Management of complications of sutureless intrascleral intraocular lens fixation.

PURPOSE: The purpose of the study was to report the complications of sutureless intrascleral (SIS) intraocular lens (IOL) fixation and its management. MATERIALS AND METHODS: A multicenter, retrospective, consecutive interventional case series of patients with intra or postoperative complications after SIS IOL fixation during the technical learning curve of vitreoretinal surgeons from three Taiwanese referral hospitals. The used surgical techniques were the Scharioth technique for intrascleral tunnel fixation, Yamane technique (double-needle scleral fixation), and modified Yamane technique (double-needle flanged haptic scleral fixation). The IOL models and surgical instruments used as well as each patient's ocular characteristics and complication management were recorded. RESULTS: Of the eight included patients, the complications of 3 (37.5%) and 5 (62.5%) were noted intraoperatively and postoperatively, respectively. Haptic-related complications, including haptic breakage, slippage, and haptic disinsertion, occurred in six eyes. Other complications included uveitis-glaucoma-hyphema syndrome, retinal detachment, and IOL tilt. For the two patients with haptic slippage, repositioning was achieved using a modified cow-hitch technique that resulted in favorable IOL centration and restored visual acuity. CONCLUSION: Most complications surgeons encountered during their early exposure to SIS IOL fixation were haptic related. Surgeons should be aware of such complications to prevent and manage them during surgery. Our modified cow-hitch technique could be used to reposition IOLs with unilateral haptic slippage.

Nitrogen sensing and regulatory networks: it's about time and space.

A plant's response to external and internal nitrogen signals/status relies on sensing and signaling mechanisms that operate across spatial and temporal dimensions. From a comprehensive systems biology perspective, this involves integrating nitrogen responses in different cell types and over long distances to ensure organ coordination in real time and yield practical applications. In this prospective review, we focus on novel aspects of nitrogen (N) sensing/signaling uncovered using temporal and spatial systems biology approaches, largely in the model Arabidopsis. The temporal aspects span: transcriptional responses to N-dose mediated by Michaelis-Menten kinetics, the role of the master NLP7 transcription factor as a nitrate sensor, its nitrate-dependent TF nuclear retention, its "hit-and-run" mode of target gene regulation, and temporal transcriptional cascade identified by "network walking." Spatial aspects of N-sensing/signaling have been uncovered in cell type-specific studies in roots and in root-to-shoot communication. We explore new approaches using single-cell sequencing data, trajectory inference, and pseudotime analysis as well as machine learning and artificial intelligence approaches. Finally, unveiling the mechanisms underlying the spatial dynamics of nitrogen sensing/signaling networks across species from model to crop could pave the way for translational studies to improve nitrogen-use efficiency in crops. Such outcomes could potentially reduce the detrimental effects of excessive fertilizer usage on groundwater pollution and greenhouse gas emissions.

BROAD VITREOMACULAR ATTACHMENT-INDUCED MACULAR HOLE: Structural Changes and Surgical Outcome.

PURPOSE: This study aims to describe the structural changes and surgical outcomes of full-thickness macular holes (FTMHs) induced by vitreomacular traction with broad vitreomacular attachment (VMA). METHODS: A retrospective analysis of idiopathic FTMHs from October 2010 to May 2022 was conducted. Patients with FTMHs and no retinal detachment (RD) induced by broad VMA (the study group) were compared with a control group consisting of typical FTMHs with focal VMA. RESULTS: Thirty-one eyes had broad VMA-associated FTMH, among which seven eyes (22%) were with concurrent RD. Among the total of 24 cases without RD, 8 (33%) exhibited schisis. The incidence of lamellar holes associated epithelial proliferation and multiple membrane traction was significantly higher in the study group. One hundred percent FTMH closure was observed postoperatively in both groups. Although the postoperative visual acuity was not significantly different, the study group showed a greater ellipsoid zone disruption length. CONCLUSION: Broad VMA-induced FTMHs are characterized by diverse macular structural changes, including schisis and macular detachment. These FTMHs are associated with a higher incidence of lamellar holes associated epithelial proliferation and multiple membrane traction. Surgical outcomes for FTMHs induced by broad VMA are similar to those induced by typical focal VMA, with both groups demonstrating a 100% hole-closure rate.

