Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/- drug treatment; +/- cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.

Wafer-Scale Patterning of Protein Templates for Hydrogel Fabrication.

Human-induced pluripotent stem cell-derived cardiomyocytes are a potentially unlimited cell source and promising patient-specific in vitro model of cardiac diseases. Yet, these cells are limited by immaturity and population heterogeneity. Current in vitro studies aiming at better understanding of the mechanical and chemical cues in the microenvironment that drive cellular maturation involve deformable materials and precise manipulation of the microenvironment with, for example, micropatterns. Such microenvironment manipulation most often involves microfabrication protocols which are time-consuming, require cleanroom facilities and photolithography expertise. Here, we present a method to increase the scale of the fabrication pipeline, thereby enabling large-batch generation of shelf-stable microenvironment protein templates on glass chips. This decreases fabrication time and allows for more flexibility in the subsequent steps, for example, in tuning the material properties and the selection of extracellular matrix or cell proteins. Further, the fabrication of deformable hydrogels has been optimized for compatibility with these templates, in addition to the templates being able to be used to acquire protein patterns directly on the glass chips. With our approach, we have successfully controlled the shapes of cardiomyocytes seeded on Matrigel-patterned hydrogels.

Higher Peak Fat Oxidation During Rowing vs. Cycling in Active Men and Women.

ABSTRACT: Astorino, TA, Oriente, C, Peterson, J, Alberto, G, Castillo, EE, Vasquez-Soto, U, Ibarra, E, Guise, V, Castaneda, I, Marroquin, JR, Dargis, R, and Thum, JS. Higher peak fat oxidation during rowing vs. cycling in active men and women. J Strength Cond Res 35(1): 9-15, 2021-This study compared fat and carbohydrate oxidation (CHOOx) between progressive rowing and cycling. Initially, 22 active healthy adults (age = 27 ± 8 years) performed incremental cycling and rowing to volitional fatigue to assess maximal oxygen uptake (V̇o2max) and maximal heart rate (HRmax). The order of 2 subsequent sessions was randomized, performed 2 hours postmeal, and included a warm-up followed by three 8-minute stages of rowing or cycling at 60-65, 70-75, and 80-85 %HRmax. During exercise, power output was modified to maintain work rate in the desired range. Gas exchange data and blood samples were obtained to measure fat and CHOOx and blood lactate concentration. Fat oxidation (FOx) increased during exercise (p < 0.001) and there was a main effect of mode (p = 0.03) but no modeXintensity interaction (p = 0.33). Peak FOx was higher in response to rowing vs. cycling (0.23 ± 0.09 g·min-1 vs. 0.18 ± 0.07 g·min-1, p = 0.01). Carbohydrate oxidation increased during exercise (p < 0.001) but there was no effect of mode (p = 0.25) or modeXintensity interaction (p = 0.08). Blood lactate concentration was lower (p = 0.007) at the end of rowing vs. cycling (3.1 ± 1.0 mM vs. 3.9 ± 1.6 mM, d = 1.1). Prolonged rowing having equivalent calorie expenditure and intensity vs. cycling elicits higher peak FOx, which is likely attributed to greater muscle mass used during rowing.

Micromechanobiology: Focusing on the Cardiac Cell-Substrate Interface.

Engineered, in vitro cardiac cell and tissue systems provide test beds for the study of cardiac development, cellular disease processes, and drug responses in a dish. Much effort has focused on improving the structure and function of engineered cardiomyocytes and heart tissues. However, these parameters depend critically on signaling through the cellular microenvironment in terms of ligand composition, matrix stiffness, and substrate mechanical properties-that is, matrix micromechanobiology. To facilitate improvements to in vitro microenvironment design, we review how cardiomyocytes and their microenvironment change during development and disease in terms of integrin expression and extracellular matrix (ECM) composition. We also discuss strategies used to bind proteins to common mechanobiology platforms and describe important differences in binding strength to the substrate. Finally, we review example biomaterial approaches designed to support and probe cell-ECM interactions of cardiomyocytes in vitro, as well as open questions and challenges.

A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations.

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic. Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management. Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.

Engineering hiPSC cardiomyocyte in vitro model systems for functional and structural assessment.

The study of human cardiomyopathies and the development and testing of new therapies has long been limited by the availability of appropriate in vitro model systems. Cardiomyocytes are highly specialized cells whose internal structure and contractile function are sensitive to the local microenvironment and the combination of mechanical and biochemical cues they receive. The complementary technologies of human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) and microphysiological systems (MPS) allow for precise control of the genetics and microenvironment of human cells in in vitro contexts. These combined systems also enable quantitative measurement of mechanical function and intracellular organization. This review describes relevant factors in the myocardium microenvironment that affect CM structure and mechanical function and demonstrates the application of several engineered microphysiological systems for studying development, disease, and drug discovery.

Using mobile phones as acoustic sensors for high-throughput mosquito surveillance.

The direct monitoring of mosquito populations in field settings is a crucial input for shaping appropriate and timely control measures for mosquito-borne diseases. Here, we demonstrate that commercially available mobile phones are a powerful tool for acoustically mapping mosquito species distributions worldwide. We show that even low-cost mobile phones with very basic functionality are capable of sensitively acquiring acoustic data on species-specific mosquito wingbeat sounds, while simultaneously recording the time and location of the human-mosquito encounter. We survey a wide range of medically important mosquito species, to quantitatively demonstrate how acoustic recordings supported by spatio-temporal metadata enable rapid, non-invasive species identification. As proof-of-concept, we carry out field demonstrations where minimally-trained users map local mosquitoes using their personal phones. Thus, we establish a new paradigm for mosquito surveillance that takes advantage of the existing global mobile network infrastructure, to enable continuous and large-scale data acquisition in resource-constrained areas.