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Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have emerged as a pivotal model for research. Specialized devices can generate Extracellular Field Potential (EFP) measurements from these cells, analogous to the ventricular complex of the electrocardiogram. However, electrophysiological analysis can be complex and requires specialized expertise, posing a barrier to broader adoption in non-specialized labs. We present the EFP-Analyzer (EFPA), a semi-automized analyzer for EFP traces, which identifies and averages beats, identifies landmarks, and calculates intervals. We demonstrate an analysis of 358 EFP traces from 22 patient-derived lines. We analyzed spontaneously beating iPSC-CMs and optically paced iPSC-CMs through channelrhodopsin. We developed stringent quality criteria and measured EFP intervals, including Field Potential Duration (FPD). We further analyzed the usability and data replicability of EFPA through an inter-intra observer analysis. Correlation coefficient for inter-reader tangent and threshold measurements for these FPD ranged between r: 0.93–1.00. Bland–Altman plots comparing inter observer results for spontaneously beating and paced iPSC-CMs showed 95% limits of agreement (− 13.6 to 19.4 ms and − 13.2 to 15.3 ms, respectively). EFPA could accurately detect FPD prolongation due to drug (moxifloxacin) or pathogenic loss of function mutations (CACNA1C N639T). This program and instructions are available for download at https://github.com/kroncke-lab/EFPA .

Genetic diseases such as ion channelopathies substantially burden human health. Existing treatments are limited and not genotype specific. Here, we report a 2-step high-throughput approach to rapidly identify drug candidates for repurposing as genotype-specific therapy. We first screened 1,680 medicines using a thallium-flux trafficking assay against Kv11.1 gene variants causing long QT syndrome (LQTS), an ion channelopathy associated with fatal cardiac arrhythmia. We identified evacetrapib as a suitable drug candidate that improves membrane trafficking and activates channels. We then used deep mutational scanning to prospectively identify all Kv11.1 missense variants in an LQTS hotspot region responsive to treatment with evacetrapib. Combining high-throughput drug screens with deep mutational scanning establishes a paradigm for mutation-specific drug discovery translatable to personalized treatment of carriers with rare genetic disorders.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an emerging model for determining drug effects and modeling disease. Specialized devices can generate Extracellular Field Potential (EFP) measurements from these cells, analogous to the ventricular complex of the electrocardiogram. The objective of this study was to develop an easy-to-use, easy-to-teach, reproducible software tool to measure EFPs. We present the EFP-Analyzer (EFPA), a semi-automized analyzer for EFP traces, which identifies and averages beats, identifies landmarks, and calculates intervals. We evaluated the tool in an analysis of 358 EFP traces from 22 patient-derived lines. We analyzed spontaneously beating iPSC-CMs, as well as optically paced iPSC-CMs through channelrhodopsin. We developed stringent quality criteria and measured EFP intervals, including Field Potential Duration (FPD). FPD from optically paced iPSC-CMs were shorter than those of spontaneously beating iPSC-CMs (283.7.0±54.2 vs. 293.0±47.5, p: 0.32, respectively). We further analyzed the usability and data replicability of EFPA through an inter-intra observer analysis. Correlation coefficient for inter-reader tangent and threshold measurements for these FPD ranged between r: 0.93-1.00. Bland-Altman plots comparing inter observer results for spontaneously beating and paced iPSC-CMs showed 95% limits of agreement (-13.6 to 19.4ms and -13.2 to 15.3ms, respectively). The EFP-analyzer could accurately detect FPD prolongation due to drug (moxifloxacin) or pathogenic loss of function mutations ( N639T). This program is available for download at https://github.com/kroncke-lab/EFPA . The instructions will be available at the same listed website under the README section of the Github main page. The EFP-Analyzer tool is a useful tool that enables the efficient use of iPSC-CMs as a model to study drug effects and disease.