Effects of Online Video Sport Spectatorship on the Subjective Well-Being of College Students: The Moderating Effect of Sport Involvement.

Individuals' engagement in sports and sport-related entertainment is reported to improve their subjective well-being (SWB). We investigated whether online video sport spectatorship (OVSS) enhances the SWB of college students and whether sport involvement moderates the correlation between OVSS and SWB. For this, a pretest-posttest experimental design with a 3-week-long intervention (OVSS) was adopted. Two groups, intervention and control, were formed. The findings revealed that OVSS improved SWB (p = 0.017). Furthermore, sport involvement moderated the correlation between OVSS and SWB (p = 0.024). Specifically, participants with high levels of sport involvement in the intervention group exhibited better SWB (M = 5.51) than did the corresponding controls (M = 4.69). By contrast, among participants with low levels of sport involvement, only the intervention group showed improved SWB; however, it remained unchanged in the control group. The present study enriches the relevant literature and provides empirical evidence for the psychological benefits conferred by OVSS. Our findings may serve as a reference for designing interventions aimed at improving individuals' overall quality of life.

Validation of a high-confidence regulatory network for gene-to-NUE phenotype in field-grown rice.

Nitrogen (N) and Water (W) - two resources critical for crop productivity - are becoming increasingly limited in soils globally. To address this issue, we aim to uncover the gene regulatory networks (GRNs) that regulate nitrogen use efficiency (NUE) - as a function of water availability - in Oryza sativa, a staple for 3.5 billion people. In this study, we infer and validate GRNs that correlate with rice NUE phenotypes affected by N-by-W availability in the field. We did this by exploiting RNA-seq and crop phenotype data from 19 rice varieties grown in a 2x2 N-by-W matrix in the field. First, to identify gene-to-NUE field phenotypes, we analyzed these datasets using weighted gene co-expression network analysis (WGCNA). This identified two network modules ("skyblue" & "grey60") highly correlated with NUE grain yield (NUEg). Next, we focused on 90 TFs contained in these two NUEg modules and predicted their genome-wide targets using the N-and/or-W response datasets using a random forest network inference approach (GENIE3). Next, to validate the GENIE3 TF→target gene predictions, we performed Precision/Recall Analysis (AUPR) using nine datasets for three TFs validated in planta. This analysis sets a precision threshold of 0.31, used to "prune" the GENIE3 network for high-confidence TF→target gene edges, comprising 88 TFs and 5,716 N-and/or-W response genes. Next, we ranked these 88 TFs based on their significant influence on NUEg target genes responsive to N and/or W signaling. This resulted in a list of 18 prioritized TFs that regulate 551 NUEg target genes responsive to N and/or W signals. We validated the direct regulated targets of two of these candidate NUEg TFs in a plant cell-based TF assay called TARGET, for which we also had in planta data for comparison. Gene ontology analysis revealed that 6/18 NUEg TFs - OsbZIP23 (LOC_Os02g52780), Oshox22 (LOC_Os04g45810), LOB39 (LOC_Os03g41330), Oshox13 (LOC_Os03g08960), LOC_Os11g38870, and LOC_Os06g14670 - regulate genes annotated for N and/or W signaling. Our results show that OsbZIP23 and Oshox22, known regulators of drought tolerance, also coordinate W-responses with NUEg. This validated network can aid in developing/breeding rice with improved yield on marginal, low N-input, drought-prone soils.

Genotypes Influence Clinical Progression in EYS-Associated Retinitis Pigmentosa.

Purpose: The purpose of this study was to investigate the genetic and clinical characteristics of eyes shut homolog (EYS)-associated retinitis pigmentosa (RP). Methods: This was a retrospective cross-sectional observational study of 36 patients with EYS-associated autosomal recessive RP (arRP). Results: The gene sequencing results revealed that c.6416G>A (p.Cys2139Tyr) and c.7228+1G>A were the two most predominant variants in our cohort and that variants near the C-terminus, which contains alternating laminin and epidermal growth factor (EGF) domains, accounted for the majority of the allele counts (58 of a total of 72) and relative allele frequencies (81%). Over half of the patients presented with pericentral-type RP (n = 19, 60%), which frequently occurred in combination with macular lesions (n = 10, 52%). Patients having both variants within the alternating laminin and EGF domains near the C-terminus had a more severe disease progression (average 0.045 logMAR increase per year) than those having one variant in the N-terminus and the other in the C-terminus (average 0.001 logMAR increase per year). Conclusions: Pericentral RP was the major phenotype in patients with EYS-associated arRP. There was also a statistically significant relationship between the location of the variants and the severity of the disease. Translational Relevance: This study may aid patients with EYS-associated arRP to predict future vision acuity based on their genetic and clinical features.

