Highly stable, fluorescent, artificial lipoprotein nanoparticles.

Here, we report a novel kind of protein nanoparticles of 11 nm in size, which have a central protein core surrounded by two layers of lipid. One layer of the lipid was covalently attached to the protein, while the other layer has been physically assembled around the protein core. Particle synthesis is highly modular, while both the size and charge of the protein nanoparticles are controlled in a predictable manner. Circular dichroism studies of the conjugate showed that the protein secondary structure is retained, while biophysical characterizations indicated the particle purity, size, and charge. The conjugate had a high thermal stability to steam sterilization conditions at 121°C (17 psi). After labeling the protein core with few different fluorescent dyes, they were strongly fluorescent with the corresponding colors independent of their size, unlike quantum dots. They are readily digested by proteases, and these water-soluble, non-toxic, highly stable, biocompatible, and biodegradable conjugates are suitable for cell imaging and drug delivery applications.

Investigating the biological relevance of measuring gastrointestinal cortisol metabolite levels to assess stress responses in Atlantic salmon (Salmo salar L.) after an acute stress.

Monitoring stress levels of farmed Atlantic salmon (Salmo salar) is important to ensure fish welfare and optimize farm operations. Feces could be a promising matrix for assessing stress responses in fish, based on their properties of low-invasive sampling and allowing repeated sampling over time. Meanwhile, elevated levels of cortisol metabolites (CMs) in feces indicate the increases in plasma cortisol levels (PLA) after exposure to acute stress. However, the dynamics of fecal CMs following acute stress in Atlantic salmon remain unclear. In this study, a confinement stress involving chasing and crowding was conducted to investigate the responses of gastrointestinal CMs to an acute stressor in Atlantic salmon. The post-smolts, with an average weight of 155.21 g, were sampled before and at 30 min, 1.5, 6, 12, 18, 24, 36, and 48 h after the onset of stress. Blood and gastrointestinal contents from the stomach, proximal intestine, and distal intestine of each fish were collected and subsequently analyzed, using competitive enzyme-linked immunosorbent assay (ELISA). The results demonstrated that the pre-stress level of PLA was low (4.28 ± 6.13 ng/ml) and reached a peak within 30 min following stress. The levels of CMs in gastrointestinal contents from stomach (SCMs), proximal intestine (PCMs), and distal intestine (DCMs) in pre-stress group were 0.82 ± 0.50, 18.31 ± 6.14 and 16.04 ± 6.69 ng/g, respectively. Gastrointestinal CMs increased significantly within 30 min and the peak levels of SCMs (3.51 ± 3.75 ng/g), PCMs (68.19 ± 23.71 ng/g) and DCMs (65.67 ± 23.37 ng/g) were found at 1.5 h post-stress. The significant increases in PCMs and DCMs post-stress validate the biological relevance of measuring intestinal CMs for assessing acute stress responses in Atlantic salmon. No significant difference was noted between PCMs and DCMs across all samples, suggesting that intestinal contents can serve as a suitable matrix compared with feces when measuring the responses of CMs to acute stress. The time lag between the peak of PLA levels and their reflection in the intestinal contents exceeded 1 h, indicating that using intestinal contents as a matrix to assess stress levels in fish can extend and delay the sampling window. This study highlights valuable guidance for determining the optimal times to utilize intestinal contents for measuring stress responses, providing further insights into the dynamics of fecal CM following acute stress.

Case Report: Thrombus aspiration and in situ thrombolysis via a Guidezilla guide extension catheter in a patient with high-risk pulmonary embolism.

Standard catheter-directed thrombolysis (CDT) and thrombus aspiration are considered potentially promising approaches for reopening the embolism-related pulmonary artery in patients with pulmonary embolism (PE) with high thrombotic burden and deteriorating hemodynamics, especially in those for whom systemic thrombolysis is contraindicated or has failed. However, the constrained accessibility of dedicated catheters has impeded the potential benefits of standard CDT in developing countries. The Guidezilla guide extension catheter (GEC) with a larger diameter and extended length is widely used in challenging coronary anatomy. Nevertheless, there have been few reports on the application of the Guidezilla GEC as a novel option for patients with massive PE when dedicated catheters and surgical thrombectomy are not available. In this case report, we demonstrated that thrombus aspiration and in situ thrombolysis through the Guidezilla GEC are applicable to patients with PE in whom systemic thrombolysis is contraindicated, resulting in successful reperfusion and positive clinical outcomes.

