Adebrelimab plus chemotherapy vs. chemotherapy for treatment of extensive-stage small-cell lung cancer from the US and Chinese healthcare sector perspectives: a cost-effectiveness analysis to inform drug pricing

Purpose: The aim of this study was to evaluate the cost-effectiveness of a recently approved first-line therapy (adebrelimab plus chemotherapy vs. chemotherapy alone) for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the US and China, and to estimate the reasonable range of adebrelimab price from the decision-makers.Methods: Several partitioned survival models were built to compare the cost and effectiveness of adebrelimab plus chemotherapy vs. chemotherapy alone over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CAPSTONE-1 trial. Costs and utilities were obtained from previously published studies. Sensitivity, scenario and subgroup analyses were performed to explore the uncertainty of the model outcomes. Price simulation was conducted at three thresholds of willingness-to-pay (WTP), including WTP of $100,000 in the US and of$37,422 in China, 0.5WTP of $50,000 in the US and of$18,711 in China, and 1.5WTP of 150,000 in the US and of $56,133 in China.Findings: Base-case analysis at$1382.82/600 mg of adebrelimab price indicated that adebrelimab plus chemotherapy would be cost-effective in the US at the WTP threshold of $100,000, but not in China at the WTP threshold of$37,422. If PAP was taken into account, the regimen would be cost-effective in China at the given WTP. The results of price simulation indicated that adebrelimab plus chemotherapy was completely favored in the US if adebrelimab price was less than $8894.98/600 mg (total quality-adjusted life years [QALYs] were calculated with progression-based utility [PB-utility]) or$8912.51/600 mg (total QALYs were calculated with time-to-death utility [TTD-utility]) at the WTP threshold of $100,000; if adebrelimab price was reduced by at least$202.03/600 mg (total QALYs were calculated with PB-utility) or $103.06/600 mg (total QALYs were calculated with TTD-utility), the regimen was also cost-effective in China without PAP at the WTP threshold of$37,422. The above results were stable in the sensitivity analyses. Subgroup analysis found that the subgroup with better survival benefits tended to have a higher probability of cost-effectiveness, which was also associated with adebrelimab price.Implications: First-line adebrelimab plus chemotherapy represented a dominant treatment strategy comparing with chemotherapy alone in the US and also did in China with PAP at $1382.82/600 mg of adebrelimab price. Decision-makers could benefit from pricing strategy provided by this study in making optimal decisions. More evidences were needed to verify and improve the results

Cost-effectiveness of durvalumab plus tremelimumab in combination with chemotherapy for the treatment of metastatic non-small-cell lung cancer from the US healthcare sector’s and societal perspectives

PurposeMetastatic non-small cell lung cancer (mNSCLC) has a high incidence rate, and economic burdens to patients, healthcare systems, and societies. Durvalumab plus tremelimumab and chemotherapy (T+D+CT) is a novel therapeutic strategy for mNSCLC, which demonstrated promising efficacy in a phase-3 randomized clinical trial, but its economic value remains unclear.MethodsThis economic evaluation used a hypothetical cohort of patients with mNSCLC, with characteristics mirroring those of the participants in the POSEIDON trial. Several partitioned survival models were constructed to estimate 15-year costs and health outcomes associated with the T+D+CT, durvalumab plus chemotherapy (D+CT) and chemotherapy alone (CT) strategies, discounting costs and effectiveness at 3% annually. Costs were in 2023 US dollars. Data were derived from the POSEIDON trial and published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 2022 to March 2023. To evaluate the cost-effectiveness of T+D+CT, compared with CT and D+CT, for mNSCLC from the perspectives of the US healthcare sector and society.FindingsFrom the healthcare sector’s perspective, the T+D+CT yielded an additional 0.09 QALYs at an increased cost of $7,108 compared with CT, which resulted in an ICER of$82,501/QALY. The T+D+CT strategy yielded an additional 0.02 QALYs at an increased cost of $27,779 compared with the D+CT, which resulted in an ICER of$1,243,868/QALY. The economic results of T+D+CT vs. CT were most sensitive to the annual discount rate, subsequent immunotherapy cost, tremelimumab cost, palliative care and death cost, pemetrexed cost, and durvalumab cost. The T+D+CT strategy was considered cost-effective relative to CT in 59%–82% of model iterations against willingness-to-pay. thresholds of $100,000/QALY gained to$150,000/QALY gained. From the societal perspective, the T+D+CT can be considered as cost-effective as compared with CT or D+CT, independent of histology.ImplicationsIn this cost-effectiveness analysis, the T+D+CT strategy represented good value compared with CT for patients with mNSCLC from the perspectives of the healthcare sector and the society. This treatment strategy may be prioritized for mNSCLC patients at high risks of disease progression

A Survey of Foundation Models for Music Understanding

Music is essential in daily life, fulfilling emotional and entertainment needs, and connecting us personally, socially, and culturally. A better understanding of music can enhance our emotions, cognitive skills, and cultural connections. The rapid advancement of artificial intelligence (AI) has introduced new ways to analyze music, aiming to replicate human understanding of music and provide related services. While the traditional models focused on audio features and simple tasks, the recent development of large language models (LLMs) and foundation models (FMs), which excel in various fields by integrating semantic information and demonstrating strong reasoning abilities, could capture complex musical features and patterns, integrate music with language and incorporate rich musical, emotional and psychological knowledge. Therefore, they have the potential in handling complex music understanding tasks from a semantic perspective, producing outputs closer to human perception. This work, to our best knowledge, is one of the early reviews of the intersection of AI techniques and music understanding. We investigated, analyzed, and tested recent large-scale music foundation models in respect of their music comprehension abilities. We also discussed their limitations and proposed possible future directions, offering insights for researchers in this field.20 pages, 2 figure

