Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

Retinal dysfunction in APOE4 knock-in mouse model of Alzheimer's disease.

Introduction: Late-onset Alzheimer's Disease (LOAD) is the predominant form of Alzheimer's disease (AD), and apolipoprotein E (APOE) ε4 is a strong genetic risk factor for LOAD. As an integral part of the central nervous system, the retina displays a variety of abnormalities in LOAD. Our study is focused on age-dependent retinal impairments in humanized APOE4-knock-in (KI) and APOE3-KI mice developed by the Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease (MODEL-AD) consortium.

Exploring Virus Diversity in the (), an Economically Important Agricultural Pest.

The potato leafhopper (, PLH) is a serious pest that feeds on a wide range of agricultural crops and is found throughout the United States but is not known to be a vector for plant-infecting viruses. We probed the diversity of virus sequences in field populations of PLH collected from four Midwestern states: Illinois, Indiana, Iowa, and Minnesota. High-throughput sequencing data from total RNAs extracted from PLH were used to assemble sequences of fifteen positive-stranded RNA viruses, two negative-stranded RNA viruses, and one DNA virus.

Structural bone grafting for glenoid bone loss in primary anatomic total shoulder arthroplasty: a case series and technique report.

Background: Posterior glenoid bone loss in glenohumeral osteoarthritis poses significant challenges in shoulder arthroplasty. Anatomic total shoulder arthroplasty (TSA) with a humeral head autograft to address the glenoid bone deficiency is an option for these difficult cases. Variable results with this procedure are reported in the literature.

Physician Specialty Differences in Unprofessional Behaviors Observed and Reported by Coworkers.

Importance: Because unprofessional behaviors are associated with patient complications, malpractice claims, and well-being concerns, monitoring concerns requiring investigation and individuals identified in multiple reports may provide important opportunities for health care leaders to support all team members.

Objective: To examine the distribution of physicians by specialty who demonstrate unprofessional behaviors measured through safety reports submitted by coworkers.

Design, Setting, And Participants: This retrospective cohort study was conducted among physicians who practiced at the 193 hospitals in the Coworker Concern Observation Reporting System (CORS), administered by the Vanderbilt Center for Patient and Professional Advocacy.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.

Evaluating spatially enabled machine learning approaches to depth to bedrock mapping, Alberta, Canada.

Maps showing the thickness of sediments above the bedrock (depth to bedrock, or DTB) are important for many geoscience studies and are necessary for many hydrogeological, engineering, mining, and forestry applications. However, it can be difficult to accurately estimate DTB in areas with varied topography, like lowland and mountainous terrain, because traditional methods of predicting bedrock elevation often underestimate or overestimate the elevation in rugged or incised terrain. Here, we describe a machine learning spatial prediction approach that uses information from traditional digital elevation model derived estimates of terrain morphometry and satellite imagery, augmented with spatial feature engineering techniques to predict DTB across Alberta, Canada.

Tracking flight activity of potato leafhopper (Hemiptera: Cicadellidae) with the Midwest Suction Trap Network.

Potato leafhopper (PLH), Empoasca fabae Harris (Hemiptera: Cicadellidae), is an economic pest of a variety of crops that migrates between overwintering sites in the southern United States and northern breeding grounds. Since 2005, the Midwest Suction Trap Network (STN) has monitored the magnitude and timing of aerially dispersing aphids' activity, but the potential of the network to monitor other taxa is only beginning to be explored. Here, we use the Midwest STN to examine how the magnitude and timing of PLH activity vary with weather, cropland cover, and time of year.

The fauna from Mughr el-Hamamah, Jordan: Insights on human hunting behavior during the Early Upper Paleolithic.

As a corridor for population movement out of Africa, the southern Levant is a natural laboratory for research exploring the dynamics of the Middle-to-Upper Paleolithic transition. Yet, the number of well-preserved sites dating to the initial millennia of the Early Upper Paleolithic (EUP; ∼45-30 ka) remains limited, restricting the resolution at which we can study the biocultural and techno-typological changes evidenced across the transition. With EUP deposits dating to 45-39 ka cal BP, Mughr el-Hamamah, Jordan, offers a key opportunity to expand our understanding of EUP lifeways in the southern Levant.

The discovery of novel and potent indazole NLRP3 inhibitors enabled by DNA-encoded library screening.

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1β and IL-18 as well as to gasdermin d-mediated pyroptotic cell death.

Let Kids Play: Using Virtual Reality as a Substitute for General Anesthesia for Minor Procedures in Pediatric Population.

Background: In the pediatric population, virtual reality (VR) has been used as an adjunct to augment analgesia and reduce the need for opioids. In this study, we review our experience using VR in lieu of anesthesia or sedation to enable minor procedures in children.

Methods: A retrospective chart review study was performed on patients who presented to our institution from 2019 to 2022 for hormone implant placement, exchange, or removal with VR distraction.

