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The document "Clinical Aspects of Infectious Diseases" provides an overview of various infectious diseases and their clinical aspects, including COVID-19, hepatitis B and C, HIV/AIDS, tuberculosis, malaria, and others. It also includes summaries of research articles on topics such as Klebsiella pneumoniae infection, candidemia, otitis and sinusitis in HIV-positive patients, myalgic encephalomyelitis/chronic fatigue syndrome, urinary tract infections, neurotuberculosis, community-acquired pneumonia, hospital-acquired pneumonia, vulvovaginal candidiasis, colorectal cancer, leptospirosis, and methicillin-resistant Staphylococcus aureus (MRSA) infections. These summaries provide insights into the prevalence, diagnosis, treatment, and impact of these diseases. The article emphasizes the importance of timely diagnosis, interdisciplinary collaboration, and increased funding for the control of infectious diseases. [Extracted from the article]

The Hepatitis B virus (HBV) HBx and HBc proteins play a crucial role in associating with covalently closed circular DNA (cccDNA), the primary factor contributing to intrahepatic viral persistence and a major obstacle in achieving a cure for HBV. The cccDNA serves as a reservoir for viral persistence. Targeting the viral HBc and HBx proteins' interaction with cccDNA could potentially limit HBV replication. In this study, we present epitopes identified from global consensus sequences of HBx and HBc proteins that have the potential to serve as targets for the development of effective vaccine candidates. Furthermore, conserved residues identified through this analysis can be utilized in designing novel, site-specific anti-HBV agents capable of targeting all major genotypes of HBV. Our approach involved designing global consensus sequences for HBx and HBc proteins, enabling the analysis of variable regions and highly conserved motifs. These identified motifs and regions offer potent sites for the development of peptide vaccines, the design of site-specific RNA interference, and the creation of anti-HBV inhibitors. The epitopes derived from global consensus sequences of HBx and HBc proteins emerge as promising targets for the development of effective vaccine candidates. Additionally, the conserved residues identified provide valuable insights for the development of innovative, site-specific anti-HBV agents capable of targeting all major genotypes of HBV from A to J. [ABSTRACT FROM AUTHOR]

Dentistry is a branch of healthcare where nanobiotechnology is reverberating in multiple ways to produce beneficial outcomes. The purpose of this review is to bring into the awareness of the readers the various practical dimensions of the nano-dental complex (nanodentistry) in healthcare and how novelties linked with the field are revolutionizing dentistry. A methodological approach was adopted to collect the latest data on nanotechnology and dentistry from sources, including PubMed, Google Scholar, Scopus, and official websites like the WHO. Nanodentistry is an emerging field in dentistry that involves the use of nanomaterials, nanorobots, and nanotechnology to diagnose, treat, and prevent dental diseases. The results summarize the descriptive analyses of the uses of nanodentistry within orthodontics, preventive dentistry, prosthodontics, restorative dentistry, periodontics, dental surgeries, dental restoration technologies, and other areas of dentistry. The future directions of nano-industries and nano-healthcare have been included to link them with the oral healthcare sector, treatment plans, and improved medical services which could be explored in the future for advanced healthcare regulation. The major limitations to the use of dental nanoproducts are their cost-effectiveness and accessibility, especially in financially constrained countries. These data will help the readers to experience a detailed analysis and comprehensive covering of the diverse achievements of nanodentistry with past analyses, present scenarios, and future implications. [ABSTRACT FROM AUTHOR]

Knowing the beneficial aspects of nanomedicine, scientists are trying to harness the applications of nanotechnology in diagnosis, treatment, and prevention of diseases. There are also potential uses in designing medical tools and processes for the new generation of medical scientists. The main objective for conducting this research review is to gather the widespread aspects of nanomedicine under one heading and to highlight standard research practices in the medical field. Comprehensive research has been conducted to incorporate the latest data related to nanotechnology in medicine and therapeutics derived from acknowledged scientific platforms. Nanotechnology is used to conduct sensitive medical procedures. Nanotechnology is showing successful and beneficial uses in the fields of diagnostics, disease treatment, regenerative medicine, gene therapy, dentistry, oncology, aesthetics industry, drug delivery, and therapeutics. A thorough association of and cooperation between physicians, clinicians, researchers, and technologies will bring forward a future where there is a more calculated, outlined, and technically programed field of nanomedicine. Advances are being made to overcome challenges associated with the application of nanotechnology in the medical field due to the pathophysiological basis of diseases. This review highlights the multipronged aspects of nanomedicine and how nanotechnology is proving beneficial for the health industry. There is a need to minimize the health, environmental, and ethical concerns linked to nanotechnology. [ABSTRACT FROM AUTHOR]

