Cataract surgery with new monofocal intraocular lens enhanced for intermediate vision and standard monofocal intraocular lens for retinal disorder.

AIM: To investigate the difference in the initial surgical results between a new monofocal intraocular lens (IOL) with enhanced intermediate vision and the standard monofocal IOL in patients with retinal disease. METHODS: We retrospectively reviewed the medical records of patients with retinal disease who underwent cataract surgery due to accompanying cataracts. Types of retinal diseases were investigated and best-corrected distant visual acuity, distant uncorrected visual acuity (UCVA), intermediate UCVA, near UCVA, and spherical equivalent were recorded at each visit. The surgical results were investigated at 1 day, 1 week, and 1 month after surgery. RESULTS: Seventeen eyes treated with a new monofocal IOL enhanced for intermediate vision (ICB00 group) and 18 eyes treated with the standard monofocal IOL (AAB00 group) were included in this study. There were no significant differences in the baseline characteristics, including the type of underlying retinal disease, between the groups. There were no significant differences between the groups in terms of distant, intermediate, or near UCVA at day 1 and week 1 after surgery. However, at 1 month after surgery, the ICB00 group showed a significantly better intermediate vision improvement than the AAB00 group (p = 0.001). CONCLUSION: Even in patients with cataract accompanied by retinal disease, the use of the ICB00 IOL showed significant improvement in intermediate vision compared to the use of the AAB00 (standard monofocal) IOL. The ICB00 IOL might be a good option for patients with cataract and retinal disease in the era of increased intermediate vision needs in daily life.

Hybrid Deep Neural Network Framework Combining Skeleton and Gait Features for Pathological Gait Recognition.

Human skeleton data obtained using a depth camera have been used for pathological gait recognition to support doctor or physician diagnosis decisions. Most studies for skeleton-based pathological gait recognition have used either raw skeleton sequences directly or gait features, such as gait parameters and joint angles, extracted from raw skeleton sequences. We hypothesize that using skeleton, joint angles, and gait parameters together can improve recognition performance. This study aims to develop a deep neural network model that effectively combines different types of input data. We propose a hybrid deep neural network framework composed of a graph convolutional network, recurrent neural network, and artificial neural network to effectively encode skeleton sequences, joint angle sequences, and gait parameters, respectively. The features extracted from three different input data types are fused and fed into the final classification layer. We evaluate the proposed model on two different skeleton datasets (a simulated pathological gait dataset and a vestibular disorder gait dataset) that were collected using an Azure Kinect. The proposed model, with multiple types of input, improved the pathological gait recognition performance compared to single input models on both datasets. Furthermore, it achieved the best performance among the state-of-the-art models for skeleton-based action recognition.

Discovery of a novel NAMPT inhibitor that selectively targets NAPRT-deficient EMT-subtype cancer cells and alleviates chemotherapy-induced peripheral neuropathy.

