Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014

In 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures.     

Phage-Displayed Mimotopes of SARS-CoV-2 Spike Protein Targeted to Authentic and Alternative Cellular Receptors

The evolution of the SARS-CoV-2 virus during the COVID-19 pandemic was accompanied by the emergence of new heavily mutated viral variants with increased infectivity and/or resistance to detection by the human immune system. To respond to the urgent need for advanced methods and materials to empower a better understanding of the mechanisms of virus’s adaptation to human host cells and to the immuno-resistant human population, we suggested using recombinant filamentous bacteriophages, displaying on their surface foreign peptides termed “mimotopes”, which mimic the structure of viral receptor-binding sites on the viral spike protein and can serve as molecular probes in the evaluation of molecular mechanisms of virus infectivity. In opposition to spike-binding antibodies that are commonly used in studying the interaction of the ACE2 receptor with SARS-CoV-2 variants in vitro, phage spike mimotopes targeted to other cellular receptors would allow discovery of their role in viral infection in vivo using cell culture, tissue, organs, or the whole organism. Phage mimotopes of the SARS-CoV-2 Spike S1 protein have been developed using a combination of phage display and molecular mimicry concepts, termed here “phage mimicry”, supported by bioinformatics methods. The key elements of the phage mimicry concept include: (1) preparation of a collection of p8-type (landscape) phages, which interact with authentic active receptors of live human cells, presumably mimicking the binding interactions of human coronaviruses such as SARS-CoV-2 and its variants; (2) discovery of closely related amino acid clusters with similar 3D structural motifs on the surface of natural ligands (FGF1 and NRP1), of the model receptor of interest FGFR and the S1 spike protein; and (3) an ELISA analysis of the interaction between candidate phage mimotopes with FGFR3 (a potential alternative receptor) in comparison with ACE2 (the authentic receptor).     

Structure of Sputnik,a virophage,at 3.5-? resolution

“Sputnik” is a dsDNA virus, referred to as a virophage, that is coassembled with Mimivirus in the host amoeba. We have used cryo-EM to produce an electron density map of the icosahedral Sputnik virus at 3.5-Å resolution, sufficient to verify the identity of most amino acids in the capsid proteins and to establish the identity of the pentameric protein forming the fivefold vertices. It was also shown that the virus lacks an internal membrane. The capsid is organized into a T = 27 lattice in which there are 260 trimeric capsomers and 12 pentameric capsomers. The trimeric capsomers consist of three double “jelly-roll” major capsid proteins creating pseudohexameric capsomer symmetry. The pentameric capsomers consist of five single jelly-roll proteins. The release of the genome by displacing one or more of the pentameric capsomers may be the result of a low-pH environment. These results suggest a mechanism of Sputnik DNA ejection that probably also occurs in other big icosahedral double jelly-roll viruses such as Adenovirus. In this study, the near-atomic resolution structure of a virus has been established where crystallization for X-ray crystallography was not feasible.     

Clinical trial with traditional Chinese medicine intervention 'tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment' for chronic hepatitis B-associated liver failure

AIM: To study the clinical efficacy of traditional Chinese medicine (TCM) intervention “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) for treating liver failure due to chronic hepatitis B.METHODS: We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a “tonifying qi and detoxification” (“TQD”) group (72 patients); and (3) a “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the “TQD” group were given a TCM formula “tonifying qi and detoxification” and general internal medicine treatment; patients in the “TTK” group were given a TCM formula of “TTK” and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS: At the 48-wk post-treatment time point, the patient fatality rates in the MMC, “TQD”, and “TTK” groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups (P > 0.05). Patients in the “TTK” group had significantly higher levels of serum total bilirubin compared to MMC subjects (339.40 μmol/L ± 270.09 μmol/L vs 176.13 μmol/L ± 185.70 μmol/L, P = 0.014). Serum albumin levels were significantly increased in both the “TQD” group and “TTK” group as compared with the MMC group (31.30 g/L ± 4.77 g/L, 30.72 g/L ± 2.89 g/L vs 28.57 g/L ± 4.56 g/L, P < 0.05). There were no significant differences in levels of alanine transaminase among the three groups (P > 0.05). Safety data showed that there was one case of stomachache in the “TQD” group and one case of gastrointestinal side effect in the “TTK” group.CONCLUSION: Treatment with “TTK” improved the survival rates of patients with liver failure due to chronic hepatitis B. Additionally, liver tissue was regenerated and liver function was restored.     

