Dynamic video recognition for cell-encapsulating microfluidic droplets.

Droplet microfluidics is a highly sensitive and high-throughput technology extensively utilized in biomedical applications, such as single-cell sequencing and cell screening. However, its performance is highly influenced by the droplet size and single-cell encapsulation rate (following random distribution), thereby creating an urgent need for quality control. Machine learning has the potential to revolutionize droplet microfluidics, but it requires tedious pixel-level annotation for network training. This paper investigates the application software of the weakly supervised cell-counting network (WSCApp) for video recognition of microdroplets. We demonstrated its real-time performance in video processing of microfluidic droplets and further identified the locations of droplets and encapsulated cells. We verified our methods on droplets encapsulating six types of cells/beads, which were collected from various microfluidic structures. Quantitative experimental results showed that our approach can not only accurately distinguish droplet encapsulations (micro-F1 score > 0.94), but also locate each cell without any supervised location information. Furthermore, fine-tuning transfer learning on the pre-trained model also significantly reduced (>80%) annotation. This software provides a user-friendly and assistive annotation platform for the quantitative assessment of cell-encapsulating microfluidic droplets.

Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis.

Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring.

Tunable, Low-Cost, Multi-Channel, Broadband Liquid Crystal Shutter for Fluorescence Imaging in Widefield Microscopy.

Bistable liquid crystal (LC) shutters have attracted much interest due to their low energy consumption and fast response time. In this paper, we demonstrate an electrically tunable/switchable biostable LC light shutter in biological optics through a three-step easy-assembly, inexpensive, multi-channel shutter. The liquid crystal exhibits tunable transparency (100% to 10% compared to the initial light intensity) under different voltages (0 V to 90 V), indicating its tunable potential. By using biomedical images, the response time, resolution, and light intensity changes of the LC under different voltages in three common fluorescence wavelengths are displayed intuitively. Particularly, the shutter's performance in tumor images under the near-infrared band shows its application potential in biomedical imaging fields.

Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease.

Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

Repositioned Drugs for COVID-19-the Impact on Multiple Organs.

This review summarizes published findings of the beneficial and harmful effects on the heart, lungs, immune system, kidney, liver, and central nervous system of 47 drugs that have been proposed to treat COVID-19. Many of the repurposed drugs were chosen for their benefits to the pulmonary system, as well as immunosuppressive and anti-inflammatory effects. However, these drugs have mixed effects on the heart, liver, kidney, and central nervous system. Drug treatments are critical in the fight against COVID-19, along with vaccines and public health protocols. Drug treatments are particularly needed as variants of the SARS-Cov-2 virus emerge with some mutations that could diminish the efficacy of the vaccines. Patients with comorbidities are more likely to require hospitalization and greater interventions. The combination of treating severe COVID-19 symptoms in the presence of comorbidities underscores the importance of understanding the effects of potential COVID-19 treatments on other organs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42399-021-00874-8.

A fully transparent, flexible PEDOT:PSS-ITO-Ag-ITO based microelectrode array for ECoG recording.

Integrative neural interfaces combining neurophysiology and optogenetics with neural imaging provide numerous opportunities for neuroscientists to study the structure and function of neural circuits in the brain. Such a comprehensive interface demands miniature electrode arrays with high transparency, mechanical flexibility, electrical conductivity, and biocompatibility. Conventional transparent microelectrodes made of a single material, such as indium tin oxide (ITO), ultrathin metals, graphene and poly-(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS), hardly possess the desired combination of those properties. Herein, ultra-flexible, highly conductive and fully transparent microscale electrocorticogram (µECoG) electrode arrays made of a PEDOT:PSS-ITO-Ag-ITO assembly are constructed on thin parylene C films. The PEDOT:PSS-ITO-Ag-ITO assembly achieves a maximum ∼14% enhancement in light transmission over a broad spectrum (350-650 nm), a significant reduction in electrochemical impedance by 91.25%, and an increase in charge storage capacitance by 1229.78 µC cm-2. Peeling, bending, and Young's modulus tests verify the enhanced mechanical flexibility and robustness of the multilayer assembly. The µECoG electrodes enable electrical recordings with high signal-to-noise ratios (SNRs) (∼35-36 dB) under different color photostimulations, suggesting that the electrodes are resilient to photon-induced artifacts. In vivo animal experiments confirm that our array can successfully record light-evoked ECoG oscillations from the primary visual cortex (V1) of an anesthetized rat.

