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Artificial Intelligence Applications for Optimizing Population and Clinical Drug Decision-Making Processes
No full textIntroduction: In our study, we evaluated the application of ChatGPT4, an artificial intelligence chatbot, in the pharmacy field, specifically the capability of ChatGPT4 to extract and analyze FDA drug information, conduct a cost-effectiveness analysis of two antibiotics, and identify and classify adverse drugs events (ADE). We compare the results of ChatGPT4 with those from manual searches and specialized software programs. Methods: The first study used ChatGPT4 to extract and assess the quality of regulatory information for antibiotics indicated for complicated urinary tract infections (cUTI) approved by the FDA in 2014-2023. The second study involved comparing the cost-effectiveness analysis of cefiderocol and imipenem/cilastatin indicated for cUTI using MS Excel, the software program TreeAge, and ChatGPT4. The third and last study evaluated ChatGPT4’s validity and reliability in identifying and classifying adverse drug events of fluoroquinolone antibiotics. Results: ChatGPT4 was efficient in collecting and evaluating regulatory data, with the Wilcoxon signed-rank test showing a significant difference favoring ChatGPT (p = 1.708 x10-05). ChatGTP4 conducted a CEA that included cost-effectiveness ratios (ICER) and sensitivity analysis. Additionally, ChatGPT4 had an 87.5% overall accuracy in identifying and classifying adverse drug events, identifying common and rare side effects but failing to identify some uncommon ADE. Conclusions: ChatGPT4 is an efficient tool for extracting and evaluating FDA drug information, and it can identify errors in data collection using manual methods. However, ChatGPT4 responses varied under different conditions, such as time of the day, file size, and question complexity. ChatGPT4 performs cost-effectiveness analysis, creating decision trees and calculating ICER, though its accuracy depends on the precision of input data and the way the questions are formulated. ChatGPT4 can identify and categorize most adverse drug events
Toward Intuitive 3D Interactions in Virtual Reality: A Deep Learning- Based Dual-Hand Gesture Recognition Approach
Get PDFDual-hand gesture recognition is crucial for intuitive 3D interactions in virtual reality (VR), allowing the user to interact with virtual objects naturally through gestures using both handheld controllers. While deep learning and sensor-based technology have proven effective in recognizing single-hand gestures for 3D interactions, research on dual-hand gesture recognition for VR interactions is still underexplored. In this work, we introduce CWT-CNN-TCN, a novel deep learning model that combines a 2D Convolution Neural Network (CNN) with Continuous Wavelet Transformation (CWT) and a Temporal Convolution Network (TCN). This model can simultaneously extract features from the time-frequency domain and capture long-term dependencies using 3D position and orientation data from handheld controllers for gesture classification. To evaluate the performance of the proposed model, we designed 13 dual-hand gestures representing fundamental 3D interaction tasks: translation, rotation, scaling, and selection, and then collected data from 26 participants using a VR system. The model’s performance was rigorously tested under various hand-tracking scenarios, including dual-hand versus single-hand inputs and complete versus partial motion features. Benchmarking against four state-of-the-art neural networks revealed that CWT-CNN-TCN reliably detects dual-hand gestures with limited tracking data and outperforms the benchmarks. This result paves the way for a dual-hand gesture-based interface that enriches intuitive 3D interactions in VR
Socioeconomic Constraints on Low-income Individuals\u27 Perceptions Toward Food Safety
Get PDFFood safety has emerged as a critical concern in Vietnam, posing a significant threat to public health due to the prevalence of unsafe foods in the market. Among those most vulnerable to contaminated foods, low-income individuals are significantly affected. This study aimed to investigate the perceptions of food safety among this demographic, utilizing qualitative and quantitative approaches, including focus groups, survey questionnaires, and behavioral experiments using steamed bun as a stimulus. Participants were generally from low-income classes with certain variations in household monthly income. Results from focus groups and the survey highlighted that the factors influencing food purchases included perception of safety, sensory properties, and acceptable pricing. The behavioral experiment revealed that participants with lower incomes were more inclined to select foods containing unsafe chemicals. In conclusion, the study underscored the heightened vulnerability of low-income individuals to unsafe foods, with their perception of food safety bounded by socioeconomic status
Design and Evaluation of Cyclic Peptide-Epirubicin Conjugate for Enhanced Anticancer Activity and Reduced Myocardial Toxicity
No full textDespite the introduction of molecularly targeted drugs, chemotherapy remains at the frontline of cancer therapy. However, multi-drug resistance and the non-specific distribution of anticancer drugs to healthy cells pose challenges that limit the clinical application of these drugs.