Impact of Red Imported Fire Ant Nest-Building on Soil Properties and Bacterial Communities in Different Habitats

The red imported fire ant (Solenopsis invicta Buren) is a highly adaptable invasive species that can nest and reproduce in different habitat soils. We aimed to explore the adaptability of red imported fire ants in different habitats by analyzing changes in the physicochemical properties of nest soils and bacterial communities. Five habitat types (forest, tea plantation, rice field, lawn, and brassica field) were selected. The results showed that the pH of the nest soils increased significantly in all five habitats compared to the control soils of the same habitat. A significant increase in nitrogen content was detected in the nests. The Cr, Pb, Cu, and Ni levels were significantly reduced in the soils of the five habitats, due to nesting activities. Analysis of the composition and diversity of the soil microbial community showed that, although the richness and diversity of bacteria in the nest soils of red imported fire ants in the five habitats varied, the relative abundance of Actinobacteria significantly increased and it emerged as the dominant bacterial group. These results indicate that red imported fire ants modify the physicochemical properties of nest soils and bacterial communities to create a suitable habitat for survival and reproduction

Study on Performance Enhancement of Shell and Tube Phase Change Thermal Energy Storage Heat Exchangers

Based on the computational fluid dynamics (CFD) software, the effect of fins on the heat transfer process of a phase-change heat exchanger was considered in terms of the heat transfer area and flow field. The influences of the fin height and fin arrangement on the heat transfer performance under three types of structures (double-finned, triple-finned, and quadruple-finned) were analyzed, and the optimal structure and specification parameters were obtained. The results show that the fins with a double-finned structure substantially improve the thermal energy storage performance of the phase-change heat exchanger. The heat exchanger with a triple-finned structure can reach the expansion period of the flow field faster, and the symmetrical quadruple-finned heat exchanger has a relatively high melting rate in the vertical and horizontal directions. Under the same heat transfer area, the double-finned structure has obvious advantages. When the ratio of fin length to heat exchange tube length is 1.5, the discharge time is shortened by 80%, and the total solidification mass increases to 87%, which is 76% higher than that of the bare tube

Valve Vibration Induced Intake Air Flow Dynamics Analysis Using Near Valve Particle Image Velocimetry

Abstract The transient dynamics of air flow running through the moving intake valve gaps in combustion cylinders is crucial to the performance of spark-ignition direct-injection engines. However, research on the air flow behavior in the vicinity of valve exits is still limited. In this work, transient air flow characteristics of a custom-designed dual-valve system under the operating conditions of a fixed valve lift and a vibrating valve lift at two frequencies are experimentally investigated. The velocity vector field measured using planar particle image velocimetry (PIV) is first analyzed in time domain based on temporal mean and root-mean-square (RMS) values. Comparison of temporal mean flow fields reveals the difference in flow pattern while RMS represents the variation of intake air jet velocity along the inlet path of the vibration-affected jet. Instantaneous snapshots provide direct analysis of the valve vibration-induced intake air jet behavior. Furthermore, investigation in frequency domain extends insights into the dominant spectral components of flow structures. Fast Fourier transform (FFT) applied to every vector on the velocity field yields a vibration frequency affected zone (VFAZ), indicating the regions where the effect of valve vibration is significant. By employing dynamic mode decomposition (DMD) method, the spatio-temporal PIV results are decomposed into modes with specific frequencies. Reconstructed flow field using modes with the valve operating frequency visually unveils a cyclic vortex structure near the valve exit. In summary, this study elucidates the mechanism of near-valve intake air flow impingement and interaction behavior induced by the valve vibrating motion.</jats:p

Comparative Analyses of Reproductive Caste Types Reveal Vitellogenin Genes Involved in Queen Fertility in Solenopsis invicta

The red imported fire ant (Solenopsis invicta Buren) is a social pest species with a robust reproductive ability that causes extensive damage. Identification of the genes involved in queen fertility is critical in order to better understand the reproductive biology and screening for the potential molecular targets in S. invicta. Here, we used the mRNA deep sequencing (RNA-seq) approach to identify differentially expressed genes (DEGs) in the transcriptomes of three reproductive caste types of S. invicta, including queen (QA) and winged female (FA) and male (MA) ants. The genes that were specific to and highly expressed in the queens were then screened, and the Vg2 and Vg3 genes were chosen as targets to explore their functions in oogenesis and fertility. A minimum of 6.08 giga bases (Gb) of clean reads was obtained from all samples, with a mapping rate &gt; 89.78%. There were 7524, 7133, and 977 DEGs identified in the MA vs. QA, MA vs. FA, and FA vs. QA comparisons, respectively. qRT&ndash;PCR was used to validate 10 randomly selected DEGs, including vitellogenin 2 (Vg2) and 3 (Vg3), and their expression patterns were mostly consistent with the RNA-seq data. The S. invicta Vgs included conserved domains and motifs that are commonly found in most insect Vgs. SiVg2 and SiVg3 were highly expressed in queens and winged females and were most highly expressed in the thorax, followed by the fat body, head, and epidermis. Evaluation based on a loss-of-function-based knockdown analysis showed that the downregulation of either or both of these genes resulted in smaller ovaries, less oogenesis, and less egg production. The results of transcriptional sequencing provide a foundation for clarifying the regulators of queen fertility in S. invicta. The functions of SiVg2 and SiVg3 as regulators of oogenesis highlight their importance in queen fecundity and their potential as targets of reproductive disruption in S. invicta control