A Tear-Based Approach for Rapid Identification of Bacterial Pathogens in Corneal Ulcers Using Nanopore Sequencing.

Purpose: Corneal ulcers pose a significant threat to vision, with the need for prompt and precise pathogen identification being critical to effective treatment. This study assesses the efficacy of using next-generation portable sequencing (Nanopore Technology) to detect and identify bacterial pathogens directly from tear samples, providing a non-invasive alternative to traditional corneal scraping and culture, which are limited by high false-negative rates.

Design: Prospective observational study.

Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation.

Mathematical models of biochemical reaction networks are an important and emerging tool for the study of cell signaling networks involved in disease processes. One promising potential application of such mathematical models is the study of how disease-causing mutations promote the signaling phenotype that contributes to the disease. It is commonly assumed that one must have a thorough characterization of the network readily available for mathematical modeling to be useful, but we hypothesized that mathematical modeling could be useful when there is incomplete knowledge and that it could be a tool for discovery that opens new areas for further exploration.

Retinal Ischemic Perivascular Lesions Are Associated With Myocardial Infarction in Patients With Coronary Artery Disease.

Purpose: To evaluate the association of retinal ischemic perivascular lesions (RIPLs) with myocardial infarction (MI) among patients diagnosed with coronary artery diseases (CAD).

Design: Retrospective cross-sectional study.

Methods: Consecutive patients (317 patients) with CAD who underwent macular spectral domain optical coherence tomography (SD-OCT) were captured.

Determinants of overall survival in patients with metastatic uveal melanoma.

Background: Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival.

Methods: A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti-CTLA-4 and anti-PD-1 therapies.

Epigenetic dysregulation from chromosomal transit in micronuclei.

Chromosomal instability (CIN) and epigenetic alterations are characteristics of advanced and metastatic cancers, but whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei and subsequent rupture of the micronuclear envelope profoundly disrupt normal histone post-translational modifications (PTMs), a phenomenon conserved across humans and mice, as well as in cancer and non-transformed cells. Some of the changes in histone PTMs occur because of the rupture of the micronuclear envelope, whereas others are inherited from mitotic abnormalities before the micronucleus is formed.

Retinal vein occlusion is associated with stroke independent of underlying cardiovascular disease.

Background: Stroke is a leading cause of mortality and morbidity. Thus, identifying associated risk factors may lead to earlier interventions aimed at reducing the risk of stroke development. Since cardiovascular disease simultaneously increases the risk of stroke and retinal vein occlusion (RVO), we sought to determine whether RVO is associated with the risk of stroke independent of underlying cardiovascular co-morbidities.

BAP1 methylation: a prognostic marker of uveal melanoma metastasis.

Uveal melanoma, the most common intraocular primary cancer in adults, is characterized by striking variability in metastatic tendencies. BAP1 deletion in the primary tumor is associated with uveal melanoma metastasis, but it cannot always be resolved by bulk DNA sequencing of heterogeneous tumors. Here, we show that assessment of BAP1 methylation is an accurate and readily clinically actionable assay to accurately identify high-risk uveal melanoma patients.

Loss of polycomb repressive complex 1 activity and chromosomal instability drive uveal melanoma progression.

Chromosomal instability (CIN) and epigenetic alterations have been implicated in tumor progression and metastasis; yet how these two hallmarks of cancer are related remains poorly understood. By integrating genetic, epigenetic, and functional analyses at the single cell level, we show that progression of uveal melanoma (UM), the most common intraocular primary cancer in adults, is driven by loss of Polycomb Repressive Complex 1 (PRC1) in a subpopulation of tumor cells. This leads to transcriptional de-repression of PRC1-target genes and mitotic chromosome segregation errors.

A molecular single-cell lung atlas of lethal COVID-19.

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection, but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19.

Prevalence of subclinical retinal ischemia in patients with cardiovascular disease - a hypothesis driven study.

Background: Cardiovascular disease is the leading cause of mortality and disability worldwide. A noninvasive test that can detect underlying cardiovascular disease has the potential to identify patients at risk prior to the occurrence of adverse cardiovascular events. We sought to determine whether an easily observed imaging finding indicative of retinal ischemia, which we term ' (RIPLs), could serve as a biomarker for cardiovascular disease.

Relationship between Retinal Vascular Occlusions and Cognitive Dementia in a Large Cross-Sectional Cohort.

Purpose: To examine the association between cognitive dementia and retinal vascular occlusions.

Design: A retrospective, cross-sectional study.

Methods: Single-institution study population: we reviewed the electronic medical records of 37,208 individuals older than 65 years of age who were evaluated by an ophthalmologist or an optometrist and who also had a medical visit to our institution over a 6-year period.

Pseudophakic glaucoma and angle closure in a patient with an anterior chamber intraocular lens.

Purpose: To report use of ultrasound biomicroscopy (UBM) and anterior segment ocular coherence tomography (AS-OCT) in a case of pseudophakic glaucoma in a patient with an anterior chamber intraocular lens.

Observations: UBM and AS-OCT were critical in determining a non-drug related etiology of angle closure. Images indicated anterior obstruction of the pupil secondary to anterior chamber intraocular lens, but also posterior obstruction of the pupil secondary to the anterior hyaloid face.

PREVALENCE OF MISMATCH REPAIR GENE MUTATIONS IN UVEAL MELANOMA.

Purpose: Uveal melanomas are associated with characteristic genetic changes. Germline mutations in mismatch repair (MMR) genes and microsatellite instability have been implicated in the development of numerous malignant neoplasms such as colon and ovarian cancers. The frequency of MMR defects in uveal melanomas has yet to be determined.

Molecular Characteristics of Uveal Melanoma: Insights from the Cancer Genome Atlas (TCGA) Project.

The Cancer Genome Atlas (TCGA) uveal melanoma project was a comprehensive multi-platform deep molecular investigation of 80 uveal melanoma primary tissue samples supported by the National Cancer Institute. In addition to identification of important mutations for the first time, it identified four different clusters (subgroups) of patients paralleling prognosis. The findings of the TCGA marker paper are summarized in this review manuscript and other investigations that have stemmed from the findings of the TCGA project are reviewed.

Paracentral Acute Middle Maculopathy and the Ischemic Cascade Associated With Retinal Vascular Occlusion.

Purpose: To analyze the spectrum of ischemia associated with paracentral acute middle maculopathy (PAMM) in eyes with acute retinal vascular occlusion and to describe an ischemic cascade.

Design: A retrospective observational case series.

Methods: Patients presenting with PAMM secondary to acute retinal vascular occlusion were identified.

Congenital grouped albinotic spots of the retinal pigment epithelium in a patient with hemihypertrophy and café au lait spots.

Purpose: To describe the finding of circularly grouped hypomelanotic spots in the central macula of a patient with syndromic characteristics.

Methods: Case report of a patient with albinotic spots grouped within the macula, café au lait spots, and left-sided hemihypertrophy.

Results: A 15-year-old boy presented with hypomelanotic spots which were hyperautofluorescent on fundus autofluorescence imaging with no disruption of the retinal laminae or photoreceptor inner and outer segment (IS/OS) junction on spectral domain optical coherence tomography.