Evaluating Masks Through the Lens of Evidence-based Medicine (preprint)

Throughout the COVID-19 pandemic, masks have been promoted as an important tool for reducing SARS-CoV-2 transmission. However, even though masks are plausible experimental interventions, their mechanistic effectiveness has not been validated by randomized clinical trials (RCTs), with reduction risks of just 1.1-fold (11%) or less. Several meta-analyses have suggested that masks effectively reduce viral transmission, but all of them rely heavily or exclusively on observational data. Indeed, there is a strong inverse correlation between the effectiveness of masks and the number of RCTs included in the meta-analysis. RCTs on alternative therapies often show similar low levels of effectiveness. Thus, masks can be compared with potential new drugs or therapies that failed clinical trials despite showing mechanistic evidence.

Discovery of Natural Products to SARS-CoV-2 with Comparative Molecular Docking and Moderate Cell Proliferation Inhibition in vitro (preprint)

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

Ribavirin’s Daily Dose Growth Determined as the Result of Medicament Testing May Be a Predictor of the Chronic Course of the Disease in Long COVID Syndrome Patients (preprint)

Introduction Long COVID syndrome, a multisystemic condition resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, affects at least 65 million people worldwide. The disease pathogenesis is unclear, and many different assumptions still exist. This study aimed to explore the use of medicament testing to determine the optimal daily dose of ribavirin through the use of electroacupuncture via the Voll (EAV) diagnostic system for acupuncture points. Materials and methods One hundred one patients (aged 16 to 50) with long COVID syndrome were recruited from the Research Institute of Virology and were eligible according to the inclusion criteria. Patients were randomized to the experimental or the placebo groups. The patients were further examined with EAV diagnostics based on the level of electrodermal activity at the acupuncture points, followed by medicament testing with ribavirin (tablets) to determine the daily doses of the drug. Fifty-two participants were randomized to the experimental group and fourty nine to the placebo group and were considered for data analyses. Results The results of this study demonstrated the feasibility of using EAV to identify meridians with decreased levels of electrodermal activity at acupuncture points, followed by medicament testing with ribavirin to restore the decreased electrodermal conductivity at the studied acupuncture points and to measure the daily dose of the drug. Conclusions The measured daily doses of ribavirin in patients with long COVID syndrome may indirectly serve as a prognostic marker of the course of the disease. However, further clinical and instrumental studies are needed to evaluate the clinical application of medicament testing in assessing long-term COVID syndrome.

Combinatorial biomedicine: A novel discipline (preprint)

Based on the author’s previous work, this article proposed a novel discipline– combinatorial biomedicine. Currently, there are several classical examples. One is a magic “polypill” covering the “Health Essential (HE) 5”, that is, “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] lifestyle; Another is an innovative “traditional Chinese medicine (TCM) Hot Pot”. In addition, the iRT-ABCDEFG program is indeed suitable for better management of human diseases. In fact, combinatorial biomedicine is pivotal in the development of life science, biology and medicine, in particular the pandemic and post-COVID-19 era, and has obvious advantages in screening, diagnosis, treatments, prevention and rehabilitation of both major non-communicable diseases (such as cardiovascular disease, diabetes, cancer, stroke, and neurodegenerative diseases) and major infectious diseases (such as AIDS, Helicobacter pylori infection, and COVID-19). As a novel discipline, combinatorial biomedicine plays a crucial role in combating human diseases and improving population health. It is about time to propose and establish this novel discipline.

