Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Autologous Conditioned Serum in Lumbar and Cervical Radiculopathy: A Systemic Review

Background: Intervertebral disc degeneration causing radiculopathy is driven by catabolic cytokines like IL-1β and TNFα. Autologous conditioned serum (ACS) was found to be rich in IL-1Ra (Interleukin-1 Receptor Antagonist), and thus, can impede disc degeneration. A systematic review of available literature was conducted to ascertain the potential therapeutic application of ACS in radiculopathy. Methods: Systematic literature reviews were conducted in PubMed, Scopus and Embase databases, up to September 2020. Randomised controlled trials (RCTs), prospective, retrospective studies and case series with lumbar or cervical radiculopathy and reporting use of ACS were included, with at least one of the outcome measures like VAS (Visual Analogue Scale) for pain, SF-12 (Short Form of Health Survey-12), Oswestry Disability Index, with a minimum follow up of 3 months. Animal studies, s, review articles and case reports were excluded. Results: A total of four studies, including 107 patients who received ACS were included based on the eligibility criteria. Two were RCTs and two were prospective non-comparative studies. Three studies evaluated the effect of IL-1Ra on lumbar radiculopathy and one on cervical radiculopathy. The mean age of patients in the studies ranged from 37.15 to 53.9. The dose of ACS used was 2-4 mL injection. In 1 RCT, methylprednisolone was used as control, in the other 5 mg and 10 mg triamcinolone was used. All studies reported a statistically significant reduction in pre-injection and post-injection VAS, there was also a significant difference as compared to 5 mg triamcinolone. Three studies reported significant improvement in ODI. Two studies reported statistically significant improvement in SF-12 scores post injection (p < 0.001). For cervical radiculopathy, Neck pain disability score showed a decrease of 73.76% from pre-injection to final follow up and Neck disability index showed a decrease of 74.47%. Conclusion: All of the four studies concluded that epidural perineural injection with ACS, reduced pain scores (VAS, NPDS) and improved functional scores (ODI, SF-12 and NPDS), as compared to placebo and other conventional therapeutic modalities like steroids, and analgesic-anaesthetic-steroid cocktail. Hence, ACS is a promising new therapeutic modality in both lumbar and cervical radiculopathy, and further studies can strengthen the present evidence regarding its efficacy and safety profile. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Recent Development in Detection Systems for Human Viral Pathogens from Clinical Samples with Special Reference to Biosensors

Over the last few decades, the emergence and re-emergence of various pathogenic viruses have significantly impacted human health. The continuous rise in cases with increasing mortality rates has driven the chase for effective treatment options and early diagnosis to combat this global health issue. Currently, used laboratory techniques for virus detection require complex equipment, trained personnel, and, most importantly, are time-consuming. In times of outbreaks and epidemics like COVID-19 and Ebola, easy-to-use and point-of-care tests, especially for developing and underdeveloped countries, are indispensable. This chapter explicitly discusses the availability of the detection methods for various human viral pathogens with their shortcomings and recent advancements in biosensors. With the ongoing improvement in biosensors, these hold important avenues for rapid, sensitive, and scalable devices for viral diagnostic purposes. The effectiveness of previously known and current approaches/devices/methods that utilize different principles for detection has also been reviewed here, with the listing of all the available tests for various human pathogens. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Zero-COVID policy and stock market sectoral performance in China

