The Effective Inhibitory Concentration of Interferon-ß Correlates with Infectivity and Replication Fitness of SARS-CoV-2 Variants.

India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-ß (IFN-ß) treatment and found that XBB.1.16 variant was most sensitive to IFN-ß. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.

To be remembered: B cell memory response against SARS-CoV-2 and its variants in vaccinated and unvaccinated individuals.

COVID-19 disease has plagued the world economy and affected the overall well-being and life of most of the people. Natural infection as well as vaccination leads to the development of an immune response against the pathogen. This involves the production of antibodies, which can neutralize the virus during future challenges. In addition, the development of cellular immune memory with memory B and T cells provides long-lasting protection. The longevity of the immune response has been a subject of intensive research in this field. The extent of immunity conferred by different forms of vaccination or natural infections remained debatable for long. Hence, understanding the effectiveness of these responses among different groups of people can assist government organizations in making informed policy decisions. In this article, based on the publicly available data, we have reviewed the memory response generated by some of the vaccines against SARS-CoV-2 and its variants, particularly B cell memory in different groups of individuals.

Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

A quest for universal anti-SARS-CoV-2 T cell assay: systematic review, meta-analysis, and experimental validation.

Measuring SARS-CoV-2-specific T cell responses is crucial to understanding an individual's immunity to COVID-19. However, high inter- and intra-assay variability make it difficult to define T cells as a correlate of protection against COVID-19. To address this, we performed systematic review and meta-analysis of 495 datasets from 94 original articles evaluating SARS-CoV-2-specific T cell responses using three assays - Activation Induced Marker (AIM), Intracellular Cytokine Staining (ICS), and Enzyme-Linked Immunospot (ELISPOT), and defined each assay's quantitative range. We validated these ranges using samples from 193 SARS-CoV-2-exposed individuals. Although IFNγ ELISPOT was the preferred assay, our experimental validation suggested that it under-represented the SARS-CoV-2-specific T cell repertoire. Our data indicate that a combination of AIM and ICS or FluoroSpot assay would better represent the frequency, polyfunctionality, and compartmentalization of the antigen-specific T cell responses. Taken together, our results contribute to defining the ranges of antigen-specific T cell assays and propose a choice of assay that can be employed to better understand the cellular immune response against viral diseases.

Biocompatible Human Placental Extracellular Matrix Derived Hydrogels.

Solubilizing extracellular matrix (ECM) materials and transforming them into hydrogels has expanded their potential applications both in vitro and in vivo. In this study, hydrogels are prepared by decellularization of human placental tissue using detergent and enzymes and by the subsequent creation of a homogenized acellular placental tissue powder (P-ECM). A perfusion-based decellularization approach is employed using detergent and enzymes. The P-ECM with and without gamma irradiation is then utilized to prepare P-ECM hydrogels. Physical and biological evaluations are conducted to assess the suitability of the P-ECM hydrogels for biocompatibility. The decellularized tissue has significantly reduced cellular content and retains the major ECM proteins. Increasing the concentration of P-ECM leads to improved mechanical properties of the P-ECM hydrogels. The biocompatibility of the P-ECM hydrogel is demonstrated through cell proliferation and viability assays. Notably, gamma-sterilized P-ECM does not support the formation of a stable hydrogel. Nonetheless, the use of HCl during the digestion process effectively decreases spore growth and bacterial bioburden. The study demonstrates that P-ECM hydrogels exhibit physical and biological attributes conducive to soft tissue reconstruction. These hydrogels establish a favorable microenvironment for cell growth and the need for investigating innovative sterilization methods.

Role of FDG PET/CT in definitive and presumed autoimmune encephalitis.

