- A preliminary mindsponge-based analysis of Generation Z’s relationship with technologies -
In terms of human-machine relationship, Gen Z, those who were born between 1997-2012, is the first generation who becomes productive members of society under so much technological disruption in a short period of time. For example, as a consequence of remote work caused by the COVID-19 pandemic, the global industry of emotional AI is forecasted to almost double from $19.5 in 2020 to $37.1 billion by 2026, at the compound annual growth rate of 11.3% in this period, according to Markets and Markets (Madhumita, 2021). Consequently, as Gen Z is poised to become the largest demographics for entry-level jobs (Pichler, Kohli & Granitz, 2021), they are expected to confront with a so much uncertain time of the various effects of emotion auto-tracking practices on mental and physical health, productivity, security, etc., have only gathered research interests in recent years. In this essay, using the mindsponge framework (Vuong and Napier, 2015), I reflect on the relationship of Gen Z with emotional AI technologies.
- Yếu tố văn hóa và tâm lý của Việt Nam trong ứng phó với COVID-19 -
This paper points out some notable cultural and psychological factors that contribute to the success of Vietnam’s COVID-19 response.
- Learnings From The Case of Maple Refugees: A Story of Loot Boxes, Probability Disclosures, and Gamer Consumer Activism -
The article synthesises what we learned from reviewing the player activism of the “Maple refugee” incident and applies the insights to the European video game industry and commercial context. The Maple Refugee incident was perhaps one of the most disruptive video game incidents that occurred in South Korea in recent years. It saw tens of thousands of Korean players from the game Maple Story (Nexon, 2003) mobilised in unprecedented online and offline protests in Spring 2021. Together with players from other free-to-play (F2P) games, Maple Story players rallied against the industry norms of monetising with loot boxes and the industry self-regulatory approach to probability disclosures to address potential harms. This culminated in the social phenomenon of the proxy activism method of ’truck protests,’ rallies of crowdfunded rented trucks displaying protest messages instead of people mass-gathering in public during the COVID-19 pandemic. Based on the English timeline of the incident collated by Park et al. (2023), we dive deeper into the case with a multidisciplinary group of experts from game studies, law, and human-computer interaction and highlight various issues present in this case: the regulation of loot boxes and probability disclosures, the social pillars of player activism, player trust and theorycrafting, and game production. The paper contributes to the deepening of the industry’s understanding of F2P game business while diversifying the Western-centric discourse of the game research landscape by calling for further cross-cultural and cross-disciplinary inquiries into current video game issues.
- Comparison of timing of booster vaccination for COVID-19 to prevent severe disease by risk group in the United States -
While waning protection from vaccination and natural infection against SARS-CoV-2 infection is well-documented, recent analyses have also found waning of protection against severe COVID-19. This highlights a broader need to understand how different frequency of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. Here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. Analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, we estimated that in persons 75+ years, annual and semiannual boosters would reduce annual absolute risk of severe COVID-19 by 199 (uncertainty interval: 188-229) and 368 (344-413) cases per 100,000 persons, respectively, compared to a one-time booster dose. In contrast, for persons 18-49 years, the model estimated that annual and semiannual boosters would reduce annual absolute risk of severe COVID-19 by 14 (11-19) and 26 (21-35) cases per 100,000 persons, respectively, compared to a one-time booster dose. Persons with prior infection had lower benefit of more frequent boosting, while immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance, and ensuring at least annual boosters in high-risk populations.
- Neglected consequences of spatio-temporal heterogeneity and dispersal: Metapopulations, the inflationary effect, and real-world consequences for public health -
The metapopulation perspective is an important conceptual framework in ecology, biogeography, and evolutionary ecology. Metapopulations are spatially distributed populations linked by dispersal. Both metapopulation models and their community and ecosystem level analogues, metacommunity and meta-ecosystem models, tend to be more stable regionally than locally and display an enhancement in abundance because of the interplay of spatio-temporal heterogeneity and dispersal (an effect that has been called the "inflationary effect"). We highlight the essential role of spatio-temporal heterogeneity in metapopulation biology, sketch empirical demonstrations of the inflationary effect, and provide a mechanistic interpretation of how the inflationary effect arises and impacts population growth and abundance. The spread of infectious disease is used to illustrate how this effect, emerging from the interplay of spatiotemporal variability and dispersal, can have serious real-world consequences. Namely, failure to recognize the full possible effects of spatio-temporal heterogeneity likely enhanced the spread of COVID-19, and a comparable lack of understanding of emergent population processes at large scales may hamper the control and eradication of other infectious diseases. We finish by noting how the effects of spatio-temporal heterogeneity, including the inflationary effect, have implicitly played roles in many traditional themes in the history of ecology. The inflationary effect is implicit in processes explored in subdisciplines as far ranging as natural enemy-victim dynamics, species coexistence, and conservation biology. Seriously confronting the complexity of spatiotemporal heterogeneity has the potential to push many of these subdisciplines forward.
