Development and validation of a random survival forest model for predicting long-term survival of early-stage young breast cancer patients based on the SEER database and an external validation cohort.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

Longitudinal Changes in Choroidal Thickness Varied With Refractive Progression in Myopic and Non-Myopic Children: A Two-Year Cohort Study.

Purpose: To evaluate the longitudinal changes in subfoveal choroidal thickness (SFCT) in children with different refractive status. Methods: A total of 2290 children 3 to 14 years old who attended the first year of kindergarten (G0), first year of primary school (G1), fourth year of primary school (G4), or first year of junior high school (G7) in Guangzhou, China, were recruited and followed up for 2 years. All participants received cycloplegic autorefraction, axial length measurement and SFCT measurement using a CIRRUS HD-OCT device. Children were divided into groups of persistent non-myopia (PNM), persistent myopia (PM), or newly developed myopia (NDM). Children in the PNM and PM groups were further divided into subgroups of stable refraction (absolute mean annual spherical equivalent refraction [SER] change < 0.5 D) and refractive progression (absolute mean annual SER change ≥ 0.5 D). Results: The mean ± SD ages for the G1 to G7 cohorts were 3.89 ± 0.30, 6.79 ± 0.47, 9.71 ± 0.34, and 12.54 ± 0.38, years, respectively. SFCT consistently decreased in the NDM group across the G1 to G7 cohorts (all P < 0.001) and exhibited variability across different age cohorts in the PNM and PM groups. Further subgroup analysis revealed significant thickening of SFCT in the PNM-stable group among the G0, G1, and G7 cohorts (all P < 0.05), whereas it remained stable among all cohorts in the PM-stable group (all P > 0.05). Conversely, SFCT exhibited thinning in the G4 and G7 cohorts in the PM-progressive group (both P < 0.01) and for the entire cohort of children in the PNM-progressive group (P = 0.012). Conclusions: SFCT increased in nonmyopic children with stable refraction, remained stable in myopic children maintained stable refraction, and decreased in those with refractive progression, whether they were myopic or not.

Pathogenic mechanisms and therapeutic implications of extracellular matrix remodelling in cerebral vasospasm.

Cerebral vasospasm significantly contributes to poor prognosis and mortality in patients with aneurysmal subarachnoid hemorrhage. Current research indicates that the pathological and physiological mechanisms of cerebral vasospasm may be attributed to the exposure of blood vessels to toxic substances, such as oxyhaemoglobin and inflammation factors. These factors disrupt cerebral vascular homeostasis. Vascular homeostasis is maintained by the extracellular matrix (ECM) and related cell surface receptors, such as integrins, characterised by collagen deposition, collagen crosslinking, and elastin degradation within the vascular ECM. It involves interactions between the ECM and smooth muscle cells as well as endothelial cells. Its biological activities are particularly crucial in the context of cerebral vasospasm. Therefore, regulating ECM homeostasis may represent a novel therapeutic target for cerebral vasospasm. This review explores the potential pathogenic mechanisms of cerebral vasospasm and the impacts of ECM protein metabolism on the vascular wall during ECM remodelling. Additionally, we underscore the significance of an ECM protein imbalance, which can lead to increased ECM stiffness and activation of the YAP pathway, resulting in vascular remodelling. Lastly, we discuss future research directions.

Recycling coral waste into eco-friendly UHPC: Mechanical strength, microstructure, and environmental benefits.

On islands far away from the mainland, the raw materials for concrete production are often more difficult to obtain. Converting the coral waste generated during the island construction process into a marine ultra-high performance concrete (UHPC) mixture is an eco-friendly strategy. Coral powder (CP) is used to partially replace cement and silica fume (SF), and its mechanical strength, microstructure and environmental benefits are evaluated. Results show that using a small amount of CP (5%) to replace cement can improve the mechanical properties of UHPC, but the strength of UHPC decreases with the further increase of CP content. From the perspective of nanoindentation test, an appropriate amount of CP refines the pore structure of the UHPC matrix and increases the content of C-S-H, especially the proportion of high-density C-S-H. When 15% of SF is replaced by CP (SF15), the strength of UHPC decreases due to the decrease of C-S-H phase and the deterioration of microstructure. In terms of the width of the interface transition zone, the width of the C5 sample (CP replace 5% cement) is decreased by 16.7% compared with the control group, while the width of the SF15 group is increased by 38.9%. Compared with conventional UHPC, CP-based UHPC has lower carbon emission and non-renewable energy consumption, which effectively utilizes waste and promotes sustainability.

