Equity in Digital Health: Assessing Access and Utilization of Remote Patient Monitoring, Medical Apps, and Wearables in Underserved Communities.

This study examined access to, and use of remote patient monitoring (RPM), medical applications, and wearables in a racially diverse, lower-income population. Data were obtained via a cross-sectional survey of adults from low-income communities in Houston, Los Angeles, and New York between April and August 2023. The survey examined access to, and use of RPM, medical applications, and wearables, among respondents.

HiLo microscopy with caustic illumination.

HiLo microscopy is an optical sectioning structured illumination microscopy technique based on computationally combining two images: one with uniform illumination and the other with structured illumination. The most widely used structured illumination in HiLo microscopy is random speckle patterns, due to their simplicity and resilience to tissue scattering. Here, we present a novel HiLo microscopy strategy based on random patterns.

Resolution enhancement with deblurring by pixel reassignment.

Improving the spatial resolution of a fluorescence microscope has been an ongoing challenge in the imaging community. To address this challenge, a variety of approaches have been taken, ranging from instrumentation development to image postprocessing. An example of the latter is deconvolution, where images are numerically deblurred based on a knowledge of the microscope point spread function.

High-throughput deep tissue two-photon microscopy at kilohertz frame rates.

High-speed laser scanning microscopes are essential for monitoring fast biological phenomena. However, existing strategies that achieve millisecond time resolution with two-photon microscopes (2PMs) are generally technically challenging and suffer from compromises among imaging field of view, excitation efficiency, and depth penetration in thick tissue. Here, we present a versatile solution that enables a conventional video-rate 2PM to perform 2D scanning at kilohertz frame rates over large fields of view.

Large-scale deep tissue voltage imaging with targeted-illumination confocal microscopy.

Voltage imaging with cellular specificity has been made possible by advances in genetically encoded voltage indicators. However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines the signal-to-noise ratio and induces crosstalk between cells, making reliable in vivo imaging in densely labeled tissue highly challenging.

Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers.

Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently in advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative chromatin state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability in the context of ARID1A mutations. In this study, we describe the discovery of tulmimetostat, an orally available, clinical stage EZH2 inhibitor, and it elucidates the aspects of its application potential in ARID1A mutant tumors.

Paul Berg and the origins of recombinant DNA.

In fall 1972, Paul Berg's laboratory published articles in PNAS describing two methods for constructing recombinant DNAs in vitro. He received half of the 1980 Nobel Prize in Chemistry for this landmark accomplishment. Here, we describe how this discovery came about, revolutionizing both biological research and the pharmaceutical industry.

Computational phylogenetics reveal histories of sign languages.

Sign languages are naturally occurring languages. As such, their emergence and spread reflect the histories of their communities. However, limitations in historical recordkeeping and linguistic documentation have hindered the diachronic analysis of sign languages.

Multiplane HiLo microscopy with speckle illumination and non-local means denoising.

Significance: HiLo microscopy synthesizes an optically sectioned image from two images, one obtained with uniform and another with patterned illumination, such as laser speckle. Speckle-based HiLo has the advantage of being robust to aberrations but is susceptible to residual speckle noise that is difficult to control. We present a computational method to reduce this residual noise without undermining resolution.

Assessing depth sensitivity in laser interferometry speckle visibility spectroscopy (iSVS) through source-to-detector distance variation and cerebral blood flow monitoring in humans and rabbits.

Recently, speckle visibility spectroscopy (SVS) was non-invasively applied on the head to monitor cerebral blood flow. The technique, using a multi-pixel detecting device (e.g.

Interferometric speckle visibility spectroscopy (iSVS) for measuring decorrelation time and dynamics of moving samples with enhanced signal-to-noise ratio and relaxed reference requirements.

Diffusing wave spectroscopy (DWS) is a group of techniques used to measure the dynamics of a scattering medium in a non-invasive manner. DWS methods rely on detecting the speckle light field from the moving scattering medium and measuring the speckle decorrelation time to quantify the scattering medium's dynamics. For DWS, the signal-to-noise (SNR) is determined by the ratio between measured decorrelation time to the standard error of the measurement.

High-speed multiplane confocal microscopy for voltage imaging in densely labeled neuronal populations.