- Experiencing herd immunity in virtual reality increases COVID-19 vaccination intention: Evidence from a large-scale field intervention study -
This study investigates the impact of an immersive virtual reality (VR) simulation of herd immunity on vaccination intentions and its potential underlying mechanisms. In this preregistered field study, N = 654 participants were randomly assigned to one of the three VR conditions: (1) Gamified Herd Immunity; (2) Gamified Herd Immunity + Empathy (with additional narrative elements); (3) Control (gamified with no vaccination-related content). In the Gamified Herd Immunity simulation, participants embodied a vulnerable person and navigated the wedding venue trying to avoid getting infected. A total of n = 455 participants with below maximum intentions to take a novel vaccine and without severe cybersickness symptoms were included in the analyses. The Gamified Herd Immunity + Empathy and the Gamified Herd Immunity conditions increased vaccination intentions by 6.68 and 7.06 points on a 0-100 scale, respectively, compared to 1.91 for the Control condition. The Gamified Herd Immunity + Empathy condition enhanced empathy significantly more than the Gamified Herd Immunity condition but did not result in higher vaccination intentions. The results suggest that immersive VR vaccination communication can effectively increase COVID-19 vaccine intentions; the effect is not solely a consequence of the technological experience itself and does not depend on empathy.
- Discontinuous or Kinked Response? Dynamics of Unemployment Insurance and Public Assistance under the COVID-19 Crisis -
This study investigates the responsiveness of Unemployment Insurance (UI) and Public Assistance (PA) programs during the COVID-19 employment shock in Japan. Estimating “excess” UI and PA caseloads under the COVID-19 crisis, we reveal heterogeneous responses to the COVID-19 shock: UI caseloads exhibit an instantaneous and discontinuous increase and subsequent decrease, while PA caseloads show a kinked and incremental increase. These contrasting safety net responses highlight a potential delay in safety net support for workers who are not eligible for UI benefits when a large employment shock occurs.
- Exploring the landscape of the genomic wastewater surveillance ecosystem: a roadmap towards standardization -
The landscape of genomic wastewater surveillance in the context of infectious disease monitoring is rapidly evolving, and this came into sharp focus during the COVID-19 pandemic. Here we highlight the significance of wastewater surveillance as a passive monitoring system complementary to clinical genomic surveillance activities. Emphasizing the need for coordination, standardization, and the development of a unified catalog of software tools and services, we aim to streamline the implementation of end-to-end genomic wastewater surveillance pipelines. Key considerations such as defining variants, understanding antimicrobial resistance, and assessing viral fitness within the framework of wastewater surveillance are explored, linking to examples of respective tools and existing pipelines. The challenges of wastewater data analysis, the need for specialized tools and bioinformatics workflows, and the significance of integrated pipelines are also discussed in detail. The article presents case studies, including the V-pipe integrated bioinformatics workflow and the integration of tools into the Galaxy platform, underscoring their role in enhancing data analysis efficiency and standardization within the field. Overall, the review highlights the critical importance of continued research efforts to advance understanding and implementation of bioinformatic approaches in wastewater surveillance for the effective monitoring and management of infectious diseases.
