In-lab Validation Research Articles

Abstract P464: Performance of an Automated Sleep Scoring Approach for Actigraphy Data in Children and Adolescents

Background: Actigraphy has advanced the measurement of sleep for cardiometabolic research in childhood. However, actigraphy methods lack standardization, limiting rigor and reproducibility. GGIR, an open-source R package, facilitates raw accelerometer data processing to generate sleep data in a standardized manner. This tool has been validated and applied to adult data, but less is known about the suitability of this tool for generating sleep estimates among children. We aimed to (1) determine the validity of multiple sleep scoring settings available within GGIR in children, and (2) evaluate how this tool automatically generates sleep data in community-based pediatric studies. Method: The validation study included 30 children (14 female, 8-16y) referred for in-lab overnight polysomnography at Children’s Hospital of Philadelphia. Participants wore a GENEActiv during polysomnography that captured data at 50 Hz, which were aligned into 30-second epochs against the sleep stages from polysomnography scored by a sleep medicine physician. Balanced accuracy was the primary validation metric, which is the average of sensitivity and specificity. For community-based testing, three pediatric cohorts were used: Study 1 (Philadelphia; 12-16y; GENEActiv, N=251), Study 2 (Mexico City, 9-18y; ActiGraph GT3X-BT; N=543), and Study 3 (Houston; 5-8y; ActiGraph GT3X+, N=226). We processed raw accelerometry data with the Cole-Kripke (CK), Sadeh (S), and Van Hees (VH) algorithm settings. Result: For in-lab validation, 271.5 hours of polysomnography data were collected with 80% of the epochs scored as sleep; sleep duration averaged 7.3 hours (SD = 1.3). In rank order, average balanced accuracies were 0.81 (SD = 0.08) for GGIR-CK, 0.77 (SD = 0.09) for GGIR-VH, and 0.68 (SD = 0.11) for GGIR-S. The GGIR-S algorithm had the poorest detection of night awakenings (specificity: 0.38 [SD = 0.21]). For community-based data, without manually altering the data, the average sleep duration was highest when using the Sadeh algorithm in each study (8.3 [SD = 1.6], 8.0 [SD = 1.9], and 5.2 [SD = 4.4] hours for studies 1-3) and lower when using the GGIR-CK algorithm (7.1 [SD = 1.4], 6.9 [SD = 1.7], 4.3 [SD = 3.7] hours for studies 1-3). Approximately 2% of the data were affected by obvious errors (e.g., negative wake after sleep onset), with almost all such errors detected with the Sadeh algorithm. Conclusion: In a controlled setting, GGIR-CK had the optimal balanced accuracy performance for estimating sleep duration in children. In keeping with the lab-based finding of poorer detection of night awakenings, sleep duration was highest in the community samples when using GGIR-S. When applied to community-based data the automated GGIR approach generated sleep data that included errors, necessitating additional data cleaning. Incorporating standardized data cleaning steps within GGIR would improve rigor and reproducibility.

Towards ultrasound wearable technology for cardiovascular monitoring: from device development to clinical validation.

The advent of flexible, compact, energy-efficient, robust, and user-friendly wearables has significantly impacted the market growth, with an estimated value of 61.30billion USD in 2022. Wearable sensors have revolutionized in-home health monitoring by warranting continuous measurements of vital parameters. Ultrasound is used to non-invasively, safely, and continuously record vital parameters. The next generation of smart ultrasonic devices for healthcare integrates microelectronics with flexible, stretchable patches and body-conformable devices. They offer not only wearability, and user comfort, but also higher tracking accuracy of immediate changes of cardiovascular parameters. Moreover, due to the fixed adhesion to the skin, errors derived from probe placement or patient movement are mitigated, even though placement at the correct anatomical location is still critical and requires a user's skill and knowledge. In this review, the steps required to bring wearable ultrasonic systems into the medical market (technologies, device development, signal-processing, in-lab validation, and, finally, clinical validation) are discussed. The next generation of vascular ultrasound and its future research directions offer many possibilities for modernizing vascular health assessment and the quality of personalized care for home and clinical monitoring.

Abstract 2920: Targeting integrin alpha V beta 5 heterodimer stability using a novel small molecular inhibitor for tumor suppression