Background: The years 2022–2023 witnessed a monkeypox virus (mpox) outbreak in some countries worldwide, where it exists in an endemic form. However, the number of infectious cases is continuously on the rise, and there has been an unexpected, drastic increase in cases that result from sustained transmission in non-endemic regions of the world. Under this scenario, it is pertinent for the world to be aware of healthcare threats to mpox infection. This review aimed to compile advanced data regarding the different aspects of mpox disease. Methods: A comprehensive strategy for the compilation of recent data was adopted to add data regarding mpox, biology, viral pathology, immune response, and brief details on the antiviral strategies under trial; the search was limited to 2016–2023. The aim is to make the scientific community aware of diverse aspects of mpox. Results: Consequently, detailed insights have been drawn with regard to the nature, epidemiology, etiology, and biological nature of mpox. Additionally, its host interaction and viral infectious cycle and immune interventions have been briefly elaborated. This comprehensively drawn literature review delivers brief insights into the biological nature, immune responses, and clinical developments in the form of therapeutics against mpox. This study will help scientists understand the biological nature and responses in hosts, which will further help clinicians with therapeutic handling, diagnosis, and treatment options. Conclusions: This study will provide updated information on mpox's pathology, immune responses, and antiviral strategies. Moreover, it will also help the public to become educated on the healthcare-associated threat and take timely mitigation measures against expected mpox outbreaks in the future. [ABSTRACT FROM AUTHOR]

Background: Nearly half of the world is at risk of developing dengue infection. Dengue virus is the causative agent behind this public healthcare concern. Millions of dengue cases are reported every year, leading to thousands of deaths. The scientific community is working to develop effective therapeutic strategies in the form of vaccines and antiviral drugs against dengue. Methods: In this review, a methodological approach has been used to gather data from the past five years to include the latest developments against the dengue virus. Results: Different therapeutics and antiviral targets against the dengue virus are at different stages of development, but none have been approved by the FDA. Moreover, various vaccination strategies have also been discussed, including attenuated virus vaccines, recombinant subunit vaccines, viral vector vaccines, DNA vaccines, nanotechnology, and plant-based vaccines, which are used to develop effective vaccines for the dengue virus. Many dengue vaccines pass the initial phases of evaluation, but only two vaccines have been approved for public use. DENGVAXIA is the only FDA-approved vaccine against all four stereotypes of the dengue virus, but it is licensed for use only in individuals 6–16 years of age with laboratory-confirmed previous dengue infection and living in endemic countries. Takeda is the second vaccine approved for use in the European Union, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand. It produced sustained antibody responses against all four serotypes of dengue virus, regardless of previous exposure and dosing schedule. Other dengue vaccine candidates at different stages of development are TV-003/005, TDENV PIV, V180, and some DNA vaccines. Conclusion: There is a need to put more effort into developing effective vaccines and therapeutics for dengue, as already approved vaccines and therapeutics have limitations. DENGVAXIA is approved for use in children and teenagers who are 6–16 years of age and have confirmed dengue infection, while Takeda is approved for use in certain countries, and it has withdrawn its application for FDA approval. [ABSTRACT FROM AUTHOR]

Introduction: H5N1 is a highly pathogenic avian influenza virus that can infect humans and has an estimated fatality rate of 53%. As shown by the current situation of the COVID-19 pandemic, emerging and re-emerging viruses such as H5N1 have the potential to cause another pandemic. Thus, this study outlined the hub genes and pathways associated with H5N1 infection in humans. Methods: The genes associated with H5N1 infection in humans were retrieved from the NCBI Gene database using "H5N1 virus infection" as the keyword. The genes obtained were investigated for protein–protein interaction (PPI) using STRING version 11.5 and studied for functional enrichment analysis using DAVID 2021. Further, the PPI network was visualised and analysed using Cytoscape 3.7.2, and the hub genes were obtained using the local topological analysis method of the cytoHubba plugin. Results: A total of 39 genes associated with H5N1 infection in humans significantly interacted with each other, forming a PPI network with 38 nodes and 149 edges modulating 74 KEGG pathways, 76 biological processes, 13 cellular components, and 22 molecular functions. Further, the PPI network analysis revealed that 33 nodes interacted, forming 1056 shortest paths at 0.282 network density, along with a 1.947 characteristic path length. The local topological analysis predicted IFNA1, IRF3, CXCL8, CXCL10, IFNB1, and CHUK as the critical hub genes in human H5N1 infection. Conclusion: The hub genes associated with the H5N1 infection and their pathways could serve as diagnostic, prognostic, and therapeutic targets for H5N1 infection among humans. [ABSTRACT FROM AUTHOR]