With the outbreak of COVID-19, the Chinese government implemented the "zero-COVID” policy as a measure to curb the spread of the virus. The different measures of the policy include widespread testing, contact tracing, and strict quarantine and isolation protocols. In view of recent changes in COVID-19 trends and other economic indicators, the Chinese government withdrew significant provisions of the zero-COVID policy in China. The present study investigates the sectoral performance of the Chinese stock market after the withdrawal of the zero-COVID policy. The study considers eighteen sectoral indices of the Shenzhen Stock Exchange of China as a sample and applies the event study methodology to study the impact of the policy withdrawal on the stock prices performance. The results of the study indicate that sectors such as hotel, consumer staples, the financial sector, real estate, media, and culture have reported significant positive movement after the withdrawal of the zero-COVID policy, while other sectors such as consumer discretionary, energy, healthcare, information technology, manufacturing, mining, technology, telecom, transportation, utilities, wholesale, and retail have shown insignificant reactions. These results also indicate that when the COVID-19 outbreak happened in China, different sectors of the economy reacted negatively except the retail and wholesale sectors, while with the withdrawal of the zero-COVID policy by the Chinese government, the reaction of investors is optimistic as different sectors are reporting either positive reactions in the stock price movement or no reaction. © Prashant Sharma, Surender Kumar, 2023.

The psychiatric effects of COVID-19 in the elderly

The coronavirus (COVID-19) pandemic has exposed and highlighted pre-existing psychiatric illness in the elderly as well as predisposed them to new and emerging psychiatric pathology. The impact of this devastating illness has been felt in each setting including nursing homes and prisons and has been a barrier toward healthy aging. Despite the many challenges faced by our elderly, resilience and wisdom have served as protective factors in our fight against the pandemic. This chapter highlights the psychiatric effects of the illness and ways to manage the burden associated with psychopathology. © 2023 Elsevier Inc. All rights reserved.

Uptake of vaccination in older Indian patients with cancer: A cross-sectional observational study

Background: Older patients with cancer are at a higher risk of invasive infections. Vaccination is an effective approach to decrease the mortality and morbidity associated with infections. Objective(s): Our primary objective was to evaluate the proportion of older patients with cancer who had received routine vaccinations against pneumococcal, influenza, and coronavirus disease 2019 (COVID-19). Our secondary objective was to identify the factors associated with vaccine uptake such as age, sex, education, marital status, comorbidities, and place of residence. Material(s) and Method(s): This cross-sectional observational study was conducted in the geriatric oncology outpatient clinic of the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary care cancer hospital in Mumbai, India, from February 2020 to January 2023. We included all patients aged >=60 years who were evaluated in the geriatric oncology clinic during the study period and for whom the immunization details were available. The uptake of COVID-19 vaccine was calculated from March 2021 onwards, which was when the COVID-19 vaccine became available to patients aged >=60 years in India. Result(s): We enrolled 1762 patients;1342 (76.2%) were male. The mean age was 68.4 (SD, 5.8) years;795 (45%) patients were from the west zone of India. Only 12 (0.68%) patients had received the pneumococcal vaccine, and 13 (0.7%) had received the influenza vaccine. At least one dose of the COVID-19 vaccine had been taken by 1302 of 1562 patients (83.3%). On univariate logistic regression, education, marital status, geographic zone of residence, and primary tumor site were correlated with the uptake of COVID-19 vaccine. Factors associated with a greater COVID-19 vaccine uptake included education (up to Std 10 and higher vs. less than Std 10: Odds Ratio [OR], 1.46;95% confidence interval [CI], 1.07-1.99;P = 0.018, and illiterate vs. less than Std 10: OR, 0.70;95% CI, 0.50-0.99;P = 0.041), marital status (unmarried vs. married: OR, 0.27;95% CI, 0.08-1.08;P = 0.046, and widow/widower vs. married: OR, 0.67;95% CI, 0.48-0.94;P = 0.017), lung and gastrointestinal vs. head-and-neck primary tumors (lung cancer vs. head-and-neck cancer: OR, 1.60;95% CI, 1.02-2.47;P = 0.038, and gastrointestinal vs.head-and-neck cancer: OR, 2.18;95% CI, 1.37-3.42;P < 0.001), and place of residence (west zone vs. central India: OR, 0.34;95% CI, 0.13-0.75;P = 0.015). Conclusion(s): Fewer than 1 in 100 older Indian patients with cancer receive routine immunization with influenza and pneumococcal vaccines. Hearteningly, the uptake of COVID-19 vaccination in older Indian patients with cancer is over 80%, possibly due to the global recognition of its importance during the pandemic. Similar measures as those used to increase the uptake of COVID-19 vaccines during the pandemic may be beneficial to increase the uptake of routine vaccinations.Copyright © 2023 Cancer Research, Statistics, and Treatment.