OBJECTIVE: F-18 Fluorodeoxyglucose PET/CT (FDG-PET) is emerging as a useful imaging adjunct to MRI in the initial diagnostic evaluation of autoimmune encephalitis (AIE)-though presently it is not included in the diagnostic criteria. MATERIALS AND METHODS: In this prospective study we enrolled a total of 52 patients with clinically diagnosed and treated AIE. MRI evaluation was done in each case along with CSF and EEG where feasible. FDG-PET was done for all and images were interpreted visually and using SPM. RESULTS: The mean age group of patients included was 38.5 ± 22.6 years with 31 females and 21 males. 23 antibody-positive cases underwent PET, the most common antibody detected was anti-NMDAR type followed by anti-LGI 1. Most common metabolic pattern in NMDARE was hypermetabolism in basal ganglia and hypometabolism in parieto-occipital cortices and ovarian teratoma was detected in two of these patients on whole-body PET. A metabolic pattern consistent with AIE was demonstrated in 22/29 (75.8%) antibody-negative patients with hypermetabolism in basal ganglia and mesial temporal cortices. The overall sensitivity of FDG PET was 86% (45/52). MRI abnormalities were detected in 22/52 (42%) cases, 10/23 antibody positive and 12/29 antibody negative cases. PET was positive in 23/30 (76%) MRI negative cases. CONCLUSION: Sensitivity of FDG PET for supporting a diagnosis of AIE was higher compared to MRI in both antibody-positive (definitive) and antibody-negative (presumed) AIE. Specific metabolic patterns can be demonstrated on FDG PET in AIE, prompting an early diagnosis so that timely treatment can be instituted.

Near-lossless Compression of Tc-99 m DMSA Scan Images Using Discrete Cosine Transformation.

Aim and Objective: The objective of this study was to optimize the threshold for discrete cosine transform (DCT) coefficients for near-lossless compression of Tc-99 m Dimercaptosuccinic acid (DMSA) scan images using discrete cosine transformation. Materials and Methods: Two nuclear medicine (NM) Physicians after reviewing several Tc-99 m DMSA scan images provided 242 Tc-99 m DMSA scan images that had scar. These Digital imaging and communication in medicine (DICOM) images were converted in the Portable Network Graphics (PNG) format. DCT was applied on these PNG images, which resulted in DCT coefficients corresponding to each pixel of the image. Four different thresholds equal to 5, 10, 15, and 20 were applied and then inverse discrete cosine transformation was applied to get the compressed Tc-99 m DMSA scan images. Compression factor was calculated as the ratio of the number of nonzero elements after thresholding DCT coefficients to the number of nonzero elements before thresholding DCT coefficients. Two NM physicians who had provided the input images visually compared the compressed images with its input image, and categorized the compressed images as either acceptable or unacceptable. The quality of compressed images was also assessed objectively using the following eight image quality metrics: perception-based image quality evaluator, structural similarity index measure (SSIM), multiSSIM, feature similarity indexing method, blur, global contrast factor, contrast per pixel, and brightness. Pairwise Wilcoxon signed-rank sum tests were applied to find the statistically significant difference between the value of image quality metrics of the compressed images obtained at different thresholds and the value of the image quality metrics of its input images at the level of significance = 0.05. Results: At threshold 5, (1) all compressed images (242 out of 242 Tc-99 m DMSA scan images) were acceptable to both the NM Physicians, (2) Compressed image looks identical to its original image and no loss of clinical details was noticed in compressed images, (3) Up to 96.65% compression (average compression: 82.92%) was observed, and (4) Result of objective assessment supported the visual assessment. The quality of compressed images at thresholds 10, 15, and 20 was significantly better than that of input images at P < 0.0001. However, the number of unacceptable compressed images at thresholds 10, 15, and 20 was 6, 38, and 70, respectively. Conclusions: Up to 96.65%, near-losses compression of Tc-99 m DMSA images was found using DCT by thresholding DCT coefficients at a threshold value equal to 5.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.

Impact of forced diuresis at two different time points on pelvic imaging in prostatic carcinoma with 68 Ga-PSMA PET/CT.

OBJECTIVE: We compared diagnostic quality of 68 Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. MATERIAL AND METHODS: A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68 Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68 Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. RESULTS: Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points ( P  > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P  < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P  = 0.002). CONCLUSION: The simultaneous furosemide and 68 Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.

Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

99m-Tc TRODAT Single-Photon Emission Computerized Tomography Scan Image Compression using Singular Value Decomposition.

Introduction: The objective of the study was to compress 99m-Tc TRODAT single-photon emission computerized tomography (SPECT) scan image using Singular Value Decomposition (SVD) into an acceptable compressed image and then calculate the compression factor. Materials and Methods: The SVD of every image from the image dataset of 2256 images (of forty-eight 99m-Tc TRODAT SPECT studies [48 studies X 47 trans-axial images = 2256 trans-axial images]) was computed and after truncating singular values smaller than a threshold, the compressed image was reconstructed. The SVD computation time and percentage compression achieved were calculated for each image. Two nuclear medicine physicians visually compared compressed image with its original image, and labeled it as either acceptable or unacceptable. Compressed image having loss of clinical details or presence of compression artifact was labeled unacceptable. The quality of compressed image was also assessed objectively using the following image quality metrics: Error, structural similarity (SSIM), brightness, global contrast factor (GCF), contrast per pixel (CPP), and blur. We also compared the TRODAT uptake in basal ganglia estimated from the compressed image and original image. Results: Nuclear Medicine Physician labeled each image acceptable, as they found compressed image identical to its original image. The values of brightness, GCF, CPP, and blur metrics show that compressed images are less noisy, brighter, and sharper than its original image. The median values of error (0.0006) and SSIM (0.93) indicate that the compressed images were approximately identical to its original image. In 39 out of 48 studies, the percentage difference in TRODAT uptake (in basal ganglia from compressed and original image) was negligible (approximately equal to zero). In remaining 9 studies, the maximum percentage difference was 13%. The SVD computation time and percentage compression achieved for a TRODAT study were 0.17398 s and up to 54.61%, respectively. Conclusions: The compression factor up to 54.61% was achieved during 99m-Tc TRODAT SPECT scan image compression using SVD, for an acceptable compressed image.

Targeting DPP4-RBD interactions by sitagliptin and linagliptin delivers a potential host-directed therapy against pan-SARS-CoV-2 infections.

Highly mutated SARS-CoV-2 is known aetiological factor for COVID-19. Here, we have demonstrated that the receptor binding domain (RBD) of the spike protein can interact with human dipeptidyl peptidase 4 (DPP4) to facilitate virus entry, in addition to the usual route of ACE2-RBD binding. Significant number of residues of RBD makes hydrogen bonds and hydrophobic interactions with α/ß-hydrolase domain of DPP4. With this observation, we created a strategy to combat COVID-19 by circumventing the catalytic activity of DPP4 using its inhibitors. Sitagliptin, linagliptin or in combination disavowed RBD to establish a heterodimer complex with both DPP4 and ACE2 which is requisite strategy for virus entry into the cells. Both gliptins not only impede DPP4 activity, but also prevent ACE2-RBD interaction, crucial for virus growth. Sitagliptin, and linagliptin alone or in combination have avidity to impede the growth of pan-SARS-CoV-2 variants including original SARS-CoV-2, alpha, beta, delta, and kappa in a dose dependent manner. However, these drugs were unable to alter enzymatic activity of PLpro and Mpro. We conclude that viruses hijack DPP4 for cell invasion via RBD binding. Impeding RBD interaction with both DPP4 and ACE2 selectively by sitagliptin and linagliptin is an potential strategy for efficiently preventing viral replication.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Denoising Tc-99m DMSA images using Denoising Convolutional Neural Network with comparison to a Block Matching Filter.

