Inter-Individual Topographic Variation of Choroidal Thickness in Healthy Eyes on Swept-Source Optical Coherence Tomography.

Purpose: To investigate the topographic characters of inter-individual variations of the macular choroidal thickness (CT). Methods: This was a retrospective study. Macular CT data for 900 0.2 × 0.2-mm grids from 410 healthy eyes were collected from swept-source optical coherence tomography. Following the analysis of factors associated with mean CT, the ß-coefficients of the included associated factors in each grid were summarized for choroidal thickness changes analysis. Additionally, the coefficient of variance (CoV), coefficient of determination (CoD), and coefficient of variance unexplained (CoVU) for CT were calculated in each individual grid to investigate the inter-individual choroidal variations pattern. Results: Sex (ß = -17.26, female vs. male), age (ß = -1.61, per 1 year), and axial length (ß = -18.62, per 1 mm) were associated with mean macular CT. Females had a thinner choroid in all 900 grids (0.5-26.9 µm). As age increased, the CT noticeably decreased (8.74-19.87 µm per 10 years) in the temporal regions. With axial length elongation, the thinning (7.94-24.91 µm per 1 mm) was more evident in subfoveal and nasal regions. Both the CoV (34.69%-58.00%) and CoVU (23.05%-40.78%) were lower in the temporal regions, whereas the CoD (18.41%-39.66%) was higher in the temporal regions. Conclusions: Choroidal thinning is more predominant in the subfoveal and nasal regions with axial length elongation, but in the temporal region with aging. The inter-individual variation of CT is higher and less determined by sex, age, or axial length in the nasal regions. Translational Relevance: Topographic variation should be considered when interpreting choroidal thickness.

Dual-Spatial Domain Generalization for Fundus Lesion Segmentation in Unseen Manufacturer's OCT Images.

OBJECTIVE: Optical Coherence Tomography (OCT) images can provide non-invasive visualization of fundus lesions; however, scanners from different OCT manufacturers largely vary from each other, which often leads to model deterioration to unseen OCT scanners due to domain shift. METHODS: To produce the T-styles of the potential target domain, an Orthogonal Style Space Reparameterization (OSSR) method is proposed to apply orthogonal constraints in the latent orthogonal style space to the sampled marginal styles. To leverage the high-level features of multi-source domains and potential T-styles in the graph semantic space, a Graph Adversarial Network (GAN) is constructed to align the generated samples with the source domain samples. To align features with the same label based on the semantic feature in the graph semantic space, Graph Semantic Alignment (GSA) is performed to focus on the shape and the morphological differences between the lesions and their surrounding regions. RESULTS: Comprehensive experiments have been performed on two OCT image datasets. Compared to state-of-the-art methods, the proposed method can achieve better segmentation. CONCLUSION: The proposed fundus lesion segmentation method can be trained with labeled OCT images from multiple manufacturers' scanners and be tested on an unseen manufacturer's scanner with better domain generalization. SIGNIFICANCE: The proposed method can be used in routine clinical occasions when an unseen manufacturer's OCT image is available for a patient.

Designing a size exclusion-based hapten and the development of a quantitative and visual time-resolved fluorescence immunochromatography assay strip for detecting dimethomorph and flumorph in a group-specific manner.

Based on the size and surface properties of dimethomorph and flumorph, we used a computer simulation-assisted size exclusion hapten design strategy to develop group-specific monoclonal antibodies that can simultaneously recognize dimethomorph and flumorph. For this, we performed quantitative and visual semi-quantitative time-resolved fluorescence immunochromatography (TRFICA) to simultaneously detect dimethomorph and flumorph in potatoes and apples. In potato samples, the visual limit of detection (vLOD) for dimethomorph and flumorph was 4 ng/mL and 8 ng/mL, respectively, whereas the quantitative limit of detection (qLOD) for dimethomorph and flumorph was 0.26 and 0.33 ng/mL, respectively. The vLOD of dimethomorph and flumorph in apple samples was 8 ng/mL, whereas the qLOD of dimethomorph and flumorph was 0.17 and 0.38 ng/mL, respectively. The average recovery of potato and apple samples ranged from 77.5% to 121.7%, which indicated that the method can be used to rapidly detect dimethomorph and flumorph in food samples.

Photoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.

Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination. In this reaction, the flavin-dependent ene-reductase photocatalytically generates the aminium radical cation from the corresponding hydroxylamine and catalyzes the asymmetric intermolecular hydroamination to furnish the enantioenriched tertiary amine, whereby enantioinduction occurs through enzyme-mediated hydrogen atom transfer. This work highlights the use of photoenzymatic catalysis to generate and control highly reactive radical intermediates for asymmetric synthesis, addressing a long-standing challenge in chemical synthesis.

Assessing greenhouse gas emissions from the printing and dyeing wastewater treatment and reuse system: Potential pathways towards carbon neutrality.

The urgency of achieving carbon neutrality needs a reduction in greenhouse gas (GHG) emissions from the textile industry. Printing and dyeing wastewater (PDWW) plays a crucial role in the textile industry. The incomplete assessment of GHG emissions from PDWW impedes the attainment of carbon neutrality. Here, we firstly introduced a more standardized and systematic life-cycle GHG emission accounting method for printing and dyeing wastewater treatment and reuse system (PDWTRS) and proposed possible low-carbon pathways to achieve carbon neutrality. Utilizing case-specific operational data over 12 months, the study revealed that the PDWTRS generated 3.49 kg CO2eq/m3 or 1.58 kg CO2eq/kg CODrem in 2022. This exceeded the GHG intensity of municipal wastewater treatment (ranged from 0.58 to 1.14 kg CO2eq/m3). The primary contributor to GHG emissions was energy consumption (33 %), with the energy mix (sensitivity = 0.38) and consumption (sensitivity = 0.33) exerting the most significant impact on GHG emission intensity respectively. Employing prospective life cycle assessment (LCA), our study explored the potential of the anaerobic membrane bioreactor (AnMBR) to reduce emissions by 0.54 kg CO2eq/m3 and the solar-driven photocatalytic membrane reactor (PMR) to decrease by 0.20 kg CO2eq/m3 by 2050. Our projections suggested that the PDWTRS could achieve net-zero emissions before 2040 through an adoption of progressive transition to low-carbon management, with a GHG emission intensity of -0.10 kg CO2eq/m3 by 2050. Importantly, the study underscored the escalating significance of developing sustainable technologies for reclaimed water production amid water scarcity and climate change. The study may serve as a reminder of the critical role of PDWW treatment in carbon reduction within the textile industry and provides a roadmap for potential pathways towards carbon neutrality for PDWTRS.

Causal role of immune cells in inflammatory bowel disease: A Mendelian randomization study.

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.

MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Regional choroidal thickness estimation from color fundus images based on convolutional neural networks.

Purpose: This study aims to estimate the regional choroidal thickness from color fundus images from convolutional neural networks in different network structures and task learning models. Method: 1276 color fundus photos and their corresponding choroidal thickness values from healthy subjects were obtained from the Topcon DRI Triton optical coherence tomography machine. Initially, ten commonly used convolutional neural networks were deployed to identify the most accurate model, which was subsequently selected for further training. This selected model was then employed in combination with single-, multiple-, and auxiliary-task training models to predict the average and sub-region choroidal thickness in both ETDRS (Early Treatment Diabetic Retinopathy Study) grids and 100-grid subregions. The values of mean absolute error and coefficient of determination (R2) were involved to evaluate the models' performance. Results: Efficientnet-b0 network outperformed other networks with the lowest mean absolute error value (25.61 µm) and highest R2 (0.7817) in average choroidal thickness. Incorporating diopter spherical, anterior chamber depth, and lens thickness as auxiliary tasks improved predicted accuracy (p-value = 6.39×10-44, 2.72×10-38, 1.15×10-36 respectively). For ETDRS regional choroidal thickness estimation, multi-task model achieved better results than single task model (lowest mean absolute error = 31.10 µm vs. 33.20 µm). The multi-task training also can simultaneously predict the choroidal thickness of 100 grids with a minimum mean absolute error of 33.86 µm. Conclusions: Efficientnet-b0, in combination with multi-task and auxiliary task models, achieve high accuracy in estimating average and regional macular choroidal thickness directly from color fundus photographs.

