Epub 2021 Feb 10.

Associate Director, ENT, Department of Otolaryngology and Head & Neck Surgery, 204687Medanta-The Medicity, Gurugram, India.

Rhino-orbital mucormycosis is an uncommon, rapidly progressive, fulminant, angio-invasive deep mycosis usually affecting individuals with underlying immunosuppression, the most common being diabetes mellitus. In such, the course may be fatal with dissemination. Early detection with control of underlying predisposing conditions is critical with respect to the prognosis. Rarely, mucormycosis may develop in an immunocompetent host, when its non-specific symptomatology and inconspicuous radiological findings may obscure its diagnosis. Any delay in treatment predisposes to multi-organ morbidity and potential mortality. We present an immunocompetent adult with no underlying predisposing illness who was harbouring invasive sinonasal mucormycosis causing orbital cellulitis. A high index of suspicion is mandatory.
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http://dx.doi.org/10.1177/0049475521991354DOI Listing
February 2021

Effect of offset-frequency step size and interpolation methods on chemical exchange saturation transfer MRI computation in human brain.

NMR Biomed 2021 04 4;34(4):e4468. Epub 2021 Feb 4.

Center for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, India.

Chemical exchange saturation transfer (CEST) MRI is a non-invasive molecular imaging technique with potential applications in pre-clinical and clinical studies. Applications of amide proton transfer-weighted (APT-w), glutamate-weighted (Glu-w) and creatine-weighted (Cr-w) CEST, among others, have been reported. In general, CEST data are acquired at multiple offset-frequencies. In reported studies, different offset-frequency step sizes and interpolation methods have been used during B inhomogeneity correction of data. The objective of the current study was to evaluate the effects of different step sizes and interpolation methods on CEST value computation. In the current study, simulation (Glu-w, Cr-w and APT-w) and experimental data from the brain were used. Experimental CEST data (Glu-w) were acquired from human volunteers at 7 T and brain tumor patients (APT-w) at 3 T. During B inhomogeneity correction, different interpolation methods (polynomial [degree-1, 2 and 3], cubic-Hermite, cubic-spline and smoothing-spline) were compared. CEST values were computed using asymmetry analysis. The effects of different step sizes and interpolation methods were evaluated using coefficient of variation (CV), normalized mean square error (nMSE) and coefficient of correlation parameters. Additionally, an optimum interpolation method for APT-w values was selected based upon fitting accuracy, T-test, receiver operating characteristic analysis, and its diagnostic performance in differentiating low-grade and high-grade tumors. CV and nMSE increase with an increase in step size irrespective of the interpolation method (except for cubic-Hermite and cubic-spline). The nMSE of Cr-w and Glu-w CEST values were least for polynomial (degree-2 and 3). The quality of Glu-w CEST maps became coarse with the increase in step size. There was a significant difference (P < .05) between low-grade and high-grade tumors using polynomial interpolation (degree-1, 2 and 3); however, linear interpolation outperforms other methods for APT-w data, providing the highest sensitivity and specificity. In conclusion, depending upon the saturation parameters and field strength, optimization of step size and interpolation should be carried out for different CEST metabolites/molecules. Glu-w, Cr-w and APT-w CEST data should be acquired with a step size of between 0.2 and 0.3 ppm. For B inhomogeneity correction, polynomial (degree-2) should be used for Glu-w and Cr-w CEST data at 7 T and linear interpolation should be used for APT-w data at 3 T for a limited frequency range.
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http://dx.doi.org/10.1002/nbm.4468DOI Listing
April 2021

Comparative evaluation of intracranial oligodendroglioma and astrocytoma of similar grades using conventional and T1-weighted DCE-MRI.

Neuroradiology 2021 Aug 19;63(8):1227-1239. Epub 2021 Jan 19.

Department of Radiology, Fortis Memorial Research Institute, Sector 44, Gurgaon, Haryana, 122002, India.

Purpose: This retrospective study was performed on a 3T MRI to determine the unique conventional MR imaging and T1-weighted DCE-MRI features of oligodendroglioma and astrocytoma and investigate the utility of machine learning algorithms in their differentiation.

Methods: Histologically confirmed, 81 treatment-naïve patients were classified into two groups as per WHO 2016 classification: oligodendroglioma (n = 16; grade II, n = 25; grade III) and astrocytoma (n = 10; grade II, n = 30; grade III). The differences in tumor morphology characteristics were evaluated using Z-test. T1-weighted DCE-MRI data were analyzed using an in-house built MATLAB program. The mean 90th percentile of relative cerebral blood flow, relative cerebral blood volume corrected, volume transfer rate from plasma to extracellular extravascular space, and extravascular extracellular space volume values were evaluated using independent Student's t test. Support vector machine (SVM) classifier was constructed to differentiate two groups across grade II, grade III, and grade II+III based on statistically significant features.