Effective prime factorization via quantum annealing by modular locally-structured embedding.

This paper investigates novel techniques to solve prime factorization by quantum annealing (QA). First, we present a very-compact modular encoding of a multiplier circuit into the architecture of current D-Wave QA devices. The key contribution is a compact encoding of a controlled full-adder into an 8-qubit module in the Pegasus topology, which we synthesized using Optimization Modulo Theories. This allows us to encode up to a 21 × 12-bit multiplier (and a 22 × 8-bit one) into the Pegasus 5760-qubit topology of current annealers. To the best of our knowledge, these are the largest factorization problems ever encoded into a quantum annealer. Second, we investigated the problem of actually solving encoded PF problems by running an extensive experimental evaluation on a D-Wave Advantage 4.1 quantum annealer. In the experiments we introduced different approaches to initialize the multiplier qubits and adopted several performance enhancement techniques. Overall, 8,219,999 = 32,749 × 251 was the highest prime product we were able to factorize within the limits of our QPU resources. To the best of our knowledge, this is the largest number which was ever factorized by means of a quantum annealer; also, this is the largest number which was ever factorized by means of any quantum device without relying on external search or preprocessing procedures run on classical computers.

Non-Covalent Assembly of Multiple Fluorophores in Edible Protein/Lipid Hydrogels for Applications in Multi-Step Light Harvesting and White-Light Emission.

The design and production of biodegradable and sustainable non-toxic materials for solar-energy harvesting and conversion is a significant challenge. Here, our goal was to report the preparation of novel protein/lipid hydrogels and demonstrate their utility in two orthogonal fundamental studies-light harvesting and white-light emission. Our hydrogels contained up to 90% water, while also being self-standing and injectable with a syringe. In one application, we loaded these hydrogels with suitable organic donor-acceptor dyes and demonstrated the energy-transfer cascade among four different dyes, with the most red-emitting dye as the energy destination. We hypothesized that the dyes were embedded in the protein/lipid phase away from the water pools as monomeric entities and that the excitation of any of the four dyes resulted in intense emission from the lowest-energy acceptor. In contrast to the energy-transfer cascade, we demonstrate the use of these gels to form a white-light-emitting hydrogel dye assembly, in which excitation migration is severely constrained. By restricting the dye-to-dye energy transfer, the blue, green, and red dyes emit at their respective wavelengths, thereby producing the composite white-light emission. The CIE color coordinates of the emission were 0.336 and 0.339-nearly pure white-light emission. Thus, two related studies with opposite requirements could be accommodated in the same hydrogel, which was made from edible ingredients by a simple method. These gels are biodegradable when released into the environment, sustainable, and may be of interest for energy applications.

The impact of supply chain management on a company's operation and decision based on the multidimensional data analysis of upstream and downstream industry market states.

This study provides data analysis support for the entire enterprise procurement management process, thereby improving the management effectiveness of supply chain operations. It analyzes upstream and downstream industry market status data in the supply chain and various primary data in enterprise management activities. By utilizing the Delphi method to screen and verify multimode market status data indicators, which significantly impact upstream and downstream industries in multiple rounds, 28 types of market status data were selected for analysis. This analysis aimed to investigate the effect of supply chain management on operational decisions within the company. The data reduction method based on adaptive statistics was the most effective in revealing the market status and promoting efficient operation decision-making based on supply chain management. This study also suggests a brand-new technique for measuring supply chain performance based on the Levenberg-Marquardt Back Propagation (LMBP) algorithm, offering a more impartial manner of doing so. The performance evaluation results showed a maximum error level of less than 0.4% when paired with empirical analysis. The proposed optimization model provides strategic guidance for optimizing supply chain management and improving overall performance.