Testing for high-risk human papillomavirus (HPV) as part of primary cervical cancer screening has become more common recently. The Cobas 6800, an FDA-approved cervical screening platform, detects 14 high-risk HPVs, including HPV16 and HPV18. However, this test is limited to only women, which leads to low screening rates in trans men and other non-binary people. The cervical screening of trans men and other genders, especially those lying on the female-to-male spectrum, is equally important. Furthermore, cisgender males, particularly homosexuals, are also prone to chronic HPV infections and serve as HPV carriers, transmitting it to women and other men through sexual contact. Another limitation of the test is its invasive specimen collection, which induces discomfort and genital dysphoria. Therefore, there is a need for an innovative, less invasive method that would allow the sampling process to be more comfortable. In this study, we assess the performance of the Cobas 6800 for high-risk HPV detection in urine samples spiked with HPV16, HPV18, and HPV68. The limit of detection (LOD) was calculated using a dilution series (1.25–10,000 copies/mL) over a course of three days. Furthermore, the clinical validation was performed by calculating sensitivity, specificity, and accuracy. The limit of detection ranged from 50–1000 copies/mL depending upon the genotype. Moreover, the urine test demonstrated a high clinical sensitivity of 93%, 94%, and 90% for HPV16, HPV18, and HPV68, with 100% specificity. The overall percent agreement was calculated to be 95% for both HPV16 and HPV18, and 93% for HPV68. The high concordance, reproducibility, and clinical performance of the current assay suggest that the urine-based HPV test fulfills the requirements for its use in primary cervical screening. Moreover, it has the potential to be used for mass screening to not only identify high-risk individuals, but also to monitor vaccine effectiveness. [ABSTRACT FROM AUTHOR]

Human mpox is an emerging epidemic in the world. The monkey pox virus (MPXV) belongs to the same family of zoonotic Orthopoxviridae as that of the smallpox virus and exhibits similar clinical symptomology. Information regarding its diagnostics, disease epidemiology, surveillance, preventive methods, and treatment strategies are being collated with time. The purpose of this review is to trace the recent events in the scientific platform that have defined new preventive and treatment strategies against mpox. A methodological approach has been used to gather data from the latest literature to comprehensively overview the emerging treatment options. The results portion will cover details regarding the prevention of mpox. It will also shed light on a brief description of contemporary vaccines and antiviral agents that have been evaluated for their treatment potential since the emergence of the mpox threat. These treatment options are setting the pace for controlling the widespread monkeypox infection. However, the limitations attached to these treatment strategies need to be tackled quickly to increase their efficacy so that they can be deployed on a large scale for the prevention of this epidemic becoming another pandemic in this decade. [ABSTRACT FROM AUTHOR]