Evolution and trends in entrepreneurial finance: reflections and insights from COVID-19

Entrepreneurship contributes substantially to the modernization and commercial development of an economy. Access to financial resources is key to the successful operation of new ventures which is arrested by COVID-19. Therefore, the present study aims to address the architecture of entrepreneurial finance since the inception of COVID-19. The research adopts a Systematic literature review approach to study the 127 articles chosen for analysis. The findings reveal the usage of novel sources of finance such as crowdfunding, and Initial Coin Offerings during COVID-19. Apart from this, the research also encapsulates the contributions of the articles on venture capital, P2P lending, and angel finance. Also, the study highlights promising avenues for future research focusing on different financing options and drivers of financing choices. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Intelligent Approach to Combat COVID-19: An Insight Analysis

COVID-19 – the utmost global crisis and the major global pandemic is literally changing our life. Every person is observing at the everyday rise of the death toll and the fast, exponential growth of this novel and dynamic strain of the virus. To find the effective treatment, the virus source prediction, infection classifications are important issues to be addressed. As we are waiting to get rid of this situation and waiting to know the peak and down fall timing of this pandemic, forecasting of epidemic development is also important issue to be addressed. In this present chapter we have used some mathematical modeling and Artificial Intelligence based or more specifically Machine learning based approaches to combat this pandemic. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

A phenoxy-bridged trinuclear Ni(ii) complex: synthesis, structural elucidation and molecular docking with viral proteins

A novel phenoxy-bridged trinuclear nickel(ii) complex [Ni3(mu-L)2(bipy)3](1) (where H3L= (E)-2-hydroxy-N-(2-hydroxy-3,5-diiodophenyl)-3,5-diiodobenzohydrazonic acid, bipy = 2,2'-bipyridyl) has been designed and synthesized as a potential antivirus drug candidate. The trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) was fully characterized via single crystal X-ray crystallography. The unique structure of the trinuclear nickel(ii) complex crystallized in a trigonal crystal system with P3221 space group and revealed distorted octahedral coordination geometry around each Ni(ii) ion. The X-ray diffraction analysis established the existence of a new kind of trinuclear metal system containing nickel(ii)-nickel(ii) interactions with an overall octahedral-like geometry about the nickel(ii) atoms. The non-bonded Ni-Ni distance seems to be 3.067 and 4.455 A from the nearest nickel atoms. The detailed structural analysis and non-covalent supramolecular interactions are also investigated by single crystal structure analysis and computational approaches. Hirshfeld surfaces (HSs) and 2D fingerprint plots (FPs) have been explored in the crystal structure to investigate the intermolecular interactions. The preliminary analysis of redox and magnetic characterization was conducted using cyclic voltammetry measurements and a vibrating sample magnetometer (VSM), respectively. This unique structure shows good inhibition performance for SARS-CoV-2, Omicron and HIV viruses. For insight into the potential application of the Ni(ii) coordination complex as an effective antivirus drug, we have examined the molecular docking of the trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) with the receptor binding domain (RBD) from SARS-CoV-2 (PDB ID: 7MZF), Omicron BA.3 variant spike (PDB ID: 7XIZ), and HIV protease (PDB ID: 7WCQ) viruses. This structure shows good inhibition performance for SARS-CoV-2, Omicron S protein and HIV protease viruses;the binding energies (DELTAG) and the respective Ki/Kd (inhibition/dissociation constants) correlation values are -8.9 (2.373 muM or 2373 nM), -8.1 (1.218 muM or 1218 nM) and -7.9 (0.874 muM or 874 nM), respectively. The results could be used for rational drug design against SARS-CoV-2 Omicron variant and HIV protease viruses.Copyright © 2023 The Royal Society of Chemistry.

