Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer.

Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine.

Cell-type-specific asynchronous modulation of PKA by dopamine in learning.

Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release1. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron2. However, the real-time relationship between dopamine and PKA in spiny projection neurons remains untested in behaving animals. Here we monitor the activity of dopamine-releasing neurons, extracellular levels of dopamine and net PKA activity in spiny projection neurons in the nucleus accumbens of mice during learning. We find positive and negative modulation of dopamine that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in the PKA activity of spiny projection neurons. Modulations of PKA in spiny projection neurons that express type-1 and type-2 dopamine receptors are dichotomous, such that these neurons are selectively sensitive to increases and decreases, respectively, in dopamine that occur at different phases of learning. Thus, PKA-dependent pathways in each class of spiny projection neuron are asynchronously engaged by positive or negative dopamine signals during learning.

L-type Ca2+ channels mediate regulation of glutamate release by subthreshold potential changes.

Subthreshold depolarization enhances neurotransmitter release evoked by action potentials and plays a key role in modulating synaptic transmission by combining analog and digital signals. This process is known to be Ca2+ dependent. However, the underlying mechanism of how small changes in basal Ca2+ caused by subthreshold depolarization can regulate transmitter release triggered by a large increase in local Ca2+ is not well understood. This study aimed to investigate the source and signaling mechanisms of Ca2+ that couple subthreshold depolarization with the enhancement of glutamate release in hippocampal cultures and CA3 pyramidal neurons. Subthreshold depolarization increased presynaptic Ca2+ levels, the frequency of spontaneous release, and the amplitude of evoked release, all of which were abolished by blocking L-type Ca2+ channels. A high concentration of intracellular Ca2+ buffer or blockade of calmodulin abolished depolarization-induced increases in transmitter release. Estimation of the readily releasable pool size using hypertonic sucrose showed depolarization-induced increases in readily releasable pool size, and this increase was abolished by the blockade of calmodulin. Our results provide mechanistic insights into the modulation of transmitter release by subthreshold potential change and highlight the role of L-type Ca2+ channels in coupling subthreshold depolarization to the activation of Ca2+-dependent signaling molecules that regulate transmitter release.

Ceramide promotes lytic reactivation of Epstein-Barr virus in gastric carcinoma.

Epstein-Barr virus (EBV) has a lifelong latency period after initial infection. Rarely, however, when the EBV immediate early gene BZLF1 is expressed by a specific stimulus, the virus switches to the lytic cycle to produce progeny viruses. We found that EBV infection reduced levels of various ceramide species in gastric cancer cells. As ceramide is a bioactive lipid implicated in the infection of various viruses, we assessed the effect of ceramide on the EBV lytic cycle. Treatment with C6-ceramide (C6-Cer) induced an increase in the endogenous ceramide pool and increased production of the viral product as well as BZLF1 expression. Treatment with the ceramidase inhibitor ceranib-2 induced EBV lytic replication with an increase in the endogenous ceramide pool. The glucosylceramide synthase inhibitor Genz-123346 inhibited C6-Cer-induced lytic replication. C6-Cer induced extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB phosphorylation, c-JUN expression, and accumulation of the autophagosome marker LC3B. Treatment with MEK1/2 inhibitor U0126, siERK1&2, or siCREB suppressed C6-Cer-induced EBV lytic replication and autophagy initiation. In contrast, siJUN transfection had no impact on BZLF1 expression. The use of 3-methyladenine (3-MA), an inhibitor targeting class III phosphoinositide 3-kinases (PI3Ks) to inhibit autophagy initiation, resulted in reduced beclin-1 expression, along with suppressed C6-Cer-induced BZLF1 expression and LC3B accumulation. Chloroquine, an inhibitor of autophagosome-lysosome fusion, increased BZLF1 protein intensity and LC3B accumulation. However, siLC3B transfection had minimal effect on BZLF1 expression. The results suggest the significance of ceramide-related sphingolipid metabolism in controlling EBV latency, highlighting the potential use of drugs targeting sphingolipid metabolism for treating EBV-positive gastric cancer.IMPORTANCEEpstein-Barr virus remains dormant in the host cell but occasionally switches to the lytic cycle when stimulated. However, the exact molecular mechanism of this lytic induction is not well understood. In this study, we demonstrate that Epstein-Barr virus infection leads to a reduction in ceramide levels. Additionally, the restoration of ceramide levels triggers lytic replication of Epstein-Barr virus with increase in phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB. Our study suggests that the Epstein-Barr virus can inhibit lytic replication and remain latent through reduction of host cell ceramide levels. This study reports the regulation of lytic replication by ceramide in Epstein-Barr virus-positive gastric cancer.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Differential involvement of mitochondria in post-tetanic potentiation at intracortical excitatory synapses of the medial prefrontal cortex.