Evolutionarily informed machine learning enhances the power of predictive gene-to-phenotype relationships.

Inferring phenotypic outcomes from genomic features is both a promise and challenge for systems biology. Using gene expression data to predict phenotypic outcomes, and functionally validating the genes with predictive powers are two challenges we address in this study. We applied an evolutionarily informed machine learning approach to predict phenotypes based on transcriptome responses shared both within and across species. Specifically, we exploited the phenotypic diversity in nitrogen use efficiency and evolutionarily conserved transcriptome responses to nitrogen treatments across Arabidopsis accessions and maize varieties. We demonstrate that using evolutionarily conserved nitrogen responsive genes is a biologically principled approach to reduce the feature dimensionality in machine learning that ultimately improved the predictive power of our gene-to-trait models. Further, we functionally validated seven candidate transcription factors with predictive power for NUE outcomes in Arabidopsis and one in maize. Moreover, application of our evolutionarily informed pipeline to other species including rice and mice models underscores its potential to uncover genes affecting any physiological or clinical traits of interest across biology, agriculture, or medicine.

Review, analysis, and education of antiseptic related ocular injury in the surgical settings.

Preoperative skin antiseptic preparation is the gold standard for prevention of surgical infection. However, improper use of antiseptics may lead to severe ocular damage. Currently, the most common surgical antiseptics can be divided into aqueous-based and alcohol-based disinfectants, with chlorhexidine and iodine/iodophors being the two major components. Chlorhexidine has a persistent antimicrobial effect and is resistant to neutralization by blood or organic products in surgical wounds. Nevertheless, due to its toxicity to the ears, meninges, and eyes, application of chlorhexidine should be prohibited in these surgical fields. Iodine/iodophor is better tolerated by the ocular surface and is the recommended antiseptic for ophthalmic or head and neck surgeries close to the periocular area. Alcohol is less pricey and has a rapid antiseptic effect, though its desiccating effect and flammability restrict the use in mucosal or laser surgeries. The single or combined use of these antiseptics may inadvertently induce severe ocular damage, especially during time-consuming head and neck surgeries with prone, hyperextension, or lateral tilt positions, or surgeries under general anesthesia. Apart from the choice of antiseptics, appropriate selection and attachment of bio-occlusive dressings are key to avoiding antiseptic-related ocular injuries. In this review, we provided a comprehensive summary of the characteristics of antiseptics used in surgical settings and the possible mechanisms and outcomes of antiseptic-related ocular injuries. The prevention, diagnosis, and acute management of these complications were also discussed.

EXO70D isoforms mediate selective autophagic degradation of type-A ARR proteins to regulate cytokinin sensitivity.

The phytohormone cytokinin influences many aspects of plant growth and development, several of which also involve the cellular process of autophagy, including leaf senescence, nutrient remobilization, and developmental transitions. The Arabidopsis type-A response regulators (type-A ARR) are negative regulators of cytokinin signaling that are transcriptionally induced in response to cytokinin. Here, we describe a mechanistic link between cytokinin signaling and autophagy, demonstrating that plants modulate cytokinin sensitivity through autophagic regulation of type-A ARR proteins. Type-A ARR proteins were degraded by autophagy in an AUTOPHAGY-RELATED (ATG)5-dependent manner, and this degradation is promoted by phosphorylation on a conserved aspartate in the receiver domain of the type-A ARRs. EXO70D family members interacted with type-A ARR proteins, likely in a phosphorylation-dependent manner, and recruited them to autophagosomes via interaction of the EXO70D AIM with the core autophagy protein, ATG8. Consistently, loss-of-function exo70D1,2,3 mutants exhibited compromised targeting of type-A ARRs to autophagic vesicles, have elevated levels of type-A ARR proteins, and are hyposensitive to cytokinin. Disruption of both type-A ARRs and EXO70D1,2,3 compromised survival in carbon-deficient conditions, suggesting interaction between autophagy and cytokinin responsiveness in response to stress. These results indicate that the EXO70D proteins act as selective autophagy receptors to target type-A ARR cargos for autophagic degradation, demonstrating modulation of cytokinin signaling by selective autophagy.