- Gods Lockdown: the effect of the April 2022 Colorado low blizzard on SARS-Cov-2 transmission in the midwest United States -
Background: Lockdowns have been used as a primary non-pharmaceutical intervention to stop transmission of COVID19. There are many issues with interpreting the causal effects of most of these intentional, policy driven interventions. We leverage a natural experiment to avoid many of these issues to better understand the direct effects of lockdown like conditions on COVID19 transmission. Methods: We exploit a blizzard that interrupted activity across several midwestern states in April 2022. This blizzard broke records for snowfall and caused economic disruption. We leverage this to create control and treatment counties that were more or less affected by the snowfall. We demonstrate effects using event studies comparing these treatment and control counties. Results: We find that mobility within treatment counties was severely curtailed as a result of the blizzard relative to control counties. We find cumulative declines in the number of COVID19 cases per country by 400 and cumulative declines in COVID19 deaths by 1 per county over the 30 days after the storm. We find declines in by one per hospitalization due to COVID19. Conclusions: The April 2022 blizzard caused disruption in activity across the midwest United States akin to a lockdown. It reduced the number of COVID19 cases, deaths, and hospitalizations in treatment counties relative to control counties suggesting that similar policies do limit transmissions of SARS-Cov-2.
- Phylogenetic meta-analysis of chronic SARS-CoV-2 infections in immunocompromised patients shows no evidence of elevated evolutionary rates -
Genomic sequences from rapidly evolving pathogens, sampled over time, hold information on disease origin, transmission, and evolution. Together with their sampling times, sequences can be used to estimate the rates of molecular evolution and date evolutionary events through molecular tip-dating. The validity of this approach, however, depends on whether detectable levels of genetic variation have accumulated over the given sampling interval, generating temporal signal. Moreover, different molecular dating methods have demonstrated varying degrees of systematic biases under different biologically realistic scenarios, such as the presence of phylo-temporal clustering. Chronic SARS-CoV-2 infection in immunocompromised patients has been linked to remarkably higher intra-host molecular rates than those of global lineages, facilitating the emergence of novel viral lineages. Yet, most studies reporting accelerated rates lack the evaluation of temporal signal or comparison of multiple methods of inference, both required to reliably estimate molecular rates. In this study, we use 26 previously published longitudinally sampled sequence series obtained from chronically infected immunocompromised patients to re-evaluate the rate of SARS-CoV-2 intrahost evolution. Using a range of methods, we analyse the strength of temporal signal and infer evolutionary rates from tip-calibrated phylogenies. Regardless of heterogeneity in rate estimates between sample series and methods, we find within-host rates to be in good agreement with rates derived from host-to-host transmission chains. Our findings suggest that when certain limitations of the methodology are disregarded, such as the underlying assumption of phylogenetic independence or the method's sensitivity to phylo-temporal grouping, evolutionary rates can be substantially overestimated. We demonstrate that estimating within-host rates is a challenging question necessitating careful interpretation of findings. While our results do not support faster evolution across the complete viral genome during chronic SARS-CoV-2 infection, prolonged viral shedding together with relapsing viral load dynamics may nevertheless promote the emergence of new viral variants in immunocompromised patients.
- SARS-CoV-2 infection leads to sustained testicular injury and functional impairments in K18 hACE2 mice -
Compromised male reproductive health is one of the symptoms of long COVID with a decrease in male fertility markers including testosterone levels and sperm count for months in recovering patients. However, the long-term impact of SARS-CoV-2 infection on testicular injury and underlying mechanisms remains unknown. We previously demonstrated a disrupted tissue architecture with no evidence of virus replication in the testis during the acute stage of the disease in K18-hACE2 mice. Here, we systematically delineate the consequences of SARS-CoV-2 infection on the testis injury and function both during the acute stage of the disease and up to 4 weeks after recovery in survivor K18-hACE2 mice. The gross morphological defects included sloughing of healthy spermatids and spermatocytes into the lumen, lack of lumen, and increase in apoptotic cells that sustained for at least 2 weeks after infection. Testis injury correlated with systemic and testicular inflammation, and infiltration of immune cells in the interstitial space and seminiferous tubules. Transcriptomic analysis identified dysregulation of key pathways associated with testicular immune homeostasis, spermatogenesis, and cell death at the symptomatic stage and immediately after recovery. Further, a significant reduction in testosterone levels was associated with transient reduction in sperm count and mouse fertility. Most of the testicular impairments except testosterone levels were resolved within 4 weeks, which is almost one spermatogenesis cycle in mice. These findings provide much-needed mechanistic insights beyond our current understanding of testicular pathogenesis, suggesting that recovering COVID-19 patients should be closely monitored to rescue the pathophysiological effects on male reproductive health.