Creation of a ready-to-use brexpiprazole suspension and the inflammation-mediated pharmacokinetics by intramuscular administration.

Brexpiprazole (BPZ), which is approved for the treatment of schizophrenia and major depressive disorder, has the potential to meet diverse clinical needs. This study aimed to develop a long-acting injectable (LAI) formulation of BPZ that could provide sustained therapeutic benefits. A library of BPZ prodrugs was screened through esterification, and BPZ laurate (BPZL) was identified as an optimal candidate. To achieve stable aqueous suspensions, a pressure- and nozzle size-controlled microfluidization homogenizer was utilized. The pharmacokinetics (PK) profiles, considering dose and particle size modulation, were investigated following a single intramuscular injection in beagles and rats. BPZL treatment resulted in sustained plasma concentrations above the median effective concentration (EC50) for 2 âˆ¼ 3 weeks, without exhibiting an initial burst release. Histological examination of foreign body reaction (FBR) in rats revealed the morphological evolution of an inflammation-mediated drug depot, confirming the sustained release mechanism of BPZL. These findings provide strong support for the further development of a ready-to-use LAI suspension of BPZL, which could potentially enhance treatment outcomes, improve patient adherence, and address the clinical challenges associated with long-term regimens of schizophrenia spectrum disorders (SSD).

Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly.

With the development of society, the incidence of dementia and type 2 diabetes (T2DM) in the elderly has been increasing. Although the correlation between T2DM and mild cognitive impairment (MCI) has been confirmed in the previous literature, the interaction mechanism remains to be clarified. To explore the co-pathogenic genes in the blood of MCI and T2DM patients, clarify the correlation between T2DM and MCI, achieve the purpose of early disease prediction, and provide new ideas for the prevention and treatment of dementia. We downloaded T2DM and MCI microarray data from GEO databases and identified the differentially expressed genes associated with MCI and T2DM. We obtained co-expressed genes by intersecting differentially expressed genes. Then, we performed GO and KEGG enrichment analysis of co-DEGs. Next, we constructed the PPI network and found the hub genes in the network. By constructing the ROC curve of hub genes, the most valuable genes for diagnosis were obtained. Finally, the correlation between MCI and T2DM was clinically verified by means of a current situation investigation, and the hub gene was verified by qRT-PCR. A total of 214 co-DEGs were selected, 28 co-DEGs were up-regulated, and 90 co-DEGs were down-regulated. Functional enrichment analysis showed that co-DEGs were mainly enriched in metabolic diseases and some signaling pathways. The construction of the PPI network identified the hub genes in MCI and T2DM co-expression genes. We identified nine hub genes of co-DEGs, namely LNX2, BIRC6, ANKRD46, IRS1, TGFB1, APOA1, PSEN1, NPY, and ALDH2. Logistic regression analysis and person correlation analysis showed that T2DM was correlated with MCI, and T2DM increased the risk of cognitive impairment. The qRT-PCR results showed that the expressions of LNX2, BIRC6, ANKRD46, TGFB1, PSEN1, and ALDH2 were consistent with the results of bioinformatic analysis. This study screened the co-expressed genes of MCI and T2DM, which may provide new therapeutic targets for the diagnosis and treatment of diseases.

Shared peripheral blood biomarkers for Alzheimer's disease, major depressive disorder, and type 2 diabetes and cognitive risk factor analysis.

