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The present study investigated a size illusion composed of two horizontal lines that were vertically separated and parallel to each other. When the two lines were of equal length, the upper line was consistently perceived to be a little longer than the lower line, therefore it was termed as horizontal parallel lines (HPL) illusion. We investigated the effect of color and luminance contrast on the HPL illusion by manipulating the color and luminance of the two lines. Results indicated the following: (1) differences in color between the two lines reduced the illusion; (2) differences in luminance between the two lines reduced the illusion; (3) Effect 1 was greater than Effect 2; (4) the illusory effect could not be affected as long as both of the lines were of the same color or luminance. The results suggest that the color or luminance contrast may contribute to the overall decrease in the illusory effect for lines with different colors/luminances, but generally the illusion decreases as the two lines are less similar to each other. These findings indicate that the similarity or ‘sameness’ effect dominates the effect of color/luminance contrast on the size illusion over the effect resulted from contrast difference or depth perception.

Background Current copy number variation (CNV) identification methods have rapidly become mature. However, the postdetection processes such as variant interpretation or reporting are inefficient. To overcome this situation, we developed REDBot as an automated software package for accurate and direct generation of clinical diagnostic reports for prenatal and products of conception (POC) samples. Methods We applied natural language process (NLP) methods for analyzing 30,235 in‐house historical clinical reports through active learning, and then, developed clinical knowledge bases, evidence‐based interpretation methods and reporting criteria to support the whole postdetection pipeline. Results Of the 30,235 reports, we obtained 37,175 CNV‐paragraph pairs. For these pairs, the active learning approaches achieved a 0.9466 average F1‐score in sentence classification. The overall accuracy for variant classification was 95.7%, 95.2%, and 100.0% in retrospective, prospective, and clinical utility experiments, respectively. Conclusion By integrating NLP methods in CNVs postdetection pipeline, REDBot is a robust and rapid tool with clinical utility for prenatal and POC diagnosis.

Reticular chemistry has been focused on making simple structures in which a few kinds of components are linked to make crystals such as metal–organic frameworks (MOFs). While this chemistry has grown into a large field, a more extensive area with fascinating directions is emerging through the introduction of multiplicity and variation into the components of MOFs. When the MOF backbone is composed of more than two kinds of components, the resulting backbone multiplicity is regular repeats of those units. However, when variations involve multiple functionalization of the organic linkers or multiple metalation of metal-containing building units, it results in an aperiodic spatial arrangement of these variations, without altering the regularity of the MOF backbone. Such variance is represented by unique sequences of functionality or metal, and the very aperiodic nature of their spatial arrangement gives rise to anisotropy. These MOF constructs represent a new form of matter in which the sequences of such units are bound to an ordered backbone, thus adding complexity to an otherwise simple system, while preserving its overall crystallinity. It’s worth noting that, when a molecule capable of either continuous or multistate anisotropic motion is integrated within a sequence in a MOF, the resulting property goes beyond what is possible in simple systems. We term this emerging area ‘anisotropic reticular chemistry’. Introducing multiplicity and variation into the components of metal–organic frameworks has emerged as new fascinating directions in reticular chemistry. In this Review, the variances in the framework backbone, functionality and metal, and their leading to sequences of chemical information, are highlighted. Anisotropy in these structures is imposed by the variance and realized along a specific direction.