Elucidation of microstructural changes in leaves during senescence using spectral domain optical coherence tomography.

Leaf senescence provides a unique window to explore the age-dependent programmed degradation at organ label in plants. Here, spectral domain optical coherence tomography (SD-OCT) has been used to study in vivo senescing leaf microstructural changes in the deciduous plant Acer serrulatum Hayata. Hayata leaves show autumn phenology and change color from green to yellow and finally red. SD-OCT image analysis shows distinctive features among different layers of the leaves; merging of upper epidermis and palisade layers form thicker layers in red leaves compared to green leaves. Moreover, A-scan analysis showed a significant (p < 0.001) decrease in the attenuation coefficient (for wavelength range: 1100-1550 nm) from green to red leaves. In addition, the B-scan analysis also showed significant changes in 14 texture parameters extracted from second-order spatial gray level dependence matrix (SGLDM). Among these parameters, a set of three features (energy, skewness, and sum variance), capable of quantitatively distinguishing difference in the microstructures of three different colored leaves, has been identified. Furthermore, classification based on k-nearest neighbors algorithm (k-NN) was found to yield 98% sensitivity, 99% specificity, and 95.5% accuracy. Following the proposed technique, a portable noninvasive tool for quality control in crop management can be anticipated.

Challenges and Future Perspectives on Electroencephalogram-Based Biometrics in Person Recognition.

The emergence of the digital world has greatly increased the number of accounts and passwords that users must remember. It has also increased the need for secure access to personal information in the cloud. Biometrics is one approach to person recognition, which can be used in identification as well as authentication. Among the various modalities that have been developed, electroencephalography (EEG)-based biometrics features unparalleled universality, distinctiveness and collectability, while minimizing the risk of circumvention. However, commercializing EEG-based person recognition poses a number of challenges. This article reviews the various systems proposed over the past few years with a focus on the shortcomings that have prevented wide-scale implementation, including issues pertaining to temporal stability, psychological and physiological changes, protocol design, equipment and performance evaluation. We also examine several directions for the further development of usable EEG-based recognition systems as well as the niche markets to which they could be applied. It is expected that rapid advancements in EEG instrumentation, on-device processing and machine learning techniques will lead to the emergence of commercialized person recognition systems in the near future.

Role of BASIC PENTACYSTEINE transcription factors in a subset of cytokinin signaling responses.

Cytokinin plays diverse roles in plant growth and development, generally acting by modulating gene transcription in target tissues. The type-B Arabidopsis response regulators (ARR) transcription factors have emerged as primary targets of cytokinin signaling and are required for essentially all cytokinin-mediated changes in gene expression. The diversity of cytokinin function is likely imparted by the activity of various transcription factors working with the type-B ARRs to alter specific sets of target genes. One potential set of co-regulators modulating the cytokinin response are the BARLEY B-RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family of plant-specific transcription factors. Here, we show that disruption of multiple BPCs results in reduced sensitivity to cytokinin. Further, the BPCs are necessary for the induction of a subset of genes in response to cytokinin. We identified direct in vivo targets of BPC6 using ChIP-Seq and found an enrichment of promoters of genes differentially expressed in response to cytokinin. Further, a significant number of BPC6 regulated genes are also direct targets of the type-B ARRs. Potential cis-binding elements for a number of other transcription factors linked to cytokinin action are enriched in the BPC binding fragments, including those for the cytokinin response factors (CRFs). In addition, several BPCs interact with a subset of type-A ARRs. Consistent with these results, a significant number of genes whose expression is altered in bpc mutant roots are also mis-expressed in crf1,3,5,6 and type-A arr3,4,5,6,7,8,9,15 mutant roots. These results suggest that the BPCs are part of a complex network of transcription factors that are involved in the response to cytokinin.

Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan.