Mpox (previously named Monkeypox) is one of the neglected viral infectious diseases that remained silent for a long period before finally emerging as a threat to the healthcare system in endemic regions of the world in recent years. It has been mostly centered in African countries but has now been reported in other non-endemic regions as well. While keeping a strict eye on COVID pandemic handling, there is a need to remain concerned and alert about viral threats such as Mpox infections in the future. This situation has altered the healthcare system of endemic regions, including Pakistan, to stay vigilant against the expected Mpox outbreaks in the coming months. Though no specific cases have been reported in Pakistan, the healthcare system needs to take mitigation measures to tackle an expected threat before it arrives. This is important in order to avoid another major shock to the health care system of Pakistan. Moreover, since no specific treatment is available for Mpox, we can only rely upon mitigation measures, involving preventive and treatment strategies devised around some already in-use antiviral agents against Mpox viruses. Moreover, there is an imperative need to proactively prepare the healthcare system against Mpox outbreaks, spread awareness, and involve the public in a participatory approach to stay well prepared against any such infection. Moreover, there is a need to utilize financial sources, aids, and funds wisely, to create awareness in the public about such expected healthcare outbreaks in the future. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a major healthcare concern, especially for immune-compromised individuals and infants below 5 years of age. Worldwide, it is known to be associated with incidences of morbidity and mortality in infants. Despite the seriousness of the issue and continuous rigorous scientific efforts, no approved vaccine or available drug is fully effective against RSV. The purpose of this review article is to provide insights into the past and ongoing efforts for securing effective vaccines and therapeutics against RSV. The readers will be able to confer the mechanism of existing therapies and the loopholes that need to be overcome for future therapeutic development against RSV. A methodological approach was applied to collect the latest data and updated results regarding therapeutics and vaccine development against RSV. We outline the latest throughput vaccination technologies and prophylactic development efforts linked with RSV. A range of vaccination approaches with the already available vaccine (with limited use) and those undergoing trials are included. Moreover, important drug regimens used alone or in conjugation with adjuvants or vaccines are also briefly discussed. After reading this article, the audience will be able to understand the current standing of clinical management in the form of the vaccine, prophylactic, and therapeutic candidates against RSV. An understanding of the biological behavior acting as a reason behind the lack of effective therapeutics against RSV will also be developed. The literature indicates a need to overcome the limitations attached to RSV clinical management, drugs, and vaccine development that could be explained by dealing with the challenges of current study designs with continuous improvement and further work and approval on novel therapeutic applications. [ABSTRACT FROM AUTHOR]

Herpes simplex virus (HSV) is a great concern of the global health community due to its linked infection of inconspicuous nature and resultant serious medical consequences. Seropositive patients may develop ocular disease or genital herpes as characteristic infectious outcomes. Moreover, the infectious nature of HSV is so complex that the available therapeutic options have been modified in certain ways to cure it. However, no permanent and highly effective cure has been discovered. This review generates insights into the available prophylactic and therapeutic interventions against HSV. A methodological research approach is used for study design and data complication. Only the latest data from publications are acquired to shed light on updated therapeutic approaches. These studies indicate that the current antiviral therapeutics can suppress the symptoms and control viral transmission up to a certain level, but cannot eradicate the natural HSV infection and latency outcomes. Most trials that have entered the clinical phase are made part of this review to understand what is new within the field. Some vaccination approaches are also discussed. Moreover, some novel therapeutic options that are currently in research annals are given due consideration for future development. The data can enable the scientific community to direct their efforts to fill the gaps that remain unfilled in terms of therapies for HSV. The need is to integrate scientific efforts to produce a proper cure against HSV to control the virus spread, resistance, and mutation in future disease management. [ABSTRACT FROM AUTHOR]

The US FDA approved Dengvaxia vaccine is available for use in children and adolescents 9-16 years old, with laboratory confirmed evidence of previous dengue virus, and living in dengue endemic areas. Dengvaxia, however, causes a more severe dengue infection if administered to a person who has never had a dengue infection [[8]]. The coverage of the Hepatitis B virus vaccine is 90% among children, but there is a need to increase the birth dose of HBV vaccination in newborns to prevent the vertical transmission of the Hepatitis B virus [[16]]. Several vaccine development techniques, including inactivated vaccines, DNA base vaccines, virus-like particles, virus-like replicon particles, recombinant viral vector vaccines, and plant-based vaccines were used to develop vaccines for the Ebola virus [[18]]. [Extracted from the article]