The Role of Thromboelastography as a Predictor of Acute Kidney Injury in COVID-19 Patients in ICU (preprint)

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

Serum proteomic and metabolomic characteristics of fatigue patients with Long Covid fatigue

Clinical RCT on the improvement of cardiopulmonary function in patients with novel coronavirus infection during the recovery period by comprehensive sequential therapy of Chinese medicine

Meditating in Live Stream: An Autoethnographic and Interview Study to Investigate Motivations, Interactions and Challenges (preprint)

Mindfulness practice has many mental and physical well-being benefits. With the increased popularity of live stream technologies and the impact of COVID-19, many people have turned to live stream tools to participate in online meditation sessions. To better understand the practices, challenges, and opportunities in live-stream meditation, we conducted a three-month autoethnographic study, during which two researchers participated in live-stream meditation sessions as the audience. Then we conducted a follow-up semi-structured interview study with 10 experienced live meditation teachers who use different live-stream tools. We found that live meditation, although having a weaker social presence than in-person meditation, facilitates attendees in establishing a practice routine and connecting with other meditators. Teachers use live streams to deliver the meditation practice to the world which also enhances their practice and brand building. We identified the challenges of using live-stream tools for meditation from the perspectives of both audiences and teachers, and provided design recommendations to better utilize live meditation as a resource for mental wellbeing.

Analysis of Prognostic Factors and Establishment of a Nomogram to Predict Risk for COVID-19 Convalescent Patients Based on Metabolomic and Lipidomic (preprint)

Ethnopharmacological relevance: Qimai Feiluoping Mixture (QM) is a traditional Chinese herbal formulation that has demonstrated efficacy in improving both clinical symptoms and radiological indications of pulmonary fibrosis in patients convalescing from Coronavirus Disease 2019 (COVID-19).Aim of the study: To analyze factors associated with the prognosis of COVID-19 patients. It seeks to develop and validate a nomogram based on metabolomic and lipidomic for predicting improvements in lung imaging in COVID-19 patients. Additionally, the study evaluates the clinical application value of this nomogram.Methods and materials: A retrospective analysis was conducted on the clinical data of COVID-19 recovery patients from January 2020 to April 2022. Non-targeted metabolomic and lipidomic plasma analysis of the patients were performed using LC-MS and normal phase (NP)-HPLC coupled with mass spectrometry. Patients were divided into training and validation sets in a 7:3 ratio based on their omics data. Multivariate logistic regression analysis was conducted to identify independent risk factors associated with the recovery of lung imaging. Based on these factors, a nomogram prediction model was developed. The efficacy of the model was evaluated using receiver operating characteristic (ROC) curves and calibration curves. In addition, decision curve analysis (DCA) was performed to assess the performance of the predictive model in clinical applications.Results The use of QM was found to be associated with the recovery of lung imaging in COVID-19 patients (P < 0.05). Among the 75 metabolites detected in the metabolomic test and 32 lipids identified in the lipidomic test, Pro Ser Ser Val, PC36:1(18:0_18:1), and BMP36:3(18:2_18:1) were utilized for constructing the predictive model. The model demonstrated good discriminative ability, with an Area Under the Curve (AUC) of 0.821 (95% CI: 0.718–0.924) in the training set and 0.808 (95% CI: 0.627–0.989) in the validation set. The calibration curves indicated good agreement between predicted probabilities and actual probabilities in both the training and validation sets. Finally, the DCA curve suggested that the model has good clinical utility.Conclusion The utilization of QM may beneficially influence the recovery of lung imaging in patients with COVID-19. A straightforward nomogram, developed based on metabolomic and lipidomic, could be a valuable tool for clinicians to predict the likelihood of lung imaging recovery in COVID-19 patients.

In-vitro Assessment of PHELA and its Components in Modulating the Innate Immune Response against SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV) 2 induces severe illness, often characterized by an excessive release of proinflammatory cytokines, leading to a cytokine storm associated with disease severity. Traditional medicinal plants have been proposed as promising, cost-effective treatments for SARS-CoV-2. PHELA, a traditional medicine prepared from the extracts of four South African plants, has been proposed for use as an immune booster. This study evaluates the ability of PHELA and its constituents to regulate cytokine release and influence viral replication in SARS-CoV-2 Omicron-infected mammalian cells. Cells were treated with plant extracts before or after viral infection, measuring cytokine levels (IL-1β, IL-2Rα, IL-6, TNF-α, IFN-γ) and viral load at various intervals. No significant difference in viral load was observed between infected cells treated with plant extracts and untreated infected cells. However, PHELA-treated cells showed a delay in viral load increase. Infected cells treated with PHELA exhibited significantly lower levels of IL-1β, IL-2Rα, and TNF-α compared to untreated infected cells at 48 and 72 hours post-infection. Post-treatment was more effective in reducing proinflammatory cytokine production than pre-treatment, highlighting the potential of PHELA and its constituents in modulating cytokine responses during SARS-CoV-2 infection.