AimsTo investigate the function and the corresponding neurovascular structures in patients with diabetes without clinically detectable retinopathy.Methods Sixty-six patients with type 2 diabetes without retinopathy (NDR) and 62 healthy controls were recruited. The 16 and 32 Tds flicker electroretinography (ERG) was performed using a mydriasis-free, full-field flicker ERG recording device (RETeval). The vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP), FD300 and ganglion cell complex (GCC) thickness in the macula were quantified using optical coherence tomography angiography (OCTA). The retinal nerve fibre layer (RNFL) thickness and the radial peripapillary capillary (RPC) density in the peripapillary area were also measured with OCTA.ResultsParafoveal and perifoveal VD in both SCP and DCP decreased in NDR group in comparison to control group (all p<0.01). However, macular GCC thickness was comparable between the two groups (p=0.661). Peripapillary RNFL thickness and RPC density were significantly lower in NDR group (p<0.001 and p=0.009, respectively). With regard to ERG parameters, delayed implicit time and decreased amplitude were found in NDR group in comparison to the control group (all p<0.01). In the multiple linear regression analyses, delayed implicit time for 16 and 32 Tds stimuli was significantly correlated with increased HbA1c (β=0.350, p<0.001; β=0.328, p<0.001, respectively) and decreased VD of SCP in the parafoveal region (β=−0.266, p=0.013; β=−0.253, p=0.005, respectively). However, delayed implicit time for 16 and 32 Tds stimuli was not correlated with the thickness of GCC (β=−0.008, p=0.818) in multiple linear regression analyses.ConclusionFunctional and structural impairments have already started in diabetic retina even in the absence of visible retinal lesions. Subtle microvascular abnormalities rather than ganglion cell loss might be associated with early functional changes in NDR patients. Poor control of blood glucose was associated with delayed implicit time of flicker ERG in preclinical diabetic retinopathy.

Objective This study aimed to identify features of white matter network attributes based on diffusion tensor imaging (DTI) that might lead to progression from mild cognitive impairment (MCI) and construct a comprehensive model based on these features for predicting the population at high risk of progression to Alzheimer’s disease (AD) in MCI patients. Methods This study enrolled 121 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Among them, 36 progressed to AD after four years of follow-up. A brain network was constructed for each patient based on white matter fiber tracts, and network attribute features were extracted. White matter network features were downscaled, and white matter markers were constructed using an integrated downscaling approach, followed by forming an integrated model with clinical features and performance evaluation. Results APOE4 and ADAS scores were used as independent predictors and combined with white matter network markers to construct a comprehensive model. The diagnostic efficacy of the comprehensive model was 0.924 and 0.919, sensitivity was 0.864 and 0.900, and specificity was 0.871 and 0.815 in the training and test groups, respectively. The Delong test showed significant differences ( P  < 0.05) in the diagnostic efficacy of the combined model and APOE4 and ADAS scores, while there was no significant difference ( P  > 0.05) between the combined model and white matter network biomarkers. Conclusions A comprehensive model constructed based on white matter network markers can identify MCI patients at high risk of progression to AD and provide an adjunct biomarker helpful in early AD detection.

Background: As one of the important components of immunotherapies, mRNA vaccines have displayed promising clinical outcomes in solid tumors. Nonetheless, their efficacy remains unclear in pancreatic adenocarcinoma (PAAD). Given the interaction of pyroptosis with anticancer immunity, our study aims to identify pyroptosis-related antigens for mRNA vaccine development and discern eligible candidates for vaccination. Methods: Utilizing gene expression data from TCGA and ICGC, we integrated RNA-seq data and compared genetic alterations through cBioPortal. Differential gene expressions were integrated using GEPIA. Relationships between immune cell abundance and tumor antigens were analyzed and visualized via TIMER. WGCNA facilitated the clustering of pyroptosis-related genes, identification of hub genes, and pathway enrichment analyses. Pyroptosis landscape was depicted through graph learning-based dimensional reduction. Results: Four overexpressed and mutant pyroptosis-related genes associated with poor prognosis were identified as potential antigens for mRNA vaccines in PAAD, including ANO6, PAK2, CHMP2B, and RAB5A. These genes displayed positive associations with antigen-presenting cells. PAAD patients were stratified into three pyroptosis subtypes. Notably, the PS3 subtype, characterized by a lower mutation count and TMB, exhibited “cold” immunological traits and superior survival compared to other subtypes. The pyroptosis landscape exhibited considerable heterogeneity among individuals. Furthermore, the turquoise module emerged as an independent prognostic indicator and patients with high expressions of hub genes might not be suitable candidates for mRNA vaccination. Conclusions: In PAAD, ANO6, PAK2, CHMP2B, and RAB5A are prospective pyroptosis-related antigens for mRNA vaccine development, which holds potential benefits for patients classified as PS3 and those with diminished hub gene expressions, providing insights into personalized mRNA vaccine strategies.