Nanotechnology, contrary to its name, has massively revolutionized industries around the world. This paper predominantly deals with data regarding the applications of nanotechnology in the modernization of several industries. A comprehensive research strategy is adopted to incorporate the latest data driven from major science platforms. Resultantly, a broad-spectrum overview is presented which comprises the diverse applications of nanotechnology in modern industries. This study reveals that nanotechnology is not limited to research labs or small-scale manufacturing units of nanomedicine, but instead has taken a major share in different industries. Companies around the world are now trying to make their innovations more efficient in terms of structuring, working, and designing outlook and productivity by taking advantage of nanotechnology. From small-scale manufacturing and processing units such as those in agriculture, food, and medicine industries to larger-scale production units such as those operating in industries of automobiles, civil engineering, and environmental management, nanotechnology has manifested the modernization of almost every industrial domain on a global scale. With pronounced cooperation among researchers, industrialists, scientists, technologists, environmentalists, and educationists, the more sustainable development of nano-based industries can be predicted in the future. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPVs) are high-risk causative factors for HPV infection. This infection does not come alone; it is often seen with co-infection with other viruses and acts as a causative agent for several malignancies. The major purpose of this comprehensive study was to highlight some recent advances in biotechnology associated with HPV infection, including understanding its host interactions and cancerous progression. A systematic research strategy was used to gather data from recent, and the most advanced published electronic sources. The compiled data explain the recent understanding of biology, host–viral interaction cycles, co-infection with other viral diseases, and cellular transformation toward malignancies associated with HPV. In recent years, some vaccination protocols have been introduced in the form of live attenuated, subunit, and DNA-based vaccines. Moreover, some strategies of nanotechnology are being employed to synthesize drugs and vaccines with a whole new approach of plant-based products. The data are immense for the proposed research question, yet the need is to implement modern follow-up screening and modern therapeutics at the clinical level and to conduct wide-scale public awareness to lessen the HPV-related disease burden. [ABSTRACT FROM AUTHOR]

The two most familiar scores used for prognostication of liver cirrhosis are the Model for End-stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP), while the Glasgow-Blatchford (GB) score is used for sorting non-variceal upper gastrointestinal hemorrhage into high- or low-risk categories. This study evaluates the validity of the CTP, MELD, and GB scoring systems in prognosticating the in-hospital outcome of bleeding portal hypertensive patients. In this study, the ROC curve and Younden index determine the efficacy of three scoring systems. The results indicate that CTP was the most efficient score as the predictor of outcome (AUC = 0.9, cut-off value > 7); followed by MELD (AUC = 0.8, cut-off value > 18) and then the GB score (AUC = 0.64, cut-off value > 14) (p < 0.05). In pair-wise comparison, the difference between CTP and MELD was insignificant (p > 0.05). Patients with a CTP score of >7 had notably higher in-hospital mortality (19.8% vs. 0.9%, p < 0.0001). Similarly, mortality with a MELD score > 18 was significant (14.8% vs. 5.9% (p < 0.0001). The GB score was not a good indicator of the outcome. Platelets, albumin, CTP, and MELD scores were the independent contributors to mortality. Thus, as liver cirrhosis prognosticators, CTP and MELD scores can also both be used as predictive scores of the in-hospital outcomes of bleeding patients due to portal hypertension. Compared to the GB score, CTP and MELD scores are fairly efficient predictors in these patients. [ABSTRACT FROM AUTHOR]

Mycoplasma genitalium, besides urethritis, causes a number of other sexually transmitted diseases, posing a significant health threat to both men and women, particularly in developing countries. In light of the rapid appearance of multidrug-resistant strains, M. genitalium is regarded as an emerging threat and has been placed on the CDC's "watch list". Hence, a protective vaccine is essential for combating this pathogen. In this study, we utilized reverse vaccinology to develop a chimeric vaccine against M. genitalium by identifying vaccine targets from the reference proteome (Strain G-37) of this pathogen. A multiepitope vaccine was developed using proteins that are non-toxic, non-allergic, and non-homologous to human proteins. Several bioinformatic tools identified linear and non-linear B-cell epitopes, as well as MHC epitopes belonging to classes I and II, from the putative vaccine target proteins. The epitopes that showed promiscuity among the various servers were shortlisted and subsequently selected for further investigation based on an immunoinformatic analysis. Using GPGPG, AAY, and KK linkers, the shortlisted epitope sequences were assembled to create a chimeric construct. A GPI anchor protein immunomodulating adjuvant was adjoined to the vaccine construct's N-terminus through the EAAK linker so as to improve the overall immunogenicity. For further investigations of the designed construct, various bioinformatic tools were employed to study the physicochemical properties, immune profile, solubility, and allergenicity profile. A tertiary chimeric design was computationally modeled using I-TASSER and Robetta and was subsequently refined through GalaxyRefine. ProSA-Web was exploited to corroborate the quality of the construct by detecting errors and the Ramachandran plot was used to identify possible quality issues. Simulation studies of the molecular dynamics demonstrated the robustness and flexibility of the designed construct. Following the successful docking of the designed model to the immune receptors, the construct was computationally cloned into Escherichia coli plasmids to affirm the efficient expression of the designed construct in a biological system. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) usually causes respiratory tract infections of upper airways in infants and young children. Despite recent medical advances, no approved vaccine is available to control RSV infections. Therefore, we conducted an immunoinformatics study to design and evaluate a potential multi-epitope vaccine against RSV. Sequence-based analyses of the glycoproteins F and G revealed a total of eight CD8 T-cell and three CD4 T-cell epitopes after considering antigenicity, binding affinity and other parameters. Molecular docking analysis confirmed that these T-cell epitopes developed strong structural associations with HLA allele(s). By integrating these prioritized epitopes with linkers and a cholera toxin-derived adjuvant, a multi-epitope vaccine was designed. The developed vaccine was found to be stable, non-allergenic, flexible and antigenic. Molecular docking analysis revealed a striking mean HADDOCK score (−143.3) of top-ranked vaccine-TLR cluster and a Gibbs free energy change (ΔG) value of −11.3 kcal mol−1. As per computational immune simulation results, the vaccine generated a high titer of antibodies (especially IgM) and effector T-cells. Also, codon optimization and in silico cloning ensured the increased expression of vaccine in Escherichia coli. Altogether, we anticipate that the multi-epitope vaccine reported in this study will stimulate humoral and cellular responses against RSV infection, subject to follow-up experimental validation. [ABSTRACT FROM AUTHOR]

