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Danny Barash

Publications and source records attributed to Danny Barash.

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Mathematical Modeling of HDV RNA, HBV DNA, and HBsAg Dynamics during Lonafarnib-Based Therapy: Insights from the LOWR HDV-1 Study

Lonafarnib (LNF) is an investigational drug targeting hepatitis delta virus (HDV) but not hepatitis B virus (HBV), providing a unique opportunity to model HDV kinetics and how changes in HDV affect HBV. We performed a detailed kinetic analysis and developed a mathematical model to explain serum HBV DNA, HDV RNA and hepatitis B surface antigen (HBsAg) kinetics in 15 HBV/HDV coinfected patients receiving LNF-based treatment. After a delay of 0-2 days, patients experienced a rapid 1st-phase HDV-decline followed by either a viral plateau, 2nd slower-decline phase, or viral breakthrough (VB). LNF monotherapy led to a flat-partial-response (often followed by VB), while LNF combination therapy with ritonavir or pegylated interferon-$\alpha$ (PEG-IFN$\alpha$) was associated with a biphasic HDV decline (without VB). All treatments except LNF+PEG-IFN$\alpha$ had at least one patient experiencing an increase in HBV on-treatment. Our model successfully reproduced the observed HDV and HBV kinetics. We estimated an HDV RNA half-life of 1.26 days [95% confidence interval, CI: 1.05--1.47] in serum and treatment efficacy of 94% in inhibiting HDV RNA production across all treatments [95% CI: 89%--97%], as reflected by the 1st phase HDV decline. The 2nd phase of HDV decline was explained by a time-dependent increase in efficacy, reaching a maximum of 98.9%. The model explained the increase in serum HBV DNA by a median 4-fold [interquartile range, IQR: 1--28] increase in HBV DNA production rate when HDV declined below an inhibitory threshold. The stability of serum HBsAg was explained by a constant number of HBsAg-producing cells.

physics.soc-ph

Leveraging Computational Pathology AI for Noninvasive Optical Imaging Analysis Without Retraining

Noninvasive optical imaging modalities can probe patient's tissue in 3D and over time generate gigabytes of clinically relevant data per sample. There is a need for AI models to analyze this data and assist clinical workflow. The lack of expert labelers and the large dataset required (>100,000 images) for model training and tuning are the main hurdles in creating foundation models. In this paper we introduce FoundationShift, a method to apply any AI model from computational pathology without retraining. We show our method is more accurate than state of the art models (SAM, MedSAM, SAM-Med2D, CellProfiler, Hover-Net, PLIP, UNI and ChatGPT), with multiple imaging modalities (OCT and RCM). This is achieved without the need for model retraining or fine-tuning. Applying our method to noninvasive in vivo images could enable physicians to readily incorporate optical imaging modalities into their clinical practice, providing real time tissue analysis and improving patient care.

cs.CV

Optimal Shrinkage of Singular Values Under Random Data Contamination

A low rank matrix X has been contaminated by uniformly distributed noise, missing values, outliers and corrupt entries. Reconstruction of X from the singular values and singular vectors of the contaminated matrix Y is a key problem in machine learning, computer vision and data science. In this paper we show that common contamination models (including arbitrary combinations of uniform noise,missing values, outliers and corrupt entries) can be described efficiently using a single framework. We develop an asymptotically optimal algorithm that estimates X by manipulation of the singular values of Y , which applies to any of the contamination models considered. Finally, we find an explicit signal-to-noise cutoff, below which estimation of X from the singular value decomposition of Y must fail, in a well-defined sense.

cs.IT