Background: Exploiting synthetic lethality (SL) relationships between protein pairs has emerged as an important avenue for the development of anti-cancer drugs. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme of the NAD+ salvage pathway, having an SL relationship with nicotinic acid phosphoribosyltransferase (NAPRT), the key enzyme in the NAD+ Preiss-Handler pathway. NAMPT inhibitor holds clinical potential not only as a promising cancer treatment but also as a means of protection against chemotherapy-induced-peripheral-neuropathy (CIPN). However, as NAD+ is essential for normal cells, the clinical use of NAMPT inhibitors is challenging. This study aimed to identify a novel NAMPT inhibitor with enhanced selective cytotoxicity against NAPRT-deficient cancer cells as well as prominent efficacy in alleviating CIPN. Methods: We began by conducting drug derivatives screening in a panel of lung cancer cell lines to select an agent with the broadest therapeutic window between the NAPRT-negative and-positive cancer cell lines. Both in vitro and In vivo comparative analyses were conducted between A4276 and other NAMPT inhibitors to evaluate the NAPRT-negative cancer cell selectivity and the underlying distinct NAMPT inhibition mechanism of A4276. Patient-derived tumor transcriptomic data and protein levels in various cancer cell lines were analyzed to confirm the correlation between NAPRT depletion and epithelial-to-mesenchymal transition (EMT)-like features in various cancer types. Finally, the efficacy of A4276 for axonal protection and CIPN remedy was examined in vitro and in vivo. Results: The biomarker-driven phenotypic screening led to a discovery of A4276 with prominent selectivity against NAPRT-negative cancer cells compared with NAPRT-positive cancer cells and normal cells. The cytotoxic effect of A4276 on NAPRT-negative cells is achieved through its direct binding to NAMPT, inhibiting its enzymatic function at an optimal and balanced level allowing NAPRT-positive cells to survive through NAPRT-dependent NAD+ synthesis. NAPRT deficiency serves as a biomarker for the response to A4276 as well as an indicator of EMT-subtype cancer in various tumor types. Notably, A4276 protects axons from Wallerian degeneration more effectively than other NAMPT inhibitors by decreasing NMN-to-NAD+ ratio. Conclusion: This study demonstrates that A4276 selectively targets NAPRT-deficient EMT-subtype cancer cells and prevents chemotherapy-induced peripheral neuropathy, highlighting its potential as a promising anti-cancer agent for use in cancer monotherapy or combination therapy with conventional chemotherapeutics.

Simple method of measuring ocular rotation in supine position during small incision lenticule extraction.

AIM: To introduce a novel measurement method of static cyclotorsion in small incision lenticule extraction (SMILE) and to investigate the effect of preoperative parameters on cyclotorsion and the effect of cyclotorsion on postoperative outcomes. METHODS: The medical records of 242 patients and 484 eyes who underwent SMILE surgery were retrospectively reviewed. Preoperative intraocular pressure, refractive error, and corneal thickness were investigated. Refractive values and visual acuity were measured at 1d, 1, 3, and 6mo. Ocular cyclotorsion in the supine position was measured by calculating the location and angle of the incision site of the cornea in the anterior slit photograph taken after surgery. RESULTS: Of the total 484 eyes in 242 patients, preoperative mean spherical equivalent (SE) was -4.10±1.64 D, and the mean astigmatism was -0.82±0.74 D. Uncorrected distance visual acuity (UCVA) and SE improved significantly after the surgery. Moreover, 219 (45.2%) eyes had excyclotorsion, 235 (48.6%) eyes had incyclotorsion, and 30 (6.2%) eyes had no torsion. The right eyes tended to be excyclotorted, and the left eyes tended to be incyclotorted (P<0.01). The mean cyclotorsion was 1.18°±3.69°, and the mean absolute value of cyclotorsion was 3.14°±2.26°. The range of cyclotorsion was 0.5°-11.4°. It was found that the smaller the preoperative sphere, the higher the amount of cyclotorsion (r=0.11, P=0.016). There was no significant association between the amount of cyclotorsion and preoperative astigmatism. There was no correlation between sex, preoperative corneal thickness, preoperative intraocular pressure, amount of cyclotorsion, and direction of cyclotorsion. The ratio of right eye excyclotorsion and left eye incyclotorsion on 1d was higher than that at 1, 3, and 6mo (all P<0.01). There was no difference between the 1, 3, and 6mo results in the right and left eyes (P=0.15, P=0.16, respectively). CONCLUSION: The newly devised ocular cyclotorsion measurement method can be used to evaluate ocular cyclotorsion after SMILE. Preoperative SE is associated with the amount of cyclotorsion, however, cyclotorsion doesn't have a significant effect on the results of SMILE surgery.

Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling.

The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.

SYSTEMIC FACTORS AND EARLY TREATMENT RESPONSE TO INTRAVITREAL INJECTION FOR DIABETIC MACULAR EDEMA: The Role of Renal Function.