Genetically encoded voltage indicators (GEVIs) hold immense potential for monitoring neuronal population activity. To date, best-in-class GEVIs rely on one-photon excitation. However, GEVI imaging of dense neuronal populations remains difficult because out-of-focus background fluorescence produces low contrast and excess noise when paired with conventional one-photon widefield imaging methods.

Resolution enhancement with deblurring by pixel reassignment (DPR).

Improving the spatial resolution of a fluorescence microscope has been an ongoing challenge in the imaging community. To address this challenge, a variety of approaches have been taken, ranging from instrumentation development to image post-processing. An example of the latter is deconvolution, where images are numerically deblurred based on a knowledge of the microscope point spread function.

Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation.

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice.

Large-scale deep tissue voltage imaging with targeted illumination confocal microscopy.

Voltage imaging with cellular specificity has been made possible by the tremendous advances in genetically encoded voltage indicators (GEVIs). However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines signal-to-noise ratio (SNR) and induces crosstalk between cells, making reliable imaging in densely labeled tissue highly challenging.

High-resolution multi-z confocal microscopy with a diffractive optical element.

There has been recent interest in the development of fluorescence microscopes that provide high-speed volumetric imaging for life-science applications. For example, multi-z confocal microscopy enables simultaneous optically-sectioned imaging at multiple depths over relatively large fields of view. However, to date, multi-z microscopy has been hampered by limited spatial resolution owing to its initial design.

Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator.

The ability to optically image cellular transmembrane voltages at millisecond-timescale resolutions can offer unprecedented insight into the function of living brains in behaving animals. Here, we present a point mutation that increases the sensitivity of Ace2 opsin-based voltage indicators. We use the mutation to develop Voltron2, an improved chemigeneic voltage indicator that has a 65% higher sensitivity to single APs and 3-fold higher sensitivity to subthreshold potentials than Voltron.

Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells.

Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV's latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we tested three classes of these drugs for preferential killing of the EBV-positive gastric cancer AGS-Akata cell line compared to its matched EBV-negative AGS control.

Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment.

Recent proteome and transcriptome profiling of Alzheimer's disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N40K-Tg), in which N40K expression exerts a dominant-negative effect to downregulate full-length U1-70K. N40K-Tg recapitulates N40K insolubility, erroneous splicing events, neuronal degeneration and cognitive impairment.

Correcting sampling bias in speckle contrast imaging.

When performing spatial or temporal laser speckle contrast imaging (LSCI), contrast is generally estimated from localized windows containing limited numbers of independent speckle grains N. This leads to a systematic bias in the estimated speckle contrast. We describe an approach to determine N and largely correct for this bias, enabling a more accurate estimation of the speckle decorrelation time without recourse to numerical fitting of data.

Direct characterization of tissue dynamics with laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) has gained broad appeal as a technique to monitor tissue dynamics (broadly defined to include blood flow dynamics), in part because of its remarkable simplicity. When laser light is backscattered from a tissue, it produces speckle patterns that vary in time. A measure of the speckle field decorrelation time provides information about the tissue dynamics.

Flatfield ultrafast imaging with single-shot non-synchronous array photography.

We present a method for acquiring a sequence of time-resolved images in a single shot, called single-shot non-synchronous array photography (SNAP). In SNAP, a pulsed laser beam is split by a diffractive optical element into an array of angled beamlets whose illumination fronts remain perpendicular to the optical axis. Different time delays are imparted to each beamlet by an echelon, enabling them to probe ultrafast dynamics in rapid succession.

Scan multiplier unit for ultrafast laser scanning beyond the inertia limit.

A passive add-on greatly multiplies the sweep rate of any mechanical scanner while also enhancing throughput, enabling a single linear scanner to produce ultrafast 1D or 2D laser scans for general applications.

Large-scale voltage imaging in behaving mice using targeted illumination.

Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold transmembrane voltage . To perform high-speed voltage imaging of many neurons simultaneously over a large anatomical area, widefield microscopy remains an essential tool. However, the lack of optical sectioning makes widefield microscopy prone to background cross-contamination.

High-speed multifocus phase imaging in thick tissue.

Phase microscopy is widely used to image unstained biological samples. However, most phase imaging techniques require transmission geometries, making them unsuited for thick sample applications. Moreover, when applied to volumetric imaging, phase imaging generally requires large numbers of measurements, often making it too slow to capture live biological processes with fast 3D index-of-refraction variations.