Biomedical Engineering

Introduction: Traditional Advanced Cardiac Life Support (ACLS) courses are evaluated using written multiple-choice tests. High-fidelity simulation is a widely used adjunct to didactic content, and has been used in many specialties as a training resource as well as an evaluative tool. There are no data to our knowledge that compare simulation examination scores with written test scores for ACLS courses. Objective: To compare and correlate a novel high-fidelity simulation-based evaluation with traditional written testing for senior medical students in an ACLS course.

Methods: We performed a prospective cohort study to determine the correlation between simulation-based evaluation and traditional written testing in a medical school simulation center. Students were tested on a standard acute coronary syndrome/ventricular fibrillation cardiac arrest scenario. Our primary outcome measure was correlation of exam results for 19 volunteer fourth-year medical students after a 32-hour ACLS-based Resuscitation Boot Camp course. Our secondary outcome was comparison of simulation-based vs. written outcome scores.

Results: The composite average score on the written evaluation was substantially higher (93.6%) than the simulation performance score (81.3%, absolute difference 12.3%, 95% CI [10.6-14.0%], p<0.00005). We found a statistically significant moderate correlation between simulation scenario test performance and traditional written testing (Pearson r=0.48, p=0.04), validating the new evaluation method.

Conclusion: Simulation-based ACLS evaluation methods correlate with traditional written testing and demonstrate resuscitation knowledge and skills. Simulation may be a more discriminating and challenging testing method, as students scored higher on written evaluation methods compared to simulation.

Hearing loss is a widespread and disabling condition with no current cure, underscoring the urgent need for new therapeutic approaches for treatment and prevention. A recent mitochondrial therapy approach by introducing exogenous mitochondria to the cells has shown promising results in mitigating mitochondria-related disorders. Despite the essential role of mitochondria in hearing, this novel strategy has not yet been tested for the treatment of hearing loss. More importantly, whether cochlear cells take up exogenous mitochondria and its consequence on cell bioenergetics has never been tested before. Here, we showed that exogenous mitochondria from HEI-OC1 auditory cells internalize into a new set of HEI-OC1 cells through co-incubation in a dose-dependent manner without inducing toxicity. We observed that auditory cells that received exogenous mitochondria exhibited increased bioenergetics compared to the controls that received none. Furthermore, we found that mitochondrial transplantation protects cells from oxidative stress and H2O2-induced apoptosis, while partially restoring bioenergetics diminished by H2O2 exposure. These findings support initial evidence for the feasibility and potential advantages of mitochondrial therapy in auditory cells. If successful in animal models and ultimately in humans, this novel therapy offers prominent potential for the treatment of sensorineural hearing loss.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients. RESULTS: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top genes differentially methylated between these cohorts included the obesity-protective MFAP2 gene as well as cancer risk susceptibility genes APOL3 and RNASEL. CONCLUSIONS: In this study, we provide to the scientific community high-resolution DNA methylomes for a cohort of EOCRC patients from underrepresented populations. Our exploratory findings in this cohort highlight epigenetic mechanisms underlying the pathogenesis of EOCRC and nominate novel biomarkers for EOCRC in underrepresented populations.

Although rare non-coding variants (RVs) play crucial roles in complex traits and diseases, understanding their mechanisms and identifying disease-associated RVs continue to be major challenges. Here we constructed a comprehensive atlas of alternative polyadenylation (APA) outliers (aOutliers), including 1334 3 UTR and 200 intronic aOutliers, from 15,201 samples across 49 human tissues. These aOutliers exhibit unique characteristics from transcription or splicing outliers, with a pronounced RV enrichment. Mechanistically, aOutlier-RVs alter poly(A) signals and splicing sites, and perturbation indeed triggers APA events. Furthermore, we developed a Bayesian-based APA RV prediction model, which successfully pinpointed a specific set of 1799 RVs impacting 278 genes with significantly large disease effect sizes. Notably, we observed a convergence effect between rare and common cancer variants, exemplified by regulation in the DDX18 gene. Together, this study introduced an APA-enhanced framework for genome annotation, underscoring APAs role in uncovering functional RVs linked to complex traits and diseases.

Electroacoustic imaging is an imaging modality used to detect electric field energy distribution during electroporation, offering valuable guidance for clinical procedures, particularly in deep tissues. Traditionally, single-element piezoelectric transducers or arrays have been employed for this purpose. However, these piezoelectric sensors are sensitive to electromagnetic interference and require physical contact with the sample through a coupling medium, raising concerns for both clinical and preclinical applications. To overcome these limitations, a multi-channel random quadrature ultrasonics system has been developed, enabling non-contact detection of electroacoustic signals. In this study, we demonstrated that this non-contact technique effectively detects electroacoustic signals, identifies electroporation regions, and reconstructs electric energy distribution, offering a promising approach for monitoring electroporation therapy.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue's stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without "packing foam-like" extracellular matrix.

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Conventional refractive microscope objective lenses have limited applicability to a range of imaging modalities due to the dispersive nature of their optical elements. Designing a conventional refractive microscope objective that provides well-corrected imaging over a broad spectral range can be challenging, if not impossible. In contrast, reflective optics are inherently achromatic, so a system composed entirely of reflective elements is free from chromatic aberrations and, as a result, can image over an ultra-wide spectral range with perfect color correction. This study explores the design space of unobscured high numerical aperture, allreflective microscope objectives. In particular, using freeform optical elements we obviate the need for a center obscuration, rendering the objective's modulation transfer function comparable to that of refractive lens systems of similar numerical aperture. We detail the design process of the reflective objective, from determining the design specifications to the system optimization and sensitivity analysis. The outcome is an all-reflective freeform microscope objective lens with a 0.65 numerical aperture that provides diffraction-limited imaging and is compatible with the geometric constraints of commercial microscope systems.