Distinct Site Motifs Activate O2 and H2 on Supported Au Nanoparticles in Liquid Water.

Au nanoparticles catalyze the activation and conversion of small molecules with rates and kinetic barriers that depend on the dimensions of the nanoparticle, composition of the support, and presence of catalytically culpable water molecules that solvate these interfaces. Here, molecular interpretations of steady-state rate measurements, kinetic isotope effects, and structural characterizations reveal how the interface of Au nanoparticles, liquid water, and metal oxide supports mediate the kinetically relevant activation of H2 and sequential reduction of O2-derived intermediates during the formation of H2O2 and H2O. Rates of H2 consumption are 10-100 fold greater on Au nanoparticles supported on metal oxides (e.g., titania) compared to more inert and hydrophobic materials (carbon, boron nitride). Similarly, Au nanoparticles on reducible and Lewis acidic supports (e.g., lanthana) bind dioxygen intermediates more strongly and present lower barriers (<22 kJ mol-1) for O-O bond dissociation than inert interfaces formed with silica (>70 kJ mol-1). Selectivities for H2O2 formation increase significantly as the diameters of the Au nanoparticles increase because differences in nanoparticle size change the relative fractions of exposed sites that exist at Au-support interfaces. In contrast, site-normalized rates and barriers for H2 activation depend weakly on the size of Au nanoparticles and the associated differences in active site motifs. These findings suggest that H2O aids the activation of H2 at sites present across all surface Au atoms when nanoparticles are solvated by water. However, molecular O2 preferentially binds and dissociates at Au-support interfaces, leading to greater structure sensitivity for barriers of O-O dissociation across different support identities and sizes of Au nanoparticles. These insights differ from prior knowledge from studies of gas-phase reactions of H2 and O2 upon Au nanoparticle catalysts within dilute vapor pressures of water (10-4 to 0.1 kPa H2O), in which catalysis occurs at the perimeter of the Au-support interface. In contrast, contacting Au catalysts with liquid water (55.5 M H2O) expands catalysis to all surface Au atoms and enables appreciable H2O2 formation.

Vitrectomy with Subretinal Injection of Recombinant Tissue Plasminogen Activator for Submacular Hemorrhage with or without Vitreous Hemorrhage.

PURPOSE: To evaluate the outcomes and prognostic factors of pars plana vitrectomy (PPV) combined with subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH) patients with or without vitreous hemorrhage. METHODS: Sixty-four eyes of 64 patients with SMH patients underwent PPV with subretinal injection of rt-PA. Best-corrected visual acuity (BCVA), SMH displacement, and postoperative complications were analyzed. Predictive factors of the final BCVA were determined using multivariant linear regression. RESULTS: There were 26 eyes with VH and 38 without VH BCVA significantly improved in both VH group (from 2.27±0.40 to 1.25±0.70 LogMAR) and non-VH group (from 1.76±0.55 to 0.85±0.65 LogMAR). Completely displacement of SMHs was observed in 47 (73.43%) eyes. Postoperative complications included recurrent SMH (4.69%), recurrent vitreous hemorrhage (10.94%), rhegmatogenous retinal detachment (3.13%), and epiretinal membrane (4.68%). Treatment-naive condition, early surgery, and younger age were significantly associated with better final BCVA (B =0.502, 0.303, and 0.021, respectively, with all p <0.05). CONCLUSION: PPV combined with subretinal rt-PA injection is an effective treatment for SMH patients with and without VH.

Discovery and Development of Luvangetin from Zanthoxylum avicennae as a New Fungicide Candidate for Fusarium verticillioides.

