Glaucoma Cases Following SARS-CoV-2 Vaccination: A VAERS Database Analysis

Background: To counter the rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global vaccination efforts were initiated in December 2020. We assess the risk of glaucoma following SARS-CoV-2 vaccination and evaluate its onset interval and clinical presentations in patients. Methods: We performed a retrospective analysis of the glaucoma cases reported to the Vaccine Adverse Event Reporting System (VAERS) database between 16 December 2020, and 30 April 2022. We assessed the crude reporting rate of glaucoma, clinical presentations, onset duration, and associated risk factors. Results: During this period, 161 glaucoma cases were reported, with crude reporting rates (per million doses) of 0.09, 0.06, and 0.07 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The mean age of the patients was 60.41 ± 17.56 years, and 67.7% were women. More than half (56.6%) of the cases were reported within the first week of vaccination. The cumulative-incidence analysis showed a higher risk of glaucoma in patients who received the BNT162b2 vaccines compared with mRNA-1273 (p = 0.05). Conclusions: The incidence of glaucoma following vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S is extremely rare. Amongst the patients diagnosed with glaucoma, the onset interval of adverse events was shorter among those who received the BNT162b2 and rAd26.COV2.S vaccines compared with mRNA-1273. Most glaucoma cases were reported within the first week following vaccination in female patients and from the fifth to seventh decade. This study provides insights into the possible temporal association between reported glaucoma events and SARS-CoV-2 vaccines; however, further investigations are required to identify the potential causality link and pathological mechanisms

Anodic deposition of highly efficient nickel iron oxide electrocatalysts for water oxidation and role of anions in catalyst deposition

Nickel iron oxide has acquired significant interest as a highly efficient electrocatalyst for the oxygen evolution reaction. Although anodic deposition is beneficial for its preparation, anodically deposited nickel iron oxide presents poor performance, and the detailed mechanism of its formation is ambiguous, limiting its extensive applications. In this study, we examined the anodic deposition of nickel iron oxide using electroanalytical techniques combined with an electrochemical quartz crystal microbalance. In particular, the effects of anions were investigated to determine whether the formation of a nickel iron oxide film sensitively depends on the counter anions of the metal precursors. The anions not only provide buffering to retain the solution pH but also play a significant role in scavenging the surface protons to facilitate the growth of the catalyst film. We established a modified protocol to anodically deposit nickel iron oxide electrocatalysts excellent for water oxidation, with the best ever reported performance. These findings presented important but previously neglected aspects of anodic deposition, providing implications for nonprecious metal electrocatalysts.N

Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders

Substance P (SP) is a tachykinin expressed by various cells in the nervous and immune systems. SP is predominantly released by neurons and exerts its biological and immunological effects through the neurokinin receptors, primarily the neurokinin-1 receptor (NK1R). SP is essential for maintaining ocular surface homeostasis, and its reduced levels in disorders like diabetic neuropathy disrupt the corneal tissue. It also plays an essential role in promoting corneal wound healing by promoting the migration of keratocytes. In this review, we briefly discuss the structure, expression, and function of SP and its principal receptor NK1R. In addition, SP induces pro -inflammatory effects through autocrine or paracrine action on the immune cells in various ocular surface pathologies, including dry eye disease, herpes simplex virus keratitis, and Pseudomonas keratitis. We provide an in-depth review of the pathogenic role of SP in various ocular surface diseases and several new approaches developed to counter the immune-mediated effects of SP either through modulating its production or blocking its target receptor

Retinal vascular occlusion following SARS-CoV-2 vaccination:A VAERS database analysis

PURPOSE: To evaluate the cases of retinal vessel occlusion following COVID-19 vaccination and evaluate the onset interval and clinical presentations in patients diagnosed with vaccine associated retinal artery occlusion (RAO) and retinal vein occlusion (RVO). DESIGN: Retrospective study of the cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) between December 11, 2020 and July 1, 2022. PARTICIPANTS: Patients diagnosed with retinal vessel occlusion following vaccination with BNT162b2, mRNA-1273, and Ad26.COV2.S globally. METHODS: We performed a descriptive analysis of the patient demographics and clinical presentation in patients with retinal vessel occlusion. The correlation between the vaccines and continuous and categorical variables were assessed. We performed the post-hoc analysis to evaluated the association between RAO and RVO onset post-vaccination, and vaccine and dosage. Finally, a 30-day reverse analysis for RAO and RVO onset following administration of vaccine. A major limitation in the methods of this study is the lack of control group for assessing the risk of retinal vessel occlusive disease in patients who received the vaccine compared to the patients who were unvaccinated. MAIN OUTCOME MEASURES: The crude reporting rate of retinal vessel occlusion following SARS-CoV-2 vaccine. The ocular and systemic presentations, onset duration and short term risk of RAO and RVO following vaccination. RESULTS: During the study period, 1351 retinal vessel occlusion cases were reported globally. The crude reporting rates of retinal vessel occlusion for BNT162b2, mRNA-1273, and Ad26.COV2.S were 0.36, 0.41, and 0.69, respectively. The majority of the retinal vessel occlusion cases were reported following BNT162b2 (n=606, 74.17%). The mean age of patients with RVO and RAO was 58.54 ± 16.06 years and 64.63 ± 16.16 years, respectively. In the cohort, 817 and 433 patients were diagnosed with RVO and RAO, respectively. Most cases of RVO (41.12%) and RAO (48.27%) were reported within the first week post-vaccination. We observed that the mean onset interval for RVO was significantly longer in patients who received Ad26.Cov2.S (54.07 ± 88.98 days) compared to BNT162b2 (18.07 ± 28.66 days) and mRNA-1273 (22.85 ± 38.13 days) vaccines (p<0.0001). This was further confirmed by post-hoc analysis, which revealed a significantly longer onset duration for the Ad26.Cov2.S compared to BNT162b2 and mRNA 1273 vaccines (p<0.0001). The reverse Kaplan Meier 30-day risk analysis showed a significant a higher risk of RVO onset following BNT162b2 compared to other vaccines(p<0.0001). CONCLUSIONS: The low crude reporting rate highlights a low safety concern for retinal vessel occlusion following SARS-CoV-2 vaccination. This study provides insights into possible temporal association between reported retinal vessel occlusion events with SARS-CoV-2 vaccines, however further insights are needed to understand the underlying immunopathological mechanisms that promote thrombosis of retinal vasculature on vaccine administration