In Silico Drug Repositioning for COVID-19: Progress and Challenges

he COVID-19 pandemic caused by SARS-CoV-2 has shown a rapid increase in the number of infected patients with a remarkable mortality rate, making it a global public health concern. Because there is currently no specific anti-viral drug for the treatment of COVID-19, repurposing of already approved drugs for other diseases may be explored. Drug repurposing has become a promising approach due to the opportunity to reduce development timelines and overall costs. In this chapter, we will discuss various computational drug repositioning strategies, the current COVID-19 treatment scenario, and challenges to the correct interpretation of existing preclinical/clinical evidence, as well as the generation of new evidence related to drug repurposing. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Reinforcement Learning-based Counter-Misinformation Response Generation: A Case Study of COVID-19 Vaccine Misinformation

The spread of online misinformation threatens public health, democracy, and the broader society. While professional fact-checkers form the first line of defense by fact-checking popular false claims, they do not engage directly in conversations with misinformation spreaders. On the other hand, non-expert ordinary users act as eyes-on-the-ground who proactively counter misinformation - recent research has shown that 96% counter-misinformation responses are made by ordinary users. However, research also found that 2/3 times, these responses are rude and lack evidence. This work seeks to create a counter-misinformation response generation model to empower users to effectively correct misinformation. This objective is challenging due to the absence of datasets containing ground-truth of ideal counter-misinformation responses, and the lack of models that can generate responses backed by communication theories. In this work, we create two novel datasets of misinformation and counter-misinformation response pairs from in-the-wild social media and crowdsourcing from college-educated students. We annotate the collected data to distinguish poor from ideal responses that are factual, polite, and refute misinformation. We propose MisinfoCorrect, a reinforcement learning-based framework that learns to generate counter-misinformation responses for an input misinformation post. The model rewards the generator to increase the politeness, factuality, and refutation attitude while retaining text fluency and relevancy. Quantitative and qualitative evaluation shows that our model outperforms several baselines by generating high-quality counter-responses. This work illustrates the promise of generative text models for social good - here, to help create a safe and reliable information ecosystem. The code and data is accessible on https://github.com/claws-lab/MisinfoCorrect. © 2023 Owner/Author.

MicroRNAs and COVID-19

Currently, there are no reliable biomarkers for identifying COVID-19 patients and no definite therapeutics to control this deadly disease. MicroRNAs (miRNA) have been explored in several human diseases for their potential role as biomarkers and their therapeutic potential. However, there is very little information available about the roles of miRNAs in COVID-19 infection. This chapter outlines the recent updates and developments of miRNAs in COVID-19 such as miRNAs as potential biomarkers for COVID-19, the molecular basis of miRNAs in COVID-19 infection, and the use of miRNAs as therapeutics targets for COVID-19. While a few potential miRNAs have been researched for the aforementioned reasons, more research is needed to determine the roles of individual miRNAs in COVID-19 infection. © 2023 Elsevier Inc. All rights reserved.

Food bioactive compounds, sources, and their effectiveness during COVID-19

Since the occurrence of COVID-19 pandemic in the late 2019, it has impacted to almost all the countries throughout the world by its severity of infection. The vaccines or drugs to combat the SARS-CoV-2 infection were not available till recent time, and the people looked out for healthy foods, which help to increase the immune response. Even after the vaccines have been developed for the COVID-19, the importance of food-based diet cannot be neglected due to their health beneficial properties, which are required post-COVID-19 infection or during the incubation duration of infection. Several food groups and their products have been known to provide vital nutrients, which are required for proper functioning of human body. Along with nutrients, these foods are known to have various nonnutrients components, which help in reduction or management of several physiological disorders. These compounds are collectively known as bioactive compounds, which are naturally synthesized. These compounds are widely spread and abundantly found in plant-based foods. The major groups of bioactive compounds present in foods include polyphenols, carotenoids, bioactive carbohydrates, and phytosterols. These compounds are known to have mainly the properties of antioxidant, anti-inflammatory, anticancerous, and antimicrobial, which helps in keeping the human body healthy. In this chapter, the main bioactive compounds, their classification, and food sources have been highlighted, which will give an insight of their beneficial effects. The bioactive compounds will have a major role in reduction of inflammation and infection through several complex physiological mechanism, thereby involved in increasing the immunity. Hence, these compounds play a vital role in management or reduction of COVID-19 infection through the effectiveness of bioactive compounds. © 2023 Elsevier Inc. All rights reserved.