INTRODUCTION: A DnCNN for image denoising trained with natural images is available in MATLAB. For Tc-99m DMSA images, any loss of clinical details during the denoising process will have serious consequences since denoised image is to be used for diagnosis. The objective of the study was to find whether this pre-trained DnCNN can be used for denoising Tc-99m DMSA images and compare its performance with block matching 3D (BM3D) filter. MATERIALS AND METHODS: Two hundred forty-two Tc-99m DMSA images were denoised using BM3D filter (at sigma = 5, 10, 15, 20, and 25) and DnCNN. The original and denoised images were reviewed by two nuclear medicine physicians and also assessed objectively using the image quality metrics: SSIM, FSIM, MultiSSIM, PIQE, Blur, GCF, and Brightness. Wilcoxon signed-rank test was applied to find the statistically significant difference between the value of image quality metrics of the denoised images and the corresponding original images. RESULTS: Nuclear medicine physicians observed no loss of clinical information in DnCNN denoised image and superior image quality compared to its original and BM3D denoised images. Edges/boundaries of the scar were found to be well preserved, and doubtful scar became obvious in the denoised image. Objective assessment also showed that the quality of DnCNN denoised images was significantly better than that of original images at P -value <0.0001. CONCLUSION: The pre-trained DnCNN available with MATLAB Deep Learning Toolbox can be used for denoising Tc-99m DMSA images, and the performance of DnCNN was found to be superior in comparison with BM3D filter.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

99m-Tc MDP Bone Scan Image Enhancement using Pipeline Application of Dynamic Stochastic Resonance Algorithm and Block-Matching 3D Filter.

Introduction: In this pilot study, we have proposed and evaluated pipelined application of the dynamic stochastic resonance (DSR) algorithm and block-matching 3D (BM3D) filter for the enhancement of nuclear medicine images. The enhanced images out of the pipeline were compared with the corresponding enhanced images obtained using individual applications of DSR and BM3D algorithm. Materials and Methods: Twenty 99m-Tc MDP bone scan images acquired on SymbiaT6 SPECT/CT gamma camera system fitted with low-energy high-resolution collimators were exported in DICOM format to a personal computer and converted into PNG format. These PNG images were processed using the proposed algorithm in MATLAB. Two nuclear medicine physicians visually compared each input and its corresponding three enhanced images to select the best-enhanced image. The image quality metrics (Brightness, Global Contrast Factor (GCF), Contrast per pixel (CPP), and Blur) were used to assess the image quality objectively. The Wilcoxon signed test was applied to find a statistically significant difference in Brightness, GCF, CPP, and Blur of enhanced and its input images at a level of significance. Results: Images enhanced using the pipelined application of SR and BM3D were selected as the best images by both nuclear medicine physicians. Based on Brightness, Global Contrast Factor (GCF), CPP, and Blur, the image quality of our proposed pipeline was significantly better than enhanced images obtained using individual applications of DSR and BM3D algorithm. The proposed method was found to be very successful in enhancing details in the low count region of input images. The enhanced images were bright, smooth, and had better target-to-background ratio compared to input images. Conclusion: The pipelined application of DSR and BM3D algorithm produced enhancement in nuclear medicine images having following characteristics: bright, smooth, better target-to-background ratio, and improved visibility of details in the low count regions of the input image, as compared to individual enhancements by application of DSR or BM3D algorithm.

Estimating Center of Rotation of Single-Photon Emission Computerized Tomography Projection Images Using MATLAB for Standardization and Calibration.