Intercellular cross-talk through lineage-specific gap junction of cancer-associated fibroblasts related to stromal fibrosis and prognosis

Abstract Stromal fibrosis in cancer is usually associated with poor prognosis and chemotherapy resistance. It is thought to be caused by fibroblasts; however, the exact mechanism is not yet well understood. The study aimed to identify lineage-specific cancer-associated fibroblast (CAF) subgroup and their associations with extracellular matrix remodeling and clinical significances in various tumor types using single-cell and bulk RNA sequencing data. Through unsupervised clustering, six subclusters of CAFs were identified, including a cluster with exclusively high gap junction protein beta-2 (GJB2) expression. This cluster was named GJB2-positive CAF. It was found to be a unique subgroup of terminally differentiated CAFs associated with collagen gene expression and extracellular matrix remodeling. GJB2-positive CAFs showed higher communication frequency with vascular endothelial cells and cancer cells than GJB2-negative CAFs. Moreover, GJB2 was poorly expressed in normal tissues, indicating that its expression is dependent on interaction with other cells, including vascular endothelial cells and cancer cells. Finally, the study investigated the clinical significance of GJB2 signature score for GJB2-positive CAFs in cancer and found a correlation with poor prognosis. These results suggest that GJB2-positive CAF is a unique fibroblast subtype involved in extracellular matrix remodeling, with significant clinical implications in cancer

Deep learning model improves tumor-infiltrating lymphocyte evaluation and therapeutic response prediction in breast cancer

Abstract Tumor-infiltrating lymphocytes (TILs) have been recognized as key players in the tumor microenvironment of breast cancer, but substantial interobserver variability among pathologists has impeded its utility as a biomarker. We developed a deep learning (DL)-based TIL analyzer to evaluate stromal TILs (sTILs) in breast cancer. Three pathologists evaluated 402 whole slide images of breast cancer and interpreted the sTIL scores. A standalone performance of the DL model was evaluated in the 210 cases (52.2%) exhibiting sTIL score differences of less than 10 percentage points, yielding a concordance correlation coefficient of 0.755 (95% confidence interval [CI], 0.693–0.805) in comparison to the pathologists’ scores. For the 226 slides (56.2%) showing a 10 percentage points or greater variance between pathologists and the DL model, revisions were made. The number of discordant cases was reduced to 116 (28.9%) with the DL assistance (p < 0.001). The DL assistance also increased the concordance correlation coefficient of the sTIL score among every two pathologists. In triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who underwent the neoadjuvant chemotherapy, the DL-assisted revision notably accentuated higher sTIL scores in responders (26.8 ± 19.6 vs. 19.0 ± 16.4, p = 0.003). Furthermore, the DL-assistant revision disclosed the correlation of sTIL-high tumors (sTIL ≥ 50) with the chemotherapeutic response (odd ratio 1.28 [95% confidence interval, 1.01–1.63], p = 0.039). Through enhancing inter-pathologist concordance in sTIL interpretation and predicting neoadjuvant chemotherapy response, here we report the utility of the DL-based tool as a reference for sTIL scoring in breast cancer assessment

On-Site Formation of Functional Dopaminergic Presynaptic Terminals on Neuroligin-2-Modified Gold-Coated Microspheres

Advancements in neural interface technologies have enabled the direct connection of neurons and electronics, facilitating chemical communication between neural systems and external devices. One promising approach is a synaptogenesis-involving method, which offers an opportunity for synaptic signaling between these systems. Janus synapses, one type of synaptic interface utilizing synaptic cell adhesion molecules for interface construction, possess unique features that enable the determination of location, direction of signal flow, and types of neurotransmitters involved, promoting directional and multifaceted communication. This study presents the first successful establishment of a Janus synapse between dopaminergic (DA) neurons and abiotic substrates by using a neuroligin-2 (NLG2)-mediated synapse-inducing method. NLG2 immobilized on gold-coated microspheres can induce synaptogenesis upon contact with spatially isolated DA axons. The induced DA Janus synapses exhibit stable synaptic activities comparable to that of native synapses over time, suggesting their suitability for application in neural interfaces. By calling for DA presynaptic organizations, the NLG2-immobilized abiotic substrate is a promising tool for the on-site detection of synaptic dopamine release