Repurposing of reception shaft, Mumbai Coastal Road Project – Case study

As part of Mumbai Coastal Road Project-the connection between Nariman Point and Bandra Worli, a total length of 10.58 km-Package IV (MCRP4) includes submarine twin tube tunnels. Current Package's total length is 4,480 m, of which 2,008 m are excavated by means of one slurry shield and supported/lined by precast segments. Each tube will accommodate a three-lane carriageway, for an internal diameter of 11 m and an excavation diameter 12.19 m. To enable the launching and receiving of the TBM, two shafts were constructed at North end and South end of the package. The reception shaft is 42m long and 30m wide with a depth of 26m below the ground formation level at +3.0 msl. The intention was to disassemble the TBM after the first drive to reassemble and relaunch it from the original shaft – the "launch-ing shaft”. However, due to logistical constraints, given the project location in a dense urban setting, and due to time delays, because of stoppage of works during Covid lockdown, the Contractor of the project decided to relaunch the TBM from the reception shaft itself by rotating the TBM and save approx. 60-75 days. Due to this dynamic need of the project, reception shaft was repurposed for relaunching with additional ancillary structures (like Heavy weight modular gantry crane foundations, TBM reaction frame, Slurry treatment plant on surface etc.,) in and around the shaft which weren't foreseen during the excavation of shaft. This paper discusses design aspects with special focus on challenges which were needed for this repurposing of shaft. © 2023 The Author(s).

Global inequality and global crises: Past and present

The developed, developing, and least developed countries have been experiencing differing levels of inequality over the years. The economic and financial crises have also been aggravating the extent of inequality. The Sustainable Development Goal (SDG) 10 emphasizes reducing inequality that is prevalent within and amongst the countries. The COVID-19 pandemic is expected to reverse the progress made so far in reducing inequality. Hence, the average Gini coefficient is expected to increase by 6% for emerging and developing countries. Therefore, the present study aims to undertake an analysis of the impact of past crises and the current COVID-19 crisis on global inequalities. The world inequality database has been utilized for analyzing the impact. This study will certainly enable the policymakers to implement policies with the help of which the SDG 10 can ultimately be achieved by 2030. © 2022, IGI Global. All rights reserved.

Fungal Profile in Non-Invasive Fungal Sinusitis Using PCR in Post-Covid Scenario at a Tertiary-Care Centre in India

Objective: To detect the presence of Mucorales in the sinuses of healthy individuals and non-invasive fungal sinusitis patients. Materials and methods: Post FESS specimens with appearance suggestive of fungal ball or allergic mucin from 30 immunocompetent patients was sent for KOH smear, HPE, fungal culture and PCR. Results: Fungal culture was positive for Aspergillus flavus in one specimen. PCR demonstrated Aspergillus (21), Candida (14), and Rhizopus in one case. HPE detected mainly Aspergillus in 13 specimens. No fungal presence in four cases. Discussion: There was no significant undetected Mucor colonisation. PCR proved to be the most sensitive test in reliably detecting the organisms. No significant variation in the pattern of fungi were detected between COVID-19 infected and non-infected, but for the slightly higher detection of candida in the COVID-19 infected group. Conclusion: There was no significant presence of Mucorales in non-invasive fungal sinusitis patients in our study.