Pathogenic fungi pose a significant threat to crop yields and human healthy, and the subsequent fungicide resistance has greatly aggravated these agricultural and medical challenges. Hence, the development of new fungicides with higher efficiency and greater environmental friendliness is urgently required. In this study, luvangetin, isolated and identified from the root of Zanthoxylum avicennae, exhibited wide-spectrum antifungal activity in vivo and in vitro. Integrated omics and in vitro and in vivo transcriptional analyses revealed that luvangetin inhibited GAL4-like Zn(II)2Cys6 transcriptional factor-mediated transcription, particularly the FvFUM21-mediated FUM cluster gene expression, and decreased the biosynthesis of fumonisins inFusarium verticillioides. Moreover, luvangetin binds to the double-stranded DNA helix in vitro in the groove mode. We isolated and identified luvangetin, a natural metabolite from a traditional Chinese edible medicinal plant and uncovered its multipathogen resistance mechanism. This study is the first to reveal the mechanism underlying the antifungal activity of luvangetin and provides a promising direction for the future use of plant-derived natural products to prevent and control plant and animal pathogenic fungi.

Combining WGCNA and machine learning to identify mechanisms and biomarkers of ischemic heart failure development after acute myocardial infarction.

Background: Ischemic heart failure (IHF) is a serious complication after acute myocardial infarction (AMI). Understanding the mechanism of IHF after AMI will help us conduct early diagnosis and treatment. Methods: We obtained the AMI dataset GSE66360 and the IHF dataset GSE57338 from the GEO database, and screened overlapping genes common to both diseases through WGCNA analysis. Subsequently, we performed GO and KEGG enrichment analysis on overlapping genes to elucidate the common mechanism of AMI and IHF. Machine learning algorithms are also used to identify key biomarkers. Finally, we performed immune cell infiltration analysis on the dataset to further evaluate immune cell changes in AMI and IHF. Results: We obtained 74 overlapping genes of AMI and IHF through WGCNA analysis, and the enrichment analysis results mainly focused on immune and inflammation-related mechanisms. Through the three machine learning algorithms of LASSO, RF and SVM-RFE, we finally obtained the four Hub genes of IL1B, TIMP2, IFIT3, and P2RY2, and verified them in the IHF dataset GSE116250, and the diagnostic model AUC = 0.907. The results of immune infiltration analysis showed that 8 types of immune cells were significantly different in AMI samples, and 6 types of immune cells were significantly different in IHF samples. Conclusion: We explored the mechanism of IHF after AMI by WGCNA, enrichment analysis, and immune infiltration analysis. Four potential diagnostic candidate genes and therapeutic targets were identified by machine learning algorithms. This provides a new idea for the pathogenesis, diagnosis, and treatment of IHF after AMI.

Unveiling the antibacterial mechanism of resveratrol against Aeromonas hydrophila through proteomics analysis.

This investigation delves into elucidating the mechanism by which resveratrol (Res), a natural polyterpenoid renowned for its antimicrobial properties, exerts its effects on Aeromonas hydrophila, a ubiquitous waterborne pathogen. Our findings underscore the dose-dependent manifestation of resveratrol in exhibiting antibacterial and antibiofilm formation activities against A. hydrophila. Employing a Data-independent acquisition (DIA) based quantitative proteomics methodology, we systematically compared differentially expressed proteins in A. hydrophila subjected to varying concentrations of Res. Subsequent bioinformatics analyses revealed key proteins and pathways pivotal in resveratrol's antimicrobial action, encompassing oxidative stress, energy metabolism, and cell membrane integrity. Validation of the proteomics outcomes was meticulously conducted using the qPCR method at the mRNA level. Dynamic trend analysis unveiled alterations in biological processes, notably the correlation between the cell division-related protein ZapC and resveratrol content. Furthermore, scanning electron microscopy corroborated a significant elongation of A. hydrophila cells, affirming resveratrol's capability to inhibit cell division. In concert, resveratrol emerges as a participant in the cell membrane integrity pathway, biofilm formation, and potentially, the regulation of genes associated with cell division, resulting in morphological elongation. These revelations position resveratrol as a promising natural alternative to conventional antibiotics for treating A. hydrophila infections.