Objective: The objective of the study was to develop a Personal Computer (PC) based tool to estimate the center of rotation (COR) offsets from COR projection datasets using methods mentioned in IAEA-TECDOC-602. Materials and Methods: Twenty-four COR studies were acquired on Discovery NM 630 Dual head gamma camera fitted with parallel hole collimator, and COR offsets were estimated with the software available at the terminal for processing a COR study. These COR projection images were exported in DICOM. A MATLAB script (software program) was written to estimate COR offset using Method A (using opposite pair of projections) and Method B (using curve fitting method) as mentioned in IAEA-TECDOC-602. Our program read the COR study (in DICOM) and estimated COR offsets using Method A and Method B. The accuracy of the program was verified using simulated projection dataset of a point source object acquired at 6° interval in the range of 0°-360° angle. Bland Altman plot was used for analyzing the agreement between the COR offsets estimated using (1) Method A and Method B mentioned in IAEA-TECDOC-602, and (2) Our program and vendor program available at Discovery NM 630 acquisition terminal. Results: On simulated data, offset from center of gravity (COG) in X direction (COGX) and COG in Y direction (COGY) estimated using Method A was constant (same) at each pair of angles while using Method B, it was found to be in the range (-2 × 10-10, 1 × 10-10) which is negligible. Most of the differences (23 out of 24) between the result of Method A and Method B, and between the results of our program and vendor program was found to be within 95% confidence interval (mean ± 1.96 standard deviation). Conclusions: Our PC-based tool to estimate COR offsets from COR projection datasets using methods mentioned in IAEA-TECDOC-602 was found to be accurate and provides results in agreement with vendor's program. It can be used as an independent tool to estimate COR offset for standardization and calibration purposes.

Immunogenicity and safety of Biological E's CORBEVAX™ vaccine compared to COVISHIELD™ (ChAdOx1 nCoV-19) vaccine studied in a phase-3, single blind, multicentre, randomized clinical trial.

Optimum formulation of Biological-E's protein subunit CORBEVAX™ vaccine was selected in phase-1 and -2 studies and found to be safe and immunogenic in healthy adult population. This is a phase-3 prospective, single-blinded, randomized, active controlled study conducted at 18 sites across India in 18-80 year-old subjects. This study has two groups; (i) immunogenicity-group, participants randomized either to CORBEVAX™ (n = 319) or COVISHIELD™ arms (n = 320). (ii) Safety-group containing single CORBEVAX™ arm (n = 1500) and randomization is not applicable. Healthy adults without a history of COVID-19 vaccination or SARS-CoV-2 infection were enrolled into immunogenicity arm and subjects seronegative to SARS-CoV-2 infection were enrolled into the safety arm. The safety profile of CORBEVAX™ vaccine was comparable to the comparator vaccine COVISHIELD™. Majority of reported AEs were mild in nature in both arms. The CORBEVAX™ to COVISHIELD™ GMT-ratios at day-42 time-point were 1·15 and 1·56 and the lower limit of the 95% confidence interval for the GMT-ratios was determined as 1·02 and 1·27 against Ancestral and Delta strains of SARS-COV-2 respectively. Both COVISHIELD™ and CORBEVAX™ vaccines showed comparable seroconversion post-vaccination against anti-RBD-IgG response. The subjects in CORBEVAX™ cohort also exhibited higher interferon-gamma secreting PBMC's post-stimulation with SARS-COV-2 RBD-peptides than subjects in COVISHIELD™ cohort.

BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies.

The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron sub-lineages led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant were comparable in cell culture and natural infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to the Delta variant and all the three sub-lineages of Omicron but the level of neutralizing antibodies were lowest against the BA.2.75 variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variants and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.

Antifungal activity of silver nanoparticles on fungal isolates from patients of suspected mucormycosis / Actividad antifúngica de nanopartículas de plata en aislamientos fúngicos de pacientes con sospecha de mucormicosis

Introduction: The present study aimed to investigate the antifungal activity of silver nanoparticles (SNPs) against agents of suspected rhino orbital mucormycosis. Methods: Thirty-two strains were isolated from endoscopy-guided nasal swab and/or tissue biopsy after debridement/surgery on Sabouraud dextrose agar without cyclohexamide. Antifungal activity was conducted according to Clinical and Laboratory Standards Institute’s (CLSI) guidelines, M38-A2. The average size of silver nanoparticle was less than 10 nm. Results: Minimum inhibitory concentration (MIC) of nanoparticles of all strains was in the concentration range of 1–64 μg/ml and minimal fungicidal concentration (MFC) at 16–512 μg/ml. Conclusion: The SNPs revealed significant antifungal activity against agents of invasive mycosis.(AU)