Epirubicin (EPI) is a topoisomerase II Inhibitor and an antineoplastic agent used to treat acute myeloid leukemias, multiple sclerosis (relapsing or secondary progressive), and prostate cancer. However, this agent causes myocardial toxicity and potentially fatal heart failure (HF). It is also important to note that this side effect increases with cumulative dosing. Cardiotoxicity may occur during therapy or may be delayed (months or years after completion of treatment). Furthermore, enhanced resistance to EPI has been shown to reduce intracellular drug accumulation and activity.
We have previously shown that conjugation of doxorubicin (DOX), another topoisomerase inhibitor that is also known for its cardiotoxicity and development of resistance, with cyclic peptides containing tryptophan (W) and arginine (R) residues showed comparable or higher activity against cancer cells and reduced the toxicity to heart cells when compared to free DOX. [(WR)4WK]bA-DOX conjugate exhibited enhanced uptake, retention, and sustained intracellular hydrolysis of DOX. The objective of this work was to conjugate EPI to cyclic peptide [(WR)4WK]bA by a linker to enhance drug delivery and efficacy against cancer cells and drug-resistant cells and diminish cardiotoxicity. We hypothesized that an optimized peptide-EPI conjugate would have potential applications for selective delivery to different cancer cells as a molecular transporter of EPI.
The cyclic peptide was synthesized through Fmoc solid-phase peptide synthesis, followed by cyclization in the solution phase. Since EPI has one free amine group, it was protected with Fmoc as a protecting group before conjugation with [(WR)4WK]bA through a glutarate linker.
The cytotoxicity of the conjugate, physical mixture, and EPI alone were compared at different concentrations in ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7) triple-negative breast (MDA-MB-231), DOX/EPI-resistant uterine sarcoma (MES-SA/MX2), and normal rat cardiomyoblast (H9C2) cells. The conjugate (5 µM) exhibited significantly higher antiproliferative activity against breast cancer cells and DOX/EPI-resistant cells and less antiproliferative activity against SK-OV-3 cells, while it showed minimal cytotoxicity against heart cells after 24 and 72 h incubation when compared to EPI (5 µM).
Flow cytometry and confocal microscopy were used to evaluate the cellular uptake of the conjugate in MDA-MB-231, MES-SA/MX2, and H9C2 cells compared to EPI. Confocal microscopy images revealed that at a concentration of 5 µM, the conjugate exhibited enhanced nuclear uptake compared to EPI in MDA-MB-231 and MES-SA/MX cells. Notably, there was no significant uptake in H9C2 cells after 24 h incubation. The cellular uptake was not significantly changed in the presence and absence of endocytosis inhibitors in MDA-MB-231 and MES-SA/MX cells, suggesting an endocytosis-independent cell entry.
Overall, the data suggest that the [W(RW)4K]βA-EPI conjugate offers a potential therapeutic advantage over free EPI and physical mixtures by improving efficacy, reducing cardiotoxicity, and exhibiting selective targeting to cancer cells. These findings highlight the promise of peptide-drug conjugates as a novel approach for enhancing cancer therapy effectiveness and reducing side effects
Strategic Justice, Conventions, and Game Theory: Introduction to a \u3cem\u3eSynthese\u3c/em\u3e Topical Collection
Get PDFEvolutionary, game-theoretic approaches to justice and the social contract have become increasingly popular in contemporary moral and political philosophy. (Vanderschraaf, Strategic justice: convention and problems of balancing divergent interests, Oxford University Press, 2019) theory of strategic justice represents the most recent contribution to this tradition and, in many ways, can be viewed as a culmination of it. This article discusses some of the central features of Vanderschraaf’s theory and relates them to the contributions in this collection. Some of the contributions directly address Vanderschraaf’s work, while others explore related topics in game theory, bargaining theory, formal philosophy, rationality, equality, justice, and the theory of conventions. This collection aims to bridge a gap between disjoint but closely related literature spanning a wide range of disciplines. The contributions allow readers to systematically engage with the topic of strategic justice, advance dialogue, and more easily follow this rich and expanding field of study
Sustainable Development of Private Art Museums in China: A Narrative Inquiry Study