Background: Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), and Major Depressive Disorder (MDD) have a higher incidence rate in modern society. Although increasing evidence supports close associations between the three, the mechanisms underlying their interrelationships remain elucidated. Objective: The primary purpose is to explore the shared pathogenesis and the potential peripheral blood biomarkers for AD, MDD, and T2DM. Methods: We downloaded the microarray data of AD, MDD, and T2DM from the Gene Expression Omnibus database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis to identify differentially expressed genes. We took the intersection of differentially expressed genes to obtain co-DEGs. Then, we performed GO and KEGG enrichment analysis on the common genes in the AD, MDD, and T2DM-related modules. Next, we utilized the STRING database to find the hub genes in the protein-protein interaction network. ROC curves were constructed for co-DEGs to obtain the most diagnostic valuable genes and to make drug predictions against the target genes. Finally, we conducted a present condition survey to verify the correlation between T2DM, MDD and AD. Results: Our findings indicated 127 diff co-DEGs, 19 upregulated co-DEGs, and 25 down-regulated co-DEGs. Functional enrichment analysis showed co-DEGs were mainly enriched in signaling pathways such as metabolic diseases and some neurodegeneration. Protein-protein interaction network construction identified hub genes in AD, MDD and T2DM shared genes. We identified seven hub genes of co-DEGs, namely, SMC4, CDC27, HNF1A, RHOD, CUX1, PDLIM5, and TTR. The current survey results suggest a correlation between T2DM, MDD and dementia. Moreover, logistic regression analysis showed that T2DM and depression increased the risk of dementia. Conclusion: Our work identified common pathogenesis of AD, T2DM, and MDD. These shared pathways might provide novel ideas for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosing and treating.

Actinomycotic primary canaliculitis: Predisposing factors, clinical characteristics, and treatment outcomes.

OBJECTIVE: Ocular actinomycosis is an uncommon progressive infection. The study aims to investigate the predisposing factors, clinical characteristics and treatment outcomes of culture-proven cases of Actinomycotic primary canaliculitis. METHODS: Single-center, retrospective, interventional case series. Culture-proven cases of Actinomyces-associated primary canaliculitis diagnosed and treated between January 2017 and December 2021 at the Beijing Tongren Eye Center, Capital Medical University were identified and reviewed for ocular and systemic risk factors, clinical presentations, microbiological profile, treatment modalities and outcomes. RESULTS: Of the 201 patients diagnosed with primary canaliculitis, 22 (10.9%) were caused by Actinomyces. The mean age at onset of 22 patients (21 women and one men) was 54 years. The lower canaliculus was most commonly involved (54.6%). The most frequent symptom was mattering without epiphora (77.3%) and clinical signs were punctal regurgitation of purulent discharge (100%) and expressible concretions (95.5%). Dry eye co-existed in 77.3% of patients, whereas no obvious systemic factors were found. Among 19 cases (86.0%) of identified Actinomyces species, A. odontolyticus (43.5%) was the predominant causative microorganism. There were 50% of patients with polymicrobial infection and the most common additional bacteria isolated were Streptococcus species. Conservative therapy combining repeated canalicular expression and irrigation with susceptible topical antibiotics achieved complete resolution in 86.4% of patients. CONCLUSIONS: Dry eye was identified in the vast majority of patients with Actinomycotic canaliculitis. Most cases are odontogenic in origin and the infection occurs in immunocompetent individuals. The conservative method combining canalicular expression and irrigation with topical susceptible antibiotics is recommendable as initial therapy.

Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis.

Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients. For this purpose, we first analysed both early intervention and later treatment with PPAR-γ agonists, according to the disease status. The involved studies indicated that early PPAR-γ agonist intervention is beneficial for patients and that high-dose PPAR-γ therapy may have a better clinical effect, especially in reversing the effects of cognitive impairment. Furthermore, the efficacy of pioglitazone (PIO) seems to be promising, particularly for patients with comorbid diabetes. PIO presented a better clinical curative effect and safety, compared with rosiglitazone (RSG). Thus, PPAR-γ agonists play an important role in the inflammatory response of AD or DM patients, and clinical therapeutics should focus more on relevant metabolic indices.

Bidirectional tightening of the anterior lamella for involutional lower eyelid entropion.

