In recent years, several network models have been introduced to elucidate the relationships between diseases. However, important risk factors that contribute to many human diseases, such as age, gender and prior diagnoses, have not been considered in most networks. Here, we construct a diagnosis progression network of human diseases using large-scale claims data and analyze the associations between diagnoses. Our network is a scale-free network, which means that a small number of diagnoses share a large number of links, while most diagnoses show limited associations. Moreover, we provide strong evidence that gender, age and disease class are major factors in determining the structure of the disease network. Practically, our network represents a methodology not only for identifying new connectivity that is not found in genome-based disease networks but also for estimating directionality, strength, and progression time to transition between diseases considering gender, age and incidence. Thus, our network provides a guide for investigators for future research and contributes to achieving precision medicine.

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Neuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases. Although there have been several studies related to ultrasonic neuromodulation, these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers. In addition, the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown. To determine these mechanisms and accurately modulate neural circuits, researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level. Herein, we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution. The piezoelectric micromachined ultrasonic transducers (pMUTs) with small membranes (sub-mm membranes) generate enough power to stimulate neurons and enable precise modulation of neural circuits. We designed the ultrasound transducer as an array structure to enable localized modulation in the target region. In addition, we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments, such as in vitro cell cultures and brain slices. In this work, we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound. We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.