Get PDFPrivate art museums are a relatively new phenomenon in China, having first appeared in the 20th century. This brief timeline in the larger history of art museums, coupled with the fact most Chinese private art museums close after just a few years of operation, has led many to question how to promote the sustainability of these institutions. These questions became even more pronounced with the onset of the COVID-19 global pandemic, which brought a greater sense of uncertainty to the museum industry and society at large. This dissertation inquires similarly, asking how sustainability is conceptualized by Chinese private art museum professionals and factors that affect sustainable development of this subset of museums. To respond to such questions, this study adopted a three-pronged framework that examined the cultural, economic, and social factors impacting museum sustainability (adapted from Stylianou-Lambert et al.’s (2014) study), which was then applied to interviews conducted with 10 museum professionals from private art museums throughout China. The interviewees often spoke of a Western museum model being applied to private art museum operations in China, with both positive and negative effects. Moreover, they presented sustainability as a multifaceted concept, one predicated on multiple factors or concerns. Some of the factors influencing the sustainability of private art museums that were explored include (a) desire for greater government support but more curatorial autonomy and less censorship, (b) desire to cater to changing audience preferences while maintaining the integrity of exhibits, and (c) desire to become more financially self- sufficient without being influenced by the whims of the individuals privately funding museum operations. These tensions were examined in depth to provide recommendations for increasing the visibility of Chinese private art museums, thereby promoting their long-term sustainability
Three-wave Mixing Experiments in Indium–Tin–Oxide Thin-Films with No Phase Matching
Get PDFOne challenge of using nonlinear optical phenomena for practical applications is the need to perform phase-matching. Recently, epsilon-near-zero materials have been shown to demonstrate strong optical nonlinearities, in addition to their other unique properties. As suggested by their name, the permittivity of the material is close to zero for a certain wavelength range. We demonstrate that this small permittivity allows for efficient three-wave mixing interactions to take place in indium–tin–oxide thin films without the need for phase matching the pump and signal beams. The efficiency of the second-order nonlinear interactions is characterized, and cascaded three-wave mixing is demonstrated
Liberal Freedom: Pluralism, Polarization, and Politics
No full textA review of Liberal Freedom: Pluralism, Polarization, and Politics by Eric MacGilvray
Personal Lies
Get PDFUsing the mind game, we provide experimental evidence that people are more likely to lie when they disclose non-personal information (e.g., reporting a number they thought of) compared with personal information (e.g., reporting the last digit of their birth year). Our findings suggest that the type of information is an important factor for lying behavior
Influence of Human and Viral IL-6 on KSHV Infection in Human Tonsil Lymphocytes
No full textInfection of B cells by the lymphotropic gamma-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV) causes Multicentric Castleman Disease, Primary Effusion Lymphoma, and the newly-identified inflammatory syndrome designated KICS. Despite proven connections to lymphoproliferative disorders, little is known about how KSHV invades the human immune system or the early events governing infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, where elevated hIL-6 levels are positively associated with KSHV viral load and disease progression. This dynamic is even more complex due to the co-existence of human IL-6 (hIL6) and KSHV-encoded viral IL-6 (vIL6) in these diseases. Although the impact of IL-6 signaling is well-established in the context of KSHV disease, its role in the early stages of infection in B cells remains undefined. We hypothesize that hIL6 and vIL6 play critical roles in the early stages of KSHV infection in B cells and the establishment of KSHV-infected plasma cells. In this study, we use ex vivo infection of tonsil lymphocytes with recombinant KSHV as a model to investigate early infection events. Our main objective is to utilize multiple approaches, including molecular knockout of vIL6 from the KSHV genome, knockout of human IL-6 through CRISPR-Cas9 gene editing, as well as recombinant proteins and neutralizing antibodies to manipulate signaling from hIL-6 and vIL-6. We will examine how these manipulations affect the viability, differentiation, and proliferation of tonsil lymphocyte cultures, as well as the magnitude and distribution of KSHV infection via flow cytometry analysis. In our investigations, successful knockdown of hIL-6 in non-B cells resulted in reduced B cell viability, with IL-6 knockdown correlating with decreased B cell survival in the cultures as well as decreased KSHV infection, particularly in plasma cells. Neutralization of hIL-6 reduced proliferation in B cell cultures, and this effect was more profound when hIL-6 was neutralized in the context of infection with the vIL-6 mutant virus. Moreover, hIL-6 neutralization had little effect on total infection in the context of WT KSHV, but vIL-6 mutant virus had a reduced ability to establish infection when hI-L6 was neutralized. We will also present results showing the effects of vIL-6 and hIL-6 on B cell differentiation in response to KSHV infection. Overall, our findings suggest that hIL-6 and vIL-6 have complementary but separable roles in the early stages of KSHV infection in B cells