Role of multimedia innovative technology in green banking

Purpose: Progression is an unpreventable reality of presence, and banking is no exclusion. Cash transformers and moneylenders from times gone past are great agents today. Cash held in trust became store taking, and money advancing became credit making;over an extended time, banks transformed into a need, and the occupation of banks, transformed into a critical piece of monetary reality. Banks' turn of events and headway has been mind-boggling, with the latest frenzy being intuitive media banking. The chapter additionally framed the amazing open doors and dangers for banks because of the presentation of innovations and how banks are making the most of the open doors and endeavouring to cure the risks. The financial area in India is a lifesaver for the country. Indian banks could become the fifth most prominent on earth by 2020 and the third most prominent by 2025. Methodology: This study has given auxiliary information. Furthermore, it's gathered from the holding bank of India concerning utilisation by various banks. Which utilised graphic review including mean mode middle. Finding: After the review, we find that sight, sound, and green banking have become fantastic assets for the baking area. During COVID-19, the utilisation of mixed media expanded in contrast to a year ago. Significance: The review featured sight and sound and green banking sealed spine in COVID -19 and is utilised expanded after this pandemic. © 2023 by Seval Kardes Selimoglu and Mustafa Hakan Saldi. All rights reserved.

Hybrid deep neural network for automatic detection of COVID-19 using chest x-ray images

The 2019 coronavirus (COVID-19), started in China, spreads rapidly around the entire world. In automated medical imagery diagnostic technique, due to presence of noise in medical images and use of single pre-trained model on low quality images, the existing deep network models cannot provide the optimal results with better accuracy. Hence, hybrid deep learning model of Xception model & Resnet50V2 model is proposed in this paper. This study suggests classifying X-ray images into three categories namely, normal, bacterial/viral infections and Covid positive. It utilizes CLAHE & BM3D techniques to improve visual clarity and reduce noise. Transfer learning method with variety of pre-trained models such as ResNet-50, Inception V3, VGG-16, VGG-19, ResNet50V2, and Xception are used for better feature extraction and Chest X-ray image classification. The overfitting issue were resolved using K-fold cross validation. The proposed hybrid deep learning model results high accuracy of 97.8% which is better than existing techniques.

Correlation between screen time and psychosomatic symptoms in children during COVID-19 pandemic-related lockdown.

Background: This study was planned to estimate the effect of lockdown on psychosomatic problems and sleep of children and their association with screen the time during the lockdown. Methods: A cross-sectional study was conducted among 1-12-year-old children at a tertiary care hospital in South India. A pre-validated questionnaire with 20 related questions was disseminated through pediatric OPD, telemedicine service, and social media to eligible parents. Results: A total of 278 children aged 1-12 years with a mean (SD) age of 6.92 (3.01) years were studied. Most under 5-year-oldchildren had screen time of ≤2 hours/day, whereas 58.16% of children between 5 and 12 years spent >4 hours/day (P < 0.000). A significant proportion of participants aged 5-12 years had vision problems (P = 0.019), whereas under 5-year-old children had significant associated behavioral changes (P = 0.016) and sleep problems (P = 0.043). Conclusion: Behavioral and sleep problems were significantly high and correlated with an increase in screen time among under 5-year-old children. Vision problems were more in 5-12-year-old children.

Faculty Perceptions of E-Mentoring Doctoral Dissertations: Challenges, Strategies, and Institutional Support

Faculty members who e-mentor dissertations in online doctoral programs, or remotely as a result of COVID-19 participated in an open-ended survey about strategies that helped them succeed, challenges they faced, and institutional support they would find helpful. Consistent communication, individualized support, and structure were found helpful for e-mentoring dissertations. Faculty overwhelmingly cited time, workload, and lack of institutional support as challenges, and stated that institutions could help e-mentors by providing support with the process, research resources, writing support, and time and incentives for e-mentoring. The results are discussed with recommendations for institutional support for dissertation e-mentoring.