This study investigated the "real-world" use of ranibizumab for neovascular age-related macular degeneration (nAMD) in Taiwan and assessed the visual outcome. We reviewed the medical records at National Cheng Kung University Hospital, Taiwan, during 2012-2014 for 264 consecutive eyes of 229 patients with nAMD, who applied for ranibizumab covered by national health insurance. A total of 194 eyes (73.5%) in 179 patients (65.5% men; mean ± standard deviation age 69.4 ± 10.7 years) were pre-approved for treatment. Applications for treatment increased year by year, but approval rates decreased during this time. The major causes of rejection for funding were diseases mimicking nAMD, including macular pucker/epiretinal membrane, macular scarring, dry-type AMD, and possible polypoidal choroidal vasculopathy. After completion of three injections in 147 eyes, visual acuity significantly improved, gaining ≥1 line in 51.8% of eyes and stabilising in 38.3% of 141 eyes in which visual acuity was measured. The 114 eyes approved with only one application had a better visual outcome than the 27 eyes approved after the second or third applications. In conclusion, ranibizumab is effective for nAMD; however, approval after the second or third application for national health insurance cover is a less favourable predictor of visual outcome.

Araport11: a complete reannotation of the Arabidopsis thaliana reference genome.

The flowering plant Arabidopsis thaliana is a dicot model organism for research in many aspects of plant biology. A comprehensive annotation of its genome paves the way for understanding the functions and activities of all types of transcripts, including mRNA, the various classes of non-coding RNA, and small RNA. The TAIR10 annotation update had a profound impact on Arabidopsis research but was released more than 5 years ago. Maintaining the accuracy of the annotation continues to be a prerequisite for future progress. Using an integrative annotation pipeline, we assembled tissue-specific RNA-Seq libraries from 113 datasets and constructed 48 359 transcript models of protein-coding genes in eleven tissues. In addition, we annotated various classes of non-coding RNA including microRNA, long intergenic RNA, small nucleolar RNA, natural antisense transcript, small nuclear RNA, and small RNA using published datasets and in-house analytic results. Altogether, we identified 635 novel protein-coding genes, 508 novel transcribed regions, 5178 non-coding RNAs, and 35 846 small RNA loci that were formerly unannotated. Analysis of the splicing events and RNA-Seq based expression profiles revealed the landscapes of gene structures, untranslated regions, and splicing activities to be more intricate than previously appreciated. Furthermore, we present 692 uniformly expressed housekeeping genes, 43% of whose human orthologs are also housekeeping genes. This updated Arabidopsis genome annotation with a substantially increased resolution of gene models will not only further our understanding of the biological processes of this plant model but also of other species.

ThaleMine: A Warehouse for Arabidopsis Data Integration and Discovery.

ThaleMine (https://apps.araport.org/thalemine/) is a comprehensive data warehouse that integrates a wide array of genomic information of the model plant Arabidopsis thaliana. The data collection currently includes the latest structural and functional annotation from the Araport11 update, the Col-0 genome sequence, RNA-seq and array expression, co-expression, protein interactions, homologs, pathways, publications, alleles, germplasm and phenotypes. The data are collected from a wide variety of public resources. Users can browse gene-specific data through Gene Report pages, identify and create gene lists based on experiments or indexed keywords, and run GO enrichment analysis to investigate the biological significance of selected gene sets. Developed by the Arabidopsis Information Portal project (Araport, https://www.araport.org/), ThaleMine uses the InterMine software framework, which builds well-structured data, and provides powerful data query and analysis functionality. The warehoused data can be accessed by users via graphical interfaces, as well as programmatically via web-services. Here we describe recent developments in ThaleMine including new features and extensions, and discuss future improvements. InterMine has been broadly adopted by the model organism research community including nematode, rat, mouse, zebrafish, budding yeast, the modENCODE project, as well as being used for human data. ThaleMine is the first InterMine developed for a plant model. As additional new plant InterMines are developed by the legume and other plant research communities, the potential of cross-organism integrative data analysis will be further enabled.

Bromomethylthioindole Inspired Carbazole Hybrids as Promising Class of Anti-MRSA Agents.