Abstract The cell surface proteome provides a pivotal interphase that connects the intracellular signaling with external environments, which may harbor molecular targets for therapeutic development. To identify essential cell surface proteins in cancers, we established a CRISPR library that contains 2,910 sgRNAs targeting 582 genes encoding cell surface receptors (to cytokines, extracellular matrices [ECM], etc.), molecular channels, and signaling components. We then screened this library in 3 solid cancer (MDA-MB-231, SW620, PANC1) and 3 liquid cancer (MV4-11, HUT78, CCRF-CEM) cell models expressing the Cas9 endonuclease, and observed an essential role of ITGAV (Integrin Alpha V) specifically in the solid cancer. As integrins require the dimerization between an alpha and beta subunit to function as cell surface ECM receptors, we further developed a focused CRISPR library with 650 sgRNAs targeting all 26 integrin alpha and beta subunits. This validation screen revealed a strong correlation between ITGAV and ITGB5 (Integrin Beta 5) in solid tumors. CRISPR targeting either ITGAV or ITGB5 led to attenuated cell proliferation with increased cell cycle stalling and apoptosis. Knockout of ITGAV-ITGB5 also suppressed the capacity of tumor cells to migrate and invade through the ECM, highlighting the therapeutic benefit via blocking the ITGAV-ITGB5 heterodimer. To identify novel compounds that can disrupt ITGAV-ITGB5 dimerization, we first modeled a 3D crystal structure of ITGAV (PDB ID: 3IJE) using AutoSite (Scripps) to reveal the protein surface pockets amenable to the small molecular binding. This analysis revealed an AVB pocket at the N-terminal extracellular domain of ITGAV, which is in close contact with the beta subunit. CRISPR targeting this AVB pocket abolished the ITGAV-ITGB5 heterodimers (detected by an AV-B5-complex antibody) and induced rapid cell death, rationalizing this pocket for further therapeutic development. Based on these observations, we computationally docked >100,000 compounds from the NCI DTP Open Chemicals Repository using AutoDock Vina (Scripps), subsequently obtaining the top 500 binder compounds for in-lab validation, and identified a lead AVB pocket inhibitor “Cpd_2” (C32H40N4). Treatment of Cpd_2 killed tumor cells and diminished the AV-B5-complex antibody stain. Furthermore, we confirmed the capacity of Cpd_2 to dissociate ITGAV and ITGB5 on the cell surface by a NanoBRET energy transfer system. Of note, while the traditional ITGAV inhibitor cilengitide (an RGD peptide mimic) blocked the ECM interaction and detached the cells from TC dishes, they failed to dissociate the ITGAV-ITGB5 heterodimer nor induce rapid cell death. In summary, our study highlights a novel strategy of targeting the ITGAV-ITGB5 heterodimer stability by the small molecular inhibitor Cpd_2 for future anti-tumor treatment. Citation Format: Nicole Mattson, Kazuya Miyashita, Anthony Chan, Lu Yang, Sheela Pangeni Pokharel, Wei Lu, Mingli Li, Qiao Liu, Xiaobao Xu, Mingye Feng, Chun-Wei Chen. Targeting integrin alpha V beta 5 heterodimer stability using a novel small molecular inhibitor for tumor suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2920.

An open-source and easily replicable hardware for Electrical Impedance Tomography

Electrical Impedance Tomography (EIT) is a powerful imaging tool for investigating electrical properties of tissues such as that of human bodies. The cheap, harmless and portable nature of this tool has made EIT a popular choice in many biomedical applications. However, performing EIT requires strong development at both hardware and software levels. In particular, performing in-lab experiences remains a challenge due to the cost of commercially available devices or the complexity of systems proposed in scientific literature. In this paper, an efficient and easily replicable EIT hardware is presented. This hardware was developed with the objective of making EIT accessible to as many people as possible. It has been designed for operating frequencies between 1 kHz and 50 kHz, and can be used for in-lab validation of proof of concept. Special care has been paid to the choice of components in order to optimize the performance versus cost ratio. Also, the overall footprint has been reduced by using recent and up-to-date integrated circuits. In particular, the use of a lock-in amplifier is a compact solution that allows both narrow-band filtering of the signal and provides an easily quantifiable DC signal at the output. Circuit schematics as well as manufacturing files are shared so that understanding, replication and improvement of circuits are facilitated. Fabrication and usage procedures are given as well. At last, the proposed hardware is experimentally tested and validated first by comparing experimental data to simulations, then by reconstructing an inclusion in biological tissues.

A wearable multi-sensor system for real world gait analysis.

Gait analysis is commonly performed in standardized environments, but there is a growing interest in assessing gait also in ecological conditions. In this regard, an important limitation is the lack of an accurate mobile gold standard for validating any wearable system, such as continuous monitoring devices mounted on the trunk or wrist. This study therefore deals with the development and validation of a new wearable multi-sensor-based system for digital gait assessment in free-living conditions. In particular, results obtained from five healthy subjects during lab-based and real-world experiments were presented and discussed. The in-lab validation, which assessed the accuracy and reliability of the proposed system, shows median percentage errors smaller than 2% in the estimation of spatio-temporal parameters. The system also proved to be easy to use, comfortable to wear and robust during the out-of-lab acquisitions, showing its feasibility for free-living applications.

Editorial for Wiley's IJSCN Special Issue “Satellite networks integration with 5G”

Editorial for Wiley's IJSCN Special Issue “Satellite networks integration with 5G”

Validation of the Minnesota Easy Culture System II

The objectives of this study were to perform an in-lab validation of the Minnesota Easy Culture System II tri-plate method as compared to standardized laboratory culture methods and to describe inter-reader agreement for tri-plate culture results.

Validation of the Minnesota Easy Culture System II

The objectives of this study were to perform an in-lab validation of the Minnesota Easy Culture System II bi-plate method as compared to standardized laboratory culture methods and to describeinter-reader agreement for bi-plate culture results.

A hardware-in-the-loop dynamics simulator for motorcycle rapid controller prototyping

The purpose of this research is to develop an innovative hardware-in-the-loop simulator for the purpose of motorcycle power train rapid controller prototyping. Proposed control algorithms can be validated using the developed setup. Such an in-lab validation saves time and development cost and thus is preferable during power train controller development process. The developed simulator includes an engine, a transmission, and a rear wheel from a real motorcycle. A powder brake is rigidly coupled to the rear wheel for road loading generation. A central computer is used to control the operation of the system and the measurement of system dynamics variables. An xPC system is also integrated in the system to provide the feasibility of power train control algorithm rapid prototyping. Comparison between field tests and simulation results show that the simulator can be used to evaluate the performance of different control algorithms for controller rapid prototyping in the laboratory. An example of power train control algorithm development featuring engine fuel injection control using the above rapid prototyping setup is also described.