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: “HBV”, “HCV”, “hepatocellular carcinoma”, “microRNAs”, “miRNAs”, “diagnosis”, “prognosis”, “therapy”, “treatment”. Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.     

Predictors of High Motivation Score for Performing Research Initiation Fellowship,Master 1, Research Master 2, and PhD Curricula During Medical Studies: A Strobe-Compliant Article

Translational research plays a crucial role in bridging the gap between fundamental and clinical research. The importance of integrating research training into medical education has been emphasized. Predictive factors that help to identify the most motivated medical students to perform academic research are unknown. In a cross-sectional study on a representative sample of 315 medical students, residents and attending physicians, using a comprehensive structured questionnaire we assessed motivations and obstacles to perform academic research curricula (ie, research initiation fellowship, Master 1, Research Master 2, and PhD). Independent predictive factors associated with high “motivation score” (top quartile on motivation score ranging from 0 to 10) to enroll in academic research curricula were derived using multivariate logistic regression analysis. Independent predictors of high motivation score for performing Master 1 curriculum were: “considering that the integration of translational research in medical curriculum is essential” (OR, 3.79; 95% CI, 1.49–9.59; P = 0.005) and “knowledge of at least 2 research units within the university” (OR, 3.60; 95% CI, 2.01–6.47; P < 0.0001). Independent predictors of high motivation score for performing Research Master 2 curriculum were: “attending physician” (OR, 4.60; 95% CI, 1.86–11.37; P = 0.001); “considering that the integration of translational research in medical curriculum is essential” (OR, 4.12; 95% CI, 1.51–11.23; P = 0.006); “knowledge of at least 2 research units within the university” (OR, 3.51; 95% CI, 1.91–6.46; P = 0.0001); and “male gender” (OR, 1.82; 95% CI, 1.02–3.25; P = 0.04). Independent predictors of high motivation score for performing PhD curriculum were: “considering that the integration of translational research in medical curriculum is essential” (OR, 5.94; 95% CI, 2.33–15.19; P = 0.0002) and “knowledge of at least 2 research units within the university” (OR, 2.63; 95% CI, 1.46–4.77; P = 0.001). This is the first study that has identified factors determining motivations and barriers to carry out academic research curricula among undergraduate and postgraduate medical students. Improving these 2 areas will certainly have an impact on a better involvement of the next generation of physicians in translational medicine.     

Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review

In individuals infected with hepatitis B virus (HBV), the loss of hepatitis B surface antigen (HBsAg) is the ultimate therapeutic goal, which defines “functional cure.” For individuals living with human immunodeficiency virus (HIV), functional cure occurs roughly 2 per 100 person-years during potent anti-HBV containing antiretroviral therapy. Although this rate may be higher than expected in treated HBV mono-infected individuals, rates of functional cure widely vary between studies (0.6–10.5 per 100 person-years). Similar to HBV mono-infection, the phase of HBV infection, HBV (sub-)genotypes and hepatitis B “e” Ag-negative variants are associated with functional cure in treated HIV-HBV co-infection. In specifically HIV-HBV co-infected individuals, strong increases in CD4+ T cell counts after treatment initiation have also been linked to functional cure, yet this finding is inconsistent across studies. Several markers directly or indirectly reflecting HBV activity are being developed to predict functional cure, such as quantification of HBsAg, hepatitis B core-related antigen, HBsAg protein composition, anti-hepatitis B core antibodies and interferon-gamma-inducible protein 10. Few have been assessed during treatment in HIV-HBV co-infected individuals and none have been validated to predict functional cure. Novel therapeutics for HBV cure are essential for individuals with HIV-HBV co-infection and need to be separately evaluated in this population.     

Vaccination against Borna Disease: Overview,Vaccine Virus Characterization and Investigation of Live and Inactivated Vaccines