The tick-borne bacterium, Borrelia burgdorferi has been implicated in Lyme disease—a deadly infection, formerly confined to North America, but currently widespread across Europe and Asia. Despite the severity of this disease, there is still no human Lyme disease vaccine available. A reliable immunoinformatic approach is urgently needed for designing a therapeutic vaccine against this Gram-negative pathogen. Through this research, we explored the immunodominant proteins of B. burgdorferi and developed a novel and reliable vaccine design with great immunological predictability as well as low contamination and autoimmunity risks. Our initial analysis involved proteome-wide analysis to filter out proteins on the basis of their redundancy, homology to humans, virulence, immunogenicity, and size. Following the selection of proteins, immunoinformatic tools were employed to identify MHC class I & II epitopes and B-cell epitopes, which were subsequently subjected to a rigorous screening procedure. In the final formulation, ten common MHC-I and II epitopes were used together with a suitable adjuvant. We predicted that the final chimeric multi-epitope vaccine could invoke B-cell responses and IFN-gamma-mediated immunity as well as being stable and non-allergenic. The dynamics simulations predicted the stable folding of the designed molecule, after which the molecular docking predicted the stability of the interaction between the potential antigenic epitopes and human immune receptors. Our studies have shown that the designed next-generation vaccine stimulates desirable immune responses, thus potentially providing a viable way to prevent Lyme disease. Nevertheless, further experimental studies in a wet lab are needed in order to validate the results. [ABSTRACT FROM AUTHOR]

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses. [ABSTRACT FROM AUTHOR]

Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a multi-epitope-based vaccine against hantavirus. A set of 340 experimentally reported epitopes were retrieved from Virus Pathogen Database and Analysis Resource (ViPR) and subjected to different analyses such as antigenicity, allergenicity, solubility, IFN gamma, toxicity, and virulent checks. Finally, 10 epitopes which cleared all the filters used were linked with each other through specific GPGPG linkers to construct a multi-antigenic epitope vaccine. The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and check the potency of vaccine with each adjuvant. The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability. To understand the vaccine binding affinity with immune cell receptors, molecular docking was performed between the designed vaccines and TLR4; the docked complex with a low level of global energy was then subjected to molecular dynamics simulations to validate the docking results and dynamic behaviour. The docking binding energy of vaccines with TLR4 is −29.63 kcal/mol (TLR4-agonist), −3.41 kcal/mol (β-defensin), and −11.03 kcal/mol (50S ribosomal protein L7/L12). The systems dynamics revealed all three systems to be highly stable with a root-mean-square deviation (RMSD) value within 3 Å. To test docking predictions and determine dominant interaction energies, binding free energies of vaccine(s)–TLR4 complexes were calculated. The net binding energy of the systems was as follows: TLR4-agonist vaccine with TLR4 (MM–GBSA, −1628.47 kcal/mol and MM–PBSA, −37.75 kcal/mol); 50S ribosomal protein L7/L12 vaccine with TLR4 complex (MM–GBSA, −194.62 kcal/mol and MM–PBSA, −150.67 kcal/mol); β-defensin vaccine with TLR4 complex (MM–GBSA, −9.80 kcal/mol and MM–PBSA, −42.34 kcal/mol). Finally, these findings may aid experimental vaccinologists in developing a very potent hantavirus vaccine. [ABSTRACT FROM AUTHOR]