Post-tetanic Ca2+ release from mitochondria produces presynaptic residual calcium, which contributes to post-tetanic potentiation. The loss of mitochondria-dependent post-tetanic potentiation is one of the earliest signs of Alzheimer's model mice. Post-tetanic potentiation at intracortical synapses of medial prefrontal cortex has been implicated in working memory. Although mitochondrial contribution to post-tetanic potentiation differs depending on synapse types, it is unknown which synapse types express mitochondria-dependent post-tetanic potentiation in the medial prefrontal cortex. We studied expression of mitochondria-dependent post-tetanic potentiation at different intracortical synapses of the rat medial prefrontal cortex. Post-tetanic potentiation occurred only at intracortical synapses onto layer 5 corticopontine cells from commissural cells and L2/3 pyramidal neurons. Among post-tetanic potentiation-expressing synapses, L2/3-corticopontine synapses in the prelimbic cortex were unique in that post-tetanic potentiation depends on mitochondria because post-tetanic potentiation at corresponding synapse types in other cortical areas was independent of mitochondria. Supporting mitochondria-dependent post-tetanic potentiation at L2/3-to-corticopontine synapses, mitochondria-dependent residual calcium at the axon terminals of L2/3 pyramidal neurons was significantly larger than that at commissural and corticopontine cells. Moreover, post-tetanic potentiation at L2/3-corticopontine synapses, but not at commissural-corticopontine synapses, was impaired in the young adult Alzheimer's model mice. These results would provide a knowledge base for comprehending synaptic mechanisms that underlies the initial clinical signs of neurodegenerative disorders.

The downregulation of Kv1 channels in Lgi1-/-mice is accompanied by a profound modification of its interactome and a parallel decrease in Kv2 channels.

In animal models of LGI1-dependent autosomal dominant lateral temporal lobe epilepsy, Kv1 channels are downregulated, suggesting their crucial involvement in epileptogenesis. The molecular basis of Kv1 channel-downregulation in LGI1 knock-out mice has not been elucidated and how the absence of this extracellular protein induces an important modification in the expression of Kv1 remains unknown. In this study we analyse by immunofluorescence the modifications in neuronal Kv1.1 and Kv1.2 distribution throughout the hippocampal formation of LGI1 knock-out mice. We show that Kv1 downregulation is not restricted to the axonal compartment, but also takes place in the somatodendritic region and is accompanied by a drastic decrease in Kv2 expression levels. Moreover, we find that the downregulation of these Kv channels is associated with a marked increase in bursting patterns. Finally, mass spectrometry uncovered key modifications in the Kv1 interactome that highlight the epileptogenic implication of Kv1 downregulation in LGI1 knock-out animals.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Unveiling synergistic QTLs associated with slow wilting in soybean (Glycine max [L.] Merr.).