A real-world study of blood glucose fluctuation in newly diagnosed overweight type 2 diabetes mellitus by Qingre Lishi decoction

Exploring the perceptions and experiences of older people on the use of digital technologies during the COVID-19 pandemic: A qualitative study (preprint)

Background: Physical inactivity is an ongoing problem throughout the lifespan. For older people, inactivity has a negative impact on wellbeing, which worsened during the COVID-19 pandemic. Digital technologies can be employed to encourage uptake of social and physical activity through remotely delivered interventions to improve wellbeing, however, we need to understand older people’s perceptions and experiences of using digital technologies before implementing these interventions. Aims: To explore the perceptions and experiences of older people on the use of digital technologies during the COVID-19 pandemic. Methods:Qualitative semi-structured interviews were conducted with 16 community dwelling older people from Hertfordshire, United Kingdom taking part in a remotely delivered mind-body physical activity programme called Positive Movement. Interviews were audio recorded and transcribed and thematic analysis used. Results: Four themes emerged from the data. The perceived impact of COVID-19 on social contact, perceived impact of COVID-19 on mental wellbeing, using digital platforms for health or exercise and using digital platforms for social contact. Discussion: Participants reported reduced social contact due to COVID-19. Most participants reported using digital technologies for social inclusion rather than health reasons, and there were mixed views on the willingness to use digital technologies for physical activity. Conclusion: Digital technologies offered a lifeline during COVID-19 to maintain social contact and their use was found acceptable by older people. Digital platforms such as Zoom can be further employed to conduct remotely delivered interventions with the aim to increase uptake of social and physical activity interventions within this population.

A Study to Assess Bioavailability of Rocatinlimab (AMG 451) Vial and Prefilled Syringe in Healthy Participants

High-definition Transcranial Direct Current Ctimulation and Chlorella Pyrenoidosa to Reduce Cardiovascular Risk

GS-441524 for COVID-19 SAD, FE, and MAD Study in Healthy Subjects

Traditional uses and pharmacological activities of Tetracera alnifolia (Wild) Drake (preprint)

Ethnopharmacological relevance: Tetracera alnifolia (Wild) Drake, is well used in traditional Guinean medicine for the treatment of infectious skin diseases. The present aim was to contribute to the valorization of Tetracera alnifolia leaves, focused on ethnomedical, biological and phytochemical investigations. Materials and methods: we conducted an ethnomedical survey across several markets of the city of Conakry to identify 39 healers. Chloroform, methanol, dichloromethane, and aqueous extracts were tested for activities against protozoa, bacteria, fungi, HIV, and SARS-CoV-2. Results: the traditional healers indicated that T. alnifolia is used in the treatment of more than 15 pathologies including Fassa (marasmus/malnutrition), Soukhou kouye (white discharge in women), and Temou bankhi (sexual weakness in men). Leaves were the most used part. The modes of preparation included decoction and powder. Data from biological activities identicatied good activities of the methanolic extract against Leishmania infantum (MIC = 8.11 g / ml) and a moderate activity on Trypanosoma brucei (MIC = 28.15 g / ml) and Staphylococcus aureus (MIC = 29.91 g/ ml), while dichloromethane extracts acted on live SARS-CoV-2 replication with up to 53.4% inhibition at 50 g/mL. Conclusion: these results explain at least in part the traditional use of T. alnifolia

DZD9008 In Combination With Bevacizumab in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutation (WU-KONG29)

Efficacy Evaluation of Chang Geng Healthy Drink on Patients With Non-alcoholic Fatty Liver Disease