To comprehend the volumetric neural connectivity of a brain organoid, it is crucial to monitor the spatiotemporal electrophysiological signals within the organoid, known as intra-organoid signals. However, previous methods risked damaging the three-dimensional (3D) cytoarchitecture of organoids, either through sectioning or inserting rigid needle-like electrodes. Also, the limited numbers of electrodes in fixed positions with non-adjustable electrode shapes were insufficient for examining the complex neural activity throughout the organoid. Herein, we present a magnetically reshapable 3D multi-electrode array (MEA) using direct printing of liquid metals for electrophysiological analysis of brain organoids. The adaptable distribution and the softness of these printed electrodes facilitate the spatiotemporal recording of intra-organoid signals. Furthermore, the unique capability to reshape these soft electrodes within the organoid using magnetic fields allows a single electrode in the MEA to record from multiple points, effectively increasing the recording site density without the need for additional electrodes. Conventional platforms for electrophysiological recording of organoids have limited recording site density. Here, the authors present the magnetically reshapable 3D liquid metal-based electrode array for high-resolution analysis on neural activities of brain organoids.

To build in vitro tissues for therapeutic applications, it is essential to replicate the spatial distribution of cells that occurs during morphogenesis in vivo. However, it remains technically challenging to simultaneously regulate the geometric alignment and aggregation of cells during tissue fabrication. Here, we introduce the acoustofluidic bioassembly induced morphogenesis, which is the combination of precise arrangement of cells by the mechanical forces produced by acoustofluidic cues, and the morphological and functional changes of cells in the following in vitro and in vivo cultures. The acoustofluidic bioassembly can be used to create tissues with regulated nano-, micro-, and macro-structures. We demonstrate that the neuromuscular tissue fabricated with the acoustofluidic bioassembly exhibits enhanced contraction dynamics, electrophysiology, and therapeutic efficacy. The potential of the acoustofluidic bioassembly as an in situ application is demonstrated by fabricating artificial tissues at the defect sites of living tissues. The acoustofluidic bioassembly induced morphogenesis can provide a pioneering platform to fabricate tissues for biomedical applications. Tissue engineering is essential for drug screening and regenerative medicine. Here, authors developed an acoustofluidic method that can induce morphogenesis of therapeutic tissues at varied dimensions/scales.

In radiation therapy (RT) for skin cancer, tissue-equivalent substances called boluses are widely used to ensure the delivery of an adequate dose to the skin surface and to provide a radioprotective effect for normal tissue. The aim of this study was to develop a new type of three-dimensional (3D) bolus for RT involving body parts with irregular geometries and to evaluate its clinical feasibility. Two 3D-printed boluses were designed for two patients with squamous cell carcinoma (SCC) of their distal extremities based on computed tomography (CT) images and printed with polylactic acid (PLA). The clinical feasibility of the boluses was evaluated by measuring the in vivo skin dose at the tumor site with optically stimulated luminescence detectors (OSLDs) and comparing the results with the prescribed and calculated doses from the Eclipse treatment planning system (TPS). The average measured dose distribution for the two patients was 94.75% of the prescribed dose and 98.8% of the calculated dose. In addition, the average measured dose during repeated treatments was 189.5 ± 3.7 cGy, thus demonstrating the excellent reproducibility of the proposed approach. Overall, the customized 3D-printed boluses for the RT of distal extremities accurately delivered doses to skin tumors with improved reproducibility.

Background Left ventricular hypertrophy (LVH) is one of the risk factors for cardiovascular (CV) disease and mortality. However, the relationship between socioeconomic status (SES) and LVH in chronic kidney disease remains unclear. Methods Data were collected from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at http://www.clinicaltrials.gov ). Subjects with CKD and aged ≥50 were included. SES was characterized based on monthly income and educational attainment, each of which was divided into three strata. LVH was defined as LV mass/height 2.7  ≥ 47 g/m 2.7 in female and ≥ 50 g/m 2.7 in male. Age, sex, diabetes, CKD stage, body mass index, blood pressure and physical activity were included as covariates. Results A total of 1361 patients were included. Mean age was 60.9 ± 6.9 years, and 63.2% were men. Higher education level was associated with higher monthly income ( P for trend < 0.001). The lowest education level was independently associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95% CI 1.069–2.063, P  = 0.018; completed high school, adjusted OR 1.150, 95% confidence interval [CI] 0.834–1.584, P  = 0.394; highest education level as the reference). Monthly income level was marginally associated with LVH after adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866–1.748, P  = 0.247; < $1500, adjusted OR 1.471, 95% CI 1.002–2.158, P  = 0.049; > $4500; reference). Conclusions In the CKD population, lower SES, defined by educational attainment and low income level exhibited a significant association with LVH, respectively. Longitudinal follow-up will reveal whether lower SES is associated with poor CKD outcomes.