BackgroundFlow diverter (FD) is widely used in the treatment of intracranial aneurysms. However, thromboembolic events (TEs) continue to be the major complications during the periprocedural phase. To evaluate the safety and efficacy of the prophylactic use of tirofiban, combined with the conventional dual antiplatelet therapy (DAT), as a new antiplatelet protocol in patients with intracranial aneurysms treated with FDs.MethodsAt least 3–5 days before the procedure, daily DAT were administrated to the patients. Tirofiban was administered as an intravenous bolus (5 µg/kg) over a 3 min period during or immediately after FD deployment, followed by a 0.05 µg/kg/min maintenance infusion for 24–48 hours. Periprocedural TEs and hemorrhagic events (HEs) were recorded.ResultsA total of 331 patients were included, including 229 (69.2%) who received tirofiban administration (tirofiban group) and 102 (30.8%) who received only DAT (non-tirofiban group). Periprocedural TEs occurred in 12 (3.6%) patients, including eight (7.8%) in the non-tirofiban group and four (1.7%) in the tirofiban group. In multivariate analysis, patients receiving tirofiban administration had significantly lower TEs as compared with those who received only DAT (P=0.004). Balloon angioplasty and longer procedure time (>137 min) were also risk factors for TEs. Also, no increase was observed in the rate of HEs related to tirofiban administration.ConclusionsThe current study suggested that prophylactic administration of tirofiban combined with conventional oral DAT seems safe and efficient for preventing TEs during FD treatment of unruptured intracranial aneurysms. Balloon angioplasty and prolonged procedure are associated with a high risk of TEs.

Background Cataract is a leading cause of blindness worldwide. However, little is known about sex differences in cataracts. Our study aimed to explore potential sex differences in the relationships between key social, lifestyle, and physical health risk factors and the incidence of cataracts. Methods A total of 117,972 participants from the UK Biobank were included in this prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios (HRs) and female-to-male ratios of HRs (RHRs) with 95% confidence intervals (CIs) for cataract risk factors. Poisson regression was used to assess the incidence of cataracts (per 10,000 person-years). Results A total of 117,972 individuals without preexisting eye diseases were enroled in the analysis. 4172 subjects (54.8% female) were diagnosed with cataracts during follow-up. The crude incidence rates per 10,000 person-years were 35.06 for females and 29.15 for males. The incidence of cataracts increased in both males and females with factors such as Asian or Black ethnicity, smoking status, obesity, diabetes, and myopia. However, males who consumed alcohol or were unemployed suffered a greater risk of cataracts compared to their female counterparts, while high socioeconomic status, elevated blood pressure and metabolic syndrome were associated with a greater risk of cataracts in females than in males. Conclusion This study provides a comprehensive overview of sex differences in the associations between cataracts and various risk factors. Our findings highlight that socioeconomic and lifestyle risk factors are more strongly linked to cataract risk in males, whereas females with systemic diseases face a greater risk of developing cataract.

Age-related hearing loss (AHL) is the most common sensory disorder in the elderly population, and the etiologies are diverse. To understand the underlying mechanisms of AHL, one strategy is to identify correlates of the disease for comprehensive evaluation of treatment approaches. Dysfunction and degeneration of spiral ganglion neurons (SGNs) are major contributors to AHL. Previously, we showed that one of the changes in the aging auditory system is SGN excitability increase in mice. Since hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in determining neuronal excitability, we predicted that HCN channels in SGNs are involved in AHL. To investigate the contribution of HCN channels to AHL, we examined the expression and biophysical properties of HCN channels in SGNs from adult (2-3 months) and 11-12-month-old mice. We report a dramatic increase of HCN channel current (Ih) in SGNs in old mice (11-12 months old). The results matched well with increased expression of HCN1 and HCN2 subunits, suggesting that upregulation of HCN channels in SGNs is one of the important facets of the aging SGNs. Moreover, the activity of Ih produced a major impact on the firing properties of SGNs in older mice. The upregulation of Ih may contribute to AHL by regulating SGN excitability. We assessed whether increased SGNs excitability dovetail with neurodegeneration. Apoptosis-inducing factor (AIF)-mediated apoptosis in SGNs was observed in old mice and activation of HCN channels mediates AIF activation. Thus, these findings demonstrate stark correlation between age-dependent increased expression of HCN channels and Ih, and apoptosis in SGNs, which may contribute towards the varied mechanisms of AHL.