Recruitment Strategies and Obstacles During the Zoster Eye Disease Study.

Purpose: The aim of this study was to identify successful recruitment strategies and obstacles reported by principal investigators (PIs) of the Zoster Eye Disease Study (ZEDS).

Methods: A web-based survey was created by a subset of ZEDS PIs and distributed to ZEDS PIs after study enrollment was closed. The survey queried investigators about recruitment strategies and obstacles, use of prophylactic oral antiviral medication, electronic medical records, telemedicine, COVID-19 effect, turnover of research staff, and recruitment outreach to minority and underserved populations.

Transorbital Alternating Current Stimulation in a Double-Masked Randomized Clinical Trial: Visual Functional Effect and Quality of Life.

Purpose: To determine the efficacy and safety of repetitive transorbital alternating current stimulation (rtACS) treatment by assessing vision-related quality of life and visual function outcome in subjects treated with rtACS versus sham-control.

Study Design: Double masked, randomized, sham-controlled clinical trial (NCT03188042).

Subjects: Sixteen subjects with moderate-to-advanced glaucoma (visual field [VF] mean deviation [MD] ≤-6.

Disparities in Visual Field Testing Frequency Among Subjects With Glaucoma.

Purpose: Prior evidence suggests racial disparities in the utilization of visual field testing (VFT) for the diagnosis and monitoring of glaucoma. In this study, we considered the effect of baseline glaucoma severity and socioeconomic disadvantage along with other potential confounders such as test reliability, ancillary tests, and glaucoma surgeries on racial disparity in the frequency of VFT.

Methods: The records of all subjects with a diagnosis of glaucoma who received VFT at an academic, tertiary care facility from January 2018 to December 2021 were accessed.

Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

Background And Objective: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR).

Patients And Methods: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients.

Peripapillary Atrophy Area as an Indicator of Glaucomatous Structural and Functional Progression.

Purpose: To determine whether peripapillary atrophy (PPA) area is an indicator of glaucomatous structural and functional damage and progression.

Methods: In this retrospective longitudinal analysis from ongoing prospective study we qualified 71 eyes (50 subjects) with glaucoma. All subjects had a comprehensive ophthalmic examination, visual field (VF), and spectral-domain optical coherence tomography (OCT) testing in at least three visits.

Estimating Causal Effects of HIV Prevention Interventions with Interference in Network-based Studies among People Who Inject Drugs.

Evaluating causal effects in the presence of interference is challenging in network-based studies of hard-to-reach populations. Like many such populations, people who inject drugs (PWID) are embedded in social networks and often exert influence on others in their network. In our setting, the study design is observational with a non-randomized network-based HIV prevention intervention.

LIMBARE: An Advanced Linear Mixed-Effects Breakpoint Analysis With Robust Estimation Method With Applications to Longitudinal Ophthalmic Studies.

Purpose: Broken stick analysis is a widely used approach for detecting unknown breakpoints where the association between measurements is nonlinear. We propose LIMBARE, an advanced linear mixed-effects breakpoint analysis with robust estimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and over time, and it effectively addresses the presence of outliers.

Reducing Ophthalmic Health Disparities Through Transfer Learning: A Novel Application to Overcome Data Inequality.

Purpose: Race disparities in the healthcare system and the resulting inequality in clinical data among different races hinder the ability to generate equitable prediction results. This study aims to reduce healthcare disparities arising from data imbalance by leveraging advanced transfer learning (TL) methods.

Method: We examined the ophthalmic healthcare disparities at a population level using electronic medical records data from a study cohort (N = 785) receiving care at an academic institute.

Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.

T cells recognize several types of antigens in tumors, including aberrantly expressed, nonmutated proteins, which are therefore shared with normal tissue and referred to as self/shared-antigens (SSA), and mutated proteins or oncogenic viral proteins, which are referred to as tumor-specific antigens (TSA). Immunotherapies such as immune checkpoint blockade (ICB) can activate T-cell responses against TSA, leading to tumor control, and also against SSA, causing immune-related adverse events (irAE). To improve anti-TSA immunity while limiting anti-SSA autoreactivity, we need to understand how tumor-specific CD8+ T cells (TST) and SSA-specific CD8+ T (SST) cells differentiate in response to cognate antigens during tumorigenesis.

Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling that induces hepatocyte proliferation.

Organ size is maintained by the controlled proliferation of distinct cell populations. In the mouse liver, hepatocytes in the midlobular zone that are positive for cyclin D1 (CCND1) repopulate the parenchyma at a constant rate to preserve liver mass. Here, we investigated how hepatocyte proliferation is supported by hepatic stellate cells (HSCs), pericytes that are in close proximity to hepatocytes.

Automated 360-degree goniophotography with the NIDEK Gonioscope GS-1 for glaucoma.