(1) Background: Immune compromised hemodialysis patients are more likely to develop COVID-19 infections, which increase the risk of mortality. The benefits of Remdesivir, despite less literature support on its effectiveness in dialysis patients due to renal toxicity, can outweigh the risks if prescribed early. The aim of this study was to evaluate the efficacy of Remdesivir on the 30-day in-hospital clinical outcome of hemodialysis population with COVID-19 infection and safety endpoints of adverse events. (2) Study design: A prospective quasi-experimental study design was used in the study. (3) Methods: The sample population consisted of 83 dialysis patients with COVID-19 who were administered Remdesivir at a dose of 100 mg before hemodialysis, as per hospital protocol. After the treatment with Remdesivir, we assessed the outcomes across two endpoints, namely primary (surviving vs. dying) as well as clinical and biochemical changes (ferritin, liver function test, C-reactive protein, oxygen requirements, and lactate dehydrogenase levels) and secondary (adverse effects, such as diarrhea, rise in ALT). In Kaplan–Meier analysis, the survival probabilities were compared between patients who received Remdesivir within 48 h of diagnosis and those who received it after 48 h. Cox regression analysis was employed to determine the predictors of outcome. (4) Results: Of the 83 patients, 91.5% survived and 8.4% died. Remdesivir administration did not reduce the death rate overall. Hospital stays were shorter (p = 0.03) and a nasopharyngeal swab for COVID-19 was negative earlier (p = 0.001) in survivors who had received Remdesivir within 48 h of diagnosis compared to those who had received Remdesivir after 48 h. The only variables linked to the 30-day mortality were serum CRP (p = 0.028) and TLC (p = 0.013). No major adverse consequences were observed with Remdesivir. (5) Conclusions: Remdesivir has the potential to shorten the recovery time for dialysis patients if taken within 48 h of onset of symptoms, without any adverse effects. [ABSTRACT FROM AUTHOR]

(1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome of patients with severe COVID-19 infection. (2) Material and Methods: An analysis of a retrospective cohort was carried out on patients with severe COVID-19 infection in a high-dependency unit (HDU) between February and July 2021. In total, 557 patients were included in this study. Patients who did not receive steroids (124) were excluded. Patients were divided into three groups based on dosages of steroids (Dexamethasone = 6 mg/day, Dexamethasone > 6 mg/day, and Methylprednisolone = 500 mg/day), given for 10 days. First, clinical outcome was evaluated on the 10th day of steroid administration in relation to mode of oxygen delivery. Then, Kaplan–Meier analysis was employed to determine 30 day in-hospital survival in relation to the use of steroid. (3) Results: Three groups were statistically equal according to biochemical characteristics. After 10 days of Methylprednisolone = 500 mg/day vs. Dexamethasone = 6 mg/day, 10.9% vs. 6.2% of patients required invasive ventilation (p = 0.01). The 30 day in-hospital mortality was lowest, 3%, in individuals receiving Dexamethasone = 6 mg/day, compared to 3.9% in individuals receiving Dexamethasone > 6 mg/day and 9.9% in individuals receiving Methylprednisolone = 500 mg/day, respectively. The median elapsed time was longer than 28 days between admission and outcome for Dexamethasone = 6 mg/day, compared to 18 days for Dexamethasone > 6 mg/day and 17 days for Methylprednisolone = 500 mg/day (p = < 0.0001). Dexamethasone = 6 mg/day was found to be a positive predictor of clinical outcome in COVID-19 patients on regression analysis. (4) Conclusions: Low-dose Dexamethasone (6 mg/day) is more effective than high-dose Dexamethasone and Methylprednisolone in improving the survival outcome of severe COVID-19 cases. [ABSTRACT FROM AUTHOR]