Results: Z-test signified only calcification among conventional MR features to categorize oligodendroglioma and astrocytoma across grade III and grade II+III tumors. No statistical significance was found in the perfusion parameters between two groups and its subtypes. SVM trained on calcification also provided moderate accuracy to differentiate oligodendroglioma from astrocytoma.

Conclusion: We conclude that conventional MR features except calcification and the quantitative T1-weighted DCE-MRI parameters fail to discriminate between oligodendroglioma and astrocytoma. The SVM could not further aid in their differentiation. The study also suggests that the presence of more than 50% T2-FLAIR mismatch may be considered as a more conclusive sign for differentiation of IDH mutant astrocytoma.
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http://dx.doi.org/10.1007/s00234-021-02636-8DOI Listing
August 2021

Iron Isomaltoside-Induced Anaphylaxis.

Am J Ther 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Departments of Pharmacology, Geriatric Medicine, and General Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

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http://dx.doi.org/10.1097/MJT.0000000000001315DOI Listing
December 2020

Induction of APOBEC3B expression by chemotherapy drugs is mediated by DNA-PK-directed activation of NF-κB.

Oncogene 2021 02 15;40(6):1077-1090. Epub 2020 Dec 15.

Department of Surgery & Cancer, Imperial College London, London, W12 0NN, UK.

The mutagenic APOBEC3B (A3B) cytosine deaminase is frequently over-expressed in cancer and promotes tumour heterogeneity and therapy resistance. Hence, understanding the mechanisms that underlie A3B over-expression is important, especially for developing therapeutic approaches to reducing A3B levels, and consequently limiting cancer mutagenesis. We previously demonstrated that A3B is repressed by p53 and p53 mutation increases A3B expression. Here, we investigate A3B expression upon treatment with chemotherapeutic drugs that activate p53, including 5-fluorouracil, etoposide and cisplatin. Contrary to expectation, these drugs induced A3B expression and concomitant cellular cytosine deaminase activity. A3B induction was p53-independent, as chemotherapy drugs stimulated A3B expression in p53 mutant cells. These drugs commonly activate ATM, ATR and DNA-PKcs. Using specific inhibitors and gene knockdowns, we show that activation of DNA-PKcs and ATM by chemotherapeutic drugs promotes NF-κB activity, with consequent recruitment of NF-κB to the A3B gene promoter to drive A3B expression. Further, we find that A3B knockdown re-sensitises resistant cells to cisplatin, and A3B knockout enhances sensitivity to chemotherapy drugs. Our data highlight a role for A3B in resistance to chemotherapy and indicate that stimulation of A3B expression by activation of DNA repair and NF-κB pathways could promote cancer mutations and expedite chemoresistance.
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http://dx.doi.org/10.1038/s41388-020-01583-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116738PMC
February 2021

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India.

Aging Dis 2020 Dec 1;11(6):1339-1344. Epub 2020 Dec 1.

12Department of Biochemistry and Central Research Cell, Maharishi Markandeshwar (deemed to be) University, Mullana, India.

India has witnessed a high number of COVID-19 cases, but mortality has been quite low, and most cases have been asymptomatic or mild. In early April, we had hypothesized a low COVID-19 mortality in India, based on the concept of cross-immunity. The presence of cross-immunity is presumed to lead to a milder course of disease and allow the time necessary for the development of adaptive immunity by the body to eliminate the virus. Evidence supporting our hypothesis has started showing up. Multiple studies have shown the generation of different T cell subsets and B cells responding to epitopes of viral proteins, especially of the spike protein, as a part of adaptive immunity against SARS-CoV-2. Cross-reactive T-cells have been demonstrated in patients who have been previously exposed to endemic coronaviruses. The interplay of cross-immunity and herd immunity is apparent in the COVID-19 scenario in India from the presence of a large number of asymptomatic or mild cases, a low infection-fatality ratio and a generally flat curve of percentage positivity of cases with respect to total testing, both in periods of strict lock-down and step-wise unlocking. It seems that cross-immunity resulted in faster generation of herd immunity. Although the initial restrictive measures such as lockdown prevented the rapid spread of the outbreak, further extension of such measures and overly expensive ones such as enhanced testing in India will result in a huge burden on the health economics as well as the society. Hence, we propose a restructuring of the health services and approach to COVID-19. The restructured health services should move away from indiscriminate testing, isolation and quarantine, and instead, the emphasis should be on improving facilities for testing and management of only critical COVID cases and the replacement of complete lockdowns by the selective isolation and quarantine of susceptible persons such as the aged and those with co-morbidities. In the process of describing India-specific plans, we emphasize why the development of country-specific plans for tackling epidemics is important, instead of adopting a "one policy fits all" approach.
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http://dx.doi.org/10.14336/AD.2020.1104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673860PMC
December 2020
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