KEY MESSAGE: A stable QTL qSW_Gm10 works with a novel locus, qSW_Gm01, in a synergistic manner for controlling slow-wilting traits at the early vegetative stage under drought stress in soybean. Drought is one of the major environmental factors which limits soybean yield. Slow wilting is a promising trait that can enhance drought resilience in soybean without additional production costs. Recently, a Korean soybean cultivar SS2-2 was reported to exhibit slow wilting at the early vegetative stages. To find genetic loci responsible for slow wilting, in this study, quantitative trait loci (QTL) analysis was conducted using a recombinant inbred line (RIL) population derived from crossing between Taekwangkong (fast-wilting) and SS2-2 (slow-wilting). Wilting score and leaf moisture content were evaluated at the early vegetative stages for three years. Using the ICIM-MET module, a novel QTL on Chr01, qSW_Gm01 was identified, together with a previously known QTL, qSW_Gm10. These two QTLs were found to work synergistically for slow wilting of the RILs under the water-restricted condition. Furthermore, the SNP markers from the SoySNP50K dataset, located within these QTLs, were associated with the wilting phenotype in 30 diverse soybean accessions. Two genes encoding protein kinase 1b and multidrug resistance-associated protein 4 were proposed as candidate genes for qSW_Gm01 and qSW_Gm10, respectively, based on a comprehensive examination of sequence variation and gene expression differences in the parental lines under drought conditions. These genes may play a role in slow wilting by optimally regulating stomatal aperture. Our findings provide promising genetic resources for improving drought resilience in soybean and give valuable insights into the genetic mechanisms governing slow wilting.

Ocular motor and vestibular dysfunction in central nervous system lymphoma.

BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.

Digital Twin Smart City: Integrating IFC and CityGML with Semantic Graph for Advanced 3D City Model Visualization.

The growing interest in building data management, especially the building information model (BIM), has significantly influenced urban management, materials supply chain analysis, documentation, and storage. However, the integration of BIM into 3D GIS tools is becoming more common, showing progress beyond the traditional problem. To address this, this study proposes data transformation methods involving mapping between three domains: industry foundation classes (IFC), city geometry markup language (CityGML), and web ontology framework (OWL)/resource description framework (RDF). Initially, IFC data are converted to CityGML format using the feature manipulation engine (FME) at CityGML standard's levels of detail 4 (LOD4) to enhance BIM data interoperability. Subsequently, CityGML is converted to the OWL/RDF diagram format to validate the proposed BIM conversion process. To ensure integration between BIM and GIS, geometric data and information are visualized through Cesium Ion web services and Unreal Engine. Additionally, an RDF graph is applied to analyze the association between the semantic mapping of the CityGML standard, with Neo4j (a graph database management system) utilized for visualization. The study's results demonstrate that the proposed data transformation methods significantly improve the interoperability and visualization of 3D city models, facilitating better urban management and planning.

Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation.

The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, ß-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.

Attosecond Imaging of Electronic Wave Packets.

An electronic wave packet has significant spatial evolution besides its temporal evolution, due to the delocalized nature of composing electronic states. The spatial evolution was not previously accessible to experimental investigations at the attosecond timescale. A phase-resolved two-electron-angular-streaking method is developed to image the shape of the hole density of an ultrafast spin-orbit wave packet in the krypton cation. Furthermore, the motion of an even faster wave packet in the xenon cation is captured for the first time: An electronic hole is refilled 1.2 fs after it is produced, and the hole filling is observed on the opposite side where the hole is born.

Prone position PET/CT is useful in reducing gravity-dependent opacity-related [18F]fluorodeoxyglucose uptake.