Effectiveness and Safety of COVID-19 Vaccines, including Vaccination Issues in Trinidad and Tobago: A Systematic Review (preprint)

Vaccination against the SARS-CoV2 virus has shown great promise in managing the spread and severity of Covid-19. While these vaccines were able to provide a favourable response in controlling the SARS-CoV2 infection, its use came with accompanying side effects. This systematic review aimed to determine the effectiveness of the different Covid-19 vaccine subtypes and discover the side effects associated with each vaccine elsewhere but specially in Trinidad and Tobago. For this systematic review, the keywords “Pfizer-BioNTech OR Moderna OR Oxford-AstraZeneca OR Janssen OR Sinopharm OR Novavax AND Covid-19 vaccine efficacy” and “Covid-19 vaccines AND Trinidad and Tobago” were researched under PubMed, MEDLINE and other internet sources through which other notable journals, and documents were discovered and searched similarly as outlined previously. In doing so, 65 relevant articles were included as part of this review. Of the studies examined, overall the vaccine with the greatest VE was found to be Pfizer-BioNTech (95%), followed by Moderna (94.1%), Novavax (89.7%), AstraZeneca (70.4%), Sinopharm (67%) and finally Janssen (66.9%). The use of Pfizer-BioNTech or Moderna was most efficacious in response to the different Covid-19 variants. Some side effects were common for all vaccine types however adverse effects were more commonly seen with vaccination by mRNA vaccines, Pfizer-BioNTech and Oxford-Astrazeneca. Researchers targeted individuals aged 18 and above residing in various geographical areas of TT, specifically focusing on those who had not received the COVID-19 vaccine and expressed hesitancy towards it. Convenience sampling was used to select the study participants, and formal in-depth virtual interviews were conducted on a one-to-one basis, employing a semi-structured questionnaire to guide the discussions. The interviews were meticulously recorded and transcribed, following the principles of reflexive thematic analysis, to distill key insights from the participants' responses. The study's findings, derived from the perspectives of 25 participants, illuminated a complex tapestry of reasons underlying vaccine hesitancy in Trinidad and Tobago. Notably, prominent themes emerged, including fear, doubts regarding vaccine efficacy, a perceived inadequacy of information, a sense of susceptibility to the virus, deep-seated mistrust, alternative herbal remedies, and religious reservations. Interestingly, the motivations expressed by these vaccine-hesitant individuals for potentially receiving the vaccine in the future were rooted in notions of necessity, an increased sense of susceptibility to the virus, a desire to reach a certain health benchmark, and a need for assurance regarding the vaccine's safety and effectiveness. This comprehensive exploration of vaccine hesitancy in TT provides valuable insights for public health officials and policymakers in crafting targeted strategies to address this critical issue within the local context. Conclusion: The findings of this study determined that vaccination against the SARS-CoV2 virus provided beneficial outcomes against infection, Covid-19 related hospitalizations, ICU admissions and mortality. While vaccination was deemed highly appropriate in managing the spread of the SARS-CoV2 virus and enhancing the outcomes in infected persons, the effectiveness of the different vaccine platforms indicated that certain vaccine platforms are preferential to others in different populations. In terms of vaccine efficacy, nucleic acid vaccines such as Pfizer-BioNTech and Moderna showed the greatest effectiveness while inactivated whole virus vaccines such as Sinopharm and viral vectors like Janssen had the least effectiveness. The side effects, joint/muscle soreness, pain at the injection site, shoulder pain, headaches, fever, chills, weakness, epistaxis, renal and certain cardiovascular events were common for all vaccine types. Adverse effects were more frequent and severe with the mRNA vaccines by Pfizer-BioNTech and Oxford-Astrazeneca than inactivated whole virus vaccines. The data collected in this research can be very useful to help individuals make a decision on which vaccine would be appropriate for them. More long-term studies are needed to better gauge the scope of side effects for each vaccine type.

A Study of TAK-279 in Healthy Adults on the Effect on ECG Measurements