Series of N-substituted carbazole analogues bearing an indole ring were synthesized as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents from a molecular hybridization approach. The representative compound 19 showed an MIC = 1 µg/mL against a panel of MRSA clinical isolates as it possessed comparable in vitro activities to that of vancomycin. Moreover, compound 19 also exhibited MIC = 1 µg/mL activities against a recent identified Z172 MRSA strain (vancomycin-intermediate and daptomycin-nonsusceptible phenotype) and the vancomycin-resistant Enterococcus faecalis (VRE) strain. In a mouse model with lethal infection of MRSA (4N216), a 75% survival rate was observed after a single dose of compound 19 was intravenously administered at 20 mg/kg. In light of their equipotent activities against different MRSA isolates and VRE strain, the data underscore the importance of designed hybrid series for the development of new N-substituted carbazoles as potential anti-MRSA agents.

Important Hydrogen Bond Networks in Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Design Revealed by Crystal Structures of Imidazoleisoindole Derivatives with IDO1.

Indoleamine 2,3-dioxygenase 1 (IDO1), promoting immune escape of tumors, is a therapeutic target for the cancer immunotherapy. A number of IDO1 inhibitors have been identified, but only limited structural biology studies of IDO1 inhibitors are available to provide insights on the binding mechanism of IDO1. In this study, we present the structure of IDO1 in complex with 24, a NLG919 analogue with potent activity. The complex structure revealed the imidazole nitrogen atom of 24 to coordinate with the heme iron, and the imidazoleisoindole core situated in pocket A with the 1-cyclohexylethanol moiety extended to pocket B to interact with the surrounding residues. Most interestingly, 24 formed an extensive hydrogen bond network with IDO1, which is a distinct feature of IDO1/24 complex structure and is not observed in the other IDO1 complex structures. Further structure-activity relationship, UV spectra, and structural biology studies of several analogues of 24 demonstrated that extensive hydrophobic interactions and the unique hydrogen bonding network contribute to the great potency of imidazoleisoindole derivatives. These results are expected to facilitate the structure-based drug design of new IDO inhibitors.

The cytokinin response factors modulate root and shoot growth and promote leaf senescence in Arabidopsis.

The cytokinin response factors (CRFs) are a group of related AP2/ERF transcription factors that are transcriptionally induced by cytokinin. Here we explore the role of the CRFs in Arabidopsis thaliana growth and development by analyzing lines with decreased and increased CRF function. While single crf mutations have no appreciable phenotypes, disruption of multiple CRFs results in larger rosettes, delayed leaf senescence, a smaller root apical meristem (RAM), reduced primary and lateral root growth, and, in etiolated seedlings, shorter hypocotyls. In contrast, overexpression of CRFs generally results in the opposite phenotypes. The crf1,2,5,6 quadruple mutant is embryo lethal, indicating that CRF function is essential for embryo development. Disruption of the CRFs results in partially insensitivity to cytokinin in a root elongation assay and affects the basal expression of a significant number of cytokinin-regulated genes, including the type-A ARRs, although it does not impair the cytokinin induction of the type-A ARRs. Genes encoding homeobox transcription factors are mis-expressed in the crf1,3,5,6 mutant, including STIMPY/WOX9 that is required for root and shoot apical meristem maintenance roots and which has previously been linked to cytokinin. These results indicate that the CRF transcription factors play important roles in multiple aspects of plant growth and development, in part through a complex interaction with cytokinin signaling.

Stem cell mobilizers targeting chemokine receptor CXCR4: renoprotective application in acute kidney injury.

We have discovered a novel series of quinazoline-based CXCR4 antagonists. Of these, compound 19 mobilized CXCR4(+) cell types, including hematopoietic stem cells and endothelial progenitor cells, more efficiently than the marketed 1 (AMD3100) with subcutaneous administration at the same dose (6 mg/kg) in mice. This series of compounds thus provides a set of valuable tools to study diseases mediated by the CXCR4/SDF-1 axis, including myocardial infarction, ischemic stroke, and cancer metastasis. More importantly, treatment with compound 19 significantly lowered levels of blood urea nitrogen and serum creatinine in rats with renal ischemia-reperfusion injury, providing evidence for its therapeutic potential in preventing ischemic acute kidney injury. CXCR4 antagonists such as 19 might also be useful to increase circulating levels of adult stem cells, thereby exerting beneficial effects on damaged and/or inflamed tissues in diseases that currently are not treated by standard approaches.