OBJECTIVES: This study aimed to investigate whether performing [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in the prone position could reduce [18F]FDG uptake in dependent lungs. METHODS: Patients who underwent [18F]FDG PET/CT in both supine and prone positions from October 2018 to September 2021 were reviewed retrospectively. [18F]FDG uptake of dependent and nondependent lungs was analysed visually and semi-quantitatively. A linear regression analysis was performed to examine the association between the mean standardised uptake value (SUVmean) and the Hounsfield unit (HU). RESULTS: A total of 135 patients (median age, 66 years [interquartile range: 58-75 years]; 80 men) were included. Dependent lungs showed significantly higher SUVmean and HU than nondependent lungs on supine position PET/CT (sPET/CT, 0.59 ± 0.14 vs. 0.36 ± 0.09, p < 0.001; - 671 ± 66 vs. - 802 ± 43, p < 0.001, respectively) and prone position PET/CT (pPET/CT, 0.45 ± 0.12 vs. 0.42 ± 0.08, p < 0.001; - 731 ± 67 vs. - 790 ± 40, p < 0.001, respectively). Linear regression analysis revealed a strong association between the SUVmean and HU in sPET/CT (R = 0.86, p < 0.001) and moderate association in pPET/CT (R = 0.65, p < 0.001). One hundred and fifteen patients (85.2%) had visually discernible [18F]FDG uptake in the posterior lung on sPET/CT, which disappeared on pPET/CT in all but one patient (0.7%, p < 0.001). CONCLUSIONS: [18F]FDG uptake of the lung had moderate-to-strong associations with HU. Gravity-dependent opacity-related [18F]FDG uptake can be effectively reduced on prone position PET/CT. CLINICAL RELEVANCE STATEMENT: Prone position PET/CT effectively reduces gravity-dependent opacity-related [18F]fluorodeoxyglucose uptake in the lung, potentially improving diagnostic accuracy in evaluating nodules in dependent lungs and offering a more accurate assessment of lung inflammation parameters in interstitial lung disease evaluations. KEY POINTS: • The study evaluated whether performing [18F]fluorodeoxyglucose ([18F]FDG) PET/CT could reduce [18F]FDG uptake in lungs. • In prone and supine position PET/CT, the [18F]FDG uptake and Hounsfield unit were moderately to strongly associated. • Prone position PET/CT can reduce gravity-dependent opacity-related [18F]FDG uptake by the posterior lung.

RNA-seq profiling in leaf tissues of two soybean (Glycine max [L.] Merr.) cultivars that show contrasting responses to drought stress during early developmental stages.

Drought stress is the major environment constraint on soybean yield, and a variety of pathways underlie drought tolerance mechanisms. Transcriptomic profiling of two soybean cultivars, drought-tolerant SS2-2 and drought-sensitive Taekwang, was performed under normal and drought conditions to identify genes involved in drought tolerance. This revealed large differences in water loss during drought treatment. Genes involved in signaling, lipid metabolism, phosphorylation, and gene regulation were overrepresented among genes that were differentially expressed between cultivars and between treatments in each cultivar. The analysis revealed transcription factors from six families, including WRKYs and NACs, showed significant SS2-2-specific upregulation. Genes involved in stress defense pathways, including MAPK signaling, Ca2+ signaling, ROS scavenging, and NBS-LRR, were also identified. Expression of non-specific phospholipases, phospholipase D, and PHOSPHATIDYL INOSITOL MONOPHOSPHATE 5 KINASE (PIP5K), which act in the lipid-signaling pathway, was greatly increased in SS2-2. The roles of PIP5K in drought stress tolerance were confirmed in Arabidopsis thaliana. Arabidopsis pip5k mutants had significantly lower survival rates under drought stress than wild-type plants. This study identified additional elements in the mechanisms used by plants to protect themselves from drought stress and provides valuable information for the development of drought-tolerant soybean cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01385-1.

Carrier-Envelope Phase Controlling of Ion Momentum Distributions in Strong Field Double Ionization of Methyl Iodide.

In strong field ionization of methyl iodide initiated by elliptically polarized few-cycle pulses, a significant correlation was observed between the carrier-envelope phases (CEPs) of the laser and the preferred ejection direction of methyl cation arising from dissociative double ionization. This was attributed to the carrier-envelope phase dependent double ionization yields of methyl iodide. This observation provides a new way for monitoring the absolute CEPs of few-cycle pulses by observing the ion momentum distributions.

Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography.

BACKGROUND: The progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage. RESULTS: Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU. CONCLUSIONS: The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

Slicing Newton spheres with a two-camera 3D imaging system.