PURPOSE: To investigate the effect of systemic factors on early treatment response to intravitreal bevacizumab injection (IVBI) and intravitreal dexamethasone implant (IVDI) in patients with diabetic macular edema (DME). METHODS: We reviewed the medical records of 117 treatment naïve DME patients who underwent IVBI. We divided the patients according to their IVBI response. An IVDI was performed in patients with poor response to IVBIs. We investigated the various systemic factors of diabetic patients and examined the relationship between systemic factors and the treatment response to IVBI and IVDI. RESULTS: In a total of 117 treatment naïve DME eyes, 61 eyes (52.14%) were classified as IVBI responders. An IVDI was performed in 23 of 56 eyes with poor response to IVBI, and 17 eyes (73.91%) had a good response. Among various systemic factors of patients with diabetes, renal function (blood urea nitrogen, creatinine, and estimated glomerular filtration rate) showed a significant negative correlation with central subfield retinal thickness improvement after treatment (P < 0.05). However, there was no difference in HbA1C levels regarding the treatment response to IVBI and IVDI. CONCLUSION: Renal function was significantly worse in patients with a poor response to IVBI and IVDI. Renal function could be used as a possible predictor for treatment response in certain patients with DME. Furthermore, for patients with DME with poor responses to anti-vascular endothelial growth factor or steroid treatments, assessment of renal function could help explain the poor treatment response.

Association between Early Anatomic Response and Intraocular Pressure Change after Intravitreal Dexamethasone Implant: An Optical Coherence Tomography Study.

PURPOSE: To investigate the associations between early anatomical responses and intraocular pressure (IOP) changes in macular edema (ME) due to retinal vascular diseases treated with an intravitreal dexamethasone (DEX) implant. METHODS: A retrospective review was conducted involving ME patients who underwent intravitreal DEX implantation. The eyes were divided into increased IOP (IIOP) or non-IIOP (nIIOP) groups according to the presence or absence of significant IOP elevation. Significant IOP elevation was defined by both the absolute value of IOP elevation (5 mmHg or higher) and an elevation percentage of the baseline IOP (an increase equal to 30% of the pre-injection IOP or higher). We analyzed the difference in central subfield thickness (CST) change according to the IOP elevation after DEX implantation. Relationships between IOP change and CST reduction after intravitreal DEX implantation were analyzed by Pearson correlation coefficients. RESULTS: A total of 49 eyes, 29 with diabetic ME and 20 with ME due to retinal vein occlusion (RVO), were included in this study. Of the 49 eyes, 18 eyes (36.7%) were classified as IIOP group and 31 (63.3%) as nIIOP group. Significant differences in mean CST reductions over baseline one week after DEX implantation were observed between the groups. The degree of CST reduction from baseline to 1 week was significantly correlated with the degree of IOP change from baseline at 1 week and 1 month after intravitreal DEX implantation. CONCLUSIONS: In patients with ME due to retinal vascular diseases, we noted an early anatomical response significantly correlated with IOP change after intravitreal DEX implantation. Therefore, patients with favorable early anatomical responses to DEX implantation should be carefully monitored for IOP elevation.

Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities.

The prognostic and therapeutic relevance of molecular subtypes for the most aggressive isocitrate dehydrogenase 1/2 (IDH) wild-type glioblastoma (GBM) is currently limited due to high molecular heterogeneity of the tumors that impedes patient stratification. Here, we describe a distinct binary classification of IDH wild-type GBM tumors derived from a quantitative proteomic analysis of 39 IDH wild-type GBMs as well as IDH mutant and low-grade glioma controls. Specifically, GBM proteomic cluster 1 (GPC1) tumors exhibit Warburg-like features, neural stem-cell markers, immune checkpoint ligands, and a poor prognostic biomarker, FKBP prolyl isomerase 9 (FKBP9). Meanwhile, GPC2 tumors show elevated oxidative phosphorylation-related proteins, differentiated oligodendrocyte and astrocyte markers, and a favorable prognostic biomarker, phosphoglycerate dehydrogenase (PHGDH). Integrating these proteomic features with the pharmacological profiles of matched patient-derived cells (PDCs) reveals that the mTORC1/2 dual inhibitor AZD2014 is cytotoxic to the poor prognostic PDCs. Our analyses will guide GBM prognosis and precision treatment strategies.

