Enhancing phase I dose-finding trials design through dynamic borrowing information and handling late-onset toxicity

Introduction: In recent years, there has been a growing trend among regulatory agencies to consider the use of historical controls in clinical trials as a means of improving the efficiency of trial design. In this paper, to enhance the statistical operating characteristic of Phase I dose-finding trials, we propose a novel model-assisted design method named “MEM-Keyboard”.Methods: The proposed design is based on the multisource exchangeability models (MEMs) that allows for dynamic borrowing of information from multiple supplemental data sources, including historical trial data, to inform the dose-escalation process. Furthermore, with the frequent occurrence of delayed toxicity in novel anti-cancer drugs, we extended our proposed method to handle late-onset toxicity by incorporating historical data. This extended method is referred to as “MEM-TITE-Keyboard” and aims to improve the efficiency of early clinical trials.Results: Simulation studies have indicated that the proposed methods can improve the probability of correctly selecting the maximum tolerated dose (MTD) with an acceptable level of risk, compared to designs that do not account for information borrowing and late-onset toxicity.Discussion: The MEM-Keyboard and MEM-TITE-Keyboard, easy to implement in practice, provide a useful tool for identifying MTD and accelerating drug development

The reporting quality of randomized controlled trials in Chinese herbal medicine (CHM) formulas for diabetes based on the consort statement and its extension for CHM formulas

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors

Vortex Evolution Behavior in Self-Assembly of Flow Units in Metallic Glasses

Shear banding in amorphous metals originates from the activation and percolation of flow units. To uncover the self-assembly dynamics of flow units in metallic glasses, a rectangular sample with two flow units embedded in the matrix undergoing simple shearing was analyzed using finite element simulations. The vortex evolution behavior, including activation, growth, and collapse during the self-assembly of flow units, was revealed. It was found that the formation of a mature vortex indicates the onset of yielding, and the collapse of the vortex represents the percolation of flow units or shear localization. The effects of initial free volume distribution and the distance between flow units on vortex behavior were also studied. Increasing the initial free volume concentration within flow units or the matrix leads to a gentler vortex evolution process and better homogeneous plasticity. The shape of vortex tends to be "flatter" with the increase in flow units' spacing, and the optimal spacing was found to maximize the strength of the material

The study of characteristics through biomass burning

As a major agricultural province in China, Northeast China produces a lot of biomass while its grain yield is high. Open burning is an efficient and convenient way to remove biomass. However, air pollutants (PM2.5, CO, VOCs) will be released in the process of biomass combustion, which will have a certain impact on Regional Environmental quality, atmospheric visibility and human health. Because of the various type of biomass, their combustion products and effects are different. In this study, there collected peanut hull, rice husk, straw and wood particles, and carried out the simulated combustion experiment in the laboratory environment simulation chamber. The inorganic elements, water-soluble ions and speciation analysis of combustion products were determined. The results showed that the content of Zn was higher than that of carcinogenic element in the eight inorganic elements after combustion. The water-soluble ion emission factors of wheat straw and wood particles are larger than those of peanut hull and rice husk, and the water-soluble ions are mainly K+ and CL. Through the morphology analysis of combustion products, it can be seen that different types of biomass have different morphology after combustion, which are mainly strip, column and particle. Combined with energy spectrum analysis, it is found that the content of K and CL is high. The results lay a theoretical foundation for the study of local biomass combustion and provide data for the determination of local biomass combustion emission characteristics

Visual Affective Stimulus Database: A Validated Set of Short Videos

Two hundred and ninety-nine videos representing four categories (people, animals, objects, and scenes) were standardized using Adobe Premiere Pro CC 2018, with a unified duration of 3 s, a resolution of 1080 pixels/inch, and a size of 1920 × 1080 mm2. One-hundred and sixteen participants (mean age 22.60 ± 2.06 years; 51 males) assessed the videos by scoring, on a self-reported 9-point scale, three dimensions of emotion: valence, arousal, and dominance. The content was attributed a specific valence (positive, neutral, or negative) if more than 60% of the participants identified it with an emotion category. Results: In total, 242 short videos, including 112 positive videos, 47 neutral videos, and 83 negative videos, were retained in the video stimuli database. In the three-dimensional degree of emotion, the distribution relationship between them conformed to the fundamental characteristics of emotion. The internal consistency reliability coefficient for valence, arousal, and dominance was 0.968, 0.984, and 0.970. The internal consistency reliability of the emotional dimensions for people and faces, animals, objects, and scenes ranged between 0.799 and 0.968. Conclusions: The emotion short-video system contains multi-scene dynamic stimuli with good reliability and scoring distribution and is applicable in emotion and emotion-related research

How is intergenerational emotional cohesion linked to depression among older internal migrants in China: the mediating roles of loneliness and perceived stress

Abstract Background Late-life internal migration is frequently associated with a higher risk of depression in older parents. This research delves into the impact of intergenerational emotional cohesion (IEC) on depression in older internal migrants and the underlying mechanisms within the contemporary Chinese context. Methods Obtained from a cross-sectional survey in Nanjing, China, the research involved 654 older internal migrants (66.97% female; mean age = 66.05 years; SD = 4.67). Variables were assessed using the Intergenerational Solidarity Inventory, 3-item R-UCLA Loneliness Scale, Perceived Stress Scale, and 9-item Patient Health Questionnaire (PHQ-9). For mediation exploration, a serial mediation model was utilized, and the Bootstrap method was employed to test the signifcance of these mediation effects. Results IEC demonstrates a negative correlation with depression. Through IEC, three significant mediation pathways were identified that directly affect depression: (1) loneliness (β=-0.06; Ratio=17.14%), (2) perceived stress (β=-0.09; Ratio=25.71%), and (3) loneliness and perceived stress (β=-0.03; Ratio=8.57%). Conclusions IEC can impact the depression of older internal migrants by mitigating negative psychological emotions during the migration process. This finding provides valuable theoretical insights for the prevention of mental health problems among this demographic

A Bayesian phase I–II clinical trial design to find the biological optimal dose on drug combination

In recent years, combined therapy shows expected treatment effect as they increase dose intensity, work on multiple targets and benefit more patients for antitumor treatment. However, dose -finding designs for combined therapy face a number of challenges. Therefore, under the framework of phase I–II, we propose a two-stage dose -finding design to identify the biologically optimal dose combination (BODC), defined as the one with the maximum posterior mean utility under acceptable safety. We model the probabilities of toxicity and efficacy by using linear logistic regression models and conduct Bayesian model selection (BMS) procedure to define the most likely pattern of dose–response surface. The BMS can adaptively select the most suitable model during the trial, making the results robust. We investigated the operating characteristics of the proposed design through simulation studies under various practical scenarios and showed that the proposed design is robust and performed well.</p