This study was registered with ClinicalTrials.gov (ID: NCT03715231). A total of 20 participants (37 eyes) who were 18 or older and had glaucoma or were glaucoma suspects were enrolled from the NYU Langone Eye Center and Bellevue Hospital.

LIMBARE: an Advanced Linear Mixed-effects Breakpoint Analysis with Robust Estimation Method with Applications to Longitudinal Ophthalmic Studies.

Purpose: Broken stick analysis is a widely used approach for detecting unknown breakpoints where association between measurements is non-linear. We propose LIMBARE, an advanced near ixed-effects reakpoint nalysis with obust stimation, especially designed for longitudinal ophthalmic studies. LIMBARE accommodates repeated measurements from both eyes and overtime, and effectively address the presence of outliers.

A maximum-type microbial differential abundance test with application to high-dimensional microbiome data analyses.

Background: High-throughput metagenomic sequencing technologies have shown prominent advantages over traditional pathogen detection methods, bringing great potential in clinical pathogen diagnosis and treatment of infectious diseases. Nevertheless, how to accurately detect the difference in microbiome profiles between treatment or disease conditions remains computationally challenging.

Results: In this study, we propose a novel test for identifying the difference between two high-dimensional microbiome abundance data matrices based on the centered log-ratio transformation of the microbiome compositions.

Evaluating the Mediating Role of Recall of Intervention Knowledge in the Relationship Between a Peer-Driven Intervention and HIV Risk Behaviors Among People Who Inject Drugs.

Peer-driven interventions can be effective in reducing HIV injection risk behaviors among people who inject drugs (PWID). We employed a causal mediation framework to examine the mediating role of recall of intervention knowledge in the relationship between a peer-driven intervention and subsequent self-reported HIV injection-related risk behavior among PWID in the HIV Prevention Trials Network (HPTN) 037 study. For each intervention network, the index participant received training at baseline to become a peer educator, while non-index participants and all participants in the control networks received only HIV testing and counseling; recall of intervention knowledge was measured at the 6-month visit for each participant, and each participant was followed to ascertain HIV injection-related risk behaviors at the 12-month visit.

Targeting cancer stemness mediated by BMI1 and MCL1 for non-small cell lung cancer treatment.

Lung cancer is the leading cause of cancer-associated death, with a global 5-year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug-resistance, and is a potential target for drug development.

TAZ negatively regulates the novel tumor suppressor ANKRD52 and promotes PAK1 dephosphorylation in lung adenocarcinomas.

Lung cancer is the leading cause of cancer death, and therefore the discovery of novel therapeutic targets is crucial. P21-activated kinase (PAK1) is an important oncogene involved in the signaling of actin cytoskeleton organization. Although PAK1 inhibition has been shown to suppress cancer progression, specific PAK1 inhibitors are not available due to the complex structure and insufficient understanding of this kinase.

Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap.

Activation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activation of the p62/Sqstm1-Nrf2 axis. Here, we show that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis.

Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas.

Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance.

YAP1 is essential for tumor growth and is a potential therapeutic target for EGFR-dependent lung adenocarcinomas.

Epidermal growth factor receptor (EGFR) mutations are found in lung adenocarcinomas leading to tumor cells proliferation and survival. EGFR tyrosine kinase inhibitors (TKIs) that block EGFR activity are effective therapeutics for EGFR-mutant lung adenocarcinoma patients, but TKI-resistance inevitably occurs. The YES-associated protein (YAP1) transcription coactivator has been implicated as an oncogene and is amplified in human cancers and provides tumor cells strong proliferation and survival cues.

Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells.

Background: Non-alcoholic steatohepatitis (NASH) is associated with hepatic fibrogenesis. Despite well-known cholesterol-lowering action of statins, their mechanisms against NASH-mediated fibrogenesis remain unclear. This study aimed at investigating the in vitro and in vivo anti-fibrotic properties of fluvastatin (Flu).

Codistribution of collagen type IV and laminin in liver fibrosis of elderly cadavers: immunohistochemical marker of perisinusoidal basement membrane formation.

Liver sinusoids are lined by a fenestrated endothelium that lacks a basement membrane. Formation of perisinusoidal basement membranes beneath the endothelium is an integral feature of capillarization of sinusoids that is a significant pathology found in advanced fibrosis. Liver fibrosis is prevalent in elderly cadavers; however, basement membrane formation in these liver samples has yet to be studied.

A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice.

Unlabelled: We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo.

Paeoniae radix reduces PDGF-stimulated hepatic stellate cell migration.

Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver fibrosis. In chronic liver injury, HSCs undergo transdifferentiation to an activated myofibroblastic phenotype and migrate to injured areas in response to chemotactic factors, producing extracellular matrix proteins such as collagen type I to repair the damage as well as overexpression of α-smooth muscle actin (α-SMA). Paeoniae Radix, the root of Paeonia lactiflora Pall, was investigated for PDGF-BB-induced HSC chemotaxis.