We demonstrate a simple approach to achieve three-dimensional ion momentum imaging. The method employs two complementary metal-oxide-semiconductor cameras in addition to a standard microchannel plates/phosphor screen imaging detector. The two cameras are timed to measure the decay of luminescence excited by ion hits to extract the time of flight. The achieved time resolution is better than 10 ns, which is mainly limited by camera jitters. A better than 5 ns resolution can be achieved when the jitter is suppressed.

New technology using crystalline lens autofluorescence for presbyopia and cataract grading.

PURPOSE: To investigate whether fundus autofluorescence (FAF) obtained using an ultra-wide field (UWF) fundus camera with an artificial opacity pattern can grade the degree of presbyopia and nuclear cataract. METHODS: Sixty eyes of 30 patients were enrolled in this prospective diagnostic study. The nuclear cataract (nuclear color/opalescence (NC/NO)) was graded according to the Lens Opacity Classification System III. The monocular near point of accommodation (NPA) was measured in eyes with NC3/NO3 or less. The mean gray value difference between the central 8 artificial opacity lesions and peripheral 8 artificial opacity lesions in the retinal AF was measured. The correlation between the mean gray value difference, NPA, and nuclear cataract grade was analyzed. RESULTS: The mean nuclear cataract grade of 60 eyes was 3.2 ± 1.6 and mean NPA of 37 eyes was 45.3 ± 16.1 cm. The mean gray value differences increased with increasing nuclear cataract grade (eyes with NC/NO grade 1, 53.3 ± 11.4; 2, 78.3 ± 13.6; 3, 95.2 ± 12.2; 4, 101.6 ± 11.9; 5, 109.0 ± 22.9; and 6, 121.1 ± 12.0; p < 0.001). The mean gray value difference was positively correlated with both the monocular NPA (R2 = 0.637; ß coefficient = 1.009; 95% CI, 0.748 to 1.271; p < 0.001) and nuclear cataract grade (R2 = 0.661; ß coefficient = 12.437; 95% CI, 10.097 to 14.778; p < 0.001). CONCLUSIONS: The FAF camera with an artificial opacity pattern attached can be used to effectively diagnose the degree of presbyopia and nuclear cataract.

Long-term evaluation of the effects of vitreous degeneration on cataracts and retinal detachment in dogs.

OBJECTIVE: We aimed to track and evaluate the association between vitreous degeneration and the development of cataracts or retinal detachments in dogs over a long period. ANIMAL STUDIED: Data on vitreous degeneration, cataracts, and retinal detachment in 102 eyes were collected from 68 dogs who underwent ocular ultrasonography at least twice between March 2017 and November 2021 at the Veterinary Medical Teaching Hospital, Konkuk University. The mean follow-up time was 515 ± 256 (mean ± standard deviation; range: 81-1196) days. PROCEDURE: Development of cataracts and retinal detachment, according to the severity of vitreous degeneration grade (VDG), was evaluated during long-term follow-up. RESULTS: In the cataract study (87 eyes, 61 dogs), the number of cataracts developed according to VDG (grade: 0-3) were as follows: VDG 0: 1 in 10 (10%) eyes, VDG 1: 15 in 35 (43%) eyes, VDG 2: 15 in 30 (50%) eyes, and VDG 3: 10 in 12 (83%) eyes. It was significantly different among grades (p = .026). In the retinal detachment study (95 eyes, 64 dogs), the number of retinal detachments developed according to each VDG were as follows: VDG 0: 0 in 11 (0%) eyes, VDG 1: 1 in 36 (3%) eyes, VDG 2: 5 in 35 (14%) eyes, and VDG 3: 4 in 13 (30%) eyes. It was also significantly different among grades (p = .019). CONCLUSIONS: During long-term follow-up, dogs with severe vitreous degeneration had an increased risk of cataract and retinal detachment development than those without or with mild vitreous degeneration.