Abstract Introduction COVID-19, a global health crisis, prompted rapid vaccine development. Bivalent vaccines by Pfizer-BioNTech and Moderna target both original and Omicron strains. Despite vaccination efforts, the persistence of adverse events underscores the importance of ongoing safety monitoring. Method We collected COVID-19 bivalent vaccine adverse event reports from the Vaccine Adverse Event Reporting System (VAERS) (September 15, 2022, to September 1, 2023). The Medical Dictionary for Regulatory Activities (MedDRA) categorized reported symptoms into corresponding concepts. Statistical analyses included zero-truncated Poisson regression for estimating symptom rates, logistic regression for identifying risk factors, and Spearman correlation for assessing non-parametric relationships between adverse events in different System Organ Classes (SOCs). Results Our analysis of COVID-19 bivalent vaccine adverse events identified significant correlations between SOCs. Notably, a positive correlation (ρ = 0.3) linked Infections (SOC 1) with Respiratory disorders (SOC 13), while a negative correlation (ρ=-0.3) connected Investigations (SOC 23) with Injury (SOC 24). Zero-truncated Poisson modeling estimated an average of 6.179 symptoms per individual, varying by age, gender, and vaccine. Gender and age significantly influence reported adverse events associated with COVID-19 bivalent vaccines. Females generally experienced higher odds for most SOCs compared to males, except for cardiac and product-related issues. Older adults showed a higher likelihood of symptoms across various SOCs, while children and adolescents had distinct susceptibility patterns. Additionally, Moderna and Pfizer vaccines were associated with different SOCs, with Moderna linked mainly to immune and skin disorders and Pfizer associated primarily with cardiac and metabolic issues. Conclusion In conclusion, our study aligned self-reported items with widely-accepted medical terminology and rigorously analyzed adverse events following COVID-19 bivalent vaccine using advanced statistical methods. The significant findings provide crucial insights, guiding evidence-based strategies and interventions for vaccine safety.
RefAI: a GPT-powered retrieval-augmented generative tool for biomedical literature recommendation and summarization
Abstract Objectives Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes—real-time search and pretrained model utilization—it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. Materials and Methods RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics (“cancer immunotherapy and target therapy” and “LLMs in medicine”) were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. Results The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions—relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). Discussion RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. Conclusion By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.
Unpacking adverse events and associations post COVID-19 vaccination: a deep dive into vaccine adverse event reporting system data
SummaryBackgroundPrevious studies have demonstrated an association between nonselective beta‐blockers (NSBBs) and lower risk of hepatocellular carcinoma (HCC) in cirrhosis. However, there has been no population‐based study investigating the risk of HCC among cirrhotic patients treated using carvedilol.AimsTo determine the risk of HCC among cirrhotic patients with NSBBs including carvedilol.MethodsThis retrospective cohort study utilised the Cerner Health Facts database in the United States from 2000 to 2017. Kaplan‐Meier estimate, Cox proportional hazards regression, and propensity score matching (PSM) were used to test the HCC risk among the carvedilol, nadolol, and propranolol groups compared with no beta‐blocker group.ResultsThe final cohort comprised 107 428 eligible patients. The 100‐month cumulative HCC incidence of NSBBs was significantly lower than the no beta‐blocker group (carvedilol (11.24%) vs no beta‐blocker (15.69%), nadolol (27.55%) vs no beta‐blocker (32.11%), and propranolol (26.17%) vs no beta‐blocker (28.84%) (P values < 0.0001). NSBBs were associated with a significantly lower risk of HCC (Hazard ratio: carvedilol 0.61 (95% CI 0.51‐0.73), nadolol 0.74 (95% CI 0.63‐0.87), propranolol 0.75 (95% CI 0.66‐0.84) after PSM in the multivariate cox analysis. In subgroup analysis, NSBBs reduced the risk of HCC in cirrhosis with complications and non‐alcoholic cirrhosis.ConclusionsNSBBs, including carvedilol, were associated with a significantly decreased risk of HCC in patients with cirrhosis when compared with no beta‐blocker regardless of complications status. Future randomised‐controlled studies comparing the incidence of HCC among NSBBs should elucidate which NSBB would be the best option to prevent HCC in cirrhosis.
Chemokine Expression in the Central Nervous System of Mice with a Viral Disease Resembling Multiple Sclerosis: Roles of CD4+and CD8+T Cells and Viral Persistence
ABSTRACTDuring the first 45 days after intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV), the levels of mRNAs encoding chemokines MCP-1/CCL2, RANTES/CCL5, and IP-10/CXCL10 in the central nervous system (CNS) are closely related to the sites of virus gene expression and tissue inflammation. In the present study, these chemokines were monitored during the latter 135 days of a 6-month course of TMEV-induced disease in susceptible (PLJ) or resistant (C57BL/6) mice that possessed or lacked either CD4+or CD8+T cells. These data were additionally correlated to mouse genotype, virus persistence in the CNS, antiviral antibody titers, mortality, and the severity of neurological disease. Surprisingly, the major determinant of chemokine expression was virus persistence: the factors of susceptible or resistant genotype, severity of neuropathology, and presence or absence of regulatory T cells exerted minimal effects. Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.