(1) Background: Severe coronavirus disease can be complicated by a hypercoagulable state in conjunction with sepsis, increasing the risk of venous thromboembolism. This study aimed to observe the effect of anticoagulants on 30-day high-dependency unit (HDU) outcomes of moderate to severe coronavirus disease 2019 (COVID-19) patients of a tertiary care hospital at Rawalpindi, Pakistan. (2) Methods: A retrospective propensity-based case–control study was carried out to examine COVID-19 patients admitted to the HDU. Patient groups who did and did not receive anticoagulants were labeled as "anticoagulant" and "non-anticoagulant", respectively. Case–control matching (1:1) was performed via propensity scores (calculated by a regression model). Kaplan–Meier and logrank analyses were used to study survival probability. Single predictors of outcomes were determined by Cox regression analysis. (3) Results: The anticoagulant group had elevated D-dimers, advanced age, more comorbidities and a higher frequency of severe disease compared to the non-anticoagulant group (p < 0.05). Therefore, 47 cases and 47 matched controls were selected based on their propensity scores. The primary endpoint was outcome (survived vs. died). The 30-day in-HDU mortality was 25.5% for cases and 61.7% for controls (p = 0.0004). The median time from admission to death was 16 days for the case group and 7 days for the control group (p < 0.0001). The 30-day mortality was 19.1% for the enoxaparin group and 16.4% for the heparin group (p > 0.05). Enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose) were found to be independent factors affecting the outcomes of these patients (p < 0.001). (4) Conclusions: Anticoagulants play a beneficial role in reducing mortality among COVID-19 patients. Both anticoagulant formulations, enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose), were associated with improving survival among these patients. [ABSTRACT FROM AUTHOR]

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine–TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is the world's most prevalent chronic viral infection. More than 350 million individuals are chronic carriers of the virus, with an estimated 2 billion infected persons. For instance, the role of HBx protein in attachment and infection is very obvious and consequently deemed as an important druggable target. Targeting the interface and discovering novel drugs greatly advanced the field of therapeutics development. Therefore, in the current study, HBx to Bcl-xL is abrogated on high-affinity carbon nanotubes using computational structural biology tools. Our analysis revealed that among the total 62 carbon fullerenes, only 13 compounds exhibited inhibitory activity against HBx, which was further confirmed through IFD-based rescoring. Structural dynamics investigation revealed stable binding, compactness, and hydrogen bonds reprogramming. Moreover, the binding free energy calculation results revealed that the top hits1-4 possess the total binding energy of −54.36 kcal/mol (hit1), −50.81 kcal/mol (hit2), −47.09 kcal/mol (hit3), and −45.59 kcal/mol for hit4. In addition, the predicted KD values and bioactivity scores further validated the inhibitory potential of these top hits. The identified compounds need further in vitro and in vivo validation to aid the treatment process of HBV. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes. [ABSTRACT FROM AUTHOR]

With the emergence and global spread of the COVID-19 pandemic, the scientific community worldwide has focused on search for new therapeutic strategies against this disease. One such critical approach is targeting proteins such as helicases that regulate most of the SARS-CoV-2 RNA metabolism. The purpose of the current study was to predict a library of phytochemicals derived from diverse plant families with high binding affinity to SARS-CoV-2 helicase (Nsp13) enzyme. High throughput virtual screening of the Medicinal Plant Database for Drug Design (MPD3) database was performed on SARS-CoV-2 helicase using AutoDock Vina. Nilotinib, with a docking value of −9.6 kcal/mol, was chosen as a reference molecule. A compound (PubChem CID: 110143421, ZINC database ID: ZINC257223845, eMolecules: 43290531) was screened as the best binder (binding energy of −10.2 kcal/mol on average) to the enzyme by using repeated docking runs in the screening process. On inspection, the compound was disclosed to show different binding sites of the triangular pockets collectively formed by Rec1A, Rec2A, and 1B domains and a stalk domain at the base. The molecule is often bound to the ATP binding site (referred to as binding site 2) of the helicase enzyme. The compound was further discovered to fulfill drug-likeness and lead-likeness criteria, have good physicochemical and pharmacokinetics properties, and to be non-toxic. Molecular dynamic simulation analysis of the control/lead compound complexes demonstrated the formation of stable complexes with good intermolecular binding affinity. Lastly, affirmation of the docking simulation studies was accomplished by estimating the binding free energy by MMPB/GBSA technique. Taken together, these findings present further in silco investigation of plant-derived lead compounds to effectively address COVID-19. [ABSTRACT FROM AUTHOR]