Molecular Characterization and Pathogenicity of an Infectious cDNA Clone of Youcai Mosaic Virus on Solanum nigrum.

Virus infections cause devastative economic losses for various plant species, and early diagnosis and prevention are the most effective strategies to avoid the losses. Exploring virus genomic evolution and constructing virus infectious cDNA clones is essential to achieve a deeper understanding of the interaction between host plant and virus. Therefore, this work aims to guide people to better prevent, control, and utilize the youcai mosaic virus (YoMV). Here, the YoMV was found to infect the Solanum nigrum under natural conditions. Then, an infectious cDNA clone of YoMV was successfully constructed using triple-shuttling vector-based yeast recombination. Furthermore, we established phylogenetic trees based on the complete genomic sequences, the replicase gene, movement protein gene, and coat protein gene using the corresponding deposited sequences in NCBI. Simultaneously, the evolutionary relationship of the YoMV discovered on S. nigrum to others was determined and analyzed. Moreover, the constructed cDNA infectious clone of YoMV from S. nigrum could systematically infect the Nicotiana benthamiana and S. nigrum by agrobacterium-mediated infiltration. Our investigation supplied a reverse genetic tool for YoMV study, which will also contribute to in-depth study and profound understanding of the interaction between YoMV and host plant.

DRFNet: a deep radiomic fusion network for nAMD/PCV differentiation in OCT images.

Objective.Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) present many similar clinical features. However, there are significant differences in the progression of nAMD and PCV. and it is crucial to make accurate diagnosis for treatment. In this paper, we propose a structure-radiomic fusion network (DRFNet) to differentiate PCV and nAMD in optical coherence tomography (OCT) images.Approach.The subnetwork (RIMNet) is designed to automatically segment the lesion of nAMD and PCV. Another subnetwork (StrEncoder) is designed to extract deep structural features of the segmented lesion. The subnetwork (RadEncoder) is designed to extract radiomic features from the segmented lesions based on radiomics. 305 eyes (155 with nAMD and 150 with PCV) are included and manually annotated CNV region in this study. The proposed method was trained and evaluated by 4-fold cross validation using the collected data and was compared with the advanced differentiation methods.Main results.The proposed method achieved high classification performace of nAMD/PCV differentiation in OCT images, which was an improvement of 4.68 compared with other best method.Significance. The presented structure-radiomic fusion network (DRFNet) has great performance of diagnosing nAMD and PCV and high clinical value by using OCT instead of indocyanine green angiography.

Directed Network Comparison Using Motifs.

Analyzing and characterizing the differences between networks is a fundamental and challenging problem in network science. Most previous network comparison methods that rely on topological properties have been restricted to measuring differences between two undirected networks. However, many networks, such as biological networks, social networks, and transportation networks, exhibit inherent directionality and higher-order attributes that should not be ignored when comparing networks. Therefore, we propose a motif-based directed network comparison method that captures local, global, and higher-order differences between two directed networks. Specifically, we first construct a motif distribution vector for each node, which captures the information of a node's involvement in different directed motifs. Then, the dissimilarity between two directed networks is defined on the basis of a matrix, which is composed of the motif distribution vector of every node and the Jensen-Shannon divergence. The performance of our method is evaluated via the comparison of six real directed networks with their null models, as well as their perturbed networks based on edge perturbation. Our method is superior to the state-of-the-art baselines and is robust with different parameter settings.

Stable expression of mucin glycoproteins GP40 and GP15 of Cryptosporidium parvum in Toxoplasma gondii.