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds -
Protein homeostasis is tightly regulated, with damaged or misfolded proteins quickly eliminated by the proteasome and autophagosome pathways. By co-opting these processes, targeted protein degradation technologies enable pharmacological manipulation of protein abundance. Recently, cysteine-reactive molecules have been added to the degrader toolbox, which offer the benefit of unlocking the therapeutic potential of undruggable protein targets. The proteome-wide impact of these molecules remains to be fully understood and given the general reactivity of many classes of cysteine-reactive electrophiles, on- and off-target effects are likely. Using chemical proteomics, we identified a cysteine-reactive small molecule degrader of the SARS-CoV-2 non-structural protein 14 (nsp14), which effects degradation through direct modification of cysteines in both nsp14 and in host chaperones together with activation of global cell stress response pathways. We find that cysteine-reactive electrophiles increase global protein ubiquitylation, trigger proteasome activation, and result in widespread aggregation and depletion of host proteins, including components of the nuclear pore complex. Formation of stress granules was also found to be a remarkably ubiquitous cellular response to nearly all cysteine-reactive compounds and degraders. Collectively, our study sheds light on complexities of covalent target protein degradation and highlights untapped opportunities in manipulating and characterizing proteostasis processes via deciphering the cysteine-centric regulation of stress response pathways.
- Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents -
Background and Objectives. Methylation profile scores (MPSs) index biological aging and aging-related disease in adults and are cross-sectionally associated with social determinants of health in childhood. MPSs thus provide an opportunity to trace how aging-related biology responds to environmental changes in early life. Information regarding the stability of MPSs in early life is currently lacking. Method. We use longitudinal data from children and adolescents ages 8-18 (N = 428, M age = 12.15 years) from the Texas Twin Project. Participants contributed two waves of salivary DNA-methylation data (mean lag = 3.94 years), which were used to construct four MPSs reflecting multi-system physiological decline and mortality risk (PhenoAgeAccel and GrimAgeAccel), pace of biological aging (DunedinPACE), and cognitive function (Epigenetic-g). Furthermore, we exploit variation among participants in whether they were exposed to the COVID-19 pandemic during the course of study participation, in order to test how a historical period characterized by environmental disruption might affect children's aging-related MPSs. Results. All MPSs showed moderate longitudinal stability (test-retest rs = 0.42, 0.44, 0.46, 0.51 for PhenoAgeAccel, GrimAgeAccel, and Epigenetic-g, and DunedinPACE, respectively). No differences in the stability of MPSs were apparent between those whose second assessment took place after the onset of the COVID-19 pandemic vs. those for whom both assessments took place prior to the pandemic. Conclusions. Aging-related DNA-methylation patterns are less stable in childhood than has been previously observed in adulthood. Further developmental research on the methylome is necessary to understand which environmental perturbations in childhood impact trajectories of biological aging and when children are most sensitive to those impacts.
- Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine -
In order to improve vaccine effectiveness and safety profile of existing synthetic RNA-based vaccines, we have developed a self-amplifying RNA (saRNA)-based vaccine expressing membrane-anchored receptor binding domain (RBD) of SARS-CoV-2 S protein (S-RBD) and have demonstrated that a minimal dose of this saRNA vaccine elicits robust immune responses. Results from a recent clinical trial with 5-methylcytidine (5mC) incorporating saRNA vaccine demonstrated reduced vaccine-induced adverse effects while maintaining robust humoral responses. In this study, we investigate the mechanisms accounting for induction of efficient innate and adaptive immune responses and attenuated adverse effects induced by the 5mC-incorporated saRNA. We show that the 5mC-incorporating saRNA platform leads to prolonged and robust expression of antigen, while induction of type-I interferon (IFN-I), a key driver of reactogenicity, is attenuated in peripheral blood mononuclear cells (PBMCs), but not in macrophages and dendritic cells. Interestingly, we find that the major cellular source of IFN-I production in PBMCs is plasmacytoid dendritic cells (pDCs), which is attenuated upon 5mC incorporation in saRNA. In addition, we demonstrate that monocytes also play an important role in amplifying proinflammatory responses. Furthermore, we show that the detection of saRNA is mediated by a host cytosolic RNA sensor, RIG-I. Importantly, 5mC-incorporating saRNA vaccine candidate produced robust IgG responses against S-RBD upon injection in mice, thus providing strong support for the potential clinical use of 5mC-incorporating saRNA vaccines.
- SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2 -
Cytokine release syndrome (CRS) is one of the leading causes of mortality in COVID-19 patients caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague. This study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more IL-2, which subsequently cooperates with spike protein to facilitate peripheral blood mononuclear cells to release IL-1{beta}, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release TNF- and IFN-{gamma}, as well as T cells to release IFN-{gamma}. Mechanistically, IFN-{gamma} and TNF- enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of TLR4 which serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of NF-{kappa}B. Furthermore, TNF- also activates NF-{kappa}B signaling in monocytes, which further cooperates with IFN-{gamma} and spike protein to modulate NF-{kappa}B-dependent transcription of CRS-related inflammatory cytokines. Targeting TNF-/IFN-{gamma} in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting - Conditions: Post COVID-19 Condition (PCC)
Interventions: Device: RDX-19
Sponsors: KNOWBio Inc.; NAMSA
Recruiting
CPAP Therapy Through a Helmet or an Oronasal Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study - Conditions: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia
Interventions: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate
Sponsors: I.M. Sechenov First Moscow State Medical University
Recruiting
A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection
Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.
Recruiting
Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease - Conditions: COVID-19 Pneumonia; Virus Diseases; COVID-19
Interventions: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment
Sponsors: AVB Biotechnology
Recruiting
A PhaseⅠ Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 (COVID-19) Vaccine( ZSVG-02-O) - Conditions: SARS-CoV-2 Infection
Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital
Recruiting
SAFE Workplace Intervention for People With IDD - Conditions: Developement of Infectious Airborne Disease Prevention Workplace Curriclulm
Interventions: Behavioral: SAFE Employment Training
Sponsors: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research
Recruiting
Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms - Conditions: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame
Interventions: Behavioral: EMDR
Sponsors: University of Pisa
Completed
Lithium Long COVID Dose-finding Study - Conditions: Long COVID
Interventions: Dietary Supplement: Lithium
Sponsors: State University of New York at Buffalo
Not yet recruiting
Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function - Conditions: COVID-19 Pneumonia
Interventions: Drug: GST-HG171 Tablets
Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
Recruiting
Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic - Conditions: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children
Interventions: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education
Sponsors: Chung Shan Medical University
Completed
Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Liver Function - Conditions: COVID-19 Pneumonia
Interventions: Drug: GST-HG171 Tablets
Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
Completed
Evaluation of Concordance Between Exhaled Air Test (eBAM-CoV) and RT-PCR to Detect SARS-CoV-2 - Conditions: SARS-CoV-2 Infection; COVID-19; Coronavirus
Interventions: Device: eBAM Cov Testing
Sponsors: Centre Hospitalier Universitaire de Nīmes; University of Nimes; brains’ laboratory sas, FRANCE
Not yet recruiting
Study to Safety, Tolerability and Immunogenicity of EG-COVII in Healthy Adult - Conditions: COVID-19
Interventions: Biological: EG-COVII
Sponsors: EyeGene Inc.
Recruiting
Pharmacokinetics and Bioequivalence of Aterixen 100 mg Tablets and Aterixen 100 mg Film-coated Tablets in Healthy Volunteers - Conditions: Viral Infection COVID-19
Interventions: Drug: Aterixen
Sponsors: Valenta Pharm JSC
Not yet recruiting
A Practical RCT of TCM in the Treatment of LCOVID and Analysis of Syndrome Types and Medication Characteristics. - Conditions: Long COVID
Interventions: Drug: Traditional Chinese medicine treatment; Drug: Western medicine treatment
Sponsors: Chinese University of Hong Kong
Not yet recruiting
Promising role of Vitamin D and plant metabolites against COVID-19: Clinical trials review - Vitamin D possesses immunomodulatory qualities and is protective against respiratory infections. Additionally, it strengthens adaptive and cellular immunity and boosts the expression of genes involved in oxidation. Experts suggested taking vitamin D supplements to avoid and treat viral infection and also COVID-19, on the other hand, since the beginning of time, the use of plants as medicines have been vital to human wellbeing. The WHO estimates that 80 % of people worldwide use plants or herbs…
Plant-Derived Antioxidants for Management of COVID-19: A Comprehensive Review of Molecular Mechanisms - We aimed to review the literature to introduce some effective plant-derived antioxidants to prevent and treat COVID-19. Natural products from plants are excellent sources to be used for such discoveries. Among different plant-derived bioactive substances, components including luteolin, quercetin, glycyrrhizin, andrographolide, patchouli alcohol, baicalin, and baicalein were investigated for several viral infections as well as SARS-COV-2. The mechanisms of effects detected for these agents were…
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was…
A novel cell-permeable peptide prevents protein sumoylation and supports the mislocalization and aggregation of TDP-43 - SUMOylation is a post-translational modification (PTM) that exerts a regulatory role in different cellular processes, including protein localization, aggregation, and biological activities. It consists of the dynamic formation of covalent isopeptide bonds between a family member of the Small Ubiquitin Like Modifiers (SUMOs) and the target proteins. Interestingly, it is a cellular mechanism implicated in several neurodegenerative pathologies and potentially it could become a new therapeutic…
Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions - CONCLUSIONS: The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.
Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis - Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe COVID-19 upon infection with SARS-CoV-2. The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis. Serum from 53 SARS-CoV-2 unexposed and unvaccinated individuals, with decompensated liver…
Surface enhanced Raman scattering investigation of tecovirimat on silver, gold and platinum loaded silica nanocomposites: Theoretical analysis (DFT) and molecular modeling - As of today, there have been 612 million confirmed cases of coronavirus disease (COVID-19) around the world, with over 6 million fatalities. Tecovirimat (TPOXX) is an anti-viral drug, and it was the first drug approved for the treatment of anti-pox virus in the US. However, the effectiveness of this drug against COVID-19 has not yet been explored. Since TPOXX is an anti-viral drug, an attempt has been made to determine its ability to act as a COVID inhibitor. Recent medical advances have…
Plasma cell leukemia in a 34-year-old male: rare scenario case report - CONCLUSION: This report showcases a rare age presentation with unique manifestations of secondary plasma cell leukaemia. Multiple myeloma should be a differential diagnosis for cases with unexplained back pain despite an unclassical age.
Exploring Pharmacy Student Experiences with Student Debt and Perspectives on Future Burnout and Loan Relief - CONCLUSION: Pharmacy students burdened with debt described a variety of different experiences and attitudes toward that debt and provided their perspectives on how student debt influences short-term education and career decisions. While students accept the trade-off of debt for their education as an inevitable burden, reported coping mechanisms and strategies shared suggest some solutions may be available to ameliorate this burden.
Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung…
Proteomic analyses of smear-positive/negative tuberculosis patients uncover differential antigen-presenting cell activation and lipid metabolism - CONCLUSION: Our study provides valuable insights into the differential molecular mechanisms underlying SNPT and SPPT, reveals the critical role of antigen-presenting cell activation in SNPT for effectively clearing the majority of Mtb in bodies, and shows the possibility of APC activation as a novel TB treatment strategy.
Antrodia cinnamomea May Interfere with the Interaction Between ACE2 and SARS-CoV-2 Spike Protein in vitro and Reduces Lung Inflammation in a Hamster Model of COVID-19 - CONCLUSION: AC shows potential as a nutraceutical for reducing the risk of SARS-CoV-2 infection by disrupting the interaction between ACE2 and the SARS-CoV-2 spike protein, and for preventing COVID-19-associated lung inflammation.
Computational Screening Using a Combination of Ligand-Based Machine Learning and Molecular Docking Methods for the Repurposing of Antivirals Targeting the SARS-CoV-2 Main Protease - CONCLUSION: Results demonstrated the efficiency of LBVS combined with MD. This combined strategy provided positive evidence showing that the top screened drugs, including CCX-140, which had the lowest MD score, can be reasonably advanced to the in vitro phase. This combined method may accelerate the discovery of therapies for novel or orphan diseases from existing drugs.
Defining neutralization and allostery by antibodies against COVID-19 variants - The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein. We identified epitope…
Impact of influenza immunity on the mortality among older adults hospitalized with COVID-19: a retrospective cohort study - It has been suggested that the outcomes of coronavirus disease 2019 (COVID-19) are better in individuals having recently received an influenza vaccine than in non-vaccinated individuals. We hypothesized that this association depends on the humoral responses against influenza viruses. We aim to assess the relationship between the humoral immunity against influenza and the 3-month all-cause mortality among hospitalized older patients with COVID-19. We performed an exploratory retrospective study…