The Temporal Window of Visual Processing in Aging.

Purpose: Aging affects a variety of visual functions. In this study, we aim to quantitatively investigate the temporal characteristics of visual processing in aging. Methods: Twelve younger (24.1 ± 1.6 years) and 12 older observers (58.4 ± 3.6 years) participated in the study. All participants had normal or corrected-to-normal vision. The contrast thresholds of the participants were measured using an orientation discrimination task with white external noise masks. The target-mask stimulus onset asynchronies were 16.7 ms, 33.4 ms, 50.0 ms, 83.4 ms, and ∞ (no external noise masks) in separate conditions. The signal stimulus was carefully chosen such that it was equally visible for the younger and older participants. An elaborated perceptual template model (ePTM) was fit to the data of each participant. Results: Without masks, there was no difference in contrast thresholds between the younger and older groups (P = 0.707). With masks, contrast thresholds in the older group elevated more than those in the younger group, and the pattern of threshold elevation differed in the two groups. The ePTM fitted the data well, with the older observers having lower template gains than the younger observers (P = 3.58 × 10-6). A further analysis of the weight parameters of the temporal window revealed that the older observers had a flatter temporal window than the younger observers (P = 0.025). Conclusions: Age-related temporal processing deficits were found in older observers with normal contrast sensitivity to the signal stimuli. The deficits were accounted for by the inferior temporal processing window of the visual system in aging.

Comparing Spatial Contrast Sensitivity Functions Measured With Digit and Grating Stimuli.

PURPOSE: The contrast sensitivity function (CSF) is measured traditionally with grating stimuli. Recently, we introduced a new set of digit stimuli to improve the efficiency of CSF tests for people unfamiliar with the Latin alphabet. Given the significant differences between grating and digit stimuli, we conducted this study to evaluate whether the estimated CSFs from the digit test are equivalent to those from the grating test. METHODS: The CSFs of five young (with Psi) and five older (with quick CSF [qCSF]) participants were measured with a two-alternative forced choice (2AFC) grating orientation identification task and a 10-digit identification task. The CSFs obtained from the two tasks were compared. RESULTS: The estimated CSFs from the two tasks matched well after controlling for stimulus types and performance levels. The root mean square error (RMSE) between the CSFs from the two tasks was 0.093 ± 0.029 (300 trials) and 0.131 ± 0.016 (100 trials) log10 units for young and older observers, respectively. To reach the same standard deviation (0.1 log10 units), the digit CSF test required fewer trials/less time than the classic grating CSF for young (60 vs. 90 trials) and older (15 vs. 21 trials) observers. The complicated behavioral responses of the observer in the 10-AFC digit identification task can be accounted by a model that consists of digit similarity and one single parameter of sensory noise (χ2[99] = 3.42, P = 0.999). CONCLUSIONS: The estimated CSFs from the digit test highly matched those obtained from the grating test; however, the digit test is much more efficient. TRANSLATIONAL RELEVANCE: The digit CSF test provides a compatible assessment of the CSF as the traditional grating CSF test with more efficiency.

Measuring the Contrast Sensitivity Function Using the qCSF Method With 10 Digits.