Long-Term Visual/Anatomic Outcome in Patients with Fovea-Involving Fibrovascular Pigment Epithelium Detachment Presenting Choroidal Neovascularization on Optical Coherence Tomography Angiography.

BACKGROUND: To evaluate long-term visual/anatomic outcome after anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with fovea-involving fibrovascular pigment epithelium detachment (PED) presenting with choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA). METHODS: Patients with fibrovascular PED or subretinal CNV confirmed by OCTA who were treated by a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. The best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) before and after anti-VEGF injection were analyzed. Furthermore, changes in photoreceptor layer (PRL) thickness and outer retinal bands in the fovea after injection were evaluated. RESULTS: A total of 31 eyes with fibrovascular PED and 24 eyes with subretinal CNV were included. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST were improved, and the PRL thickness was decreased significantly. There were no differences in BCVA, CST, changes in PRL thickness, or the status of outer retinal bands between the groups. However, the difference in the amount of decrease in PRL thickness between the two groups was increased at 2 years, and the slope tended to be steeper in the subretinal CNV group. CONCLUSIONS: Exudative age-related macular degeneration (AMD) with fibrovascular PED or subretinal CNV showed good visual/anatomic outcomes after anti-VEGF treatment, regardless of the CNV type. By 2 years, fibrovascular PED did not have an additional protective effect on the outer retina, compared with subretinal CNV over 2 years. Further follow-up study might be needed to conclude that fibrovascular PED has a protective effect on the surrounding photoreceptor area.

Capillary Hemangioma of the Tympanic Membrane and External Auditory Canal.

Hemangiomas are very common tumors characterized by large numbers of vessels filled with blood. Capillary hemangioma is the most common type of hemangioma, whereas capillary hemangiomas of the tympanic membrane and external auditory canal are extremely rare vascular tumors. The authors present capillary hemangioma of the tympanic membrane and external auditory canal in a 54-year-old woman with right-sided aural fullness for 3 months. Under local anesthesia, the mass was resected by transcanal microscopic surgery. Histologically, the tumor was composed of thin-walled capillaries with scant stroma and diagnosed as capillary hemangioma. After surgery, her symptoms improved and she did not exhibit any signs of recurrence for 1 year. The authors also review the relevant literature related to this report.

Diameter of vessels across the tonsillar capsule as an anatomical consideration for tonsillectomy.

The authors measured the diameters of vessels around the surgical plane of tonsillectomy to investigate an anatomical basis to reduce hemorrhage. Thirty tonsils removed from 15 adult cadavers with the mean age of 56 years (range 44-71 years) at the time of death were studied. Calibration of the vessels across the tonsillar capsule was performed at the 1-mm intracapsular, capsular, and 1-mm extracapsular plane as artery and vein, respectively. The average diameter of the arteries was 73.0 +/- 33.1 mum at the 1-mm intracapsular plane, 94.7 +/- 33.5 mum at the capsular plane, and 139.5 +/- 51.2 mum at the 1-mm extracapsular plane. For the veins, it was 62.9 +/- 38.7 mum at the 1-mm intracapsular plane, 86.8 +/- 50.4 mum at the capsular plane, and 133.6 +/- 78.6 mum at the 1-mm extracapsular plane. The diameters of the vessels at the 1-mm intracapsular plane were significantly smaller than those at the capsular plane (P < 0.01), and likewise the diameters of the vessels at the capsular plane were significantly smaller than those at the 1-mm extracapsular plane (P < 0.01). The result of this study on the diameter of the vessels across the tonsillar capsule could be considered to be an important factor providing an anatomical rationale for a change in recommendation leading to safer tonsillectomies that minimize vascular injury.