BACKGROUND: Cryptosporidium spp. are common protozoa causing diarrhea in humans and animals. There are currently only one FDA-approved drug and no vaccines for cryptosporidiosis, largely due to the limited knowledge of the molecular mechanisms involved in the invasion of the pathogens. Previous studies have shown that GP60, which is cleaved into GP40 and GP15 after expression, is an immunodominant mucin protein involved in the invasion of Cryptosporidium. The protein is highly O-glycosylated, and recombinant proteins expressed in prokaryotic systems are non-functional. Therefore, few studies have investigated the function of GP40 and GP15. METHODS: To obtain recombinant GP40 with correct post-translational modifications, we used CRISPR/Cas9 technology to insert GP40 and GP15 into the UPRT locus of Toxoplasma gondii, allowing heterologous expression of Cryptosporidium proteins. In addition, the Twin-Strep tag was inserted after GP40 for efficient purification of GP40. RESULTS: Western blotting and immunofluorescent microscopic analyses both indicated that GP40 and GP15 were stably expressed in T. gondii mutants. GP40 localized not only in the cytoplasm of tachyzoites but also in the parasitophorous vacuoles, while GP15 without the GPI anchor was expressed only in the cytoplasm. In addition, a large amount of recTgGP40 was purified using Strep-TactinXT supported by a visible band of ~ 50 kDa in SDS-PAGE. CONCLUSIONS: The establishment of a robust and efficient heterologous expression system of GP40 in T. gondii represents a novel approach and concept for investigating Cryptosporidium mucins, overcoming the limitations of previous studies that relied on unstable transient transfection, which involved complex steps and high costs.

Standardized patients' experiences of portraying characters in difficult communication scenarios: Narrative inquiry.

BACKGROUND: There are limited studies that explored the preparation and challenges faced by standardized patients (SPs) in portraying characters in difficult communication scenarios, and the strategies used to overcome these challenges. The purpose of this study was to understand the experience of SPs in interpreting difficult communication situations and the learning needs of performing similar scenarios. And it allows the researchers to explore the meaning, beliefs, values, and aspiration associated with their role as SPs. The findings could shade light on the significance of their experiences and provide valuable insights for the development of future SP training programs. METHODS: The design of this study is framed by a narrative inquiry, using semi-structured guidelines to conduct in-depth interviews with 11 SPs who have participated in the performances of difficult communication situations. Research data were analyzed by Polkinghorne narrative analysis, and Riessman's four criteria were used to establish rigor. RESULTS: Analysis revealed the following five themes: scenarios to real life connections, process of preparing for a performance, methods to detach from character, obtaining unexpected rewards, and needs for performance training. There are two to three subthemes that are subsumed under each theme. CONCLUSIONS: To strengthen training in difficult communication for healthcare professionals, the use of SPs to interpret challenging difficult communication scenarios will continue to increase. Educators need to ensure that SPs are fully prepared physically and emotionally before, during and after their performance. Offering of continuing education and training in feedback techniques are crucial to extend the tenure of SPs, reduce their frustration, prevent attrition, and ultimately, reduce training costs. In the future, SP training should also include detachment and feedback techniques to alleviate SPs' stress.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Mitochondrial dynamics and mitochondrial autophagy: Molecular structure, orchestrating mechanism and related disorders.

Mitochondrial dynamics and autophagy play essential roles in normal cellular physiological activities, while abnormal mitochondrial dynamics and mitochondrial autophagy can cause cancer and related disorders. Abnormal mitochondrial dynamics usually occur in parallel with mitochondrial autophagy. Both have been reported to have a synergistic effect and can therefore complement or inhibit each other. Progress has been made in understanding the classical mitochondrial PINK1/Parkin pathway and mitochondrial dynamical abnormalities. Still, the mechanisms and regulatory pathways underlying the interaction between mitophagy and mitochondrial dynamics remain unexplored. Like other existing reviews, we review the molecular structure of proteins involved in mitochondrial dynamics and mitochondrial autophagy, and how their abnormalities can lead to the development of related diseases. We will also review the individual or synergistic effects of abnormal mitochondrial dynamics and mitophagy leading to cellular proliferation, differentiation and invasion. In addition, we explore the mechanisms underlying mitochondrial dynamics and mitochondrial autophagy to contribute to targeted and precise regulation of mitochondrial function. Through the study of abnormal mitochondrial dynamics and mitochondrial autophagy regulation mechanisms, as well as the role of early disease development, effective targets for mitochondrial function regulation can be proposed to enable accurate diagnosis and treatment of the associated disorders.