OBJECTIVE: Involutional entropion of the lower eyelid is commonly encountered in the elderly population. An ideal surgical method is supposed to address the underlying horizontal and vertical lower lid laxity simultaneously. This study aims to assess the effectiveness of bidirectional tightening of the anterior lamella to correct involutional lower lid entropion. METHODS: A prospective, noncomparative interventional case series was conducted from January 2017 to June 2021. Patients with involutional lower eyelid entropion received procedures combining lateral canthus-sparing orbicularis suspension with marginal rotating sutures to tighten the anterior lamella horizontally and vertically. The aesthetic appearance, postoperative complications, and patient satisfaction were evaluated. RESULTS: A total of 50 patients (56 eyelids) with a mean age of 73.1 ± 10.5 years were included. The mean follow-up period was 23.7 ± 17.1 months. All patients had immediate resolution of entropion and associated ocular symptoms. There were no recurrences or other major postoperative complications. Mild temporary ectropion was observed in 4 patients (4 eyelids) without the need for surgical intervention. CONCLUSION: The procedure of bidirectional anterior lamellar tightening restores the tension balance of eyelid margin. It provides a simple, successful, and less invasive option to treat involutional lower eyelid entropion.

Elevated serum uric acid is associated with cognitive improvement in older American adults: A large, population-based-analysis of the NHANES database.

Background: The many studies revealing a connection between serum uric acid (SUA) and dementia have reported conflicting results. This study sought to investigate the relations between SUA and cognitive function in older adults. Materials and methods: The sample was 2,767 American adults aged ≥60 years from the National Health and Nutrition Examination Survey 2011-2014. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease test, animal fluency test, digit symbol substitution test, and composite z-score. Multivariate linear regression analyses were conducted to estimate the association between SUA and cognitive function. Results: SUA level and cognitive function were significantly, positively correlated. Age significantly correlated with the association between SUA and cognitive function. Conclusion: These findings support a connection between SUA and cognition, showing a positive link between SUA and cognitive scores among older American adults. We contend that a slight rise in uric acid within the normal range is advantageous for enhanced cognition. To confirm the precise dose-time-response relation, more tests will be needed.

Filling an ARHGAP in our knowledge of human brain evolution.

The human cerebral cortex has tripled in size since our divergence from a common ancestor with chimpanzees. This cortical expansion is driven by the increased proliferative capacity of radial glia (RG), a neural progenitor cell (NPC) population that generates cortical neurons. RG along the ventricular zone (VZ) produce neurons and also give rise to basal progenitors (BPs), which migrate to the embryonic subventricular zone (SVZ). Comparative studies suggest that the increased proliferative capacity of human NPCs involves cell-intrinsic mechanisms (Otani et al, 2016), and a number of human-specific genetic changes have recently been linked to NPC proliferation. In particular, overexpression studies in model organisms indicate that the human-specific gene ARHGAP11B is sufficient to increase BP abundance when introduced into the developing brain of non-human model organisms (Florio et al, 2015; Kalebic et al, 2018; Heide et al, 2020). However, studying human-specific mutations in a hominid genetic and developmental context, rather than in more divergent model organisms, could provide further insight into the evolutionary consequences and effect size of human mutations. Fischer et al (2022) now developed a novel organoid electroporation technique to establish the necessity and sufficiency of ARHGAP11B for BP proliferation in cells from humans and our closest living relative, chimpanzees (Fig 1).

Incidence of coronary drug-eluting stent fracture: A systematic review and meta-analysis.

Background: Reported evidence of coronary stent fracture (CSF) has increased in recent years. The purpose of this study was to determine reliable estimates of the overall incidence of CSF. Methods and results: The MEDLINE, Embase and Cochrane databases were searched until March 18, 2022. Pooled estimates were acquired using random effects models. Meta-regression and subgroup analysis were used to explore sources of heterogeneity, and publication bias was evaluated by visual assessment of funnel plots and Egger's test. Overall, 46 articles were included in this study. Estimates of CSF incidence were 5.5% [95% confidence interval (CI): 3.7-7.7%] among 39,953 patients based on 36 studies, 4.8% (95% CI: 3.1-6.8%) among 39,945 lesions based on 29 studies and 4.9% (95% CI: 2.5-9.4%) among 19,252 stents based on 8 studies. There has been an obvious increase in the incidence of CSF over the past two decades, and it seems that the duration of stent placement after stent implantation has no impact on incidence estimation. Conclusion: The incidence of CSF was 5.5% among patients, 4.8% for lesions and 4.9% for stents and increased over the past 20 years. The duration of stent placement after stent implantation was found to have no impact on the incidence of CSF, but drug-eluting stent (DES) types and right coronary artery (RCA) lesions influenced the pooled incidence. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022311995], identifier [CRD42022311995].

Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis.

BACKGROUND: Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients. METHODS: In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups. RESULTS: Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE. CONCLUSION: Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.

Altered Spontaneous Brain Activity and Network Property in Patients With Congenital Monocular Blindness.

Individuals with congenital monocular blindness may have specific brain changes since the brain is prenatally deprived of half the normal visual input. To explore characteristic brain functional changes of congenital monocular blindness, we analyzed resting-state functional MRI (rs-fMRI) data of 16 patients with unilateral congenital microphthalmia and 16 healthy subjects with normal vision to compare intergroup differences of amplitude of low frequency fluctuations (ALFFs), functional connectivity (FC), and network topolgoical properties. Compared with controls, patients with microphthalmia exhibited significantly lower ALFF values in the left inferior occipital and temporal gyri, superior temporal gyrus, inferior parietal lobe and post-central gyrus, whereas higher ALFF in the right middle and inferior temporal gyri, middle and superior frontal gyri, left superior frontal, and temporal gyri, such as angular gyrus. Meanwhile, FC between left medial superior frontal gyrus and angular gyrus, FC between left superior temporal gyrus and inferior parietal lobe and post-central gyrus decreased in the patients with congenital microphthalmia. In addition, a graph theory-analysis revealed increased regional network metrics (degree centrality and nodal efficiency) in the middle and inferior temporal gyri and middle and superior frontal gyri, while decreased values in the inferior occipital and temporal gyri, inferior parietal lobule, post-central gyrus, and angular gyrus. Taken together, patients with congenital microphthalmia had widespread abnormal activities within neural networks involving the vision and language and language-related regions played dominant roles in their brain networks. These findings may provide clues for functional reorganization of vision and language networks induced by the congenital monocular blindness.

Effect of the long-term lack of half visual inputs on the white matter microstructure in congenital monocular blindness.

Individuals with congenital monocular blindness are born without binocular vision and stereopsis, the effects of which on the brain microstructure are largely unknown. This study aims to investigate the microstructural characteristics of white matter tracts over the whole brain in congenital monocular blindness. We used T1-weighted MRI and diffusion tensor imaging (DTI) to investigate the microstructural characteristics of the brain in 16 patients with unilateral congenital microphthalmia (CM) and 16 matched normally sighted controls. The DTI-derived metrics were assessed using atlas-level analysis with FDR correction and TBSS-level analysis with threshold-free cluster enhancement correction (TFCE). CM exhibited significantly abnormal DTI-derived indices (p < 0.05, q < 0.05 of FDR correction) as follows: 1) declined fractional anisotropy (FA) in the inferior fronto-occipital fasciculus contralateral to the affected eye, bilateral inferior longitudinal fasciculus, while enhanced in the ipsilateral cingulum; 2) increased local diffusion homogeneity in the contralateral corticospinal tract while decreased in the ipsilateral superior longitudinal fasciculus; 3) reduced axial diffusivity (AD) in the body of corpus callosum. Meanwhile, the alteration tendencies of FA, AD, and radial diffusivity (RD) in the forceps major (increased FA and AD, decreased RD) and forceps minor (decreased FA and AD, increased RD) were interestingly opposite. These results reveal extensive microstructural abnormalities of WM ranging from sensory modalities to other cross-modal pathways involving language, execution, memory, emotion, fine movement, and interhemispheric communication as well. This study provides novel evidence of large-scale subcortical involvement subsequent to prolonged loss of half visual inputs, which may be associated with developmental delay and compensatory plasticity.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.