A Retrospective Study on “Effectiveness of Remote Patient Monitoring in Covid-19 patients"

Corona virus disease19 has spread over the world, affecting millions of people. It has put enormous strain on the global healthcare system. Due to frequent mutations, the pandemic is spreading rapidly. The world requires a technology that will facilitate the effective diagnosis, treatment, and discharge of COVID19 patients. A model like remote patient monitoring [RPM] makes it easier to handle Covid 19 patients. RPM helps in remotely diagnosis, treatment, as well as allowing for prompt interventions. The RPM makes use of mobile technology and IoT platforms to take clinical interventions. In this study out of 151 covid19 positive subjects 91% of them were shifted to home monitoring within 5 days of MVM monitoring with few readmissions. The study investigated the effectiveness of RPM in the Indian healthcare system, as well as the performance and usability of the Vigocare mobile application by patients and doctors.

Monoclonal antibodies and their target specificity against SARS-CoV-2 infections: Perspectives and challenges Short title: Monoclonal antibodies and SARS-CoV-2 infections

The world continues to be in the midst of a distressing pandemic of coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel virus with multiple antigenic systems. The virus enters via nasopharynx, oral and infects cells by the expression of the spike protein, and enters the lungs using the angiotensin-converting enzyme-2 receptor. The spectrum of specific immune responses to SARS-CoV-2 virus infection is increasingly challenging as frequent mutations have been reported and their antigen specificity varies accordingly. The development of monoclonal antibodies (mAbs) will have a more significant advantage in suppressing SARS-CoV-2 virus infectivity. Recently, mAbs have been developed to target specific neutralizing antibodies against SARS-CoV-2 infection. The use of the therapeutic index of mAbs that can elicit neutralization by binding to the viral spike protein and suppress the cytokine network is a classic therapeutic approach for a potential cure. The development of mAbs against B-cell function as well as inhibition of the cytokine network has also been a focus in recent research. Recent studies have demonstrated the efficacy of mAbs as antibody cocktail preparations against SARS-CoV-2 infection. Target specific therapeutic accomplishment with mAbs, a milestone in the modern therapeutic age, can be used to achieve a specific therapeutic strategy to suppress SARS-CoV-2 virus infection. This review focuses on the molecular aspects of the cytokine network and antibody formation to better understand the development of mAbs against SARS-CoV-2 infection.

Novel Herbal Formulation Jing Si Exhibits Multiple Functions to Inhibit Replication Activity and Subsides Viral Load of COVID-19 Variants

Background: SARS-CoV-2 is susceptible to frequent mutations and gets transformed into variants therefore identifying novel multi targeting remedies is necessary in formulating strategies to overcome the pandemic. Methods: Traditional Chinese medicine based formula Jing Si herbal (JSH) was screened and analyzed by HPLC to evaluate its ability to act against infection by SARS-CoV-2 variants. The 3CL protease and RdRp assay kit were utilized to detect the enzyme activity. In order to determine the effect of JSH on the binding efficiency and viral penetration of SARS-CoV-2 variants, Calu-3 lung cells and Caco-2 colon cells were infected with fluorescent SARS-CoV-2 pseudo type lentiviruses. In addition, the effect of JSH (16.22 mg /mice/day and 48.66 mg/mice/day) on the viral load in SKH1J mice exposed to inhalation of luminescent SARS-CoV-2 variants for three days was determined. Results: The JSH was found to be effective in inhibiting the viral entry into Calu-3 and Caco-2 cells and in mice pre-treated with JSH for 3 days also inhibited the viral load exposed to different SARS-CoV-2 variants. Interestingly, JSH also decreased 3cL and RdRp activity thereby revealing the multi targeting nature of JSH and therefore will be a potential preventive SARS-CoV-2 infection.Conclusion: Taken together, our present results revealed that JSH could be a potential candidate for COVID-19 treatment.

Somatic Mutations in TP53 Gene in Colombian Patients With Non-melanoma Skin Cancer

Background/Aim: Non-melanoma skin cancer is the most common cancer in the world. Somatic mutations in the TP53 gene are associated with the development of this cancer. To describe mutations in exons 5-8 of the TP53 gene in a sample of Colombian patients with non-melanoma skin cancer. Materials and Methods: One hundred and fifteen patients with non-melanoma skin cancer were included. Exons 5-8 were amplified and analyzed by PCR-High Resolution Melting and Sanger sequencing. Results: Fifty-seven patients with basal cell carcinomas and 58 with squamous cell carcinomas were studied. 16% of patients with basal cell carcinoma and 26% of patients with squamous cell carcinoma had mutations in the TP53 gene. The most frequent mutations were substitutions, while three patients had deletions. The most frequent mutation was p.R158G. Conclusion: The analysis showed that Colombian individuals with non-melanoma skin cancer have genetic TP53 variants different from those reported as recurrent for this disease.

Recent Advances in the Genetic of MALT Lymphomas

Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.

