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Large Language Models (LLMs) have rapidly become important tools in Biomedical and Health Informatics (BHI), enabling new ways to analyze data, treat patients, and conduct research. This bibliometric review aims to provide a panoramic view of how LLMs have been used in BHI by examining research articles and collaboration networks from 2022 to 2023. It further explores how LLMs can improve Natural Language Processing (NLP) applications in various BHI areas like medical diagnosis, patient engagement, electronic health record management, and personalized medicine. To do this, our bibliometric review identifies key trends, maps out research networks, and highlights major developments in this fast-moving field. Lastly, it discusses the ethical concerns and practical challenges of using LLMs in BHI, such as data privacy and reliable medical recommendations. Looking ahead, we consider how LLMs could further transform biomedical research as well as healthcare delivery and patient outcomes. This bibliometric review serves as a resource for stakeholders in healthcare, including researchers, clinicians, and policymakers, to understand the current state and future potential of LLMs in BHI., Comment: 51 pages, 7 figures, 4 tables

Recent years have witnessed the rapid development of large language models (LLMs) in various domains. To better serve the large number of Chinese users, many commercial vendors in China have adopted localization strategies, training and providing local LLMs specifically customized for Chinese users. Furthermore, looking ahead, one of the key future applications of LLMs will be practical deployment in industrial production by enterprises and users in those sectors. However, the accuracy and robustness of LLMs in industrial scenarios have not been well studied. In this paper, we present a comprehensive empirical study on the accuracy and robustness of LLMs in the context of the Chinese industrial production area. We manually collected 1,200 domain-specific problems from 8 different industrial sectors to evaluate LLM accuracy. Furthermore, we designed a metamorphic testing framework containing four industrial-specific stability categories with eight abilities, totaling 13,631 questions with variants to evaluate LLM robustness. In total, we evaluated 9 different LLMs developed by Chinese vendors, as well as four different LLMs developed by global vendors. Our major findings include: (1) Current LLMs exhibit low accuracy in Chinese industrial contexts, with all LLMs scoring less than 0.6. (2) The robustness scores vary across industrial sectors, and local LLMs overall perform worse than global ones. (3) LLM robustness differs significantly across abilities. Global LLMs are more robust under logical-related variants, while advanced local LLMs perform better on problems related to understanding Chinese industrial terminology. Our study results provide valuable guidance for understanding and promoting the industrial domain capabilities of LLMs from both development and industrial enterprise perspectives. The results further motivate possible research directions and tooling support.

The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing

The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing

The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing

P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks pseudovirus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks pseudovirus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks pseudovirus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells

In the network age, people have changed from passive reception of information to active creation of information carrier. Everyone can express their ideas and opinions to others, and create value through interaction between customers and customers. In this paper, a theoretical value model is constructed: interaction - brand experience - brand loyalty. Based on the mobile application software as the research background, the customer data collected are analyzed by structural equation model. The results show that customer interaction has a positive impact on value creation and brand loyalty, and brand experience has a partial mediating effect on customer value creation and brand loyalty. Finally, it is proposed that enterprises can help enterprises improve brand loyalty by strengthening the construction of customer's emotional relationship network, enhancing customer's continuous use feeling, designing and recommending content through customer segmentation, and expanding customer groups. Keywords: Customer interaction; short video; value creation; brand loyalty; brand experience DOI: 10.7176/EJBM/11-11-11 Publication date: April 30th 2019

In the network age, people have changed from passive reception of information to active creation of information carrier. Everyone can express their ideas and opinions to others, and create value through interaction between customers and customers. In this paper, a theoretical value model is constructed: interaction - brand experience - brand loyalty. Based on the mobile application software as the research background, the customer data collected are analyzed by structural equation model. The results show that customer interaction has a positive impact on value creation and brand loyalty, and brand experience has a partial mediating effect on customer value creation and brand loyalty. Finally, it is proposed that enterprises can help enterprises improve brand loyalty by strengthening the construction of customer's emotional relationship network, enhancing customer's continuous use feeling, designing and recommending content through customer segmentation, and expanding customer groups. Keywords: Customer interaction; short video; value creation; brand loyalty; brand experience DOI: 10.7176/EJBM/11-11-11 Publication date: April 30th 2019