A Review: Electrode and Packaging Materials for Neurophysiology Recording Implants.

To date, a wide variety of neural tissue implants have been developed for neurophysiology recording from living tissues. An ideal neural implant should minimize the damage to the tissue and perform reliably and accurately for long periods of time. Therefore, the materials utilized to fabricate the neural recording implants become a critical factor. The materials of these devices could be classified into two broad categories: electrode materials as well as packaging and substrate materials. In this review, inorganic (metals and semiconductors), organic (conducting polymers), and carbon-based (graphene and carbon nanostructures) electrode materials are reviewed individually in terms of various neural recording devices that are reported in recent years. Properties of these materials, including electrical properties, mechanical properties, stability, biodegradability/bioresorbability, biocompatibility, and optical properties, and their critical importance to neural recording quality and device capabilities, are discussed. For the packaging and substrate materials, different material properties are desired for the chronic implantation of devices in the complex environment of the body, such as biocompatibility and moisture and gas hermeticity. This review summarizes common solid and soft packaging materials used in a variety of neural interface electrode designs, as well as their packaging performances. Besides, several biopolymers typically applied over the electrode package to reinforce the mechanical rigidity of devices during insertion, or to reduce the immune response and inflammation at the device-tissue interfaces are highlighted. Finally, a benchmark analysis of the discussed materials and an outlook of the future research trends are concluded.

Characteristics of Transparent, PEDOT:PSS Coated Indium-Tin-Oxide (ITO) Microelectrodes.

This paper reports on electrochemical and optical characteristics of flexible, transparent microelectrodes, which consist of thin poly-(3, 4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT:PSS) spun onto indium-tin-oxide (ITO) electrodes for potential applications in biomedical optoelectronic devices. Although PEDOT:PSS/ITO combined films have been extensively investigated for applications in optical devices, such as solar cells and LEDs, PEDOT:PSS/ITO films for use in electrophysiological recording have not been well-characterized yet. In this work, PEDOT:PSS coated ITO microelectrodes with various diameters of 10 µm, 37 µm, 50 µm and 80 µm were microfabricated and characterized, and their properties were compared with plain ITO microelectrodes. Experimental results demonstrate that PEDOT:PSS coated ITO electrodes exhibit decreased electrochemical impedance, well-performed stability in saline, and increased charge storage capacity while preserving excellent optical transparency and mechanical flexibility. Equivalent circuit models were fitted to the experimental results to analytically extract interface capacitance, charge transfer resistance and solution resistance at the electrode-electrolyte interface.

[Causal analysis and management strategies of cerebrospinal fluid leakage following translabyrinthine approach for acoustic neuromas].

OBJECTIVE: The purpose of the report was to investigate the causes of CSF leakage and discuss the methods for prevention and management of CSF leakage following translabyrinthine resection of acoustic neuromas. METHODS: A retrospective review of cerebrospinal fluid leakage following translabyrinthine approach for 152 acoustic neuromas patients, from January 1983 to December 2013, was performed. The cases were divided into two groups, traditional and modified closure techniques. The incidence of CSF leakage was compared between the two groups. RESULTS: The incidence of postoperative CSF leakage by translabyrinthine approach was 5.9% (9/152), with four cases of rhinorrhea, two case of wound leakage, one case of rhinorrhea and otorrhea, one case of otorrhea, and one case of rhinorrhea and wound leakage. The CSF leakage incidence of traditional closure technique was 14.3% (5/35); the incidence of modified closure technique was 3.4% (4/117). After introducing a modified closure technique, the incidence of the CSF leakage significantly decreased. CONCLUSIONS: As a common complication of translabyrinthine approach, the incidence of CSF leakage is closely related to the closure technique. The incidence of the CSF leakage should decrease dramatically when adopting the modified closure technique.