(1) Background: Vaccination of horses and sheep against Borna disease (BD) was common in endemic areas of Germany in the 20th century but was abandoned in the early 1990s. The recent occurrence of fatal cases of human encephalitis due to Borna disease virus 1 (BoDV-1) has rekindled the interest in vaccination. (2) Methods: The full genomes of the BD live vaccine viruses “Dessau” and “Giessen” were sequenced and analyzed for the first time. All vaccination experiments followed a proof-of-concept approach. Dose-titration infection experiments were performed in rabbits, based on both cell culture- and brain-derived viruses at various doses. Inactivated vaccines against BD were produced from concentrated cell culture supernatants and investigated in rabbits and horses. The BoDV-1 live vaccine “Dessau” was administered to horses and antibody profiles were determined. (3) Results: The BD live vaccine viruses “Dessau” and “Giessen” belong to clusters 3 and 4 of BoDV-1. Whereas the “Giessen” virus does not differ substantially from field viruses, the “Dessau” virus shows striking differences in the M gene and the N-terminal part of the G gene. Rabbits infected with high doses of cell-cultured virus developed neutralizing antibodies and were protected from disease, whereas rabbits infected with low doses of cell-cultured virus, or with brain-derived virus did not. Inactivated vaccines were administered to rabbits and horses, following pre-defined vaccination schemes consisting of three vaccine doses of either adjuvanted or nonadjuvanted inactivated virus. Their immunogenicity and protective efficacy were compared to the BD live vaccine “Dessau”. Seventy per cent of horses vaccinated with the BD live vaccine “Dessau” developed neutralizing antibodies after vaccination. (4) Conclusion: Despite a complex evasion of immunological responses by bornaviruses, some vaccination approaches can protect against clinical disease. For optimal effectiveness, vaccines should be administered at high doses, following vaccination schemes consisting of three vaccine doses as basic immunization. Further investigations are necessary in order to investigate and improve protection against infection and to avoid side effects.     

DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge

Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, “native” and “modified,” inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P = 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model.     

Global trends and performances of Mediterranean diet: A bibliometric analysis in CiteSpace

Background:The Mediterranean diet (MD) is an ancient eating habit that is believed to contribute to a healthy lifestyle. Unsurprisingly, research on the MD is growing rapidly as people pay more attention to health preservation and prevention, treatment and rehabilitation of chronic diseases. Previous reviews focused more on the effects of MD on a particular disease which has enhanced its significance in the medicine field. However, few studies have attempted to provide a comprehensive summary and analysis of this topic. This study evaluates the global research trends of scientific outputs related to MD from multiple perspectives, using a bibliometric analysis and visualization tool (CiteSpace software) to scientifically analyze the knowledge from the literature.Methods:The core collection database of Web of Science was used to retrieve the bibliographic records related to MD from 1984 to March 30, 2021. CiteSpace was used to generate and analyze visual representations of the complex data input, including number of publications, research performances in journals, authors, institutions, countries and co-occurrence networks of keywords and co-citation references.Results:Overall, the number of MD publications has shown a significant upward trend since 2012. Nutrients and American Journal of Clinical Nutrition contained the most articles related to MD, indicating that they were important platforms for related research. Martinez-gonzalez Ma and Estruch Ramon are the authors with the highest number of publications related to MD, and it is noteworthy that these 2 authors have close cooperation in this field. The countries with the most publications are Spain and the United States, and the institutions with the most publications are Univ Navarra, Inst Salud Carlos III. The main research disciplines are “Mediterranean diet,” “risk,” “cardiovascular disease,” “adherence,” “obesity,” “coronary heart disease,” “diet,” “health,” “physical activity” and “risk factor”. Estruch R''s 2013 study on cerebrovascular disease and Tricopoulou A''s 2003 mortality study were cited 881 cases for 437 times, respectively, showing the importance of these 2 articles in this field.Conclusion:The current global trends of MD research as well as people''s increasing awareness of healthcare and healthy lifestyle imply that MD research is expected to become increasingly popular with further breakthroughs.     

Omicron SARS-CoV-2 variant of concern: A review on its transmissibility,immune evasion,reinfection, and severity

Omicron, the new Covid-19 variant, has already become dominant in many countries and is spreading at an unprecedented speed. The objective of this study was to review the existing literature on Omicron''s transmissibility, immune evasion, reinfection, and severity.A literature search was performed using “PubMed,” “Web of Science,” “Scopus,” “ScienceDirect,” “Google Scholar,” “medRxiv,” and “bioRxiv.” Data were extracted from articles that reported at least one of the following: transmissibility, immune evasion, reinfection, and severity related to Omicron.We found that Omicron spread faster than any other variant. This higher transmissibility can be ascribed to its extraordinary ability to evade the immunity developed by both vaccination and previous infections. However, we found that infections by Omicron were significantly less severe than those caused by Delta and other previous variants. We observed a significantly lower incidence of hospitalization, intensive care unit admission, and mechanical ventilator use in Omicron infections than in Delta or other variants. A substantially shorter median hospital stay and lower fatality rate were also observed in the Omicron infections. Despite Omicron''s higher potential to evade immunity, vaccines and booster shots were found to be still significantly effective in protecting against severe Covid-19 infections.Omicrons may be less severe than other variants of concern. However, its immune evasiveness and rapid spread pose an enormous threat to the global healthcare system.     

