Synthesis of the Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitor, 3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977, Belzutifan); Efficient Replication of Established Approaches.

A concise linear synthesis of hypoxia inducible factor-2α (HIF-2α) inhibitor, belzutifan was achieved by reproducing key components of previous synthetic approaches to this molecule as described in several publications and patents. Belzutifan is an orally bioavailable small-molecule (HIF-2α) inhibitor for the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) that received FDA approval in 2021. Herein, we report a 13-step synthesis of PT2977 that proceeded in good overall yield with high diastereoselectivity. Separation of diastereomeric mixtures at two different stages of the synthesis proved advantageous in ease of separation. The X-ray structure of belzutifan was determined.

Prednisolone Nanoprecipitation with Dean Instability Microfluidics Mixer.

Dean flow and Dean instability play an important role in inertial microfluidics, with a wide application in mixing and sorting. However, most studies are limited to Dean flow in the microscale. This work first reports the application of Dean instability on organic nanoparticles synthesis at De up to 198. The channel geometry (the tortuous channel) is optimized by simulation, in which the mixing efficiency is considered. With the optimized design, prednisolone nanoparticles are synthesized, and the size of the most abundant prednisolone nanoparticles is down to 100 nm with an increase in the Re and De and smallest size down to 46 nm. This work serves as an ice-breaker to the real application of Dean instability by demonstrating its ability in mixing and nanomaterials like nanoparticle synthesis.

High-Throughput Microfluidic Particle Counter Based on Optical Absorption.

With the utilization of advanced microfluidic techniques, the microfluidic particle counter demonstrates significant potential due to its high efficiency, precise manipulation, and portability. This work focuses on a photodetection counter based on optical absorption. To achieve precise particle detection, a Christmas tree-like structure was implemented to separate a single particle from a cluster, which was then detected in independent multiple parallel channels. The system exhibits a high degree of reliability, as evidenced by a linear correlation coefficient over 0.99 obtained during testing with gradient-concentrated beads. Furthermore, when the calculated density of NIH 3T3 cells is compared with that of a traditional flow cytometer, the system achieves a substantial agreement percentage ranging from 87.5 to 99.9%. The system's ability to perform high-throughput analysis with a high acquisition rate positions it as a promising tool for real-time point-of-care testing.

Flow study of Dean's instability in high aspect ratio microchannels.

Dean's flow and Dean's instability have always been important concepts in the inertial microfluidics. Curved channels are widely used for applications like mixing and sorting but are limited to Dean's flow only. This work first reports the Dean's instability flow in high aspect ratio channels on the deka-microns level for [Formula: see text]. A new channel geometry (the tortuous channel), which creates a rolled-up velocity profile, is presented and studied experimentally and numerically along with other three typical channel geometries at Dean's flow condition and Dean's instability condition. The tortuous channel generates a higher De environment at the same Re compared to the other channels and allows easier Dean's instability creation. We further demonstrate the use of multiple vortexes for mixing. The mixing efficiency is considered among different channel patterns and the tortuous channel outperforms the others. This work offers more understanding of the creation of Dean's instability at high aspect ratio channels and the effect of channel geometry on it. Ultimately, it demonstrates the potential for applications like mixing and cell sorting.

Evaluating Digital Health Capability at Scale Using the Digital Health Indicator.

BACKGROUND: Health service providers must understand their digital health capability if they are to drive digital transformation in a strategic and informed manner. Little is known about the assessment and benchmarking of digital maturity or capability at scale across an entire jurisdiction. The public health care system across the state of Queensland, Australia has an ambitious 10-year digital transformation strategy. OBJECTIVE: The aim of this research was to evaluate the digital health capability in Queensland to inform digital health strategy and investment. METHODS: The Healthcare Information and Management Systems Society Digital Health Indicator (DHI) was used via a cross-sectional survey design to assess four core dimensions of digital health transformation: governance and workforce; interoperability; person-enabled health; and predictive analytics across an entire jurisdiction simultaneously. The DHI questionnaire was completed by each health care system (n = 16) within Queensland in February to July 2021. DHI is scored 0 to 400 and dimension score is 0 to 100. RESULTS: The results reveal a variation in DHI scores reflecting the diverse stages of health care digitization across the state. The average DHI score across sites was 143 (range 78-193; SD35.3) which is similar to other systems in the Oceania region and global public systems but below the global private average. Governance and workforce was on average the highest scoring dimension (x̅= 54), followed by interoperability (x̅ = 46), person-enabled health (x̅ = 36), and predictive analytics (x̅ = 30). CONCLUSION: The findings were incorporated into the new digital health strategy for the jurisdiction. As one of the largest single simultaneous assessments of digital health capability globally, the findings and lessons learnt offer insights for policy makers and organizational managers.