RIGI, TLR7, and TLR3 Genes Were Predicted to Have Immune Response Against Avian Influenza in Indigenous Ducks

Avian influenza is a disease with every possibility to evolve as a human-to-human pandemic arising out of frequent mutations and genetic reassortment or recombination of avian influenza (AI) virus. The greatest concern is that till date, no satisfactory medicine or vaccines are available, leading to massive culling of poultry birds, causing huge economic loss and ban on export of chicken products, which emphasizes the need to develop an alternative strategy for control of AI. In the current study, we attempt to explore the molecular mechanism of innate immune potential of ducks against avian influenza. In the present study, we have characterized immune response molecules such as duck TLR3, TLR7, and RIGI that are predicted to have potent antiviral activities against the identified strain of avian influenza through in silico studies (molecular docking) followed by experimental validation with differential mRNA expression analysis. Future exploitation may include immunomodulation with the recombinant protein, and transgenic or gene-edited chicken resistant to bird flu.

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.

Low Represented Mutation Clustering in SARS-CoV-2 B.1.1.7 Sublineage Group with Synonymous Mutations in the E Gene

Starting in 2019, the COVID-19 pandemic is a global threat that is difficult to monitor. SARS-CoV-2 is known to undergo frequent mutations, including SNPs and deletions, which seem to be transmitted together, forming clusters that define specific lineages. Reverse-Transcription quantitative PCR (RT-qPCR) has been used for SARS-CoV-2 diagnosis and is still considered the gold standard method. Our Eukaryotic Host Pathogens Interaction (EHPI) laboratory received six SARS-CoV-2-positive samples from a Sicilian private analysis laboratory, four of which showed a dropout of the E gene. Our sequencing data revealed the presence of a synonymous mutation (c.26415 C > T, TAC > TAT) in the E gene of all four samples showing the dropout in RT-qPCR. Interestingly, these samples also harbored three other mutations (S137L—Orf1ab; N439K—S gene; A156S—N gene), which had a very low diffusion rate worldwide. This combination suggested that these mutations may be linked to each other and more common in a specific area than in the rest of the world. Thus, we decided to analyze the 103 sequences in our internal database in order to confirm or disprove our “mutation cluster hypothesis”. Within our database, one sample showed the synonymous mutation (c.26415 C > T, TAC > TAT) in the E gene. This work underlines the importance of territorial epidemiological surveillance by means of NGS and the sequencing of samples with clinical and or technical particularities, e.g., post-vaccine infections or RT-qPCR amplification failures, to allow for the early identification of these SNPs. This approach may be an effective method to detect new mutational clusters and thus to predict new emerging SARS-CoV-2 lineages before they spread globally.

Impact of SARS-CoV-2 Mutations on Global Travel and the Increasing Number of Re-Infections: A Risk-Assessment Perspective

The outbreak of coronavirus disease 2019 (COVID-19) has stunned the world owing to the surreal, unprecedented, and completely unbelievable manner in which it has spread globally within a short span of time. This spread has led to the common combination of variety and has promoted the passage of species blockade and genetic combination of these types of viruses. Despite the short history of the COVID-19 outbreak, with its global spread and frequent mutations, it has impacted the whole world and has become a worrying threat to the society. Scientific reports have disclosed that members of the coronavirus family, such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-NL63, HCoV-229E, HCoV-OC43, and HKU1 have infected the humans earlier too and that mutations in these viruses have resulted in the more complex severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the present review, we have discussed how scientists keep track of the genetic tweaks to SARS-CoV-2 as it spreads globally. Currently, the only way to prevent more such outbreaks is maintaining social distancing, adhering to the World Health Organization guidelines and de-globalizing the world. Genetic variations/mutations reported to date in coronaviruses hint at their cryptic spread. Scientists are scouring the viral genome for mutations that might reveal how dangerous the pathogen is or how fast it spreads. Cases have been documented in almost all countries, and the mutations in the virus have created problems for the researchers in formulating effective vaccines. Furthermore, global travel has been severely affected after the new mutants have been detected. Therefore, more scientific investigations are necessary to understand how SARS-CoV-2 is likely to mutate in the future.

Frequent SLC12A3 mutations in Chinese Gitelman syndrome patients: structure and function disorder

Purposes: This study was conducted to identify the frequent mutations from reported Chinese Gitelman syndrome (GS) patients, to predict three-dimensional structure change of human Na-Cl co-transporter (hNCC), and to test the activity of these mutations and some novel mutations in vitro and in vivo. Methods: SLC12A3 gene mutations in Chinese GS patients previously reported in the PubMed, CNKI and Wanfang database were summarized. Predicted configurations of wild type (WT) and mutant proteins were achieved using the I-TASSER workplace. Six missense mutations (T60M, L215F, D486N, N534K, Q617R and R928C) were generated by site-directed mutagenesis. 22Na+ uptake experiment was carried out in the Xenopus laevis oocyte expression system. 35 GS patients and 20 healthy volunteers underwent the thiazide test. Results: T60M, T163M，D486N, R913Q, R928C and R959 frameshift were frequent SLC12A3 gene mutations (mutated frequency >3%) in 310 Chinese GS families. The protein’s three-dimensional structure was predicted to be altered in all mutations. Compared with WT hNCC, the thiazide-sensitive 22Na+ uptake was significantly diminished for all 6 mutations: T60M 22±9.2%, R928C 29±12%, L215F 38±14%, N534K 41±15.5%, Q617R 63±22.1% and D486N 77±20.4%. In thiazide test, the net increase in chloride fractional excretion in 20 healthy controls was significantly higher than GS patients with or without T60M or D486N mutations. Conclusions: Frequent mutations (T60M, D486N, R928C) and novel mutations (L215F, N534K and Q617R) lead to protein structure alternation and protein dysfunction verified by 22Na+ uptake experiment in vitro and thiazide test on patients.