Gastroenterologists attitude in various clinical settings in the era of COVID-19 pandemic: An online Uni-National Israeli Survey

Coronavirus disease 2019 (COVID-19) pandemic has impacted our clinical practice. Many gastroenterologists have changed their attitudes toward various gastroenterological clinical settings. The aim of the present study is to explore the gastroenterologist''s attitudes in several clinical settings encountered in the clinical practice.An online based survey was completed by 101 of 250 Israeli gastroenterologists (40.5%).Most of the participants were males (76.2%), and most of them were in the age range of 40 to 50 (37.6%). For all questionnaire components, the 2 most common chosen options were “I perform endoscopy with N95 mask, gloves and gown protection in a standard endoscopy room without preendoscopy severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) testing” and “Tend to postpone endoscopy until SARS-CoV-2 test is performed because of fear from being infected, or virus spreading in the endoscopy suite.” Notably, 12 (11.9%) gastroenterologists were infected by Coronavirus disease 2019 during their work. Classifying the clinical settings to either elective and non-elective, most gastroenterologists (77.4%) chose the attitude of “I perform endoscopy with N95 mask, gloves and gown protection in a standard endoscopy room without SARS-COV-2 testing” in the nonelective settings as compared to 54.2% for the elective settings, (P < .00001), whereas 32.9% of the responders chose the attitude of “Tend to postpone endoscopy until SARS-COV-2 test is performed because of fear from being infected, or virus spreading in the endoscopy suite” in the elective settings (P < .00001).Gastroenterologists’ attitude in various gastroenterological settings was based on the clinical indication. Further studies are needed to assess the long-term consequences of the different attitudes.     

Feasibility of Spotlight Consultations Tool in Routine Care: Real-World Evidence

Background:Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel “smart” adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ’s feasibility in routine care.Materials and Methods:The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit.Results:A convenience sample of 49 adults took part, n=31 T1D, (n=18 female); and n=18 T2D (n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. “Psychological burden of diabetes” was the most common priority concern (T1D n = 27, 87.1%) followed by “gaining more skills about particular aspects of diabetes” (T1D n=19, 61.3%), “improving support around me” (n=8, 25.8%) and “diabetes-related treatment issues” (n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D (n=18,100%) followed by “gaining more skills about aspects of diabetes” (n=7, 38.9%), “improving support around me” (n=7, 38.9%) and “diabetes-related treatment issues” (n=4; 22.2%).Conclusions:Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.     

Global trends of researches on bone metastasis: A bibliometric and visualization study

Background:Bone metastasis (BM) has become an important health problem. In recent years, studies on BM are growing rapidly, but there were no bibliometric studies regarding BM. This study aimed to illustrate the overall knowledge structure and development trends of BM.Methods:Research datasets were acquired from the Web of Science database. The time span was defined as “1980–2020”. VOS viewer and Citespace software was provided to analyze the data and generate visualization knowledge maps. Annual trends of publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed.Results:Six hundred eighty-two publications met the requirement. USA published most papers (264, 38.7%), and both total citations (13,997) and H-index (57) of USA ranked first. The most productive institution on BM is Amgen Inc. (43). Supportive Care in Cancer (24) published the most papers on BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in the recent years.Conclusion:In this study, we conduct a systematic and comprehensive analysis on the research in BM field. The publication number was rising in recent years stably. USA contributed mostly not only in quality, but also in quantity. Amgen Inc. published the largest number of articles, Supportive Care in Cancer was the most productive journal related to BM. “Safety”, “skeletal related event”, “open label”, “management”, “health”, and “prognosis” are the research hotspots in recent years. We believe this study can not only show the global research overview in past 40 years but also point the research trend of BM in the future.     

Neoadjuvant immunotherapy in non-small cell lung cancer: a narrative review on mechanisms,efficacy and safety

Background and ObjectiveImmune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.MethodsRelevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms “non-small-cell lung cancer”, “NSCLC”, “neoadjuvant”, “immunotherapy”, “immune checkpoint inhibitors”, “mechanisms”, and “toxicity”. The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.Key Content and FindingsAfter reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83–86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.ConclusionsNeoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.