PURPOSE: The Bayesian adaptive quick contrast sensitivity function (qCSF) method with a 10-letter identification task provides an efficient CSF assessment. However, large populations are unfamiliar with letters and cannot benefit from this test. To overcome the barrier, we conducted this study. METHOD: A new font for digits (0∼9) was created. The digits were then filtered with a raised cosine filter, rescaled to different sizes to cover spatial frequencies from 0.5 to 16 cycles per degree (cpd), and used as stimuli in a 10-alternative forced choice (10AFC) digit identification task. With the 10AFC digit identification task, the CSFs of five young and five old observers were measured using the qCSF and Psi methods. The estimates from the latter served as reference. RESULTS: The new digit font showed significantly improved similarity structure, Levene's test, F(1, 88) = 6.36, P = 0.014. With the 10-digit identification task, the CSFs obtained with the qCSF method matched well with those obtained with the Psi method (root mean square error [RMSE] = 0.053 log10 units). With approximately 30 trials, the precision of the qCSF method reached 0.1 log10 units. With approximately 75 trials, the precision of the CSFs obtained with the qCSF was comparable to that of the CSFs measured by the Psi method in 150 trials. CONCLUSIONS: The qCSF with the 10 digit identification task is validated for both young and old observers. TRANSLATIONAL RELEVANCE: The qCSF method with the 10-digit identification task provides an efficient and precise CSF test especially for people who are unfamiliar with letters.

Porcine FcεRI Mediates Porcine Reproductive and Respiratory Syndrome Virus Multiplication and Regulates the Inflammatory Reaction.

Porcine reproductive and respiratory syndrome virus (PRRSV) shows characteristic antibody-dependent enhancement (ADE) of infection and causes porcine systemic inflammation, which is similar to a type I allergic reaction; however, the role of porcine FcεRI in ADE is still unclear. In this study, the expression of different Fc receptors (FcRs) on macrophages was investigated in a PRRSV 3D4/21 cell infection model in the presence or absence of PRRSV antibody. The transcription level of FcγII and FcεRI was significantly up-regulated under PRRSV-antibody complex infection. Internalization and proliferation of PRRSV were promoted by the ADE mechanism when FcεRI was expressed in permissive 3D4/21 cells and the non-permissive cell line HEK 293T. Transcriptome sequencing data showed that the expression levels of AKT, ERK and other signal molecules in the anti-inflammatory pathway were significantly increased, especially in the cells infected with the PRRSV-antibody immune complex. Inflammatory regulatory molecules such as PLA2G6, LOX, TRPM8 and TRPM4 were significantly up-regulated following PRRSV infection but significantly down-regulated in the cells infected with the PRRSV-antibody immune complex. Our results demonstrated that FcεRI could be involved in PRRSV ADE, the antigen presenting process and regulation of the inflammatory response during PRRSV infection, which provides new insights into PRRSV infection mediated by FcεRI and the PRRSV-antibody immune complex.

Staphylococcus enterotoxin profile of China isolates and the superantigenicity of some novel enterotoxins.

The genus of staphylococcus widely distributes in environments and contributes to a variety of animal and human diseases. The enterotoxins (SEs) secreted by this type of pathogen have been the leading cause of bacterial toxic shock syndrome and food poisoning, and thus present a substantial concern to public health. In this study, we analyzed the superantigen profile of 122 staphylococcus strains isolated from diverse sources. When screened for the presence and prevalence of 17 known se or se-like (sel) genes, except selj, all other genes were detected in these isolates. In particular, 95.9% of the isolates harbored at least one se/sel gene. Moreover, 47.5% of them bore at least 5. Remarkably, several non-pathogenic species of animal- and environment-origin were also found to carry multiple se/sels. The most frequent genes detected were tsst (62.3%), sei (54.1%), and seb (46.7%), followed by some sel genes (selo, selu, and selm), which also were present at relatively high frequency (20-30%). The generated data improved understanding of strain-specific differences in enterotoxin expression. The gene products of the latter (selo and selu) were subsequently analyzed for their antigenicity in a mouse model using purified E. coli-based recombinant proteins. The studies revealed a strong activity for SEO in induction of T-lymphocyte proliferation and production of various inflammatory cytokines either in vivo or in vitro. In contrast, SEU exhibited little superantigenic effects. The molecular basis for the difference in antigenicity was analyzed by 3D homology remodeling, which revealed a difference in binding and affinities for MHC-II molecules and TCR Vß region.