Use of Neoadjuvant Vandetanib in Aggressive Pediatric Medullary Thyroid Carcinoma.

Novel use of vandetanib in a child with aggressive MTC with prolonged response to treatment.

Patterns of asexual reproduction of the soybean aphid, (Matsumura), with and without the secondary symbionts and on susceptible and resistant soybean genotypes.

Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether the symbionts, () and (), affect virulence and fecundity in soybean aphid biotypes Bt1 and Bt3 cultured on whole plants and detached leaves of three resistant, , and and one susceptible, , soybean genotypes. Whole plants and individual aphid experiments of with and without and did not show differences in overall fecundity.

Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.

Neovascular eye diseases include conditions such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration. Together, they are a major cause of vision loss and blindness worldwide. The current therapeutic mainstay for these diseases is intravitreal injections of biologics targeting vascular endothelial growth factor (VEGF) signaling.

Parathyroid Autofluorescence in Pediatric Thyroid Surgery: Experience With False Positive and False Negative Results.

Devices for near-infrared light stimulation of autofluorescence (NIRAF) allow for intraoperative identification of parathyroid glands with high sensitivity in adults. However, their performance in the pediatric population is unknown. In this case series with chart review at a tertiary academic children's hospital, we investigated pediatric patients undergoing thyroid surgery and concurrent use of a probe-based NIRAF device.

Global Status of Vegetable Soybean.

Vegetable soybean, popularly known as in Japan and in China is a specialty soybean. Green pods with physiologically mature beans are harvested, and whole pods or shelled beans are used as a fresh or frozen vegetable. Vegetable soybeans are prepared in diverse ways, and they are highly nutritious, with excellent taste properties.

Identification of Novel Pathways Regulated by APE1/Ref-1 in Human Retinal Endothelial Cells.

APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1, APE1 or APEX1; redox factor-1, Ref-1) is a dual-functional enzyme with crucial roles in DNA repair, reduction/oxidation (redox) signaling, and RNA processing and metabolism. The redox function of Ref-1 regulates several transcription factors, such as NF-κB, STAT3, HIF-1α, and others, which have been implicated in multiple human diseases, including ocular angiogenesis, inflammation, and multiple cancers. To better understand how APE1 influences these disease processes, we investigated the effects of knockdown (KD) on gene expression in human retinal endothelial cells.

Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.

Neovascular or "wet" age-related macular degeneration (nAMD) is a leading cause of blindness among older adults. Choroidal neovascularization (CNV) is a major pathological feature of nAMD, in which abnormal new blood vessel growth from the choroid leads to irreversible vision loss. There is a critical need to develop novel therapeutic strategies to address limitations of the current anti-vascular endothelial growth factor biologics.

An NBS-LRR protein in the Rpp1 locus negates the dominance of Rpp1-mediated resistance against Phakopsora pachyrhizi in soybean.

The soybean Rpp1 locus confers resistance to Phakopsora pachyrhizi, causal agent of rust, and resistance is usually dominant over susceptibility. However, dominance of Rpp1-mediated resistance is lost when a resistant genotype (Rpp1 or Rpp1b) is crossed with susceptible line TMG06_0011, and the mechanism of this dominant susceptibility (DS) is unknown. Sequencing the Rpp1 region reveals that the TMG06_0011 Rpp1 locus has a single nucleotide-binding site leucine-rich repeat (NBS-LRR) gene (DS-R), whereas resistant PI 594760B (Rpp1b) is similar to PI 200492 (Rpp1) and has three NBS-LRR resistance gene candidates.

Sociodemographic Disparities in the Diagnostic Management of Pediatric Thyroid Nodules.

Importance: Thyroid cancer is the most common pediatric endocrine malignant neoplasm. Disparities in the workup of thyroid nodules may be significantly associated with thyroid cancer outcomes.

Objective: To determine the association of sociodemographic factors with the odds of receiving a biopsy, timeliness of the procedure, and risk of nodule malignancy.

An improved method for murine laser-induced choroidal neovascularization lesion quantification from optical coherence tomography images.

Laser-induced choroidal neovascularization (L-CNV) in murine models is a standard method for assessing therapies, genetics, and mechanisms relevant to the blinding eye disease neovascular or "wet" age-related macular degeneration. The evaluation of these lesions involves confocal microscopy analysis. evaluation via optical coherence tomography (OCT) has previously been established and allows longitudinal assessment of lesion development.

Diazepinone HBV capsid assembly modulators.

The HBV capsid core protein serves a number of important functions in the viral life cycle enabling chronic HBV infection to persist, and therefore is a promising drug target. Interfering with capsid assembly has shown efficacy in clinical trials with small molecule capsid assembly modulators (CAMs). Herein is described the further optimization of a progressive series of diazepinone HBV CAMs.